Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs

PubMed Central

Godman, Brian; Malmström, Rickard E.; Diogene, Eduardo; Jayathissa, Sisira; McTaggart, Stuart; Cars, Thomas; Alvarez-Madrazo, Samantha; Baumgärtel, Christoph; Brzezinska, Anna; Bucsics, Anna; Campbell, Stephen; Eriksson, Irene; Finlayson, Alexander; Fürst, Jurij; Garuoliene, Kristina; Gutiérrez-Ibarluzea, Iñaki; Hviding, Krystyna; Herholz, Harald; Joppi, Roberta; Kalaba, Marija; Laius, Ott; Malinowska, Kamila; Pedersen, Hanne B.; Markovic-Pekovic, Vanda; Piessnegger, Jutta; Selke, Gisbert; Sermet, Catherine; Spillane, Susan; Tomek, Dominik; Vončina, Luka; Vlahović-Palčevski, Vera; Wale, Janet; Wladysiuk, Magdalena; van Woerkom, Menno; Zara, Corinne; Gustafsson, Lars L.

2014-01-01

Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. Objective: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities. Methodology: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies. Results: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding. PMID:24959145

Effectiveness and Safety of an Overnight Patch Containing Allium cepa Extract and Allantoin for Post-Dermatologic Surgery Scars.

PubMed

Prager, Welf; Gauglitz, Gerd G

2018-06-14

An occlusive overnight intensive patch medical device (OIP) containing onion extract and allantoin has been developed for preventing and treating dermatologic scars and keloids. Here, we examined the efficacy and safety of the OIP for post-dermatologic surgery scars. This was an intra-individual randomized, observer-blind, controlled study in adults with post-dermatologic surgery scars. Two scars per subject were randomized to no treatment or overnight treatment with the OIP for 12-24 weeks. Scar quality was assessed using the Patient and Observer Scar Assessment Scale (POSAS) and a Global Aesthetic Improvement Scale. A total of 125 subjects were included. The decrease in observer-assessed POSAS from baseline was significantly greater for treated than untreated scars at week 6 (p < 0.001) and 24 (p = 0.001). The decrease in patient-assessed POSAS was significantly greater for the treated scar than the untreated scar at week 12 (p = 0.017) and 24 (p = 0.014). Subject- and investigator-evaluated Global Aesthetic Improvement Scale scores were higher for the treated than the untreated scar at all visits. All subjects considered the global comfort of the OIP to be good or very good, and no safety concerns were identified. This study confirmed that the OIP safely promotes scar healing after minor dermatologic surgery. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Food safety educational intervention positively influences college students' food safety attitudes, beliefs, knowledge, and self-reported practices.

PubMed

Yarrow, Linda; Remig, Valentina M; Higgins, Mary Meck

2009-01-01

In this study, the authors evaluated college students' food safety attitudes, beliefs, knowledge, and self-reported practices and explored whether these variables were positively influenced by educational intervention. Students (n=59), were mostly seniors, health or non-health majors, and responsible for meal preparation. Subjects completed a food safety questionnaire (FSQ) prior to educational intervention, which consisted of three interactive modules. Subjects completed module pre-, post-, and post-posttests. The FSQ was also administered after exposure to intervention and five weeks later to determine changes in food safety attitudes, beliefs, knowledge, and self-reported practices. Students' FSQ attitude scores increased from 114 to 122 (p < or = .001); FSQ belief and knowledge scores improved from 86 to 98 (p < or = .001) and from 11 to 13 (p < or = .001), respectively. Food safety knowledge was also measured by module pre- and posttests, and improved significantly after intervention for all students, with health majors having the greatest increase. Intervention resulted in improved food safety self-reported practices for health majors only. The educational intervention appeared effective in improving food safety beliefs and knowledge. For health majors, attitudes and some self-reported practices improved. For all areas, the strongest effects were seen in health majors.

Communicating vaccine safety during the development and introduction of vaccines.

PubMed

Kochhar, Sonali

2015-01-01

Vaccines are the best defense available against infectious diseases. Vaccine safety is of major focus for regulatory bodies, vaccine manufacturers, public health authorities, health care providers and the public as vaccines are often given to healthy children and adults as well as to pregnant woman. Safety assessment is critical at all stages of vaccine development. Effective, clear and consistent communication of the risks and benefits of vaccines and advocacy during all stages of clinical research (including the preparation, approvals, conduct of clinical trials through the post marketing phase) is critically important. This needs to be done for all major stakeholders (e.g. community members, Study Team, Health Care Providers, Ministry of Health, Regulators, Ethics Committee members, Public Health Authorities and Policy Makers). Improved stakeholder alignment would help to address some of the concerns that may affect the clinical research, licensing of vaccines and their wide-spread use in immunization programs around the world.

Promoting a Culture of Safety as a Patient Safety Strategy

PubMed Central

Weaver, Sallie J.; Lubomksi, Lisa H.; Wilson, Renee F.; Pfoh, Elizabeth R.; Martinez, Kathryn A.; Dy, Sydney M.

2015-01-01

Developing a culture of safety is a core element of many efforts to improve patient safety and care quality. This systematic review identifies and assesses interventions used to promote safety culture or climate in acute care settings. The authors searched MEDLINE, CINAHL, PsycINFO, Cochrane, and EMBASE to identify relevant English-language studies published from January 2000 to October 2012. They selected studies that targeted health care workers practicing in inpatient settings and included data about change in patient safety culture or climate after a targeted intervention. Two raters independently screened 3679 abstracts (which yielded 33 eligible studies in 35 articles), extracted study data, and rated study quality and strength of evidence. Eight studies included executive walk rounds or interdisciplinary rounds; 8 evaluated multicomponent, unit-based interventions; and 20 included team training or communication initiatives. Twenty-nine studies reported some improvement in safety culture or patient outcomes, but measured outcomes were highly heterogeneous. Strength of evidence was low, and most studies were pre–post evaluations of low to moderate quality. Within these limits, evidence suggests that interventions can improve perceptions of safety culture and potentially reduce patient harm. PMID:23460092

Pharmacovigilance in pharmaceutical companies: An overview

PubMed Central

Mammì, Maria; Citraro, Rita; Torcasio, Giovanni; Cusato, Gennaro; Palleria, Caterina; di Paola, Eugenio Donato

2013-01-01

Pharmacovigilance is responsible for monitoring the safety of medicines in normal clinical use and during clinical trials. In the light of the experience acquired and following an assessment by the Commission of the Union system of pharmacovigilance, it has become clear that it is necessary to take measures in order to improve the operation of Union law on the pharmacovigilance of medicinal products for human use. Regulation (EU) No 1235/2010 and Directive 2010/84/EU introduced new legislation on pharmacovigilance. The marketing authorization holder should be responsible for continuously monitoring the safety of its medicinal products for human use, for informing the authorities of any changes that might have an impact on the marketing authorization, and for ensuring that the product information is kept up-to-date. Marketing authorization holders (MAH) record all suspected adverse reactions occurring in the European Union or in the third countries, and which are brought to their attention spontaneously by the patients or their health care, or occurring in the context of post-authorization study. For all medicinal products is mandatory to maintain a pharmacovigilance system master file (PSMF). According to the Legislative Decree 219/2006 the MAH must submit to the competent authorities the information on suspected adverse reactions of a medicinal product, in form of a periodic safety update reports (PSURs). PMID:24347978

Pharmacovigilance in pharmaceutical companies: An overview.

PubMed

Mammì, Maria; Citraro, Rita; Torcasio, Giovanni; Cusato, Gennaro; Palleria, Caterina; di Paola, Eugenio Donato

2013-12-01

Pharmacovigilance is responsible for monitoring the safety of medicines in normal clinical use and during clinical trials. In the light of the experience acquired and following an assessment by the Commission of the Union system of pharmacovigilance, it has become clear that it is necessary to take measures in order to improve the operation of Union law on the pharmacovigilance of medicinal products for human use. Regulation (EU) No 1235/2010 and Directive 2010/84/EU introduced new legislation on pharmacovigilance. The marketing authorization holder should be responsible for continuously monitoring the safety of its medicinal products for human use, for informing the authorities of any changes that might have an impact on the marketing authorization, and for ensuring that the product information is kept up-to-date. Marketing authorization holders (MAH) record all suspected adverse reactions occurring in the European Union or in the third countries, and which are brought to their attention spontaneously by the patients or their health care, or occurring in the context of post-authorization study. For all medicinal products is mandatory to maintain a pharmacovigilance system master file (PSMF). According to the Legislative Decree 219/2006 the MAH must submit to the competent authorities the information on suspected adverse reactions of a medicinal product, in form of a periodic safety update reports (PSURs).

Post-authorization safety study of Clottafact® , a triply secured fibrinogen concentrate in congenital afibrinogenemia. A prospective observational study.

PubMed

Négrier, C; Rothschild, C; Borg, J-Y; Lambert, T; Claeyssens, S; Sanhes, L; Stieltjes, N; Bertrand, A; André, M-H; Sié, P; Gruel, Y; Tellier, Z

2016-11-01

A new fibrinogen concentrate Clottafact ® was developed according to European guidelines on plasma-derived products. A post-authorization safety study was set up in 2009 as part of the risk management plan. This was a non-interventional, prospective, non-comparative, multicenter study of the use of fibrinogen concentrate for congenital afibrinogenemia in real-life medical practice in France. The analysis was descriptive and performed on 3 subgroups: prophylaxis vs. on-demand treatment, age (<6, <12 and ≥12) and severity of the deficiency. Fourteen patients [1-78 years] were included in 7 centres and followed for 1 year. Twenty-one adverse drug reactions (ADRs) classically reported with fibrinogen (pallor, chills, cough, vomiting, headache, urticaria and erythematous rash) were reported in 5 of 14 patients. Two ADRs were serious: an anaphylactic shock and a subclavian venous thrombosis with a favourable outcome without sequelae. In the nine patients under prophylaxis, 365 of 367 infusions were considered as successful (99·5%) and 2 as failures. For the five patients treated on-demand, the efficacy was rated as excellent for 27 of 48 infusions and good for the 21 others. This study confirms that the benefit/risk balance for this fibrinogen concentrate is favourable. © 2016 International Society of Blood Transfusion.

Social media for arthritis-related comparative effectiveness and safety research and the impact of direct-to-consumer advertising.

PubMed

Curtis, Jeffrey R; Chen, Lang; Higginbotham, Phillip; Nowell, W Benjamin; Gal-Levy, Ronit; Willig, James; Safford, Monika; Coe, Joseph; O'Hara, Kaitlin; Sa'adon, Roee

2017-03-07

Social media may complement traditional data sources to answer comparative effectiveness/safety questions after medication licensure. The Treato platform was used to analyze all publicly available social media data including Facebook, blogs, and discussion boards for posts mentioning inflammatory arthritis (e.g. rheumatoid, psoriatic). Safety events were self-reported by patients and mapped to medical ontologies, resolving synonyms. Disease and symptom-related treatment indications were manually redacted. The units of analysis were unique terms in posts. Pre-specified conditions (e.g. herpes zoster (HZ)) were selected based upon safety signals from clinical trials and reported as pairwise odds ratios (ORs); drugs were compared with Fisher's exact test. Empirically identified events were analyzed using disproportionality analysis and reported as relative reporting ratios (RRRs). The accuracy of a natural language processing (NLP) classifier to identify cases of shingles associated with arthritis medications was assessed. As of October 2015, there were 785,656 arthritis-related posts. Posts were predominantly US posts (75%) from patient authors (87%) under 40 years of age (61%). For HZ posts (n = 1815), ORs were significantly increased with tofacitinib versus other rheumatoid arthritis therapies. ORs for mentions of perforated bowel (n = 13) were higher with tocilizumab versus other therapies. RRRs associated with tofacitinib were highest in conditions related to baldness and hair regrowth, infections and cancer. The NLP classifier had a positive predictive value of 91% to identify HZ. There was a threefold increase in posts following television direct-to-consumer advertisement (p = 0.04); posts expressing medication safety concerns were significantly more frequent than favorable posts. Social media is a challenging yet promising data source that may complement traditional approaches for comparative effectiveness research for new medications.

The role of the Pharmaceuticals and Medical Devices Agency and healthcare professionals in post-marketing safety.

PubMed

Mori, Kazuhiko; Watanabe, Meguru; Horiuchi, Naoya; Tamura, Atsushi; Kutsumi, Hiromu

2014-04-01

The development of drugs and medical devices is necessary for medical progress; however, safety measures need to be put in place to protect the health of the population. In order to ensure the safety of drugs and medical devices, it is important to determine measures for appropriate management of risks at any time during the development phase, the regulatory review and the post-marketing phase. Adverse events detected in clinical trials are limited due to the restricted numbers of patients enrolled in the trials. Therefore, it is almost impossible to predict rare serious adverse events during the post-marketing phase. The revised Pharmaceutical Affairs Act was established in Japan in November 20, 2013. The new act focuses on increased safety of drugs and medical devices. The Pharmaceuticals and Medical Devices Agency (PMDA) is the regulatory authority in Japan that promotes safety measures from the development phase through to the post-marketing phase. In the post-marketing phase, the PMDA collects information from the medical product companies and healthcare professionals, as well as instructing and advising them with regard to post-marketing safety measures for each drug and medical device. Since Japan has a national health insurance system, a new drug or a medical device is available throughout the country when the drug price or medical fee is listed in the National Health Insurance price list. Healthcare professionals in medical institutions must learn about the drugs and medical devices they handle, and should make an effort to maintain patient safety. The PMDA medi-navi is a very useful electronic mail delivery service that provides critical information for protecting patients from health hazards caused by adverse events. The 'risk management plan' is also important as it contains important information about safety profile and post-marketing measures of a new drug.

Statistical issues in the design, conduct and analysis of two large safety studies.

PubMed

Gaffney, Michael

2016-10-01

The emergence, post approval, of serious medical events, which may be associated with the use of a particular drug or class of drugs, is an important public health and regulatory issue. The best method to address this issue is through a large, rigorously designed safety study. Therefore, it is important to elucidate the statistical issues involved in these large safety studies. Two such studies are PRECISION and EAGLES. PRECISION is the primary focus of this article. PRECISION is a non-inferiority design with a clinically relevant non-inferiority margin. Statistical issues in the design, conduct and analysis of PRECISION are discussed. Quantitative and clinical aspects of the selection of the composite primary endpoint, the determination and role of the non-inferiority margin in a large safety study and the intent-to-treat and modified intent-to-treat analyses in a non-inferiority safety study are shown. Protocol changes that were necessary during the conduct of PRECISION are discussed from a statistical perspective. Issues regarding the complex analysis and interpretation of the results of PRECISION are outlined. EAGLES is presented as a large, rigorously designed safety study when a non-inferiority margin was not able to be determined by a strong clinical/scientific method. In general, when a non-inferiority margin is not able to be determined, the width of the 95% confidence interval is a way to size the study and to assess the cost-benefit of relative trial size. A non-inferiority margin, when able to be determined by a strong scientific method, should be included in a large safety study. Although these studies could not be called "pragmatic," they are examples of best real-world designs to address safety and regulatory concerns. © The Author(s) 2016.

[The problem of post-marketing surveillance planning on drugs for infectious disease].

PubMed

Sato, J

2001-12-01

In principle, a new drug is approved via the assessments of safety and efficacy by the Ministry of Health, Labor and Welfare (MHLW). After approval, conduct of post-marketing surveillance is requested by law in order to assess the safety and efficacy of the drug in a large number of patients. Before initiating a surveillance, submission to MHLW of a document on the plan of survey is necessary in the purpose of inspection if it includes any ethical or regulatory problem or not. Through the inspections of the plans submitted during the period of April 1998 and March 2000, many problems have been pointed out. In this report, the author introduces some of the concrete problems noted in the plans on drugs for infectious diseases and shows some of the guidance made by the authority how to improve them. It is expected that such practical analyses of cases may be useful for future planning of post-marketing surveillance on drugs for infectious diseases.

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

PubMed

Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian

2015-06-18

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

[Post-marketing drug safety measures for the attainment of safer and more effective use of drug].

PubMed

Kurokawa, Tatsuo

2011-01-01

In contrast with the 20th century's dramatic improvements in the direct and/or hazardous toxicity of drugs, indirect toxicity and/or long-term safety concerns such as relation of cancer risk and TNF-alpha receptor blockers have caused significant complexity in post-marketing surveillance (PMS) scenery. The post-marketing phase of drugs and their safety measures now appear to be much more complicated and heavier than decades ago. The spontaneous adverse drug reaction (ADR) reporting system which has been one of the main pillars of PMS measures for almost 50 years may have to be reviewed in terms of its effectiveness, and may need augmentation from medical data bases. Only a pharmaco-epidemiological analysis and integration of the output with a conventional spontaneous reporting approach offers a chance to satisfy the current complex safety issues. Today's tendency toward practical saturation at medical/pharmaceutical frontiers, by regulatory authorities and safety divisions of pharmaceutical companies with ever-increasing day-to-day safety information can also be pointed out. Such phenomena may actually reduce the productivity of safety measures and also jeopardize the maintenance of an acceptable risk/benefit drug ratio. To alleviate these potential negative implications, establishment of a consortium to act as a sentinel that would gather up-to-date and essential safety information, including epidemiological data, from all sources and provide it plus recommendations to all stakeholders can be suggested. Through such activities, we could expect significant improvement of drug safety measures in post-marketing phase which would effectively cover not only new drugs but also generic and bio-simulated drugs.

Biosimilars: pharmacovigilance and risk management.

PubMed

Zuñiga, Leyre; Calvo, Begoña

2010-07-01

Biosimilars cannot be authorized based on the same requirements that apply to generic medicines. Despite the fact that the biosimilar and reference drug can show similar efficacy, the biosimilar may exhibit different safety profile in terms of nature, seriousness or incidence of adverse reactions. However, the data from pre-authorization clinical studies normally are insufficient to identify all potential differences. Therefore, clinical safety of similar biological medicinal products must be monitored closely on an ongoing basis during the post-approval phase including continued risk-benefit assessment. The biosimilar applicant must provide the European Medicines Agency (EMEA) with a risk management plan (EU-RMP) and pharmacovigilance programme with its application, including a description of the potential safety issues associated with the similar biological medicinal product that may be a result of differences in the manufacturing process from the reference biologic. The most critical safety concern relating to biopharmaceuticals (including biosimilars) is immunogenicity. Risk management applies scientifically based methodologies to identify, assess, communicate and minimise risk throughout a drug's life cycle so as to establish and maintain a favourable benefit-risk profile in patients. The risk management plan for biosimilars should focus on heightens the pharmacovigilance measures, identify immunogenicity risk and implement special post-marketing surveillance. Although International Nonproprietary Names (INNs) served as a useful tool in worldwide pharmacovigilance, for biologicals they should not be relied upon as the only means of product identification. Biologicals should always be commercialized with a brand name or the INN plus the manufacturer's name. (c) 2010 John Wiley & Sons, Ltd.

The complementary roles of Phase 3 trials and post-licensure surveillance in the evaluation of new vaccines

PubMed Central

Lopalco, Pier Luigi; DeStefano, Frank

2015-01-01

Vaccines have led to significant reductions in morbidity and saved countless lives from many infectious diseases and are one of the most important public health successes of the modern era. Both vaccines' effectiveness and safety are keys for the success of immunisation programmes. The role of post-licensure surveillance has become increasingly recognised by regulatory authorities in the overall vaccine development process. Safety, purity, and effectiveness of vaccines are carefully assessed before licensure, but some safety and effectiveness aspects need continuing monitoring after licensure; Post-marketing activities are a necessary complement to pre-licensure activities for monitoring vaccine quality and to inform public health programmes. In the recent past, the availability of large databases together with data-mining and cross-linkage techniques have significantly improved the potentialities of post-licensure surveillance. The scope of this review is to present challenges and opportunities offered by vaccine post-licensure surveillance. While pre-licensure activities form the foundation for the development of effective and safe vaccines, post-licensure monitoring and assessment, are necessary to assure that vaccines are effective and safe when translated in real world settings. Strong partnerships and collaboration at an international level between different stakeholders is necessary for finding and optimally allocating resources and establishing robust post-licensure processes. PMID:25444788

[Post-marketing clinical study of traditional Chinese medicine--lessons learned from comprehensive evaluation of Fufang Zaoren capsule].

PubMed

Qing, Shan; Gao, Lin; Zhang, Li; Jia, Jian-Ping; Liu, Xin-Min; Ji, Shao-Liang; Yang, Xiao-Hui

2013-11-01

By comprehensive review and analysis of post-marketing clinical research on the efficacy and safety,we concluded that Fufang Zaoren capsule has certain therapeutic effects for insomnia, although current clinical research design needs improving. The post-marketing clinical studies also showed that it causes several adverse reactions at the recommended doses, such as chills, fever, dizziness, nausea, shortness of breath, chest tightness and palpitations, whereas high doses of Fufang Zaoren capsule can cause delayed extrapyramidal symptoms. Health Canada government website also prompted the L-tetrahydropalmatine in Fufang Zaoren capsule caused liver damage in pregnant women. The authors summarized the risk points, factors and risk control in the clinical use of Fufang Zaoren capsule and also present their perspective on the research status, existing problems and corresponding countermeasures in the post-marketing clinical re-evaluation of traditional Chinese medicine.

Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double-blind, placebo-controlled trials.

PubMed

Schoenfeld, P; Pimentel, M; Chang, L; Lembo, A; Chey, W D; Yu, J; Paterson, C; Bortey, E; Forbes, W P

2014-05-01

The efficacy of rifaximin, a nonsystemic, gut-targeted antibiotic for reducing non-constipation-predominant irritable bowel syndrome (non-C IBS) symptoms, has been demonstrated in one phase 2b and two phase 3 randomised, double-blind, placebo-controlled trials, but detailed data about rifaximin safety and tolerability during treatment and subsequent follow-up periods are lacking. To assess and determine the frequency of rifaximin and placebo adverse events (AEs) in phase 2b and phase 3 non-C IBS trials. A post hoc pooled safety analysis of the phase 2b (rifaximin 275, 550, and 1100 mg twice daily for 2 weeks; 550 mg twice daily for 4 weeks) and phase 3 (rifaximin 550 mg three times daily for 2 weeks) studies was performed. Data on treatment and post-treatment AEs were collected. Patients were followed up for 12 weeks and 10 weeks post-treatment in the phase 2b and phase 3 trials, respectively. Patients receiving rifaximin (n = 1103) and placebo (n = 829) had a similar incidence of drug-related AEs (12.1% vs. 10.7%), serious AEs (1.5% vs. 2.2%), drug-related AEs resulting in study discontinuation (0.8% vs. 0.8%), gastrointestinal-associated AEs (12.2% vs. 12.2%) and infection-associated AEs (8.5% vs. 9.5%). There were no cases of Clostridium difficile colitis or deaths. The safety and tolerability profile of rifaximin during treatment and post-treatment was comparable to placebo. Future research should define the safety and tolerability profile, including risk of C. difficile colitis and microbial antibiotic resistance, with repeated courses of rifaximin in patients with non-constipation-predominant irritable bowel syndrome (ClinicalTrials.gov: NCT00269412, NCT00731679, and NCT00724126). © 2014 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

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

PubMed

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

2007-08-01

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

Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

PubMed

Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

2017-10-09

Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance systems accordingly. Targeted studies are needed, especially to better understand the effects of vaccinating seronegative individuals. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Non-ablative fractional resurfacing of surgical and post-traumatic scars.

PubMed

Vasily, David B; Cerino, Mary E; Ziselman, Ethel M; Zeina, S Tannous

2009-11-01

Non-ablative, fractional lasers generate microscopic columns of coagulated tissue through the epidermis and dermis to evoke a wound healing response. In this study, the authors examined the efficacy and safety of the non-ablative 1540 nm erbium:glass fractional laser in the treatment of surgical and post-traumatic scars. Clinical studies were conducted on a range of surgical and post-traumatic scars with a 1540 nm erbium:glass fractional laser varying energy, pulse widths, treatment passes, and number of treatments. A histological study was conducted on a postsurgical scar to follow the time course of healing post-treatment and the impact of the fractional treatment on normalization of scar tissue, as compared to baseline histology of the scar. Histologic findings demonstrated rapid re-epithelialization of the epidermis within 72 hours of treatment. Remodeling of scar tissue with renewal and reorganization of collagen fibers in the dermis was noted two weeks post-treatment. Clinical subjects, with Fitzpatrick skin types II-V, received three to seven treatments with microbeam energies up to 60 mJ/pb and five passes. Relative to baseline, 73% of treated scars improved 50% or more and 43% improved 75% or more. Side effects included mild swelling (95% of subjects), erythema (94%) and purpura (5%), which all resolved within two to three days. Downtime was minimal-to-none for all subjects. These data illustrate the safety and efficacy of the 1540 nm erbium:glass fractional laser in the treatment of surgical and post-traumatic scars. Practitioners can vary energy and microbeam density in order to tailor the treatment to reflect the individual scar characteristics.

Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers.

PubMed

Hsu, Ai-Ping; Tseng, Chun-Hsien; Barrat, Jacques; Lee, Shu-Hwae; Shih, Yu-Hua; Wasniewski, Marine; Mähl, Philippe; Chang, Chia-Chia; Lin, Chun-Ta; Chen, Re-Shang; Tu, Wen-Jane; Cliquet, Florence; Tsai, Hsiang-Jung

2017-01-01

Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1-7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan.

Post-authorization safety surveillance of a liquid pentavalent vaccine in Guatemalan children.

PubMed

Asturias, Edwin J; Contreras-Roldan, Ingrid L; Ram, Malathi; Garcia-Melgar, Ana J; Morales-Oquendo, Vilma; Hartman, Katharina; Rauscher, Martina; Moulton, Lawrence H; Halsey, Neal A

2013-12-02

Combination vaccines have improved the efficiency of delivery of new vaccines in low and middle-income countries. Post-authorization monitoring of adverse events (AEs) after vaccination with a liquid pentavalent DTwP-HepB-Hib combination vaccine was conducted in Guatemalan infants. A prospective observational safety study of the incidence of medical attended events (MAEs) and serious adverse events (SAEs) in children who received pentavalent and oral polio vaccines at 2, 4 and 6 months of age was conducted in two clinics at the Institute of Guatemala. Parents were contacted by telephone after each dose. All outpatient, emergency department visits, and hospitalizations were monitored. A self-controlled analysis was conducted to determine if there was evidence of increased risk of MAEs or SAEs following vaccines as compared to control time windows. Of 3000 recruited infants, 2812 (93.7%) completed the third dose and 2805 (93.5%) completed follow-up. Ten AEs in eight infants, of which four SAEs in four infants, were classified as related to the vaccine. Thirteen deaths were reported due to common illnesses of infancy, and none were judged to be related to the vaccine. The mortality rate (4.4 per 1000) was lower than expected for the population. The incidence-rate-ratio for healthcare visits was lower in post-vaccination time windows than for control windows; after the first vaccine dose, the rate ratios for the risk periods of 0-1, 2-6, and 7-30 days post-vaccination were 0.3, 0.5, and 0.7, respectively (all statistically significantly different from the reference value of 1.0 for the 31-60 day control period). The liquid pentavalent vaccine was associated with lower rates of health care visits and not associated with increases in SAEs or hospitalizations. Systems can be set up in low to middle income countries to capture all health care visits to monitor the safety of new vaccines. Copyright © 2013 Elsevier Ltd. All rights reserved.

A deer study at Aberdeen Proving Ground: Project planning, data assimilation, and risk assessment

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

Whaley, J.; Leach, G.; Lee, R.

1995-12-31

For more than 75 years, Aberdeen Proving Ground (APG) has been in the business of research, development, and testing of munitions and military vehicles for the US Army. Currently, APG is on the National Priorities List and an installation wide human health risk assessment is underway. Like many Department of the Army facilities, APG has an active hunting program. Hunters harvest approximately 800 whitetail deer (Odocoileus virginanus) from APG annually. To assure public safety, the authors completed a study during the 1993 hunting season to identify any potential human health hazards associated with consumption of venison from APG. This papermore » will discuss the unique strategy behind the experimental design, the actual assimilation of the data, and the results of the human health risk assessment to establish an appropriate contaminant levels in APG deer. Also, based on information in the literature, the authors considered gender, age, and season in the study design. The list of chemicals for residue analysis included explosives, PCBs, organochlorine pesticides, and metals (As, Cd, Cr, Pb, Hg). Of the 150 deer sampled, metals were the only chemicals detected. The authors compared these data to metal levels in deer collected from an off post background site. Metal levels did not differ significantly between APG deer and off post deer. Finally, the authors completed a health risk assessment of eating deer harvested from both APG and off post. From a survey distributed to the hunters, they incorporated actual consumption data into the exposure assessment. Their findings concluded that the risk of eating APG deer was no higher than eating off post deer; however, total arsenic levels in muscle did appear to elevate the risk.« less

Safety culture and the 5 steps to safer surgery: an intervention study.

PubMed

Hill, M R; Roberts, M J; Alderson, M L; Gale, T C E

2015-06-01

Improvements in safety culture have been postulated as one of the mechanisms underlying the association between the introduction of the World Health Organisation (WHO) Surgical Safety Checklist with perioperative briefings and debriefings, and enhanced patient outcomes. The 5 Steps to Safer Surgery (5SSS) incorporates pre-list briefings, the three steps of the WHO Surgical Safety Checklist (SSC) and post-list debriefings in one framework. We aimed to identify any changes in safety culture associated with the introduction of the 5SSS in orthopaedic operating theatres. We assessed the safety culture in the elective orthopaedic theatres of a large UK teaching hospital before and after introduction of the 5SSS using a modified version of the Safety Attitude Questionnaire - Operating Room (SAQ-OR). Primary outcome measures were pre-post intervention changes in the six safety culture domains of the SAQ-OR. We also analysed changes in responses to two items regarding perioperative briefings. The SAQ-OR survey response rate was 80% (60/75) at baseline and 74% (53/72) one yr later. There were significant improvements in both the reported frequency (P<0.001) and perceived importance (P=0.018) of briefings, and in five of the six safety culture domain scores (Working Conditions, Perceptions of Management, Job Satisfaction, Safety Climate and Teamwork Climate) of the SAQ-OR (P<0.001 in all cases). Scores in the sixth domain (Stress Recognition) decreased significantly (P=0.028). Implementation of the 5SSS was associated with a significant improvement in the safety culture of elective orthopaedic operating theatres. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m²: A Post-hoc Analysis.

PubMed

le Roux, Carel; Aroda, Vanita; Hemmingsson, Joanna; Cancino, Ana Paula; Christensen, Rune; Pi-Sunyer, Xavier

2017-01-01

To investigate whether the efficacy and safety of liraglutide 3.0 mg differed between two subgroups, BMI 27 to <35 and BMI ≥ 35 kg/m², in individuals without and with type 2 diabetes (T2D). A post-hoc analysis of two 56-week, randomized, double-blind, placebo-controlled trials (SCALE Obesity and Prediabetes; SCALE Diabetes). Subgroup differences in treatment effects of liraglutide 3.0 mg were evaluated by testing the interaction between treatment group and baseline BMI subgroup. Significantly greater weight loss (0-56 weeks) was observed with liraglutide 3.0 mg versus placebo in all patient groups while on treatment. There was no evidence that the weight-lowering effect of liraglutide 3.0 mg differed between BMI subgroups (interaction p > 0.05). Similarly, for most secondary endpoints significantly greater improvements were observed with liraglutide 3.0 mg versus placebo, with no indication treatment effects differing between subgroups. The safety profile of liraglutide 3.0 mg was broadly similar across BMI subgroups. This post-hoc analysis did not indicate any differences in the treatment effects, or safety profile, of liraglutide 3.0 mg for individuals with BMI 27 to <35 or ≥35 kg/m². Liraglutide 3.0 mg can therefore be considered for individuals with a BMI of ≥35 as well as for those with a BMI of 27 to <35 kg/m². © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

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

PubMed

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

2014-05-01

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

Strengths, weaknesses and future challenges of biosimilars' development. An opinion on how to improve the knowledge and use of biosimilars in clinical practice.

PubMed

Scavone, Cristina; Rafaniello, Concetta; Berrino, Liberato; Rossi, Francesco; Capuano, Annalisa

2017-12-01

Biosimilars started receiving the marketing authorization by European Medicine Agency since 2006. The development of biosimilars follows a well-defined step-wise approach, the so-called comparability exercise, which aims to compare non-clinical (mainly quality features and biological activity) and clinical (efficacy and safety profiles) features of new biosimilars with their respective reference products. Despite the undeniable advantages of such procedure, some concerns (such as the absence of switching studies or the evaluation of efficacy and safety in all therapeutic indications) still exist about its. In particular, the European regulatory framework on biosimilars approval does not include the conduction of switching studies demonstrating the interchangeability to be carried out before marketing authorization. This is one of the main aspects that negatively affects healthcare professionals' clinical decisions on switch. In order to achieve a better knowledge on safety and efficacy of biosimilar drugs, real world data should be collected and post-marketing efficacy and safety clinical studies (including those evaluating specific endpoints, therapeutic regimens and patients population), should be planned. also the conduction of well-designed switching studies is highly advisable, especially in the case of biosimilar drugs used in oncology settings. Lastly, considering the critical role of antidrug antibodies on efficacy/safety profile of biologic drugs, studies based on therapeutic drug monitoring would be useful in order to achieve treatment optimization. Implementing the above strategies could be helpful to fill the gap in knowledge observed in the present European biosimilar regulatory framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

NASA's post-Challenger safety program - Themes and thrusts

NASA Technical Reports Server (NTRS)

Rodney, G. A.

1988-01-01

The range of managerial, technical, and procedural initiatives implemented by NASA's post-Challenger safety program is reviewed. The recommendations made by the Rogers Commission, the NASA post-Challenger review of Shuttle design, the Congressional investigation of the accident, the National Research Council, the Aerospace Safety Advisory Panel, and NASA internal advisory panels and studies are summarized. NASA safety initiatives regarding improved organizational accountability for safety, upgraded analytical techniques and methodologies for risk assessment and management, procedural initiatives in problem reporting and corrective-action tracking, ground processing, maintenance documentation, and improved technologies are discussed. Safety issues relevant to the planned Space Station are examined.

EU decision-making for marketing authorization of advanced therapy medicinal products: a case study.

PubMed

de Wilde, Sofieke; Coppens, Delphi G M; Hoekman, Jarno; de Bruin, Marie L; Leufkens, Hubert G M; Guchelaar, Henk-Jan; Meij, Pauline

2018-03-21

A comparative analysis of assessment procedures for authorization of all European Union (EU) applications for advanced therapy medicinal products (ATMPs) shows that negative opinions were associated with a lack of clinical efficacy and identified severe safety risks. Unmet medical need was often considered in positive opinions and outweighed scientific uncertainties. Numerous quality issues illustrate the difficulties in this domain for ATMP development. Altogether, it suggests that setting appropriate standards for ATMP authorization in Europe, similar to elsewhere, is a learning experience. The experimental characteristics of authorized ATMPs urge regulators, industry, and clinical practice to pay accurate attention to post-marketing risk management to limit patient risk. Methodologies for ATMP development and regulatory evaluations need to be continuously evaluated for the field to flourish. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Post-marketing surveillance of sertindole.

PubMed

Toumi, Mondher

2002-01-01

The atypical antipsychotic drug, sertindole, like several other drugs, causes QT interval prolongation. Prolongation of the QT interval on the electrocardiogram has been associated with an increased risk of ventricular arrhythmia, including the more serious form, torsades de pointes, and is thus a safety concern for the authorities. In the case of sertindole, however, the available pharmacoepidemiological studies gathering data from about 10 000 patients documented the lack of increased risk associated to sertindole in comparison to other atypical antipsychotics. On the basis of these data, as well as non-clinical and clinical safety data, the CPMP expert group concluded that, although sertindole has the potential to prolong the QT interval, ¤ ¤ QT interval prolongation does not seem to be a reliable proxy for the risk of severe cardiac arrhythmias'', and there are no clinical data suggesting that sertindole is more arrhythmogenic than are other atypical antipsychotics. To further substantiate this conclusion, two post-marketing surveillance studies have been initiated. One is a randomized comparison of sertindole and risperidone under normal conditions of use. Randomization minimizes selection bias and the intention is that allocation to the two treatment arms will yield comparable treatment groups. While the two drugs will be given in an open-label fashion, all safety data will be blinded and reviewed by an independent safety committee. The other study is an observational study that includes all patients prescribed sertindole who, for whatever reason, will not be included in the randomized study. In all, 10 000 patients are expected to take part in the studies, which will run for at least 1 year.

Randomized controlled trials and real-world observational studies in evaluating cardiovascular safety of inhaled bronchodilator therapy in COPD.

PubMed

Kardos, Peter; Worsley, Sally; Singh, Dave; Román-Rodríguez, Miguel; Newby, David E; Müllerová, Hana

2016-01-01

Long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist (LABA) bronchodilators and their combination are recommended for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Although the efficacy of LAMAs and LABAs has been well established through randomized controlled trials (RCTs), questions remain regarding their cardiovascular (CV) safety. Furthermore, while the safety of LAMA and LABA monotherapy has been extensively studied, data are lacking for LAMA/LABA combination therapy, and the majority of the studies that have reported on the CV safety of LAMA/LABA combination therapy were not specifically designed to assess this. Evaluation of CV safety for COPD treatments is important because many patients with COPD have underlying CV comorbidities. However, severe CV and other comorbidities are often exclusion criteria for RCTs, contributing to a lack in external validity and generalizability. Real-world observational studies are another important tool to evaluate the effectiveness and safety of COPD therapies in a broader population of patients and can improve upon the external validity limitations of RCTs. We examine what is already known regarding the CV and cerebrovascular safety of LAMA/LABA combination therapy from RCTs and real-world observational studies, and explore the advantages and limitations of data derived from each study type. We also describe an ongoing prospective, observational, comparative post-authorization safety study of a LAMA/LABA combination therapy (umeclidinium/vilanterol) and LAMA monotherapy (umeclidinium) versus tiotropium, with a focus on the relative merits of the study design.

Post-marketing safety monitoring of shenqifuzheng injection: a solution made of dangshen (Radix Codonopsis) and huangqi (Radix Astragali Mongolici).

PubMed

Ai, Qinghua; Zhang, Wen; Xie, Yanming; Huang, Wenhua; Liang, Hong; Cao, Hui

2014-08-01

To identify the potential risk factors associated with Shenqifuzheng injection (SFI), a solution made of Dangshen (Radix Codonopsis) and Huangqi (Radix Astragali Mongolici), for the timely provision of information to regulatory authorities. A comprehensive analysis of the production process, quality standards, pharmacology, post-marketing clinical studies, and safety evaluation using the primary literature of adverse reactions (ADR), case analyses, and systematic reviews, intensive hospital safety monitoring of post-marketing drugs, and data provided by the hospital information system (HIS). Sub-acute toxicity tests suggesting that a dose of 15 mL/kg (concentrated solution) had specific biological effects, whereas a smaller dose engendered no observable effects. Long-term toxicity testing in domestic rabbits showed that after SFI was administered for 90 days, the animals in each dosing group showed no chronic toxic reactions. Among 20 100 cases observed, the incidence of an ADR was 1.85 per thousand. From March to November 2013, of the leading institutions and 22 sub-centers involved in the post-marketing clinical safety intensive hospital monitoring, 21 units completed 8484 cases of monitoring, and reported 23 cases of adverse reactions. No damage to renal function was found using SFI at a dosage and a treatment course larger and longer than that recommended for the adjuvant treatment of tumors. This could reduce the mortality rate of admitted patients based on the analysis of the data provided by the HIS. A total of 16 clinical case reports of adverse reactions related to SFI in 1999-2012 were obtained through literature retrieval. These reports contained information concerning 17 cases, with adverse reaction symptoms including thrombocytopenia, rash, chills, feeling cold, palpitation, dyspnea, edema of a lower extremity, palpebral edema, and superficial vein inflammation, among others. This study introduces "get full access" to the flow of information on medicines regarding their ADR incidence rate and characteristics and factors. It supports the safety of SFI for clinical, research,and production uses based on objective, reliable, and scientific information to provide safe medication.

Using Lean to Rapidly and Sustainably Transform a Behavioral Health Crisis Program: Impact on Throughput and Safety.

PubMed

Balfour, Margaret E; Tanner, Kathleen; Jurica, Paul J; Llewellyn, Dawn; Williamson, Robert G; Carson, Chris A

2017-06-01

Lean has been increasingly applied in health care to reduce waste and improve quality, particularly in fast-paced and high-acuity clinical settings such as emergency departments. In addition, Lean's focus on engagement of frontline staff in problem solving can be a catalyst for organizational change. In this study, ConnectionsAZ demonstrates how they applied Lean principles to rapidly and sustainably transform clinical operations in a behavioral health crisis facility. A multidisciplinary team of management and frontline staff defined values-based outcome measures, mapped the current and ideal processes, and developed new processes to achieve the ideal. Phase I was implemented within three months of assuming management of the facility and involved a redesign of flow, space utilization, and clinical protocols. Phase II was implemented three months later and improved the provider staffing model. Organizational changes such as the development of shift leads and daily huddles were implemented to sustain change and create an environment supportive of future improvements. Post-Phase I, there were significant decreases (pre vs. post and one-year post) in median door-to-door dwell time (343 min vs. 118 and 99), calls to security for behavioral emergencies (13.5 per month vs. 4.3 and 4.8), and staff injuries (3.3 per month vs. 1.2 and 1.2). Post-Phase II, there were decreases in median door-to-doctor time (8.2 hours vs. 1.6 and 1.4) and hours on diversion (90% vs. 17% and 34%). Lean methods can positively affect safety and throughput and are complementary to patient-centered clinical goals in a behavioral health setting. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Post-marketing monitoring of intussusception after rotavirus vaccination in Japan.

PubMed

Bauchau, Vincent; Van Holle, Lionel; Mahaux, Olivia; Holl, Katsiaryna; Sugiyama, Keiji; Buyse, Hubert

2015-07-01

Rotarix(TM) was launched in November 2011 in Japan to prevent rotavirus gastroenteritis. Some studies suggest that Rotarix(TM) may have a temporal association with a risk of intussusception (IS). We assessed a possible association between IS and Rotarix(TM) vaccination in Japan. All IS cases spontaneously reported post-vaccination (Brighton collaboration levels 1, 2, and 3) were extracted from the GlaxoSmithKline spontaneous report database on the 11th of January 2013. Expected numbers of IS cases were estimated using the number of vaccine doses distributed and the Japanese incidence rate of IS stratified by month of age. The observed versus expected analysis considered the IS cases for each risk period (7 and 30 days post-vaccination) and for each vaccine dose (two doses). Before January 2013, approximately 601 000 Rotarix(TM) doses were distributed in Japan. For a risk period of 7 days post-dose 1 and post-dose 2, 10 and five IS cases were observed, whereas 3.4 and 7.6 were expected, providing an observed-to-expected ratio of 2.96 (95% confidence interval [CI]: 1.42; 5.45) and 0.66 (95% CI: 0.21; 1.53), respectively. For a risk period of 30 days post-dose 1 and post-dose 2, 14 and eight cases were observed, whereas 14.5 and 32.7 were expected, providing an observed-to-expected ratio of 0.97 (95% CI: 0.53; 1.62) and 0.24 (95% CI: 0.11; 0.48), respectively. A statistically significant excess of IS cases was observed within 7 days post-dose 1, but not post-dose 2. These results are consistent with previous observations in large post-marketing safety studies in other world regions. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Climate change and landscape development in post-closure safety assessment of solid radioactive waste disposal: Results of an initiative of the IAEA.

PubMed

Lindborg, T; Thorne, M; Andersson, E; Becker, J; Brandefelt, J; Cabianca, T; Gunia, M; Ikonen, A T K; Johansson, E; Kangasniemi, V; Kautsky, U; Kirchner, G; Klos, R; Kowe, R; Kontula, A; Kupiainen, P; Lahdenperä, A-M; Lord, N S; Lunt, D J; Näslund, J-O; Nordén, M; Norris, S; Pérez-Sánchez, D; Proverbio, A; Riekki, K; Rübel, A; Sweeck, L; Walke, R; Xu, S; Smith, G; Pröhl, G

2018-03-01

The International Atomic Energy Agency has coordinated an international project addressing climate change and landscape development in post-closure safety assessments of solid radioactive waste disposal. The work has been supported by results of parallel on-going research that has been published in a variety of reports and peer reviewed journal articles. The project is due to be described in detail in a forthcoming IAEA report. Noting the multi-disciplinary nature of post-closure safety assessments, here, an overview of the work is given to provide researchers in the broader fields of radioecology and radiological safety assessment with a review of the work that has been undertaken. It is hoped that such dissemination will support and promote integrated understanding and coherent treatment of climate change and landscape development within an overall assessment process. The key activities undertaken in the project were: identification of the key processes that drive environmental change (mainly those associated with climate and climate change), and description of how a relevant future may develop on a global scale; development of a methodology for characterising environmental change that is valid on a global scale, showing how modelled global changes in climate can be downscaled to provide information that may be needed for characterising environmental change in site-specific assessments, and illustrating different aspects of the methodology in a number of case studies that show the evolution of site characteristics and the implications for the dose assessment models. Overall, the study has shown that quantitative climate and landscape modelling has now developed to the stage that it can be used to define an envelope of climate and landscape change scenarios at specific sites and under specific greenhouse-gas emissions assumptions that is suitable for use in quantitative post-closure performance assessments. These scenarios are not predictions of the future, but are projections based on a well-established understanding of the important processes involved and their impacts on different types of landscape. Such projections support the understanding of, and selection of, plausible ranges of scenarios for use in post-closure safety assessments. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies

PubMed Central

Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

2017-01-01

Objectives To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act. Design Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10. Setting Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany. Main outcome measures Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions. Results Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals. Conclusions Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor. High remuneration and strict confidentiality clauses in these studies could influence the physicians’ reporting behaviours of adverse drug reactions. PMID:28174182

Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers

PubMed Central

Hsu, Ai-Ping; Tseng, Chun-Hsien; Barrat, Jacques; Lee, Shu-Hwae; Shih, Yu-Hua; Wasniewski, Marine; Mähl, Philippe; Chang, Chia-Chia; Lin, Chun-Ta; Chen, Re-Shang; Tu, Wen-Jane; Cliquet, Florence

2017-01-01

Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1–7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan. PMID:28977009

Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

PubMed

Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

2013-12-02

Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals.

PubMed

Schick, Andreas; Miller, Kathleen L; Lanthier, Michael; Dal Pan, Gerald; Nardinelli, Clark

2017-06-01

An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied. In this paper, we examine whether any pre-marketing drug characteristics are associated with serious post-marketing safety actions. We study this question using an internal FDA database containing every new small molecule drug submitted to the FDA's Center for Drug Evaluation and Research (CDER) on or after November 21, 1997, and approved and commercially launched before December 31, 2009. Serious post-marketing safety actions include whether these drugs ever experienced either a post-marketing boxed warning or a withdrawal from the market due to safety concerns. A random effects logistic regression model was used to test whether any pre-marketing characteristics were associated with either post-marketing safety action. A total of 219 new molecular entities were analyzed. Among these drugs, 11 experienced a safety withdrawal and 30 received boxed warnings by July 31, 2016. Contrary to prevailing hypotheses, we find that neither clinical trial sample sizes nor review time windows are associated with the addition of a post-marketing boxed warning or safety withdrawal. However, we do find that new drugs approved with either a boxed warning or priority review are more likely to experience post-marketing boxed warnings. Furthermore, drugs approved with boxed warnings tend to receive post-marketing boxed warnings resulting from new safety information that are unrelated to the original warning. Drugs approved with a boxed warning are 3.88 times more likely to receive a post-marketing boxed warning, while drugs approved with a priority review are 3.51 times more likely to receive a post-marketing boxed warning. Although drugs approved with a boxed warning or priority review are more likely to experience serious post-marketing safety events, other information provided during the FDA drug review that is easy to quantify is generally not associated with post-marketing safety events. It appears that these post-marketing events are not discernible during a pre-marketing review and therefore might not be avoidable using current review data.

Post-trauma coping in the context of significant adversity: a qualitative study of young people living in an urban township in South Africa.

PubMed

Hiller, Rachel M; Halligan, Sarah L; Tomlinson, Mark; Stewart, Jackie; Skeen, Sarah; Christie, Hope

2017-10-06

Compared with knowledge of the post-trauma needs of young people living in developed countries, little is known about the needs of those in low-middle-income countries. Such information is crucial, particularly as young people in these environments can be at increased risk of experiencing trauma, coupled with less available resources for formal support. The aim of this study was to explore post-trauma coping and support-seeking of young people living in a high-adversity settlement in South Africa. Semistructured qualitative interviews analysed using thematic analysis. An urban settlement ('township') in Cape Town, South Africa. 25 young people, aged 13-17 years, who had experienced trauma. Events included serious car accidents, hearing of a friend's violent death, and rape, and all reported having experienced multiple traumatic events. All participants identified as black South African and spoke Xhosa as their first language. Social support was considered key to coping after trauma, although the focus of the support differed depending on the source. Parents would most commonly provide practical support, particularly around safety. Peers often provided an avenue to discuss the event and young person's emotional well-being more openly. Outside of social support another key theme was that there were numerous community-level barriers to participants receiving support following trauma. Many young people continued to be exposed to the perpetrator of the event, while there was also the realistic concern around future traumas and safety, community stigma and a perceived lack of justice. This study provides insight into how young people cope and seek support following trauma when they are living in a context of significant adversity and risk. Overall, most young people identified helpful sources of support and thought talking about the event was a useful strategy, but concerns around safety and trust could impede this process. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An empowerment model of workplace support following disclosure, for people with MS.

PubMed

Kirk-Brown, A K; Van Dijk, P A

2014-10-01

Vocational interventions aimed at increasing job retention for people with multiple sclerosis (MS) are reliant upon a partnership with a supportive work environment. A better understanding of the types of psychosocial support that are most conducive to retaining employees' sense of work-efficacy will enhance the success of interventions aimed at reducing workplace barriers to job maintenance. The objective of this study is to identify the types of psychosocial support that people with MS require post-disclosure, in order to maintain their employment status. In particular, we examined the roles of psychological safety and work-efficacy. We interviewed 40 employees with MS either individually (n = 25) or within three focus groups (n = 15). These interviews were audio-taped and the content analysed, using an inductive thematic approach. Themes to emerge in organisational responses to disclosure were: a focus on ability (leading to enhanced perceptions of psychological safety and higher work-efficacy) and on disability (leading to diminished psychological safety and reduced perceptions of work-efficacy). Organisational responses to disclosure demonstrating trust and inclusive decision making, and focussing on employee abilities, enhance perceptions of psychological safety at work. This increases the likelihood that employees with MS will retain their sense of work-efficacy and reduce their intentions to leave. © The Author(s) 2014.

Evolution of a holistic systems approach to planning and managing road safety: the Victorian case study, 1970-2015.

PubMed

Muir, Carlyn; Johnston, Ian R; Howard, Eric

2018-06-01

The Victorian Safe System approach to road safety slowly evolved from a combination of the Swedish Vision Zero philosophy and the Sustainable Safety model developed by the Dutch. The Safe System approach reframes the way in which road safety is viewed and managed. This paper presents a case study of the institutional change required to underpin the transformation to a holistic approach to planning and managing road safety in Victoria, Australia. The adoption and implementation of a Safe System approach require strong institutional leadership and close cooperation among all the key agencies involved, and Victoria was fortunate in that it had a long history of strong interagency mechanisms in place. However, the challenges in the implementation of the Safe System strategy in Victoria are generally neither technical nor scientific; they are predominantly social and political. While many governments purport to develop strategies based on Safe System thinking, on-the-ground action still very much depends on what politicians perceive to be publicly acceptable, and Victoria is no exception. This is a case study of the complexity of institutional change and is presented in the hope that the lessons may prove useful for others seeking to adopt more holistic planning and management of road safety. There is still much work to be done in Victoria, but the institutional cultural shift has taken root. Ongoing efforts must be continued to achieve alert and compliant road users; however, major underpinning benefits will be achieved through focusing on road network safety improvements (achieving forgiving infrastructure, such as wire rope barriers) in conjunction with reviews of posted speed limits (to be set in response to the level of protection offered by the road infrastructure) and by the progressive introduction into the fleet of modern vehicle safety features. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Revealing and Resolving Patient Safety Defects: The Impact of Leadership WalkRounds on Frontline Caregiver Assessments of Patient Safety

PubMed Central

Frankel, Allan; Grillo, Sarah Pratt; Pittman, Mary; Thomas, Eric J; Horowitz, Lisa; Page, Martha; Sexton, Bryan

2008-01-01

Objective To evaluate the impact of rigorous WalkRounds on frontline caregiver assessments of safety climate, and to clarify the steps and implementation of rigorous WalkRounds. Data Sources/Study Setting Primary outcome variables were baseline and post WalkRounds safety climate scores from the Safety Attitudes Questionnaire (SAQ). Secondary outcomes were safety issues elicited through WalkRounds. Study period was August 2002 to April 2005; seven hospitals in Massachusetts agreed to participate; and the project was implemented in all patient care areas. Study Design Prospective study of the impact of rigorously applied WalkRounds on frontline caregivers assessments of safety climate in their patient care area. WalkRounds were conducted weekly and according to the seven-step WalkRounds Guide. The SAQ was administered at baseline and approximately 18 months post-WalkRounds implementation to all caregivers in patient care areas. Results Two of seven hospitals complied with the rigorous WalkRounds approach; hospital A was an academic teaching center and hospital B a community teaching hospital. Of 21 patient care areas, SAQ surveys were received from 62 percent of respondents at baseline and 60 percent post WalkRounds. At baseline, 10 of 21 care areas (48 percent) had safety climate scores below 60 percent, whereas post-WalkRounds three care areas (14 percent) had safety climate scores below 60 percent without improving by 10 points or more. Safety climate scale scores in hospital A were 62 percent at baseline and 77 percent post-WalkRounds (t=2.67, p=.03), and in hospital B were 46 percent at baseline and 56 percent post WalkRounds (t=2.06, p=.06). Main safety issues by category were equipment/facility (A [26 percent] and B [33 percent]) and communication (A [24 percent] and B [18 percent]). Conclusions WalkRounds implementation requires significant organizational will; sustainability requires outstanding project management and leadership engagement. In the patient care areas that rigorously implemented WalkRounds, frontline caregiver assessments of patient safety increased. SAQ results such as safety climate scores facilitate the triage of quality improvement efforts, and provide consensus assessments of frontline caregivers that identify themes for improvement. PMID:18671751

Pharmacist leadership in ICU quality improvement: coordinating spontaneous awakening and breathing trials.

PubMed

Stollings, Joanna L; Foss, Julie J; Ely, E Wesley; Ambrose, Anna M; Rice, Todd W; Girard, Timothy D; Wheeler, Arthur P

2015-08-01

Coordinating efforts across disciplines in the intensive care unit is a key component of quality improvement (QI) efforts. Spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) are considered key components of guidelines, yet unfortunately are often not done or coordinated properly. To determine if a pharmacist-driven awakening and breathing coordination (ABC) QI program would improve compliance (ie, process measures) as compared with the previous protocol, which did not involve pharmacists. The QI program included pharmacist-led education, daily discussion on rounds, and weekly performance reports to staff. Using a pre-QI versus during-QI versus post-QI intervention design, we compared data from 500 control ventilator-days (pre-QI period) versus 580 prospective ventilator-days (during-QI period). We then evaluated the sustainability of the QI program in 216 ventilator-days in the post-QI period. SAT safety screens were performed on only 20% pre-QI patient-days versus 97% of during-QI patient-days (P < 0.001) and 100% of post-QI patient-days (P = 0.25). The rates of passing the SAT safety screen in pre-QI and during-QI periods were 63% versus 78% (P = 0.03) and 81% in the post-QI period (P = 0.86). The rates of SATs among eligible patients on continuous infusions were only 53% in the pre-QI versus 85% in the during-QI (P = 0.0001) and 87% in the post-QI (P = 1) periods. In this QI initiative, a pharmacist-driven, interdisciplinary ABC protocol significantly improved process measures compliance, comparing the pre-QI versus during-QI rates of screening, performing, and coordinating SAT and SBTs, and these results were sustained in the 8-month follow-up period post-QI program. © The Author(s) 2015.

Challenges of post-authorization safety studies: Lessons learned and results of a French study of fentanyl buccal tablet.

PubMed

Gavrielov-Yusim, Natalie; Bidollari, Ilda; Kaplan, Sigal; Bartov, Netta

2018-05-01

Recruiting and retaining participants in real-world studies that collect primary data are challenging. This article illustrates these challenges using a post-authorization safety study (PASS) to assess adverse events (AEs) experienced with fentanyl buccal tablet (FBT) over 3 months of treatment. This was an observational, prospective, multicenter study in France conducted over 1 year. The study employed primary data collection in FBT-treated patients and their treating physicians via a site qualification questionnaire and patient log completed by physicians and a questionnaire and pain diary completed by patients. Strategies to increase participation included reminders, newsletters, frequent follow-up telephone calls, and reducing the extent of data collected. Of the 1118 physicians contacted who returned the participation form or responded to a telephone call, only 128 expressed willingness to participate. Key reasons for non-participation were lack of interest (69.7%) and FBT not being used in practice by the contacted physician (25.1%). Overall, 224 patients were screened by 31 physicians, and 97 were enrolled. Key reasons for patient non-inclusion were unwillingness or inability to complete the patient AE diary or questionnaire (40.9% [52/127]) and patients' decision (33.9% [43/127]). Despite efforts to increase participation, enrollment in this study was low. Recruitment and retention methods are limited in their capacity to optimally execute a primary data collection in a PASS. For a PASS to provide reliable and valid information on medication use, involvement from health care agencies, regulators, and pharmaceutical companies is needed to establish their importance, drive study participation, and reduce patient withdrawal. Copyright © 2017 John Wiley & Sons, Ltd.

Formal testing and utilization of streaming media to improve flight crew safety knowledge.

PubMed

Bellazzini, Marc A; Rankin, Peter M; Quisling, Jason; Gangnon, Ronald; Kohrs, Mike

2008-01-01

Increased concerns over the safety of air medical transport have prompted development of novel ways to increase safety. The objective of our study was to determine if an Internet streaming media safety video increased crew safety knowledge. 23 out of 40 crew members took an online safety pre-test, watched a safety video specific to our program and completed immediate and long-term post-testing 6 months later. Mean pre-test, post-test and 6 month follow up test scores were 84.9%, 92.3% and 88.4% respectively. There was a statistically significant difference in all scores (p

The effects of organizational commitment and structural empowerment on patient safety culture.

PubMed

Horwitz, Sujin K; Horwitz, Irwin B

2017-03-20

Purpose The purpose of this paper is to investigate the relationship between patient safety culture and two attitudinal constructs: affective organizational commitment and structural empowerment. In doing so, the main and interaction effects of the two constructs on the perception of patient safety culture were assessed using a cohort of physicians. Design/methodology/approach Affective commitment was measured with the Organizational Commitment Questionnaire, whereas structural empowerment was assessed with the Conditions of Work Effectiveness Questionnaire-II. The abbreviated versions of these surveys were administered to a cohort of 71 post-doctoral medical residents. For the data analysis, hierarchical regression analyses were performed for the main and interaction effects of affective commitment and structural empowerment on the perception of patient safety culture. Findings A total of 63 surveys were analyzed. The results revealed that both affective commitment and structural empowerment were positively related to patient safety culture. A potential interaction effect of the two attitudinal constructs on patient safety culture was tested but no such effect was detected. Research limitations/implications This study suggests that there are potential benefits of promoting affective commitment and structural empowerment for patient safety culture in health care organizations. By identifying the positive associations between the two constructs and patient safety culture, this study provides additional empirical support for Kanter's theoretical tenet that structural and organizational support together helps to shape the perceptions of patient safety culture. Originality/value Despite the wide recognition of employee empowerment and commitment in organizational research, there has still been a paucity of empirical studies specifically assessing their effects on patient safety culture in health care organizations. To the authors' knowledge, this study is the first empirical study to examine the relationship between structural empowerment as proposed by Kanter and the culture of patient safety using physicians.

Comparison of amateur boxing before and after the 2013 rules change and the impact on boxers' safety.

PubMed

Davis, Philip; Waldock, Robert; Connorton, Andrew; Driver, Sonny; Anderson, Sean

2018-06-01

The effect of the rules change in 2013 on amateur boxing strategy, technique and safety in comparison with pre-2013 is unknown. Pre-2013 and post-2013 3×3 min elite level amateur boxing was compared from video footage of 29 Olympic (pre-2013) and 50 World Championship bouts (post-2013) totalling 99 male boxers (mean±SD) age: 24.3±3.2 years, height: 177.3±11.3 cm and body mass: 70.7±16.4 kg. Many techniques that were dominant pre-2013 were used less post-2013, including: total punches thrown, rear hand punches, hook rear hand, punches landed, uppercut punches, total punches to the body (all <0.05), while movement around the ring and defensive movements were higher post-2013 (both p<0.004). Post-2013 boxers have increased their foot movement by 20% to move in and then away from their opponent, combined with long-range punches and deliberate defensive movements. The percentage of rounds where standing counts were issued changed from 9% to 3% pre-2013 to post-2013. However, pre-2013, 1.7% of bouts did not last the full duration due to referee stoppage, while post-2013, this increased to 4.2% as a result of two knockouts and eight technical knockouts. Boxers should be aware of the large changes in technical demands of boxing. An increased risk of concussive or traumatic brain injury post-2013 is equivocal. However, an increase in skin splits and technical knockouts is apparent. It is likely that boxers believe head guard removal has made them more prone to knockouts. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Safety climate and attitude toward medication error reporting after hospital accreditation in South Korea.

PubMed

Lee, Eunjoo

2016-09-01

This study compared registered nurses' perceptions of safety climate and attitude toward medication error reporting before and after completing a hospital accreditation program. Medication errors are the most prevalent adverse events threatening patient safety; reducing underreporting of medication errors significantly improves patient safety. Safety climate in hospitals may affect medication error reporting. This study employed a longitudinal, descriptive design. Data were collected using questionnaires. A tertiary acute hospital in South Korea undergoing a hospital accreditation program. Nurses, pre- and post-accreditation (217 and 373); response rate: 58% and 87%, respectively. Hospital accreditation program. Perceived safety climate and attitude toward medication error reporting. The level of safety climate and attitude toward medication error reporting increased significantly following accreditation; however, measures of institutional leadership and management did not improve significantly. Participants' perception of safety climate was positively correlated with their attitude toward medication error reporting; this correlation strengthened following completion of the program. Improving hospitals' safety climate increased nurses' medication error reporting; interventions that help hospital administration and managers to provide more supportive leadership may facilitate safety climate improvement. Hospitals and their units should develop more friendly and intimate working environments that remove nurses' fear of penalties. Administration and managers should support nurses who report their own errors. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies.

PubMed

Spelsberg, Angela; Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

2017-02-07

 To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act.  Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10.  Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany.  Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions.  Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals.  Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor. High remuneration and strict confidentiality clauses in these studies could influence the physicians' reporting behaviours of adverse drug reactions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Barrel vascular reconstruction device for endovascular coiling of wide-necked intracranial aneurysms: a multicenter, prospective, post-marketing study.

PubMed

Gory, Benjamin; Blanc, Raphaël; Turjman, Francis; Berge, Jérôme; Piotin, Michel

2018-02-02

The Barrel vascular reconstruction device (Barrel VRD) is a novel stent with design features that allow endovascular coiling of wide-necked bifurcation aneurysms while preserving adjacent branches, without necessitating dual stent implantation. This study aimed to assess the safety and effectiveness of the Barrel VRD at 12-month follow-up. The Barrel VRD trial is a prospective, multicenter, observational post-marketing registry evaluating the use of the Barrel VRD for treatment of wide-necked bifurcation aneurysms. The primary effectiveness endpoint was successful aneurysm treatment measured by digital subtraction angiography with a Raymond-Roy occlusion grade of 1 or 2 in the absence of retreatment, parent artery stenosis (>50%), or target aneurysm rupture at 12 months. The primary safety endpoint was the absence of neurological death or major stroke at 12 months. Twenty patients were enrolled from December 2013 to December 2014. The device was implanted in 19 patients with 19 aneurysms (8 middle cerebral artery, 4 anterior communicating artery, 1 internal carotid artery terminus, 4 basilar artery aneurysms; mean dome height 5.7±1.91 mm; mean neck length 4.8±1.35 mm, mean dome-to-neck ratio 1.6±2.0). Coiling was performed in all cases. The primary effectiveness endpoint was achieved in 78.9% of subjects (15/19; 12 complete occlusions, 3 neck remnants), and the primary safety endpoint was 5.3% (1/19). This prospective study demonstrates that the Barrel VRD device resulted in ~80% occlusion rates and ~5% rates of neurological complications at 1 year after endovascular treatment of wide-necked bifurcation intracranial aneurysms. REGISTERED CLINICAL TRIAL: NCT02125097;Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan.

PubMed

Goda, Maki; Yamakura, Tomoko; Sasaki, Kazuyo; Tajima, Takumi; Ueno, Makoto

2018-02-01

To evaluate the safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus (T2DM) in clinical settings. The authors conducted a 1-year post-marketing surveillance (PMS) of canagliflozin in almost all the elderly patients (≥65 years old) with T2DM who began taking canagliflozin during the first 3 months after its launch in Japan. The main outcomes included the incidences of adverse drug reactions (ADRs), serious ADRs, and the changes of laboratory tests as well as efficacy variables. An ADR was reported in 9.09% (125 of 1375 patients) in the safety analysis set. The main ADRs were dehydration, constipation, thirst, pollakiuria, dizziness, cystitis, eczema, pruritus, and rash. The incidence of serious ADRs was 1.02% (14 patients), which included urinary tract infection, dehydration, hypoglycemia, and cerebral infarction (two patients each). ADRs of special interest that had been reported in clinical trials of SGLT2 inhibitors, such as hypoglycemia, volume depletion-related events, genital/urinary tract infection, polyuria/pollakiuria, and ketone body increased were also observed in this PMS. The safety profiles were similar to the results of a previous clinical study of canagliflozin, and new safety concerns were not identified in this survey. The mean change in HbA1c was -0.77% after 12 months of treatment in the efficacy analysis set. In this PMS, the safety and efficacy profiles of canagliflozin in elderly patients with T2DM were obtained in the clinical settings in Japan and the drug was well tolerated and effective in improving glycemic control.

Safety of remifentanil in transsphenoidal surgery: A single-center analysis of 540 patients.

PubMed

Cote, David J; Burke, William T; Castlen, Joseph P; King, Chih H; Zaidi, Hasan A; Smith, Timothy R; Laws, Edward R; Aglio, Linda S

2017-04-01

Although some studies have examined the efficacy and safety of remifentanil in patients undergoing neurosurgical procedures, none has examined its safety in transsphenoidal operations specifically. In this study, all transsphenoidal operations performed by a single author from 2008 to 2015 were retrospectively reviewed to evaluate the safety of remifentanil in a consecutive series of patients. During the study period, 540 transsphenoidal operations were identified. Of these, 443 (82.0%) patients received remifentanil intra-operatively; 97 (18.0%) did not. The two groups were well-matched with regard to demographic categories, comorbidities, and pre-operative medications (p>0.05), except pre-operative tobacco use (p=0.021). Patients were also well-matched with regard to radiographic features and surgical techniques. Patients who received remifentanil were more likely to harbor a macroadenoma (78.1% vs. 67.0%, p=0.025), and had slightly longer anesthesia time on average (269.2minvs. 239.4min, p=0.024). All pathologic diagnoses were well-matched between the two groups, except that patients receiving remifentanil were more likely to harbor a non-functioning adenoma (46.5% vs. 26.8%, p<0.001). Analysis of post-operative complications showed no significant difference between patients who received remifentanil and those who did not, and length of stay and prevalence of ICU stay did not differ between the two groups. In a well-matched series of 540 patients undergoing transsphenoidal surgery, remifentanil was found to be a safe anesthetic adjunct. There were no significant differences in post-operative hospital course or complications in patients who did and did not receive intra-operative remifentanil. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurement and monitoring of safety: impact and challenges of putting a conceptual framework into practice.

PubMed

Chatburn, Eleanor; Macrae, Carl; Carthey, Jane; Vincent, Charles

2018-03-06

The Measurement and Monitoring of Safety Framework provides a conceptual model to guide organisations in assessing safety. The Health Foundation funded a large-scale programme to assess the value and impact of applying the Framework in regional and frontline care settings. We explored the experiences and reflections of key participants in the programme. The study was conducted in the nine healthcare organisations in England and Scotland testing the Framework (three regional improvement bodies, six frontline settings). Post hoc interviews with clinical and managerial staff were analysed using template analysis. Participants reported that the Framework promoted a substantial shift in their thinking about how safety is actively managed in their environment. It provided a common language, facilitated a more inquisitive approach and encouraged a more holistic view of the components of safety. These changes in conceptual understanding, however, did not always translate into broader changes in practice, with many sites only addressing some aspects of the Framework. One of the three regions did embrace the Framework in its entirety and achieved wider impact with a range of interventions. This region had committed leaders who took time to fully understand the concepts, who maintained a flexible approach to exploring the utility of the Framework and who worked with frontline staff to translate the concepts for local settings. The Measuring and Monitoring of Safety Framework has the potential to support a broader and richer approach to organisational safety. Such a conceptually based initiative requires both committed leaders who themselves understand the concepts and more time to establish understanding and aims than might be needed in a standard improvement programme. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Safety and Effectiveness of the Denali Inferior Vena Cava Filter: Intermediate Follow-Up Results.

PubMed

Reis, Stephen P; Kovoor, Jerry; Sutphin, Patrick D; Toomay, Seth; Trimmer, Clayton; Pillai, Anil; Reddick, Mark; Kalva, Sanjeeva P

2016-08-01

The purpose of the study is to evaluate the clinical safety and effectiveness of the Denali (Bard, Tempe, Arizona) retrievable inferior vena cava (IVC) filter. In this retrospective study, authors reviewed the data of Denali IVC filters placed at their institution between 2013 and 2015. The clinical presentation, indications, and procedure-related complications during placement and retrieval were evaluated. The frequency of post filter pulmonary embolism (PE) and filter-related complications was assessed. Denali filters were placed in 87 patients (47 males; mean age: 56 years). Twenty patients presented with PE, 45 with deep vein thrombosis (DVT), and 21 with both PE and DVT, 1 filter was placed prophylactically before surgery. Indications for filter placement included contraindications to anticoagulation (AC; n = 80), failure of AC (n = 4), and complications of AC (n = 3). No patients had PE on follow-up imaging after filter placement. Retrieval was attempted in 31 patients after a mean period of 125 days (range: 34-324 days). The filter was successfully removed in 31 (100%) patients. Follow-up imaging, available in 71 (82%) patients (range: 2-538 days), demonstrated penetration of 15 legs in 5 patients, caval thrombus in 3, 1 resulting in caval occlusion, <15° filter tilt in 5, and no leg fractures or crossed legs. The Denali filter is safe during deployment and readily retrievable. The overall safety following deployment is similar to those reported in the literature, and the incidence of filter fractures and migration appears to be less than the previous generation of Bard devices. © The Author(s) 2016.

Effects of Newly Designed Hospital Buildings on Staff Perceptions: A Pre-Post Study to Validate Design Decisions.

PubMed

Schreuder, Eliane; van Heel, Liesbeth; Goedhart, Rien; Dusseldorp, Elise; Schraagen, Jan Maarten; Burdorf, Alex

2015-01-01

This study investigates effects of the newly built nonpatient-related buildings of a large university medical center on staff perceptions and whether the design objectives were achieved. The medical center is gradually renewing its hospital building area of 200,000 m.(2) This redevelopment is carefully planned and because lessons learned can guide design decisions of the next phase, the medical center is keen to evaluate the performance of the new buildings. A pre- and post-study with a control group was conducted. Prior to the move to the new buildings an occupancy evaluation was carried out in the old setting (n = 729) (pre-study). Post occupation of the new buildings another occupancy evaluation (post-study) was carried out in the new setting (intervention group) and again in some old settings (control group) (n = 664). The occupancy evaluation consisted of an online survey that measured the perceived performance of different aspects of the building. Longitudinal multilevel analysis was used to compare the performance of the old buildings with the new buildings. Significant improvements were found in indoor climate, perceived safety, working environment, well-being, facilities, sustainability, and overall satisfaction. Commitment to the employer, working atmosphere, orientation, work performance, and knowledge sharing did not improve. The results were interpreted by relating them to specific design choices. We showed that it is possible to measure the performance improvements of a complex intervention being a new building design and validate design decisions. A focused design process aiming for a safe, pleasant and sustainable building resulted in actual improvements in some of the related performance measures. © The Author(s) 2015.

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

PubMed

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

2015-03-01

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

Essentials for starting a pediatric clinical study (4): Clinical pediatric safety planning based on preclinical toxicity studies and pediatric pharmacovigilance guidance.

PubMed

Sheth, Neha

2009-01-01

Juvenile toxicology studies in animals provide useful information to guide monitoring of potential adverse effects in children especially on growth and development. In order to continue to gain knowledge and build upon these preclinical studies, recent experience has suggested that additional approaches for monitoring of safety concerns in the pediatric population may be required. Recently, pediatric guidance has become available from the health authorities which provide pharmacovigilance concepts as they specifically relate to drugs being developed for pediatric indications. Clinical trials are typically not robust enough to detect rare or delayed safety effects as the pediatric trials are relatively short-term. Furthermore, such long term or rare effects may not be detected via standard voluntary postmarketing surveillance. Safety monitoring of children with Juvenile Inflammatory Arthritis (JIA) taking nonsteroid anti-inflammatory drug (NSAID)s will be used as an example to describe a post-marketing risk management and pharmacovigilance program that serves to better evaluate safety data from various sources. The intent of this program is to identify adverse events (AE), including events with longer latency, which may be associated with NSAID use in a pediatric population. In this presentation, the 4 major components of the program are to be addressed. Such a program may serve as a model to proactively generate and monitor safety data in order to identify AEs that may be associated with new therapeutics for a pediatric population.

RN assessments of excellent quality of care and patient safety are associated with significantly lower odds of 30-day inpatient mortality: A national cross-sectional study of acute-care hospitals.

PubMed

Smeds-Alenius, Lisa; Tishelman, Carol; Lindqvist, Rikard; Runesdotter, Sara; McHugh, Matthew D

2016-09-01

Quality and safety in health care has been increasingly in focus during the past 10-15 years. Stakeholders actively discuss ways to measure safety and quality of care to improve the health care system as a whole. Defining and measuring quality and safety, however, is complicated. One underutilized resource worthy of further exploration is the use of registered nurses (RNs) as informants of overall quality of care and patient safety. However, research is still scarce or lacking regarding RN assessments of patient safety and quality of care and their relationship to objective patient outcomes. To investigate relationships between RN assessed quality of care and patient safety and 30-day inpatient mortality post-surgery in acute-care hospitals. This is a national cross-sectional study. A survey (n=>10,000 RNs); hospital organizational data (n=67); hospital discharge registry data (n>200,000 surgical patients). RN data derives from a national sample of RNs working directly with inpatient care in surgical/medical wards in acute-care hospitals in Sweden in 2010. Patient data are from the same hospitals in 2009-2010. Adjusted multivariate logistic regression models were used to estimate relationships between RN assessments and 30-day inpatient mortality. Patients cared for in hospitals where a high proportion of RNs reported excellent quality of care (the highest third of hospitals) had 23% lower odds of 30-day inpatient mortality compared to patients cared for in hospitals in the lowest third (OR 0.77, CI 0.65-0.91). Similarly, patients in hospitals where a high proportion of RNs reported excellent patient safety (highest third) had is 26% lower odds of death (OR 0.74, CI 0.60-0.91). RN assessed excellent patient safety and quality of care are related to significant reductions in odds of 30-day inpatient mortality, suggesting that positive RN reports of quality and safety can be valid indicators of these key variables. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Technical challenges in designing post-marketing eCRFs to address clinical safety and pharmacovigilance needs.

PubMed

Lu, Zhengwu

2010-01-01

To identify key challenges and propose technical considerations in designing electronic case report form (eCRF) for post-marketing studies, the author undertakes a comprehensive literature review of peer reviewed and grey literature to assess the key aspects, processes, standards, recommendations, and best practices in designing eCRFs based on industry experience in designing and supporting electronic data capture (EDC) studies. Literature search using strings on MEDLINE and PUBMED returned few papers directly related to CRF design. Health informatics and general practice journals were searched and results reviewed. Many conference, government commission, health professional and special interests group websites provide relevant information from practical experience - summarization of this information is presented. Further, we presented a list of concrete technical considerations in dealing with EDC technology/system limitations based on literature assessment and industry implementation experience. It is recognized that cross-functional teams be involved in eCRF design process and decision making. To summarize the keys in designing eCRFs to address post-market study safety and pharmacovigilance needs, the first is to identify required data elements from the study protocol supporting data analyses and reporting requirements. Secondly, accepted best practices, CDASH & CDISC guidelines, and company internal or therapeutic unit standard should be considered and applied. Coding (MedDRA & WHODD) mapping should be managed and implemented as well when possible. Finally, we need to be on top of the EDC technologies, challenge the technologies, drive EDC improvement via working with vendors, and utilize the technologies to drive clinical effectiveness. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Safety and effectiveness of tofogliflozin in elderly Japanese patients with type 2 diabetes mellitus: A post-marketing study (J-STEP/EL Study).

PubMed

Utsunomiya, Kazunori; Shimmoto, Naoki; Senda, Masayuki; Kurihara, Yuji; Gunji, Ryoji; Fujii, Shoko; Kakiuchi, Seigo; Fujiwara, Hisataka; Kameda, Hiroyuki; Tamura, Masahiro; Kaku, Kohei

2017-11-01

Although sodium-glucose cotransporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, they are associated with concerns about specific adverse drug reactions. We carried out a 1-year post-marketing study of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus. This was a prospective, observational and multicenter post-marketing study carried out in the context of routine clinical practice. The study included all type 2 diabetes patients aged ≥65 years who started treatment with tofogliflozin during the first 3 months after its launch on 23 May 2014. Of 1,535 patients registered, 1,507 patients whose electronic case report forms were collected and who had at least one follow-up visit were included in the safety analysis. A total of 270 of 1,507 patients (17.92%) had at least one adverse drug reaction to tofogliflozin. The incidences of adverse drug reactions of special interest, namely, polyuria/pollakiuria, volume depletion-related events, urinary tract infection, genital infection, hypoglycemia and skin disorders were 2.92, 3.85, 2.06, 1.33, 1.06 and 2.39%, respectively. Among those patients evaluable for clinical effectiveness, the mean change in glycated hemoglobin and bodyweight from baseline to last visit was -0.46% (P < 0.0001) and -2.71 kg (P < 0.0001), respectively. The present study showed that the incidence of adverse drug reactions to tofogliflozin in this study of elderly patients aged ≥65 years differed little from the incidence in the preapproval clinical trials. It was shown that tofogliflozin significantly decreased glycated hemoglobin levels. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

PubMed

Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

2017-12-01

Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at daily doses of 1200 mg. Other adverse drug reactions reported in post-marketing surveillance are seizure (5.8%), dizziness (4.1%), rash (2.6%), and fatigue (2.1%). The safety profile of eslicarbazepine acetate in renal and hepatic impairment subjects (phase I studies) and in elderly patients (phase III study) did not raise any specific concern. After 6 years of post-marketing surveillance, eslicarbazepine acetate maintains a similar safety profile to that observed in pivotal clinical studies.

Post-licensure safety surveillance study of routine use of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MenACWY-D) in infants and children.

PubMed

Hansen, J; Zhang, L; Eaton, A; Baxter, R; Robertson, C A; Decker, M D; Greenberg, D P; Bassily, E; Klein, N P

2018-04-12

Menactra® vaccine (MenACWY-D) was licensed in the United States in 2005 for persons 11-55 years of age, in 2007 for children 2-10 years of age, and in 2011 for infants/toddlers 9-23 months of age. We conducted two studies at Kaiser Permanente Northern California (KPNC), an integrated health care organization, to assess the safety of MenACWY-D in 2-10-year-olds and 9-23-month-olds receiving the vaccine during routine clinical care. We conducted observational, retrospective studies of MenACWY-D in 2-10-year-olds (October 2007-October 2010) and in 9-23-month-olds (June 2011-June 2014). We monitored all subjects for non-elective hospitalizations, emergency department visits, and selected outpatient outcomes (specified neurological conditions, hypersensitivity reactions and new-onset autoimmune diseases) up to 6 months after vaccination, depending on the study. Using a self-control risk-interval design, we calculated incidence rate ratios (IRRs) comparing outcomes during the post-vaccination risk interval (0-30 days) with those during more remote post-vaccination comparison intervals (31-60 and 31-180 days [children] or 31-75 days [infants/toddlers]). There were 1421 children aged 2-10 years and 116 infants/toddlers aged 9-23 months who received MenACWY-D. Approximately 30% of the 2-10-year-olds and 67% of the 9-23-month-olds were considered at increased risk of meningococcal disease. Among 2-10-year-olds, there was 1 hospitalization on post-vaccination day 5 for fever, which was considered possibly related to vaccination. The only significantly elevated outcome among 2-10-year-olds was cellulitis/abscess (2 cases occurred during the risk interval versus 0 during comparison interval; IRR not evaluable [NE], 95% CI: 1.42, NE). After medical record review, the 2 cases were considered unrelated to vaccination. Among 9-23-month-olds, no outcomes were significantly elevated after vaccination and there were no hospitalizations. There were no deaths observed during the three-year accrual and subsequent six-month surveillance period for either study. Immunization of infants and young children with MenACWY-D vaccine was not associated with any new safety concerns; however, these small studies had limited power to detect rare or uncommon safety events. ClinicalTrials.gov Identifiers are NCT00728260 and NCT01689155. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Collapse Mechanisms Of Masonry Structures

NASA Astrophysics Data System (ADS)

Zuccaro, G.; Rauci, M.

2008-07-01

The paper outlines a possible approach to typology recognition, safety check analyses and/or damage measuring taking advantage by a multimedia tool (MEDEA), tracing a guided procedure useful for seismic safety check evaluation and post event macroseismic assessment. A list of the possible collapse mechanisms observed in the post event surveys on masonry structures and a complete abacus of the damages are provided in MEDEA. In this tool a possible combination between a set of damage typologies and each collapse mechanism is supplied in order to improve the homogeneity of the damages interpretation. On the other hand recent researches of one of the author have selected a number of possible typological vulnerability factors of masonry buildings, these are listed in the paper and combined with potential collapse mechanisms to be activated under seismic excitation. The procedure takes place from simple structural behavior models, derived from the Umbria-Marche earthquake observations, and tested after the San Giuliano di Puglia event; it provides the basis either for safety check analyses of the existing buildings or for post-event structural safety assessment and economic damage evaluation. In the paper taking advantage of MEDEA mechanisms analysis, mainly developed for the post event safety check surveyors training, a simple logic path is traced in order to approach the evaluation of the masonry building safety check. The procedure starts from the identification of the typological vulnerability factors to derive the potential collapse mechanisms and their collapse multipliers and finally addresses the simplest and cheapest strengthening techniques to reduce the original vulnerability. The procedure has been introduced in the Guide Lines of the Regione Campania for the professionals in charge of the safety check analyses and the buildings strengthening in application of the national mitigation campaign introduced by the Ordinance of the Central Government n. 3362/03. The main cases of out of plane mechanisms are analyzed and a possible innovative theory for masonry building vulnerability assessment, based on limit state analyses, is outlined. The paper report the first step of a research granted by the Department of the Civil Protection to Reluis within the research program of Line 10.

Collapse Mechanisms Of Masonry Structures

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

Zuccaro, G.; Rauci, M.

2008-07-08

The paper outlines a possible approach to typology recognition, safety check analyses and/or damage measuring taking advantage by a multimedia tool (MEDEA), tracing a guided procedure useful for seismic safety check evaluation and post event macroseismic assessment. A list of the possible collapse mechanisms observed in the post event surveys on masonry structures and a complete abacus of the damages are provided in MEDEA. In this tool a possible combination between a set of damage typologies and each collapse mechanism is supplied in order to improve the homogeneity of the damages interpretation. On the other hand recent researches of onemore » of the author have selected a number of possible typological vulnerability factors of masonry buildings, these are listed in the paper and combined with potential collapse mechanisms to be activated under seismic excitation. The procedure takes place from simple structural behavior models, derived from the Umbria-Marche earthquake observations, and tested after the San Giuliano di Puglia event; it provides the basis either for safety check analyses of the existing buildings or for post-event structural safety assessment and economic damage evaluation. In the paper taking advantage of MEDEA mechanisms analysis, mainly developed for the post event safety check surveyors training, a simple logic path is traced in order to approach the evaluation of the masonry building safety check. The procedure starts from the identification of the typological vulnerability factors to derive the potential collapse mechanisms and their collapse multipliers and finally addresses the simplest and cheapest strengthening techniques to reduce the original vulnerability. The procedure has been introduced in the Guide Lines of the Regione Campania for the professionals in charge of the safety check analyses and the buildings strengthening in application of the national mitigation campaign introduced by the Ordinance of the Central Government n. 3362/03. The main cases of out of plane mechanisms are analyzed and a possible innovative theory for masonry building vulnerability assessment, based on limit state analyses, is outlined. The paper report the first step of a research granted by the Department of the Civil Protection to Reluis within the research program of Line 10.« less

Risk Management Plans: are they a tool for improving drug safety?

PubMed

Frau, Serena; Font Pous, Maria; Luppino, Maria Rosa; Conforti, Anita

2010-08-01

In 2005, new European legislation authorised Regulatory Agencies to require drug companies to submit a risk management plan (RMP) comprising detailed commitments for post-marketing pharmacovigilance. The aim of the study is to describe the characteristics of RMP for 15 drugs approved by the European Medicines Agency (EMA) and their impact on post-marketing safety issues. Of the 90 new Chemical Entities approved through a centralised procedure by the EMA during 2006 and 2007, 15 of them were selected and their safety aspects and relative RMPs analysed. All post-marketing communications released for safety reasons related to these drugs were also considered. A total of 157 safety specifications were established for the drugs assessed. Risk minimisation activities were foreseen for 5 drugs as training activities. Post-marketing safety issues emerged for 12 of them, leading to 39 type II variations in Summary of Product Characteristics (SPC). Nearly half of such variations, 19 (49%), concerned safety aspects not envisaged by the RMPs. Besides this, 9 Safety Communications were published for 6 out of 15 drugs assessed. The present study reveals several critical points on the way RMPs have been implemented. Several activities proposed by the RMPs do not appear to be adequate in dealing with the potential risks of drugs. Poor communication of risk to practitioners and to the public, and above all limited transparency for the total assessment of risk, seem to transform RMPs into a tool to reassure the public when inadequately evaluated drugs are granted premature marketing authorisation.

Worldwide, 3-Year, Post-Marketing Surveillance Experience with Tofacitinib in Rheumatoid Arthritis.

PubMed

Cohen, Stanley; Curtis, Jeffrey R; DeMasi, Ryan; Chen, Yan; Fan, Haiyun; Soonasra, Arif; Fleischmann, Roy

2018-06-01

Post-marketing surveillance (PMS) is an integral part of monitoring adverse events (AEs) following approval of new drugs. Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). An analysis of PMS reports was conducted to evaluate the safety of tofacitinib in a post-marketing setting. Worldwide tofacitinib PMS data received in the Pfizer safety database from November 6, 2012 (first marketing authorization of tofacitinib) to November 5, 2015 were analyzed. Serious AEs (SAEs) of interest were reviewed and reporting rates (RRs) were calculated by dividing the number of SAEs by the estimated 100 patient-years of exposure. Patient exposure was calculated based on estimated worldwide sales and an estimated daily regimen of tofacitinib 5 mg twice daily. During the 3-year reporting period, worldwide post-marketing exposure to tofacitinib since approval was estimated to be 34,223 patient-years. In total, 9291 case reports (82.9% non-serious) were received and 25,417 AEs, 102 fatal cases, and 4352 SAEs were reported. The RRs (per 100 patient-years) for SAEs of interest by Medical Dictionary for Regulatory Activities System Organ Class were 2.57 for infections, 0.91 for gastrointestinal disorders, 0.60 for respiratory disorders, 0.45 for neoplasms, 0.43 for cardiac disorders, and 0.12 for hepatobiliary disorders. Although there are limitations to these data, no new safety risks were revealed in this real-world setting compared with the safety profile identified in the tofacitinib RA clinical development program. Any risks identified through the tofacitinib development program and PMS will continue to be monitored through pharmacovigilance surveillance. Pfizer Inc.

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

PubMed

Chen, Yuting; McCabe, Brenda; Hyatt, Douglas

2017-06-01

The construction industry has hit a plateau in terms of safety performance. Safety climate is regarded as a leading indicator of safety performance; however, relatively little safety climate research has been done in the Canadian construction industry. Safety climate may be geographically sensitive, thus it is necessary to examine how the construct of safety climate is defined and used to improve safety performance in different regions. On the other hand, more and more attention has been paid to job related stress in the construction industry. Previous research proposed that individual resilience may be associated with a better safety performance and may help employees manage stress. Unfortunately, few empirical research studies have examined this hypothesis. This paper aims to examine the role of safety climate and individual resilience in safety performance and job stress in the Canadian construction industry. The research was based on 837 surveys collected in Ontario between June 2015 and June 2016. Structural equation modeling (SEM) techniques were used to explore the impact of individual resilience and safety climate on physical safety outcomes and on psychological stress among construction workers. The results show that safety climate not only affected construction workers' safety performance but also indirectly affected their psychological stress. In addition, it was found that individual resilience had a direct negative impact on psychological stress but had no impact on physical safety outcomes. These findings highlight the roles of both organizational and individual factors in individual safety performance and in psychological well-being. Construction organizations need to not only monitor employees' safety performance, but also to assess their employees' psychological well-being. Promoting a positive safety climate together with developing training programs focusing on improving employees' psychological health - especially post-trauma psychological health - can improve the safety performance of an organization. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Measurement and study report as a part of the control system for human safety and health protection against electromagnetic fields and electromagnetic radiation (0 Hz-300 GHz)].

PubMed

Aniołczyk, Halina

2007-01-01

The National Control System for safety and health protection against electromagnetic fields (EMF) and electromagnetic radiation (EMR) (0 Hz-300 GHz) is constantly analyzed in view of Directive 2004/40/EC. Reports on the effects of investments (at the designing stage or at the stage of looking for their localization) on the environment and measurement and study reports on the objects already existing or being put into operation are important elements of this system. These documents should meet both national and European Union's legislation requirements. The overriding goal of the control system is safety and health protection of humans against electromagnetic fields in the environment and in occupational settings. The author pays a particular attention to provisions made in directives issued by relevant ministers and to Polish standards, which should be documented in measurement and study reports published by the accredited laboratories and relating to the problems of human safety and health protection. Similar requirements are valid for the Reports. Therefore, along with measurement outcomes, the reports should include data on the EMF exposure classification at work-posts and the assessment of occupational risk resulting from EMF exposure or at least thorough data facilitating such a classification.

Post-tsunami relocation of fisher settlements in South Asia: evidence from the Coromandel Coast, India.

PubMed

Bavinck, Maarten; de Klerk, Leo; van der Plaat, Felice; Ravesteijn, Jorik; Angel, Dominique; Arendsen, Hendrik; van Dijk, Tom; de Hoog, Iris; van Koolwijk, Ant; Tuijtel, Stijn; Zuurendonk, Benjamin

2015-07-01

The tsunami that struck the coasts of India on 26 December 2004 resulted in the large-scale destruction of fisher habitations. The post-tsunami rehabilitation effort in Tamil Nadu was directed towards relocating fisher settlements in the interior. This paper discusses the outcomes of a study on the social effects of relocation in a sample of nine communities along the Coromandel Coast. It concludes that, although the participation of fishing communities in house design and in allocation procedures has been limited, many fisher households are satisfied with the quality of the facilities. The distance of the new settlements to the shore, however, is regarded as an impediment to engaging in the fishing profession, and many fishers are actually moving back to their old locations. This raises questions as to the direction of coastal zone policy in India, as well as to the weight accorded to safety (and other coastal development interests) vis-à-vis the livelihood needs of fishers. © 2015 The Author(s). Disasters © Overseas Development Institute, 2015.

Safety and efficacy of gadoteric acid in pediatric magnetic resonance imaging: overview of clinical trials and post-marketing studies.

PubMed

Balassy, Csilla; Roberts, Donna; Miller, Stephen F

2015-11-01

Gadoteric acid is a paramagnetic gadolinium macrocyclic contrast agent approved for use in MRI of cerebral and spinal lesions and for body imaging. To investigate the safety and efficacy of gadoteric acid in children by extensively reviewing clinical and post-marketing observational studies. Data were collected from 3,810 children (ages 3 days to 17 years) investigated in seven clinical trials of central nervous system (CNS) imaging (n = 141) and six post-marketing observational studies of CNS, musculoskeletal and whole-body MR imaging (n = 3,669). Of these, 3,569 children were 2-17 years of age and 241 were younger than 2 years. Gadoteric acid was generally administered at a dose of 0.1 mmol/kg. We evaluated image quality, lesion detection and border delineation, and the safety of gadoteric acid. We also reviewed post-marketing pharmacovigilance experience. Consistent with findings in adults, gadoteric acid was effective in children for improving image quality compared with T1-W unenhanced sequences, providing diagnostic improvement, and often influencing the therapeutic approach, resulting in treatment modifications. In studies assessing neurological tumors, gadoteric acid improved border delineation, internal morphology and contrast enhancement compared to unenhanced MR imaging. Gadoteric acid has a well-established safety profile. Among all studies, a total of 10 children experienced 20 adverse events, 7 of which were thought to be related to gadoteric acid. No serious adverse events were reported in any study. Post-marketing pharmacovigilance experience did not find any specific safety concern. Gadoteric acid was associated with improved lesion detection and delineation and is an effective and well-tolerated contrast agent for use in children.

Rutosides for prevention of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2015-09-16

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. This is an update of the review first published in 2013. To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) ((CENTRAL) 2015, Issue 8). Clinical trials databases were searched for details of ongoing and unpublished studies. We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. Two review authors independently assessed studies for inclusion and intended to extract information from the trials. No studies were identified comparing rutosides versus any alternative in the prevention of PTS. As there were no studies identified in this review there is currently insufficient evidence to determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.

Preliminary safety analysis of the Baita Bihor radioactive waste repository, Romania

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

Little, Richard; Bond, Alex; Watson, Sarah

2007-07-01

A project funded under the European Commission's Phare Programme 2002 has undertaken an in-depth analysis of the operational and post-closure safety of the Baita Bihor repository. The repository has accepted low- and some intermediate-level radioactive waste from industry, medical establishments and research activities since 1985 and the current estimate is that disposals might continue for around another 20 to 35 years. The analysis of the operational and post-closure safety of the Baita Bihor repository was carried out in two iterations, with the second iteration resulting in reduced uncertainties, largely as a result taking into account new information on the hydrologymore » and hydrogeology of the area, collected as part of the project. Impacts were evaluated for the maximum potential inventory that might be available for disposal to Baita Bihor for a number of operational and postclosure scenarios and associated conceptual models. The results showed that calculated impacts were below the relevant regulatory criteria. In light of the assessment, a number of recommendations relating to repository operation, optimisation of repository engineering and waste disposals, and environmental monitoring were made. (authors)« less

Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: The MIRROR study.

PubMed

Bar-Or, Amit; Grove, Richard A; Austin, Daren J; Tolson, Jerry M; VanMeter, Susan A; Lewis, Eric W; Derosier, Frederick J; Lopez, Monica C; Kavanagh, Sarah T; Miller, Aaron E; Sorensen, Per S

2018-05-15

To assess dose-response effects of the anti-CD20 monoclonal antibody ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis (RMS). Patients (n = 232) were randomized to ofatumumab 3, 30, or 60 mg every 12 weeks, ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new gadolinium-enhancing lesions (per brain MRI) at week 12. Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured. Safety monitoring continued weeks 24 to 48 with subsequent individualized follow-up evaluating B-cell repletion. The cumulative number of new lesions was reduced by 65% for all ofatumumab dose groups vs placebo ( p < 0.001). Post hoc analysis (excluding weeks 1-4) estimated a ≥90% lesion reduction vs placebo (week 12) for all cumulative ofatumumab doses ≥30 mg/12 wk. Dose-dependent CD19 B-cell depletion was observed. Notably, complete depletion was not necessary for a robust treatment effect. The most common adverse event was injection-related reactions (52% ofatumumab, 15% placebo), mild to moderate severity in 97%, most commonly associated with the first dose and diminishing on subsequent dosing. Imaging showed that all subcutaneous ofatumumab doses demonstrated efficacy (most robust: cumulative doses ≥30 mg/12 wk), with a safety profile consistent with existing ofatumumab data. This treatment effect also occurred with dosage regimens that only partially depleted circulating B cells. This study provides Class I evidence that for patients with RMS, ofatumumab decreases the number of new MRI gadolinium-enhancing lesions 12 weeks after treatment initiation. © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Perioperative Lidocaine Infusions for the Prevention of Chronic Post-Surgical Pain: A Systematic Review and Meta-Analysis of Efficacy and Safety.

PubMed

Bailey, Martin; Corcoran, Tomas; Schug, Stephan; Toner, Andrew

2018-05-11

Chronic post-surgical pain (CPSP) occurs in 12% of surgical populations and is a high priority for perioperative research. Systemic lidocaine may modulate several of the pathophysiological processes linked to CPSP. This systematic review aims to identify and synthesize the evidence linking lidocaine infusions and CPSP.The authors conducted a systematic literature search of the major medical databases from inception until October 2017. Trials that randomized adults without baseline pain to perioperative lidocaine infusion or placebo were included if they reported on CPSP. The primary outcome was the presence of procedure-related pain at three months or longer after surgery. The secondary outcomes of pain intensity, adverse safety events and local anesthetic toxicity were also assessed.Six trials from four countries (n=420) were identified. CPSP incidence was consistent with existing epidemiological data. Perioperative lidocaine infusions significantly reduced the primary outcome (odds ratio, 0.29; 95% CI, 0.18 to 0.48), although the difference in intensity of CPSP assessed by the short form McGill pain questionnaire (four trials) was not statistically significant (weighted mean difference, -1.55; 95% CI, -3.16 to 0.06). Publication and other bias were highly apparent, as were limitations in trial design. Each study included a statement reporting no adverse events attributable to lidocaine, but systematic safety surveillance strategies were absent.Current limited clinical trial data and biological plausibility support lidocaine infusions use to reduce the development of CPSP without full assurances as to its safety. This hypothesis should be addressed in future definitive clinical trials with comprehensive safety assessment and reporting.

Post-approval safety issues with innovative drugs: a European cohort study.

PubMed

Mol, Peter G M; Arnardottir, Arna H; Motola, Domenico; Vrijlandt, Patrick J; Duijnhoven, Ruben G; Haaijer-Ruskamp, Flora M; de Graeff, Pieter A; Denig, Petra; Straus, Sabine M J M

2013-11-01

At time of approval, knowledge of the full benefit risk of any drug is limited, in particular with regards to safety. Post-approval surveillance of potential drug safety concerns is recognized as an important task of regulatory agencies. For innovative, often first-in-class drugs, safety knowledge at time of approval is often even less extensive and these may require tighter scrutiny post approval. We evaluated whether more post-approval serious safety issues were identified for drugs with a higher level of innovation. A cohort study was performed that included all new active substances approved under the European Centralized Procedure and for which serious safety issues were identified post-approval from 1 January 1999 to 1 January 2012. Serious safety issues were defined as issues requiring a Direct Healthcare Professional Communication to alert individual healthcare professionals of a new serious safety issue, or a safety-related drug withdrawal. Data were retrieved from publicly available websites of the Dutch Medicines Evaluation Board and the European Medicines Agency. The level of innovation was scored using a validated algorithm, grading drugs as important (A), moderate (B) or modest (C) innovations or as pharmacological or technological (pharm/tech) innovations. The data were analyzed using appropriate descriptive statistics and Kaplan-Meier analysis, with a Mantel-Cox log-rank test, and Cox-regression models correcting for follow-up duration, to identify a possible trend in serious safety issues with an increasing level of innovation. In Europe, 279 new drugs were approved between 1999 and 2011. Fifty-nine (21 %) were graded as important, 63 (23 %) moderate, or 34 (12 %) modest innovations and 123 (44 %) as non-innovative (pharm/tech), while 15 (25 %), 13 (21 %), 8 (24 %) and 17 (14 %) had post-approval safety issues, respectively (p = 0.06, linear-by-linear test). Five drugs were withdrawn from the market. The Kaplan-Meier-derived probability for having a first serious safety issue was statistically significant, log-rank (Mantel-Cox) p = 0.036. In the final adjusted Cox proportional hazard model there was no statistically significant difference in occurrence of a first serious safety issue for important, moderate and modest innovations versus non-innovative drugs; hazard ratios 1.76 (95 % CI 0.82-3.77), 1.61 (95 % CI 0.76-3.41)], and 1.25 (95 % CI 0.51-3.06), respectively. A higher level of innovation was not clearly related to an increased risk of serious safety issues identified after approval.

Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer-updated results.

PubMed

Kimura, Go; Ueda, Takeshi

2017-03-01

A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28-1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18-0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. © The Author 2016. Published by Oxford University Press.

A Novel In Vivo Protocol for Molecular Study of Radiation-Induced Fibrosis in Head and Neck Cancer Patients.

PubMed

Krisciunas, Gintas P; Platt, Michael; Trojanowska, Maria; Grillone, Gregory A; Haines, Paul C; Langmore, Susan E

2016-03-01

Radiation-induced fibrosis is a common complication for patients following head and neck cancer treatment. This study presents a novel minimally invasive protocol for molecular study of fibrosis in the stromal tissues. Subjects with radiation-induced fibrosis in the head and neck who were at least 6 months post treatment received submental core needle biopsies, followed by molecular processing and quantification of gene expression for 14 select pro-inflammatory and pro-fibrotic genes. Control biopsies from the upper arm were obtained from the same subjects. Patients were followed up at 1 and 2 weeks to monitor for safety and adverse outcomes. Six subjects were enrolled and completed the study. No subjects experienced adverse outcomes or complication. An 18 gauge core biopsy needle with a 10 mm notch inserted for up to 60 seconds was needed. Subcutaneous tissue yielded 3 ng of RNA, amplified to 6 µg of cDNA, allowing for adequately sensitive quantitative polymerase chain reaction (qPCR) analysis of approximately 28 genes. This study demonstrates the safety and utility of a novel technique for the molecular study of fibrosis in head and neck cancer patients. Longitudinal studies of patients undergoing radiation therapy will allow for identification of molecular targets that contribute to the process of fibrosis in the head and neck. © The Author(s) 2015.

Point-of-care washing of allogeneic red blood cells for the prevention of transfusion-related respiratory complications (WAR-PRC): a protocol for a multicenter randomised clinical trial in patients undergoing cardiac surgery.

PubMed

Warner, Matthew A; Welsby, Ian J; Norris, Phillip J; Silliman, Christopher C; Armour, Sarah; Wittwer, Erica D; Santrach, Paula J; Meade, Laurie A; Liedl, Lavonne M; Nieuwenkamp, Chelsea M; Douthit, Brian; van Buskirk, Camille M; Schulte, Phillip J; Carter, Rickey E; Kor, Daryl J

2017-08-18

The transfusion-related respiratory complications, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are leading causes of transfusion-related morbidity and mortality. At present, there are no effective preventive strategies with red blood cell (RBC) transfusion. Although mechanisms remain incompletely defined, soluble biological response modifiers (BRMs) within the RBC storage solution may play an important role. Point-of-care (POC) washing of allogeneic RBCs may remove these BRMs, thereby mitigating their impact on post-transfusion respiratory complications. This is a multicenter randomised clinical trial of standard allogeneic versus washed allogeneic RBC transfusion for adult patients undergoing cardiac surgery testing the hypothesis that POC RBC washing is feasible, safe, and efficacious and will reduce recipient immune and physiologic responses associated with transfusion-related respiratory complications. Relevant clinical outcomes will also be assessed. This investigation will enrol 170 patients at two hospitals in the USA. Simon's two-stage design will be used to assess the feasibility of POC RBC washing. The primary safety outcomes will be assessed using Wilcoxon Rank-Sum tests for continuous variables and Pearson chi-square test for categorical variables. Standard mixed modelling practices will be employed to test for changes in biomarkers of lung injury following transfusion. Linear regression will assess relationships between randomised group and post-transfusion physiologic measures. Safety oversight will be conducted under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained by the DSMB as well as the institutional review boards at each institution prior to enrolling the first study participant. This study aims to provide important information regarding the feasibility of POC washing of allogeneic RBCs and its potential impact on ameliorating post-transfusion respiratory complications. Additionally, it will inform the feasibility and scientific merit of pursuing a more definitive phase II/III clinical trial. ClinicalTrials.gov registration number is NCT02094118 (Pre-results). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Scoping Review of Peer-led Education in Patient Safety Training

PubMed Central

McLachlan, Andrew J.; Chen, Timothy F.

2018-01-01

Objective. To examine the literature pertaining to the use of peer-led education in patient safety. Findings. Four studies met the inclusion criteria: two were conducted in health care students and two in medical practitioners. Three studies used pre-post evaluation, with one containing a comparator group. One study a post-intervention evaluation only. All studies undertook Kirkpatrick Level 2 evaluations, showing significant improvements in attitudes and knowledge. One study undertook Level 3 and 4 evaluations, showing improvement in self-reported behaviors and engagement in quality improvement initiatives. Summary. There are few studies evaluating peer-led education in patient safety and formal and high-quality evaluations are lacking. PMID:29606704

Comparable pharmacodynamics, efficacy, and safety of linagliptin 5 mg among Japanese, Asian and white patients with type 2 diabetes.

PubMed

Sarashina, Akiko; Friedrich, Christian; Crowe, Susanne; Patel, Sanjay; Graefe-Mody, Ulrike; Hayashi, Naoyuki; Horie, Yoshiharu

2016-09-01

The efficacy and safety of drugs can vary between different races or ethnic populations because of differences in the relationship of dose to exposure, pharmacodynamic response or clinical efficacy and safety. In the present post-hoc analysis, we assessed the influence of race on the pharmacokinetics, pharmacodynamics, efficacy and safety of monotherapy with the dipeptidyl peptidase-4 inhibitor, linagliptin, in patients with type 2 diabetes enrolled in two comparable, previously reported randomized phase III trials. Study 1 (with a 12-week placebo-controlled phase) recruited Japanese patients only (linagliptin, n = 159; placebo, n = 80); study 2 (24-week trial) enrolled Asian (non-Japanese; linagliptin, n = 156; placebo, n = 76) and white patients (linagliptin, n = 180; placebo, n = 90). Linagliptin trough concentrations were equivalent across study and race groups, and were higher than half-maximal inhibitory concentration, resulting in dipeptidyl peptidase-4 inhibition >80% at trough. Linagliptin inhibited plasma dipeptidyl peptidase-4 activity to a similar degree in study 1 and study 2. Linagliptin reduced fasting plasma glucose concentrations by a similar magnitude across groups, leading to clinically relevant reductions in glycated hemoglobin in all groups. Glycated hemoglobin levels decreased to a slightly greater extent in study 1 (Japanese) and in Asian (non-Japanese) patients from study 2. Linagliptin had a favorable safety profile in each race group. Trough exposure, pharmacodynamic response, and efficacy and safety of linagliptin monotherapy were comparable among Japanese, Asian (non-Japanese) and white patients, confirming that the recommended 5-mg once-daily dose of linagliptin is appropriate for use among different race groups. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Regulatory review time and post-market safety events for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study

PubMed Central

Zeitoun, Jean-David; Lefèvre, Jérémie H; Downing, Nicholas S; Bergeron, Henri; Ross, Joseph S

2015-01-01

Aims Regulatory review time has been associated with post-market medication safety issues in the United States. Our objective was to evaluate whether regulatory review time and near deadline approval are associated with post-market safety events (PMSEs) for novel medicines approved by the European Medicines Agency (EMA). Methods We performed a cross-sectional analysis of all novel medicines approved by the EMA through the centralized authorization procedure between 2001 and 2010. PMSEs were defined as withdrawals and communications identified through Dear Healthcare Professional Communications (DHPCs). Regulatory review time was defined as the time that elapsed between the start of the assessment procedure and approval. Near regulatory deadline approval was defined as approval within the 30 days before the EMA’s 210 day regulatory deadline. Results Among 161 eligible medicines, PMSEs were identified for 49 (30.4%), 44 of which were DHPCs, five of which were withdrawals. Median regulatory review time was 337 days (IQR 276–406) and was not associated with PMSEs (P = 0.57). However, when categorized by regulatory review speed tertile, there were differences in risk of PMSEs, with higher rates among medicines in the middle tertile (25 of 55, 45.4%; P = 0.01). Finally, 26 medicines were approved near the 210 day regulatory deadline, but were not more likely to have PMSEs (38.5% vs. 28.7%; P = 0.32). Conclusions Neither faster EMA regulatory review speed nor approval near regulatory deadlines was associated with greater likelihood of PMSEs among recently approved novel medicines. PMID:25808713

Regulatory review time and post-market safety events for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study.

PubMed

Zeitoun, Jean-David; Lefèvre, Jérémie H; Downing, Nicholas S; Bergeron, Henri; Ross, Joseph S

2015-10-01

Regulatory review time has been associated with post-market medication safety issues in the United States. Our objective was to evaluate whether regulatory review time and near deadline approval are associated with post-market safety events (PMSEs) for novel medicines approved by the European Medicines Agency (EMA). We performed a cross-sectional analysis of all novel medicines approved by the EMA through the centralized authorization procedure between 2001 and 2010. PMSEs were defined as withdrawals and communications identified through Dear Healthcare Professional Communications (DHPCs). Regulatory review time was defined as the time that elapsed between the start of the assessment procedure and approval. Near regulatory deadline approval was defined as approval within the 30 days before the EMA's 210 day regulatory deadline. Among 161 eligible medicines, PMSEs were identified for 49 (30.4%), 44 of which were DHPCs, five of which were withdrawals. Median regulatory review time was 337 days (IQR 276-406) and was not associated with PMSEs (P = 0.57). However, when categorized by regulatory review speed tertile, there were differences in risk of PMSEs, with higher rates among medicines in the middle tertile (25 of 55, 45.4%; P = 0.01). Finally, 26 medicines were approved near the 210 day regulatory deadline, but were not more likely to have PMSEs (38.5% vs. 28.7%; P = 0.32). Neither faster EMA regulatory review speed nor approval near regulatory deadlines was associated with greater likelihood of PMSEs among recently approved novel medicines. © 2015 The British Pharmacological Society.

42 CFR 87.4 - For what purposes may grants be awarded?

Code of Federal Regulations, 2013 CFR

2013-10-01

... SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH... Safety and Health Act authorizes grants for research, experiments, and demonstrations relating to occupational safety and health, including studies of the psychological factors involved. This authority...

42 CFR 87.4 - For what purposes may grants be awarded?

Code of Federal Regulations, 2012 CFR

2012-10-01

... SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH... Safety and Health Act authorizes grants for research, experiments, and demonstrations relating to occupational safety and health, including studies of the psychological factors involved. This authority...

42 CFR 87.4 - For what purposes may grants be awarded?

Code of Federal Regulations, 2014 CFR

2014-10-01

... SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH... Safety and Health Act authorizes grants for research, experiments, and demonstrations relating to occupational safety and health, including studies of the psychological factors involved. This authority...

Reducing safety risk among underserved caregivers with an Alzheimer's home safety program.

PubMed

Levy-Storms, Lené; Cherry, Debra L; Lee, Linda J; Wolf, Sheldon M

2017-09-01

Older adults living with Alzheimer's disease (AD) experience more of the types of accidents and injuries prevalent among older adults. Relatively few studies specifically on safety risks have included older adults of color and tested interventions. This pilot study tested the feasibility and evaluability of educating Hispanic and African American caregivers of patients living with AD about reducing safety risks in their homes. This outpatient memory clinic-based intervention study included a pre-/post-test survey design with two nonequivalent groups and predominately serves Hispanic and African Americans. Of 60 eligible caregivers, 67% participated in a tailored, safety training class with an optional follow-up call. The results indicate a reduction in some safety risks compared to baseline and/or a no intervention group, respectively, including leaving patients at home alone part-time (p < .01 and p < .01), getting lost (p < .05 and p < .05), going outdoors alone less often (p < .05 and p < .01), and giving themselves medicine (p < .05 and p < .01). At post-test, 47 clinically significant instances occurred, in which caregivers who participated in the intervention self-reported patients living with AD to be 'completely safe' in one or more of the safety risk items compared to 8 instances among those who did not. This pilot pre/post design with non-equivalent groups study needs refinement in a future randomized control trial. Despite limitations, this pilot study demonstrates the first feasible and evaluable intervention with both statistically and clinically significant results that suggest potential for reducing safety risks among at-risk minority patients living with AD in future research.

General in-situation safety behaviors are uniquely associated with post-event processing.

PubMed

Mitchell, Melissa A; Schmidt, Norman B

2014-06-01

Research suggests that state anxiety and in-situation safety behaviors are associated with post-event processing (PEP) in social anxiety. Past research has obtained mixed results on whether one or both factors contribute to PEP. The current investigation evaluated state anxiety and in-situation safety behaviors (including subtypes of in-situation safety behaviors) simultaneously to determine their relative contributions to PEP. A prospective study assessed social anxiety, state anxiety, in-situation safety behaviors, PEP, and depression in the context of a speech stressor. Consistent with theory, in-situation safety behaviors were uniquely associated with greater PEP. State anxiety was not uniquely associated with PEP. Furthermore, restricting and active subtypes of in-situation safety behaviors showed specificity to PEP. Limitations of the present study include the use of a nonclinical analog sample and retrospective reporting of PEP. These findings highlight the importance of research on in-situation safety behaviors as a potential contributor to PEP. Published by Elsevier Ltd.

Influence of Japanese Regulatory Action on Denosumab-Related Hypocalcemia Using Japanese Adverse Drug Event Report Database.

PubMed

Takeyama, Mayu; Sai, Kimie; Imatoh, Takuya; Segawa, Katsunori; Hirasawa, Noriyasu; Saito, Yoshiro

2017-01-01

The anti-receptor activator of nuclear factor kappa-B ligand (RANKL) antibody, Denosumab (DEN), was approved in April 2012 in Japan, but a Dear Healthcare Professional Letter of Rapid Safety Communication was released in September, 2012 by the regulatory authority because of the severe hypocalcemia risks. Currently, the effectiveness of this regulatory action has not been evaluated and, therefore, this study aimed to assess its impact on DEN-induced hypocalcemia using the Japanese Adverse Drug Event Report database (JADER). The case reports from April 2012 to September 2014 were collected from the JADER, which included 151642 adverse events for the primary suspected drugs. The reporting odds ratio (ROR) of hypocalcemia as a signal of the target adverse event was analyzed for DEN and zoledronic acid (ZOL, a reference drug). Changes in RORs were compared between the pre- (Pre, April 2012 to September 2012) and post- (Post 1, October 2012 to September 2013 and Post 2, October 2013 to September 2014) periods of the regulatory action. A decrease in the hypocalcemia ROR was observed for DEN in the post-periods, especially Post 2. Multivariate logistic regression analysis showed a significant decrease in hypocalcemia signal in Post 1 (p=0.0306 vs. Pre) and Post 2 (p=0.0054 vs. Pre). ZOL caused no significant changes in ROR of hypocalcemia, and none of the drugs caused ROR changes in jaw osteonecrosis (a reference adverse event). This study suggests that the regulatory action against hypocalcemia in DEN effectively decreased hypocalcemia signal. Further studies using medical information databases are needed to confirm this result.

["Re-evaluation upon suspected event" is an approach for post-marketing clinical study: lessons from adverse drug events related to Bupleuri Radix preparations].

PubMed

Wu, Shu-Xin; Sun, Hong-Feng; Yang, Xiao-Hui; Long, Hong-Zhu; Ye, Zu-Guang; Ji, Shao-Liang; Zhang, Li

2014-08-01

We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in that it enhances the pharmaceutical manufactures the ability to control enterprise risk and eliminate the negative impact on traditional Chinese medicine. With the widely used and ADR report concentrated Radix Bupleuri injection as an example, the author provide a new approach to post-marketing clinical research.

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

PubMed

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

2009-06-01

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

Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial.

PubMed

Cadorna-Carlos, Josefina B; Nolan, Terry; Borja-Tabora, Charissa Fay; Santos, Jaime; Montalban, M Cecilia; de Looze, Ferdinandus J; Eizenberg, Peter; Hall, Stephen; Dupuy, Martin; Hutagalung, Yanee; Pépin, Stéphanie; Saville, Melanie

2015-05-15

Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate. This phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination. 1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains. In both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity criteria for adults. NCT01481454. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Patient safety goals for the proposed Federal Health Information Technology Safety Center.

PubMed

Sittig, Dean F; Classen, David C; Singh, Hardeep

2015-03-01

The Office of the National Coordinator for Health Information Technology is expected to oversee creation of a Health Information Technology (HIT) Safety Center. While its functions are still being defined, the center is envisioned as a public-private entity focusing on promotion of HIT related patient safety. We propose that the HIT Safety Center leverages its unique position to work with key administrative and policy stakeholders, healthcare organizations (HCOs), and HIT vendors to achieve four goals: (1) facilitate creation of a nationwide 'post-marketing' surveillance system to monitor HIT related safety events; (2) develop methods and governance structures to support investigation of major HIT related safety events; (3) create the infrastructure and methods needed to carry out random assessments of HIT related safety in complex HCOs; and (4) advocate for HIT safety with government and private entities. The convening ability of a federally supported HIT Safety Center could be critically important to our transformation to a safe and effective HIT enabled healthcare system. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A combined intervention to reduce interruptions during medication preparation and double-checking: a pilot-study evaluating the impact of staff training and safety vests.

PubMed

Huckels-Baumgart, Saskia; Niederberger, Milena; Manser, Tanja; Meier, Christoph R; Meyer-Massetti, Carla

2017-10-01

The aim was to evaluate the impact of staff training and wearing safety vests as a combined intervention on interruptions during medication preparation and double-checking. Interruptions and errors during the medication process are common and an important issue for patient safety in the hospital setting. We performed a pre- and post-intervention pilot-study using direct structured observation of 26 nurses preparing and double-checking 431 medication doses (225 pre-intervention and 206 post-intervention) for 36 patients (21 pre-intervention and 15 post-intervention). With staff training and the introduction of safety vests, the interruption rate during medication preparation was reduced from 36.8 to 28.3 interruptions per hour and during double-checking from 27.5 to 15 interruptions per hour. This pilot-study showed that the frequency of interruptions decreased during the critical tasks of medication preparation and double-checking after the introduction of staff training and wearing safety vests as part of a quality improvement process. Nursing management should acknowledge interruptions as an important factor potentially influencing medication safety. Unnecessary interruptions can be successfully reduced by considering human and system factors and increasing both staff and nursing managers' awareness of 'interruptive communication practices' and implementing physical barriers. This is the first pilot-study specifically evaluating the impact of staff training and wearing safety vests on the reduction of interruptions during medication preparation and double-checking. © 2017 John Wiley & Sons Ltd.

[Study of post marketing safety reevaluation of shenqi fuzheng injection].

PubMed

Ai, Qing-Hua; Li, Yuan-Yuan; Xie, Yan-Ming

2014-09-01

In order to promote the Shenqifuzheng injection (SQFZ) clinical medication safety, this study reevaluate on SQFZ post marketing safety study systematically. Including multi center large sample registration type safety monitoring research, the analysis based on national spontaneous reporting system data, the analysis based on the 20 national hospital information system data and literature research. Above the analysis, it suggests that SQFZ has good security. The more adverse drug reaction (ADR) as allergic reactions, mainly involved in the damage of skin, appendages and its systemic damage, serious person can appear allergic shock. ADR/E is more common in the elderly, may be related to medication (tumor) populations. Early warning analysis based on SRS data and literature research are of the view that "phlebitis" has a strong association with SQFZ used.

Long-term efficacy and safety of safinamide as add-on therapy in early Parkinson's disease.

PubMed

Schapira, A H V; Stocchi, F; Borgohain, R; Onofrj, M; Bhatt, M; Lorenzana, P; Lucini, V; Giuliani, R; Anand, R

2013-02-01

Safinamide is an α-aminoamide with both dopaminergic and non-dopaminergic mechanisms of action in Phase III clinical development as a once-daily add-on to dopamine agonist (DA) therapy for early Parkinson's disease (PD). Study 017 was a 12-month, randomized, double-blind, placebo-controlled pre-planned extension study to the previously reported Study 015. Patients received safinamide 100 or 200 mg/day or placebo added to a single DA in early PD. The primary efficacy endpoint was the time from baseline (Study 015 randomization) to 'intervention', defined as increase in DA dose; addition of another DA, levodopa or other PD treatment; or discontinuation due to lack of efficacy. Safinamide groups were pooled for the primary efficacy endpoint analysis; post hoc analyses were performed on each separate dose group. Of the 269 patients randomized in Study 015, 227 (84%) enrolled in Study 017 and 187/227 (82%) patients completed the extension study. Median time to intervention was 559 and 466 days in the pooled safinamide and placebo groups, respectively (log-rank test; P = 0.3342). In post hoc analyses, patients receiving safinamide 100 mg/day experienced a significantly lower rate of intervention compared with placebo (25% vs. 51%, respectively) and a delay in median time to intervention of 9 days (P < 0.05; 240- to 540-day analysis). The pooled data from the safinamide groups failed to reach statistical significance for the primary endpoint of median time from baseline to additional drug intervention. Post hoc analyses indicate that safinamide 100 mg/day may be effective as add-on treatment to DA in PD. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Prevalence of Post-tonsillectomy Bleeding as Day-case Surgery with Combination Method; Cold Dissection Tonsillectomy and Bipolar Diathermy Hemostasis

PubMed Central

Faramarzi, Abolahassan; Heydari, Seyed Taghi

2010-01-01

Objective Post-tonsillectomy hemorrhage remains an important factor in determining the safety of performing tonsillectomy as a day case procedure. The aim of this study was to determine the safety of day case tonsillectomy by using combination method, cold dissection tonsillectomy and bipolar diathermy hemostasis. Methods A prospective randomized clinical study conducted on the patients who had undergone day case tonsillectomy (DCT). There were two groups (DCT and control group) each group consisting of 150 cases. Tonsillectomy was performed by using combination method; cold dissection and hemostasis was achieved by ligation of vessels with bipolar electerocautery. Findings We found 3 cases of post-tonsillectomy bleeding in DCT group and 4 cases in the control group. There was no statistically significant difference in the rate of post-operative hemorrhage between the two groups. Conclusion The findings suggest the safety of the combination of cold dissection tonsillectomy and bipolar diathermy hemostasis as day case tonsillectomy. PMID:23056702

[Explore method about post-marketing safety re-evaluation of Chinese patent medicines based on HIS database in real world].

PubMed

Yang, Wei; Xie, Yanming; Zhuang, Yan

2011-10-01

There are many kinds of Chinese traditional patent medicine used in clinical practice and many adverse events have been reported by clinical professionals. Chinese patent medicine's safety problems are the most concerned by patients and physicians. At present, many researchers have studied re-evaluation methods about post marketing Chinese medicine safety inside and outside China. However, it is rare that using data from hospital information system (HIS) to re-evaluating post marketing Chinese traditional patent medicine safety problems. HIS database in real world is a good resource with rich information to research medicine safety. This study planed to analyze HIS data selected from ten top general hospitals in Beijing, formed a large HIS database in real world with a capacity of 1 000 000 cases in total after a series of data cleaning and integrating procedures. This study could be a new project that using information to evaluate traditional Chinese medicine safety based on HIS database. A clear protocol has been completed as for the first step for the whole study. The protocol is as follows. First of all, separate each of the Chinese traditional patent medicines existing in the total HIS database as a single database. Secondly, select some related laboratory tests indexes as the safety evaluating outcomes, such as routine blood, routine urine, feces routine, conventional coagulation, liver function, kidney function and other tests. Thirdly, use the data mining method to analyze those selected safety outcomes which had abnormal change before and after using Chinese patent medicines. Finally, judge the relationship between those abnormal changing and Chinese patent medicine. We hope this method could imply useful information to Chinese medicine researchers interested in safety evaluation of traditional Chinese medicine.

The effects of acute nicotine on contextual safety discrimination.

PubMed

Kutlu, Munir G; Oliver, Chicora; Gould, Thomas J

2014-11-01

Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients. © The Author(s) 2014.

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience.

PubMed

Willis, English D; Woodward, Meredith; Brown, Elizabeth; Popmihajlov, Zoran; Saddier, Patricia; Annunziato, Paula W; Halsey, Neal A; Gershon, Anne A

2017-12-19

Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience

PubMed Central

Willis, English D.; Woodward, Meredith; Brown, Elizabeth; Popmihajlov, Zoran; Saddier, Patricia; Annunziato, Paula W.; Halsey, Neal A.; Gershon, Anne A.

2017-01-01

Background Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. Methods All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. Results A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. Conclusions The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies. PMID:29174682

Examining the safety of menstrual cups among rural primary school girls in western Kenya: observational studies nested in a randomised controlled feasibility study.

PubMed

Juma, Jane; Nyothach, Elizabeth; Laserson, Kayla F; Oduor, Clifford; Arita, Lilian; Ouma, Caroline; Oruko, Kelvin; Omoto, Jackton; Mason, Linda; Alexander, Kelly T; Fields, Barry; Onyango, Clayton; Phillips-Howard, Penelope A

2017-05-04

Examine the safety of menstrual cups against sanitary pads and usual practice in Kenyan schoolgirls. Observational studies nested in a cluster randomised controlled feasibility study. 30 primary schools in a health and demographic surveillance system in rural western Kenya. Menstruating primary schoolgirls aged 14-16 years participating in a menstrual feasibility study. Insertable menstrual cup, monthly sanitary pads or 'usual practice' (controls). Staphylococcus aureus vaginal colonization, Escherichia coli growth on sampled used cups, toxic shock syndrome or other adverse health outcomes. Among 604 eligible girls tested, no adverse event or TSS was detected over a median 10.9 months follow-up. S. aureus prevalence was 10.8%, with no significant difference over intervention time or between groups. Of 65  S.aureus positives at first test, 49 girls were retested and 10 (20.4%) remained positive. Of these, two (20%) sample isolates tested positive for toxic shock syndrome toxin-1; both girls were provided pads and were clinically healthy. Seven per cent of cups required replacements for loss, damage, dropping in a latrine or a poor fit. Of 30 used cups processed for E. coli growth, 13 (37.1%, 95% CI 21.1% to 53.1%) had growth. E. coli growth was greatest in newer compared with established users (53%vs22.2%, p=0.12). Among this feasibility sample, no evidence emerged to indicate menstrual cups are hazardous or cause health harms among rural Kenyan schoolgirls, but large-scale trials and post-marketing surveillance should continue to evaluate cup safety. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Development of alternative wood-post MGS approach guardrail transition.

DOT National Transportation Integrated Search

2011-11-28

The objective of this study was to develop a wood-post MGS approach transition system that is equivalent to the : simplified steel-post, MGS stiffness transition recently developed at the Midwest Roadside Safety Facility. An extensive : literature re...

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 efficacy of conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation: randomized controlled trial in adult renal transplantation.

PubMed

Oh, Chang-Kwon; Huh, Kyu Ha; Lee, Jong Soo; Cho, Hong Rae; Kim, Yu Seun

2014-09-01

The purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction. This prospective, randomized, open-label, multicenter study was conducted at three institutes. Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation, while patients in the control group were maintained on tacrolimus twice daily. The efficacies, safeties, and patient satisfaction for the two drugs at 6 months post-transplantation were compared. Sixty patients were enrolled and randomized to the investigational group (28 of 29 patients completed the study) or the control group (26 of 31 patients completed the study). At 6 months post-transplantation, composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0% and 10.7%, respectively; patient survival was 100% in each group. No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation (p=0.97). The safety and satisfaction profile (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus (p=0.35). Conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective.

Is There a Role for Arnica and Bromelain in Prevention of Post-Procedure Ecchymosis or Edema? A Systematic Review of the Literature.

PubMed

Ho, Derek; Jagdeo, Jared; Waldorf, Heidi A

2016-04-01

The management of postprocedure skin care is of significant interest to dermatologists and other physicians. Ecchymosis and edema are common temporary postprocedure unwanted effects. Two botanically-derived products, arnica and bromelain, are used internationally by physicians to limit ecchymosis and edema that occur secondary to cosmetic, laser, and surgical skin procedures. The authors review the published literature and provide evidence-based recommendations on arnica and bromelain for prevention and treatment of postprocedure ecchymosis and edema. A search of the computerized bibliographic databases Medline, EMBASE, Scopus, and CINAHL was performed on March 23, 2015. The key terms used were "arnica," and "bromelain." This review contains clinical trials that evaluated prevention and/or treatment of postprocedure ecchymosis or edema with oral arnica (11), topical arnica (2), and oral bromelain (7). No studies on topical bromelain were found. Clinical trials on arnica and bromelain have demonstrated mixed results. Some randomized controlled trials reported improvement postprocedure with arnica (4/13) and bromelain (5/7). Based upon published studies, there is insufficient data to support use of arnica and bromelain post procedure, and the authors recommend additional research to determine the efficacy and safety of arnica and bromelain to prevent and/or treat ecchymosis and edema in patients.

Shifts in Medicaid and Uninsured Payer Mix at Safety-Net and Non-Safety-Net Hospitals During the Great Recession.

PubMed

Fingar, Kathryn R; Coffey, Rosanna M; Mulcahy, Andrew W; Andrews, Roxanne M; Stocks, Carol

2018-01-01

There has been ongoing concern regarding the viability of safety-net hospitals (SNHs), which care for vulnerable populations. The authors examined payer mix at SNHs and non-SNHs during a period covering the Great Recession using data from the 2006 to 2012 Healthcare Cost and Utilization Project State Inpatient Databases from 38 states. The number of privately insured stays decreased at both SNHs and non-SNHs. Non-SNHs increasingly served Medicaid-enrolled and uninsured patients; in SNHs, the number of Medicaid stays decreased and uninsured stays remained stable. These study findings suggest that SNHs were losing Medicaid-enrolled patients relative to non-SNHs before the Medicaid expansion under the Affordable Care Act (ACA). Postexpansion, Medicaid stays will likely increase for both SNHs and non-SNHs, but the increase at SNHs may not be as large as expected if competition increases. Because hospital stays with private insurance and Medicaid help SNHs offset uncompensated care, a lower-than-expected increase could affect SNHs' ability to care for the remaining uninsured population. Continued monitoring is needed once post-ACA data become available.

Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis of clinical studies and post-marketing data.

PubMed

D'Urzo, Anthony D; Kerwin, Edward M; Chapman, Kenneth R; Decramer, Marc; DiGiovanni, Robert; D'Andrea, Peter; Hu, Huilin; Goyal, Pankaj; Altman, Pablo

2015-01-01

Chronic use of inhaled anticholinergics by patients with chronic obstructive pulmonary disease (COPD) has raised long-term safety concerns, particularly cardiovascular. Glycopyrronium is a once-daily anticholinergic with greater receptor selectivity than previously available agents. We assessed the safety of inhaled glycopyrronium using data pooled from two analysis sets, involving six clinical studies and over 4,000 patients with COPD who received one of the following treatments: glycopyrronium 50 μg, placebo (both delivered via the Breezhaler device), or tiotropium 18 μg (delivered via the HandiHaler device). Data were pooled from studies that varied in their duration and severity of COPD of the patients (ie, ≤12 weeks duration with patients having moderate or severe COPD; and >1 year duration with patients having severe and very severe COPD). Safety comparisons were made for glycopyrronium vs tiotropium or placebo. Poisson regression was used to assess the relative risk for either active drug or placebo (and between drugs where placebo was not available) for assessing the incidence of safety events. During post-marketing surveillance (PMS), safety was assessed by obtaining reports from various sources, and disproportionality scores were computed using EMPIRICA. In particular, the cardiac safety of glycopyrronium during the post-marketing phase was evaluated. The overall incidence of adverse events and deaths was similar across groups, while the incidence of serious adverse events was numerically higher in placebo. Furthermore, glycopyrronium did not result in an increased risk of cerebro-cardiovascular events vs placebo. There were no new safety reports during the PMS phase that suggested an increased risk compared to results from the clinical studies. Moreover, the cardiac safety of glycopyrronium during the PMS phase was also consistent with the clinical data. The overall safety profile of glycopyrronium was similar to its comparators indicating no increase in the overall risk for any of the investigated safety end points.

The safety significance of aircraft accident post mortem findings.

DOT National Transportation Integrated Search

1969-10-01

A review of post mortem examinations obtained in 1968 of pilot victims of general aviation aircraft accidents reveals that 51 percent of the pilot victims were studied by pathologists. The post mortem examination population above was taken from 687 p...

Together We Learn: Analyzing the Interprofessional Internal Medicine Residents' and Master of Public Health Students' Quality Improvement Education Experience.

PubMed

Gupte, Gouri; Noronha, Craig; Horný, Michal; Sloan, Karin; Suen, Winnie

2016-11-01

Although the value of interprofessional collaborative education has been promoted, it is unclear how teams of clinical and nonclinical learners perceive this experience. The authors studied an interprofessional quality improvement (QI) curriculum implemented in 2013 integrating internal medicine residents (n = 90) and Master of Public Health (MPH) students (n = 33) at an urban safety net academic medical center. Pre and post curriculum surveys assessed attitudes toward QI and interprofessional education and team performance. Resident attitudes toward learning and engaging in QI work improved at the end of the curriculum. Overall, MPH students demonstrated significantly more positive attitudes about interprofessional learning and work than residents. They also agreed more strongly than residents that patients would benefit if residents and public health students worked together. As health care organizations evolve to become more integrated, it is crucial that interprofessional educational opportunities be developed and evaluated to help encourage a culture of collaboration among health care providers. © The Author(s) 2015.

Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine.

PubMed

Grupping, Katrijn; Campora, Laura; Douha, Martine; Heineman, Thomas C; Klein, Nicola P; Lal, Himal; Peterson, James; Vastiau, Ilse; Oostvogels, Lidia

2017-12-12

Protection against herpes zoster (HZ) induced by the live attenuated zoster vaccine Zostavax (ZVL) wanes within 3-7 years. Revaccination may renew protection. We assessed whether (re)vaccination with the adjuvanted HZ subunit vaccine candidate (HZ/su) induced comparable immune responses in previous ZVL recipients and ZVL-naive individuals (HZ-NonVac). In an open-label, multicenter study, adults ≥65 years of age, vaccinated with ZVL ≥5 years previously (HZ-PreVac), were matched to ZVL-naive adults (HZ-NonVac). Participants received 2 doses of HZ/su 2 months apart. The primary objective of noninferiority of the humoral immune response 1 month post-dose 2 was considered demonstrated if the upper limit of the 95% confidence interval (CI) of the adjusted anti-glycoprotein E geometric mean concentration (GMC) ratio of HZ-NonVac over HZ-PreVac was <1.5. HZ/su cellular immunogenicity, reactogenicity, and safety were also assessed. In 430 participants, humoral immune response to HZ/su was noninferior in HZ-PreVac compared with HZ-NonVac (adjusted GMC ratio, 1.04 [95% CI, .92-1.17]). Cellular immunogenicity, reactogenicity, and safety appeared to be comparable between groups. HZ/su was well-tolerated, with no safety concerns raised within 1 month post-dose 2. HZ/su induces a strong immune response irrespective of prior vaccination with ZVL, and may be an attractive option to revaccinate prior ZVL recipients. NCT02581410. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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.

Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study.

PubMed

Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

2015-01-01

The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1-4) in the tibio-femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce their required doses, and delay potential future surgical intervention.

Safety and regulation of yeasts used for biocontrol or biopreservation in the food or feed chain.

PubMed

Sundh, Ingvar; Melin, Petter

2011-01-01

Yeasts have been important components of spontaneous fermentations in food and beverage processing for millennia. More recently, the potential of utilising antagonistic yeasts, e.g. Pichia anomala and Candida spp., for post-harvest biological control of spoilage fungi during storage of plant-derived produce ('biopreservation') has been clearly demonstrated. Although some yeast species are among the safest microorganisms known, several have been reported in opportunistic infections in humans, including P. anomala and bakers' yeast, Saccharomyces cerevisiae. More research is needed about the dominant pathogenicity and virulence factors in opportunistic yeasts, and whether increased utilisation of biopreservative yeasts in general could contribute to an increased prevalence of yeast infections. The regulatory situation for yeasts used in post-harvest biocontrol is complex and the few products that have reached the market are mainly registered as biological pesticides. The qualified presumption of safety (QPS) approach to safety assessments of microorganisms intentionally added to food or feed, recently launched by the European Food Safety Authority, can lead to more efficient evaluations of new products containing microbial species with a sufficient body of knowledge or long-term experience on their safety. P. anomala is one of several yeast species that have been given QPS status, although the status is restricted to use of this yeast for enzyme and metabolite production purposes. With regard to authorisation of new biopreservative yeasts, we recommend that the possibility to regulate microorganisms for food biopreservation as food additives be considered.

Study Design and Evaluation of Risk Minimization Measures: A Review of Studies Submitted to the European Medicines Agency for Cardiovascular, Endocrinology, and Metabolic Drugs.

PubMed

Mazzaglia, Giampiero; Straus, Sabine M J; Arlett, Peter; da Silva, Daniela; Janssen, Heidi; Raine, June; Alteri, Enrica

2018-02-01

Studies measuring the effectiveness of risk minimization measures (RMMs) submitted by pharmaceutical companies to the European Medicines Agency are part of the post-authorization regulatory requirements and represent an important source of data covering a range of medicinal products and safety-related issues. Their objectives, design, and the associated regulatory outcomes were reviewed, and conclusions were drawn that may support future progress in risk minimization evaluation. Information was obtained from risk management plans, study protocols, clinical study reports, and assessment reports of 157 medicinal products authorized for cardiovascular, endocrinology, and metabolic indications. We selected observational studies measuring, as outcomes of interest, the relationship between the RMMs in place and (1) implementation measures, such as clinical knowledge or physicians` compliance to recommendations contained in the RMMs; and (2) occurrence or reduced severity of the adverse drug reactions for which the RMMs were required. Of 59 eligible studies (24 completed, 35 ongoing), 44 assessed implementation measures, whereas only 15 assessed safety outcomes (1 study as a single endpoint and 14 studies with other endpoints). Fifty-one studies used non-experimental designs and 25 studies employed electronic healthcare databases for analysis. Of the 24 completed studies, 17 were considered satisfactory and supported immediate regulatory decision making, 6 were considered inconclusive and required new evaluations, and 1 was terminated early because new safety restrictions were required, thereby necessitating a new evaluation. Compliance with agreed deadlines was considered acceptable in 21 of 24 completed studies; the average time for a submission was 37 months (standard deviation ± 17), with differences observed by type of data source employed. Three important gaps in the evaluation plans of RMMs were identified: lack of early feedback on implementation, limited evaluation of safety outcomes, and inability to provide information on the effectiveness from an integrated measurement of different elements of a set of risk minimization tools. More robust evidence is needed to advance regulatory science and support more rapid adjustment of risk minimization strategies as needed.

Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized, multicenter study in infants.

PubMed

Klein, Nicola P; Abu-Elyazeed, Remon; Cornish, Matthew; Leonardi, Michael L; Weiner, Leonard B; Silas, Peter E; Grogg, Stanley E; Varman, Meera; Frenck, Robert W; Cheuvart, Brigitte; Baine, Yaela; Miller, Jacqueline M; Leyssen, Maarten; Mesaros, Narcisa; Roy-Ghanta, Sumita

2017-06-16

Vaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination. This phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6months (primary vaccination) and 15-18months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. Of 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines' antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5-96.7% and 99.6-100% of participants achieved anti-PRP levels ≥0.15µg/mL, while 78.3-89.8% and 97.9-99.1% had anti-PRP levels ≥1µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related. Hib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3+1 schedule. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Feasibility of Virtual Reality Augmented Cycling for Health Promotion of People Post-Stroke

PubMed Central

Deutsch, Judith E; Myslinski, Mary Jane; Kafri, Michal; Ranky, Richard; Sivak, Mark; Mavroidis, Constantinos; Lewis, Jeffrey A

2013-01-01

Background and Purpose A virtual reality (VR) augmented cycling kit (VRACK) was developed to address motor control and fitness deficits of individuals with chronic stroke. In this paper we report on the safety, feasibility and efficacy of using the VRACK to train cardio-respiratory (CR) fitness of individuals in the chronic phase poststroke. Methods Four individuals with chronic stroke (47–65 years old and three or more years post-stroke), with residual lower extremity impairments (Fugl Meyer 24–26/34) who were limited community ambulators (gait speed range 0.56 to 1.1 m/s) participated in this study. Safety was defined as the absence of adverse events. Feasibility was measured using attendance, total exercise time, and “involvement” measured with the Presence Questionnaire (PQ). Efficacy of CR fitness was evaluated using a sub-maximal bicycle ergometer test before and after an 8-week training program. Results The intervention was safe and feasible with participants having 1 adverse event, 100% adherence, achieving between 90 and 125 minutes of cycling each week and a mean PQ score of 39 (SD 3.3). There was a statistically significant 13% (p = 0.035) improvement in peak VO2 with a range of 6–24.5 %. Discussion and Conclusion For these individuals post-stroke, VR augmented cycling, using their heart rate to set their avatar’s speed, fostered training of sufficient duration and intensity to promote CR fitness. In addition, there was a transfer of training from the bicycle to walking endurance. VR augmented cycling may be an addition to the therapist’s tools for concurrent training of mobility and health promotion of individuals post-stroke. Video Abstract available (see Video, Supplemental Digital Content 1) for more insights from the authors. PMID:23863828

Evaluation of post-authorization safety studies in the first cohort of EU Risk Management Plans at time of regulatory approval.

PubMed

Giezen, Thijs J; Mantel-Teeuwisse, Aukje K; Straus, Sabine M J M; Egberts, Toine C G; Blackburn, Stella; Persson, Ingemar; Leufkens, Hubert G M

2009-01-01

Since November 2005, an EU Risk Management Plan (EU-RMP) has had to be submitted as part of a marketing application for all new chemical entities in the EU. In the EU-RMP, the safety profile of the medicine has to be described and pharmacovigilance activities should be proposed to study further safety concerns during use of the drug in the real-world setting. These activities include, for example, collection of spontaneously reported adverse events and post-authorization safety studies (PASS). Since the submission of an EU-RMP is a relatively new requirement, there is limited knowledge on the quality and completeness of the study protocols of PASS at the time of approval and there are no data on the influence of certain drug characteristics on the proposed pharmacovigilance activities. To examine the types of proposed pharmacovigilance activities in a sample of EU-RMPs, describe and evaluate the methodology of PASS, identify problems and propose remedies, and compare characteristics between biologicals and small molecules. Eighteen EU-RMPs (nine for biologicals, nine for small molecules) given a positive decision regarding the marketing application by the Committee for Medicinal Products for Human Use between November 2005 and May 2007 were included in this descriptive cohort study. The EU-RMPs were selected over time and different therapeutic areas. Classification of the safety concerns ('important identified risks', 'important potential risks', 'important missing information' within the EU-RMP was studied. For PASS, data source (registry, population-based database, sponsor-owned clinical trial database), source of study population to be included in PASS and comprehensiveness of study protocol (full protocol, limited protocol, study synopsis, short description, commitment without further information) were studied. Compared to small molecules, safety concerns for biologicals were less frequently classified as important identified risks (relative risk [RR] 0.6; 95% CI 0.3, 1.0) and more frequently as important missing information (RR 1.6; 95% CI 1.0, 2.7). Forty-seven PASS were proposed; 31 for biologicals and 16 for small molecules. Compared with studies proposed in population-based databases (4 for biologicals, 8 for small molecules), studies in registries (18 for biologicals, 4 for small molecules) were more frequently proposed for biologicals than for small molecules (RR 2.5; 95% CI 1.1, 5.7). About 60% of the proposed PASS will include EU inhabitants. No full study protocols were submitted; 26% involved a limited study protocol, 33% a study synopsis, 37% a short description and 4% a commitment without further information. Approximately 40% of the study proposals for PASS were classified as a short description or a commitment to perform a study without further information, precluding an adequate scientific assessment. Studying non-EU populations may give rise to difficulties with generalizability of the results to the EU due to differences in patient characteristics, differences in the indication for the medicine and different healthcare systems. This study emphasizes the need for more complete study proposals to be submitted earlier on in the evaluation period and for the inclusion of EU inhabitants in PASS. In addition, differences in the characteristics between biologicals and small molecules, e.g. in the data source proposed, support the need for individualized tailored PASS depending on the type of drug.

Study protocol for a randomised controlled trial of cognitive processing therapy for post-traumatic stress disorder among Japanese patients: the Safety, Power, Intimacy, Esteem, Trust (SPINET) study.

PubMed

Ito, Masaya; Horikoshi, Masaru; Resick, Patricia A; Katayanagi, Akiko; Miyamae, Mitsuhiro; Takagishi, Yuriko; Takebayashi, Yoshitake; Kanie, Ayako; Hirabayashi, Naotsugu; Furukawa, Toshiaki A

2017-06-30

Cognitive processing therapy (CPT) is widely regarded as a safe and effective first-line treatment for individuals with post-traumatic stress disorder (PTSD); however, no comparative studies have been conducted to examine the treatment outcomes in an Asian population. The aim of the present trial is to investigate the efficacy of CPT (individual format) as a treatment for PTSD in a population of Japanese patients. A 16-week, single-centre, assessor-masked, randomised, parallel-group superiority trial has been designed to compare the efficacy of CPT in conjunction with treatment as usual (mostly pharmacotherapy and clinical monitoring) versus treatment as usual alone. The Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) will be our primary outcome measure of the post-traumatic stress symptoms at 17 weeks, whereas the PTSD Checklist for DSM-5 and determination of the operationally defined responder status will be used to assess the secondary outcomes. An estimated sample size of 29 participants in each group will be required to detect an expected effect size of 1.4 (95% CI 0.85 to 1.95). The institutional review board at the National Center of Neurology and Psychiatry in Japan approved this study. The results of this clinical trial will be presented at conferences and disseminated through publication in a peer-reviewed journal. UMIN000021670 (registered on 1 April 2016). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Post-quit stress mediates the relation between social support and smoking cessation among socioeconomically disadvantaged adults.

PubMed

Bandiera, Frank C; Atem, Folefac; Ma, Ping; Businelle, Michael S; Kendzor, Darla E

2016-06-01

Social support interventions have demonstrated limited effectiveness for preventing smoking relapse. The stress-buffering hypothesis may be a useful framework by which to understand social support in smoking cessation interventions. The current study evaluated the interrelations among social support, stress, and smoking cessation in both moderation and mediation models. Participants (N=139) were enrolled in a smoking cessation study at the safety-net hospital in Dallas, Texas. During the week prior to a scheduled quit attempt, general social support was measured using the Interpersonal Support Evaluation List (ISEL) questionnaire and smoking-specific social support was measured via repeated smartphone-based ecological momentary assessments (EMA). Post-quit stress was repeatedly assessed via smartphone. Logistic regression analyses evaluated potential interaction effects of pre-quit social support and post-quit stress on the likelihood of achieving biochemically-verified 7-day point prevalence abstinence at 4 weeks post-quit. Mediation models were evaluated to determine if post-quit stress mediated the association between pre-quit social support and smoking cessation. Participants were predominantly Black (63.3%) and female (57.6%); and 55% reported an annual household income of <$12,000. Analyses indicated that pre-quit social support did not significantly interact with post-quit stress to influence smoking cessation. However, post-quit stress did mediate associations between social support variables and smoking cessation. Findings indicated that social support impacts smoking cessation through its influence on post-quit stress among socioeconomically disadvantaged adults participating in cessation treatment. Increasing social support for the specific purpose of reducing stress during a quit attempt may improve smoking cessation rates in disadvantaged populations. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Distress of Routine Activities and Perceived Safety Associated with Post-Traumatic Stress, Depression, and Alcohol Use: 2002 Washington, DC, Sniper Attacks.

PubMed

Fullerton, Carol S; Herberman Mash, Holly B; Benevides, K Nikki; Morganstein, Joshua C; Ursano, Robert J

2015-10-01

For over 3 weeks in October 2002, a series of sniper attacks in the Washington, DC, area left 10 people dead and 3 wounded. This study examined the relationship of distress associated with routine activities and perceived safety to psychological and behavioral responses. Participants were 1238 residents of the Washington, DC, metropolitan area (aged 18 to 90 years, mean=41.7 years) who completed an Internet survey including the Impact of Event Scale-Revised, Patient Health Questionnaire-9, and items pertaining to distress related to routine activities, perceived safety, and alcohol use. Data were collected at one time point approximately 3 weeks after the first sniper shooting and before apprehension of the suspects. Relationships of distress and perceived safety to post-traumatic stress, depressive symptoms, and increased alcohol use were examined by using linear and logistic regression analyses. Approximately 8% of the participants met the symptom criteria for probable post-traumatic stress disorder, 22% reported mild to severe depression, and 4% reported increased alcohol use during the attacks. Distress related to routine activities and perceived safety were associated with increased post-traumatic stress and depressive symptoms and alcohol use. Distress and perceived safety are associated with specific routine activities and both contribute to psychological and behavioral responses during a terrorist attack. These findings have implications for targeted information dissemination and risk communication by community leaders.

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

PubMed

Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

2017-11-01

Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

Closing the information gap: informing better medical decisionmaking through the use of post-market safety and comparative effectiveness information.

PubMed

Fox, Bethany

2012-01-01

While FDA gathers vast amounts of data about prescription drugs prior to their marketing approval, important information about the relative effectiveness and long term safety of products is not required for approval, and often is never collected. Increased postmarket research on the safety and comparative effectiveness of products would improve medical decisionmaking and lead to better clinical outcomes. Fortunately, Congress has recognized the value of this information for healthcare professionals. In response to a congressional mandate in the FDA Amendments Act (FDAAA), FDA is developing the Sentinel Initiative, an active surveillance system for monitoring postmarket drug safety issues. FDAAA also authorized FDA to require a drug sponsor to conduct postmarket safety studies or clinical trials to address a specific safety concern. To increase the repository of comparative effectiveness information, Congress established the Patient-Centered Outcomes Research Institute (PCORI) in the Patient Protection and Affordable Care Act (PPACA), directing it to manage comparative effectiveness research (CER). This article discusses the need for better safety and comparative effectiveness information and outlines methods to efficiently conduct the research and communicate it effectively to healthcare professionals. Coordination between FDA and the PCORI in gathering and communicating postmarket information is recommended. Medical source data collected by the Sentinel Initiative should be used for CER in addition to postmarket safety surveillance, and FDA and the PCORI should adopt identical standards for the distribution and communication of CER. Coordination between the two entities is recommended to save costs, reduce duplication of efforts, and to generate and communicate more information on prescription drugs for medical decisionmakers.

[Efficacy, safety and comfort of compression therapy models in the immediate post-operative period after a greater saphenectomy. A prospective randomised study].

PubMed

Collazo Chao, Eliseo; Luque, María Antonia; González-Ripoll, Carmen

2010-10-01

There is still controversy on the best compression therapy after performing a greater saphenectomy. The purpose of this study is to establish whether the use of a controlled compression stocking has the same level of safety and efficacy as a compression bandage in the immediate post-operative period after a greater saphenectomy. A prospective, randomised, open-labelled study, comparing three groups: a) a conventional compression bandage for one week, b) a conventional compression bandage replaced by a controlled tubular compression stocking at 5h of its putting in place, c) immediate direct use of the controlled tubular compression stocking, was conducted on fifty-five consecutive outpatients with a greater saphenectomy in one of their legs, and who fulfilled the inclusion criteria. The working hypothesis was that the controlled tubular compression stocking could replace, in terms of efficacy, safety and comfort, the usual controlled compression in the immediate post-operative period after saphenous vein stripping. The analysis variables were pain, control of bleeding, analgesics in the post-operative period, bruising, incapacity during the first week after the operation and comfort level. There were no statistically significant differences found between the three types of compressions studied as regards, safety, efficacy, comfort level, pain and analgesic consumption, but there was as regards the level of convenience in favour of the use of the stocking. The controlled tubular compression stocking can replace the compression bandage with more advantages after greater saphenous vein stripping in outpatients, having the same safety and efficacy. Copyright © 2009 AEC. Published by Elsevier Espana. All rights reserved.

Sample size for post-marketing safety studies based on historical controls.

PubMed

Wu, Yu-te; Makuch, Robert W

2010-08-01

As part of a drug's entire life cycle, post-marketing studies are an important part in the identification of rare, serious adverse events. Recently, the US Food and Drug Administration (FDA) has begun to implement new post-marketing safety mandates as a consequence of increased emphasis on safety. The purpose of this research is to provide exact sample size formula for the proposed hybrid design, based on a two-group cohort study with incorporation of historical external data. Exact sample size formula based on the Poisson distribution is developed, because the detection of rare events is our outcome of interest. Performance of exact method is compared to its approximate large-sample theory counterpart. The proposed hybrid design requires a smaller sample size compared to the standard, two-group prospective study design. In addition, the exact method reduces the number of subjects required in the treatment group by up to 30% compared to the approximate method for the study scenarios examined. The proposed hybrid design satisfies the advantages and rationale of the two-group design with smaller sample sizes generally required. 2010 John Wiley & Sons, Ltd.

[Design requirements for clinical trials on re-evaluation of safety and efficacy of post-marketed Chinese herbs].

PubMed

Xie, Yanming; Wei, Xu

2011-10-01

Re-evaluation of post-marketed based on pharmacoepidemiology is to study and collect clinical medicine safety in large population under practical applications for a long time. It is necessary to conduct re-evaluation of clinical effectiveness because of particularity of traditional Chinese medicine (TCM). Right before carrying out clinical trials on re-evaluation of post-marketed TCM, we should determine the objective of the study and progress it in the assessment mode of combination of disease and syndrome. Specical population, involving children and seniors who were excluded in pre-marketed clinical trial, were brought into drug monitoring. Sample size needs to comply with statistical requirement. We commonly use cohort study, case-control study, nested case-control, pragmatic randomized controlled trials.

Efficacy and Safety of Roflumilast in Korean Patients with COPD

PubMed Central

Lee, Jae Seung; Hong, Yoon Ki; Park, Tae Sun; Lee, Sei Won; Oh, Yeon-Mok

2016-01-01

Purpose Roflumilast is the only oral phosphodiesterase 4 inhibitor approved to treat chronic obstructive pulmonary disease (COPD) patients [post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted] with chronic bronchitis and a history of frequent exacerbations. This study evaluated the efficacy and safety of roflumilast in Korean patients with COPD and compared the efficacy based on the severity of airflow limitation. Materials and Methods A post-hoc subgroup analysis was performed in Korean COPD patients participating in JADE, a 12-week, double-blinded, placebo-controlled, parallel-group, phase III trial in Asia. The primary efficacy endpoint was the mean [least-squares mean adjusted for covariates (LSMean)] change in post-bronchodilator FEV1 from baseline to each post-randomization visit. Safety endpoints included adverse events (AEs) and changes in laboratory values, vital signs, and electrocardiograms. Results A total of 260 Korean COPD patients were recruited, of which 207 were randomized to roflumilast (n=102) or placebo (n=105) treatment. After 12 weeks, LSMean post-bronchodilator FEV1 increased by 43 mL for patients receiving roflumilast and decreased by 60 mL for those taking placebo. Adverse events were more common in the roflumilast group than in the placebo group; however, the types and frequency of AEs were comparable to those reported in previous studies. Conclusion Roflumilast significantly improved lung function with a tolerable safety profile in Korean COPD patients irrespective of the severity of airflow limitation. PMID:27189287

Training health care professionals in root cause analysis: a cross-sectional study of post-training experiences, benefits and attitudes.

PubMed

Bowie, Paul; Skinner, Joe; de Wet, Carl

2013-02-07

Root cause analysis (RCA) originated in the manufacturing engineering sector but has been adapted for routine use in healthcare to investigate patient safety incidents and facilitate organizational learning. Despite the limitations of the RCA evidence base, healthcare authorities and decision makers in NHS Scotland - similar to those internationally - have invested heavily in developing training programmes to build local capacity and capability, and this is a cornerstone of many organizational policies for investigating safety-critical issues. However, to our knowledge there has been no systematic attempt to follow-up and evaluate post-training experiences of RCA-trained staff in Scotland. Given the significant investment in people, time and funding we aimed to capture and learn from the reported experiences, benefits and attitudes of RCA-trained staff and the perceived impact on healthcare systems and safety. We adapted a questionnaire used in a published Australian research study to undertake a cross sectional online survey of health care professionals (e.g. nursing & midwifery, medical doctors and pharmacists) formally trained in RCA by a single territorial health board region in NHS Scotland. A total of 228/469 of invited staff completed the survey (48%). A majority of respondents had yet to participate in a post-training RCA investigation (n=127, 55.7%). Of RCA-experience staff, 71 had assumed a lead investigator role (70.3%) on one or more occasions. A clear majority indicated that their improvement recommendations were generally or partly implemented (82%). The top three barriers to RCA success were cited as: lack of time (54.6%), unwilling colleagues (34%) and inter-professional differences (31%). Differences in agreement levels between RCA-experienced and inexperienced respondents were noted on whether a follow-up session would be beneficial after conducting RCA (65.3% v 39.4%) and if peer feedback on RCA reports would be of educational value (83.2% v 37.0%). Comparisons with the previous research highlighted significant differences such as less reported difficulties within RCA teams (P<0.001) and a greater proportion of respondents taking on RCA leadership roles in this study (P<0.001). This study adds to our knowledge and understanding of the need to improve the effectiveness of RCA training and frontline practices in healthcare settings. The overall evidence points to a potential organisational learning need to provide RCA-trained staff with continuous development opportunities and performance feedback. Healthcare authorities may wish to look more critically at whom they train in RCA, and how this is delivered and supported educationally to maximize cost-benefits, organizational learning and safer patient care.

Systematic Review on Post-Traumatic Stress Disorder Among Survivors of the Wenchuan Earthquake.

PubMed

Hong, Chunlan; Efferth, Thomas

2016-12-01

Post-traumatic stress disorder (PTSD) widely occurs among victims or witness of disasters. With flashbacks, hyperarousal, and avoidance being the typical symptoms, PTSD became a focus of psychological research. The earthquake in Wenchuan, China, on May 12, 2008, was without precedent in magnitude and aftermath and caused huge damage, which drew scientists' attention to mental health of the survivors. We conducted a systematic overview by collecting published articles from the PubMed database and classifying them into five points: epidemiology, neuropathology, biochemistry, genetics and epigenetics, and treatment. The large body of research during the past 6 years showed that adolescents and adults were among the most studied populations with high prevalence rates for PTSD. Genomic and transcriptomic studies focusing on gene × environment studies as well as epigenetics are still rare, although a few available data showed great potential to better understand the pathophysiology of PTSD as multifactorial disease. Phytotherapy with Chinese herbs and acupuncture are rarely reported as of yet, although the first published data indicated promising therapy effects. Future studies should focus on the following points: (1) The affected populations under observation should be better defined concerning individual risk factor, time of observation, spatial movement, and individual disease courses of patients. (2) The role of social support for prevalence rates of PTSD should be observed in more detail. (3) Efficacy and safety of Chinese medicine should be studied to find potential interventions and effective treatments of PTSD. © The Author(s) 2015.

Post-authorisation passive enhanced safety surveillance of seasonal influenza vaccines: protocol of a pilot study in England.

PubMed

de Lusignan, Simon; Dos Santos, Gaël; Correa, Ana; Haguinet, François; Yonova, Ivelina; Lair, Florence; Byford, Rachel; Ferreira, Filipa; Stuttard, Karen; Chan, Tom

2017-05-17

To pilot enhanced safety surveillance of seasonal influenza vaccine meeting the European Medicines Agency (EMA) requirement to rapidly detect a significant increase in the frequency or severity of adverse events of interest (AEIs), which may indicate risk from the new season's vaccine. A prospective passive enhanced safety surveillance combining data collection from adverse drug reaction (ADR) cards with automated collection of pseudonymised routinely collected electronic health record (EHR) data. This study builds on a feasibility study carried out at the start of the 2015/2016 influenza season. We will report influenza vaccine exposure and any AEIs reported via ADR card or recorded directly into the EHR, from the commencement of influenza vaccination and ends as specified by EMA (30 November 2016). Ten volunteer English general practices, primarily using the GSK influenza vaccines. They had selected this vaccine in advance of the study. People who receive a seasonal influenza vaccine, in each age group defined in EMA interim guidance: 6 months to 5 years, 6-12 years, 13-17 years, 18-65 years and >65 years. The primary outcome measure is the rate of AEIs occurring within 7 days postvaccination, using passive surveillance of general practitioner (GP) EHR systems enhanced by a card-based ADR reporting system. Extracted data will be presented overall by brand (Fluarix Tetra vs others), by age strata and risk groups. The secondary outcome measure is the vaccine uptake among the subjects registered in the enrolled general practices. Ethical approval was granted by the Proportionate Review Sub-committee of the North East-Newcastle & North Tyneside 2 on 5 August 2016. The study received approval from the Health Research Authority on 1 September 2016. We will produce an interim analysis within 8 weeks, and an end-of-study report, which will be submitted to peer-reviewed journals. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Transitioning from first- to second-generation biosimilars: An appraisal of regulatory and post-marketing challenges.

PubMed

Blandizzi, Corrado; Galeazzi, Mauro; Valesini, Guido

2018-02-01

Second-generation biosimilars (i.e. monoclonal antibodies or proteins generated by fusion of antibody and receptor moieties) differ in several respects as compared to first-generation ones (e.g. epoetins, bone marrow stimulating factors, somatotropins). In this respect, as second-generation biosimilars are endowed with much greater structural and molecular complexity, which might translate into a number of pharmacological and therapeutic issues, they raise new challenges for manufacturers and regulatory authorities as well as new concerns for clinicians. Based on these arguments, the present article was intended to review information on the main differences between first- and second-generation biosimilars for treatment of immune-mediated inflammatory diseases, as well as their impact on immunogenicity, the design of clinical trials and the critical issue of extrapolation of therapeutic indications. The positions taken by relevant medical associations and the crucial role of pharmacovigilance are also reviewed. According to current knowledge, the initial post-marketing clinical experience with second-generation biosimilars is providing encouraging results, though their long-term safety and efficacy as well as the scientific basis underlying the extrapolation of therapeutic indications are still matter of discussion. There is some consensus that marketing applications should rely on studies supporting the clinical use of biosimilars in their different target diseases and patient populations. In parallel, clinical safety must be ensured by a strict control of the manufacturing processes and a solid pharmacovigilance program. It remains then a responsibility of the physician to drive a proper use of second-generation biosimilars into clinical practice, in accordance with guidelines issued by scientific societies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Study of the post-derailment safety measures on low-speed derailment tests

NASA Astrophysics Data System (ADS)

Guo, Lirong; Wang, Kaiyun; Lin, Jianhui; Zhang, Bing; Chen, Zaigang; Song, Xinwu; Du, Gaofeng

2016-07-01

Prevention of train from derailment is the most important issue for the railway system. Keeping derailed vehicle close to the track centreline is beneficial to minimise the severe consequences associated with derailments. In this paper, the post-derailment safety measures are studied based on low-speed derailment tests. Post-derailment devices can prevent deviation of the train from the rail by catching the rail, and they are mounted under the axle box. Considering the different structures of vehicles, both trailer and motor vehicles are equipped with the safety device and then separately used in low-speed derailment tests. In derailment tests, two kinds of track, namely the CRTS-I slab ballastless track and the CRTS-II bi-block sleeper ballastless track, are adopted to investigate the effect of the track types on the derailment. In addition, the derailment speed and the weight of the derailed vehicle are also taken into account in derailment tests. The test results indicate that the post-derailment movement of the vehicle includes running and bounce. Reducing the derailment speed and increasing the weight of the head of the train are helpful to reduce the possibility for derailments. For the CRTS-I slab ballastless track, the safety device can prevent trailer vehicles from deviating from the track centreline. The gearbox plays an important role in controlling the lateral displacement of motor vehicle after a derailment while the safety device contributes less to keep derailed motor vehicles on the track centreline. The lateral distance between the safety device and rails should be larger than 181.5 mm for protecting the fasteners system. And for the CRTS-II bi-block sleeper ballastless track, it helps to decrease the post-derailment distance due to the longitudinal impacts with sleepers. It can also restrict the lateral movement of derailed vehicle due to the high shoulders. The results suggest that, CRTS-II bi-block sleeper ballastless track should be widely used in derailment prone areas.

EFFECT OF A ROAD SAFETY EDUCATION INTERVENTION ON ROAD SAFETY KNOWLEDGE OF UNIVERSITY DRIVERS IN IBADAN, NIGERIA.

PubMed

Olumide, A O; Owoaje, E T

2016-06-01

It is essential for drivers employed in the formal sector to have good knowledge of road safety in order to safeguard their lives and those of the staff they are employed to drive. The study was conducted to determine the effect of a road safety education intervention on road safety knowledge of drivers employed in the University of Ibadan, Nigeria. A quasi-experimental study of 98 intervention and 78 control drivers selected using a cluster sampling technique was conducted. The intervention comprised a two-day training on road safety and first aid. The drivers' knowledge of road safety was measured at baseline, immediately and 4-months post-intervention. Aggregate scores of road safety knowledge were computed giving minimum and maximum obtainable scores of 0 and 16 respectively. Change in mean scores over the three measurement periods was assessed using Repeated Measures Analysis of Variance (ANOVA). Independent t-test was used to compare the scores between intervention and control drivers at each of the assessment periods. Twenty-nine drivers did not complete the study (attrition rate = 16.5%). At baseline, mean road safety knowledge scores for the intervention and control drivers were 12.7±2.2 and 12.9± 2.3 (p = 0.510) respectively. Immediately and four months post intervention, the scores of the intervention drivers were 13.8±1.9 and 12.8±1.6; while scores for the controls were 13.3±2.0 and 13.2±1.8. Repeated measures ANOVA revealed that the increase in knowledge over the three assessment periods was not statistically significant. The intervention resulted in an initial increase in road safety knowledge of the intervention drivers. However, this was not sustained to the forth month post-intervention. This finding suggests periodic refresher trainings to sustain the knowledge acquired.

Design of an improved post for use in a non-proprietary high-tension cable median barrier.

DOT National Transportation Integrated Search

2015-05-01

The objective of this research study was to develop a revised post section for the non-proprietary high-tension cable : median barrier that improved the safety and function of the post by lowering strong-axis forces. A total of twenty dynamic : compo...

Improving the culture of safety on a high-acuity inpatient child/adolescent psychiatric unit by mindfulness-based stress reduction training of staff.

PubMed

Hallman, Ilze S; O'Connor, Nancy; Hasenau, Susan; Brady, Stephanie

2014-11-01

The purpose of this study was to reduce perceived levels of interprofessional staff stress and to improve patient and staff safety by implementing a brief mindfulness-based stress reduction (MBSR) training program on a high-acuity psychiatric inpatient unit. A one-group repeated measure design was utilized to measure the impact of the (MBSR) training program on staff stress and safety immediately post-training and at 2 months. Two instruments were utilized in the study: the Toronto Mindfulness Scale and the Perceived Stress Scale. The MBSR program reduced staff stress across the 2-month post-training period and increased staff mindfulness immediately following the brief training period of 8 days, and across the 2-month post-training period. A trend toward positive impact on patient and staff safety was also seen in a decreased number of staff call-ins, decreased need for 1:1 staffing episodes, and decreased restraint use 2 months following the training period. A brief MBSR training program offered to an interprofessional staff of a high-acuity inpatient adolescent psychiatric unit was effective in decreasing their stress, increasing their mindfulness, and improving staff and patient safety. © 2014 Wiley Periodicals, Inc.

[Establishment of model of traditional Chinese medicine injections post-marketing safety monitoring].

PubMed

Guo, Xin-E; Zhao, Yu-Bin; Xie, Yan-Ming; Zhao, Li-Cai; Li, Yan-Feng; Hao, Zhe

2013-09-01

To establish a nurse based post-marketing safety surveillance model for traditional Chinese medicine injections (TCMIs). A TCMIs safety monitoring team and a research hospital team engaged in the research, monitoring processes, and quality control processes were established, in order to achieve comprehensive, timely, accurate and real-time access to research data, to eliminate errors in data collection. A triage system involving a study nurse, as the first point of contact, clinicians and clinical pharmacists was set up in a TCM hospital. Following the specified workflow involving labeling of TCM injections and using improved monitoring forms it was found that there were no missing reports at the ratio of error was zero. A research nurse as the first and main point of contact in post-marketing safety monitoring of TCM as part of a triage model, ensures that research data collected has the characteristics of authenticity, accuracy, timeliness, integrity, and eliminate errors during the process of data collection. Hospital based monitoring is a robust and operable process.

Sex differences in discriminating between cues predicting threat and safety.

PubMed

Day, Harriet L L; Reed, Molly M; Stevenson, Carl W

2016-09-01

Post-traumatic stress disorder (PTSD) is more prevalent in women than men. PTSD is characterized by overgeneralization of fear to innocuous stimuli and involves impaired inhibition of learned fear by cues that predict safety. While evidence indicates that learned fear inhibition through extinction differs in males and females, less is known about sex differences in fear discrimination and safety learning. Here we examined auditory fear discrimination in male and female rats. In Experiment 1A, rats underwent 1-3days of discrimination training consisting of one tone predicting threat (CS+; presented with footshock) and another tone predicting safety (CS-; presented alone). Females, but not males, discriminated between the CS+ and CS- after one day of training. After 2-3days of training, however, males discriminated whereas females generalized between the CS+ and CS-. In Experiment 1B, females showed enhanced anxiety-like behaviour and locomotor activity in the open field, although these results were unlikely to explain the sex differences in fear discrimination. In Experiment 2, we found no differences in shock sensitivity between males and females. In Experiment 3, males and females again discriminated and generalized, respectively, after three days of training. Moreover, fear generalization in females resulted from impaired safety learning, as shown by a retardation test. Whereas subsequent fear conditioning to the previous CS- retarded learning in males, females showed no such retardation. These results suggest that, while females show fear discrimination with limited training, they show fear generalization with extended training due to impaired safety learning. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015.

PubMed

Lee, Hsin-Chun; Chen, Chi-Min; Wei, Jen-Ting; Chiu, Hsiu-Yi

2018-04-01

Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and eggs from food-producing animals, governments and relevant agencies established laws and regulations for the use of veterinary drugs. It is, therefore, necessary to monitor the content of residual drugs in livestock products at regular intervals to assess whether the regulations have resulted in the effective management of food product safety, and to prevent and manage sudden problems related to this issue. A 2011-2015 livestock product post-marketing monitoring program launched by the Taiwan Food and Drug Administration (TFDA) inspected 1487 livestock products. Over the past 5 years, there were 34 samples identified that did not conform to the regulations; these samples included residue drugs such as β-agonists, chloramphenicols, β-lactam antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial livestock products with the consistent cooperation of agricultural authorities did not detect the drugs that were banned by the government, whereas the detection of other drugs decreased annually with an increase in the post-market monitoring sample size. In the future, the TFDA will continue to monitor the status of residual veterinary drugs in commercial livestock products, adjust the sampling of food products annually according to monitoring results, and closely cooperate with agricultural authorities on source management. Copyright © 2017. Published by Elsevier B.V.

Public availability of results of observational studies evaluating an intervention registered at ClinicalTrials.gov.

PubMed

Baudart, Marie; Ravaud, Philippe; Baron, Gabriel; Dechartres, Agnes; Haneef, Romana; Boutron, Isabelle

2016-01-28

Observational studies are essential for assessing safety. The aims of this study were to evaluate whether results of observational studies evaluating an intervention with safety outcome(s) registered at ClinicalTrials.gov were published and, if not, whether they were available through posting on ClinicalTrials.gov or the sponsor website. We identified a cohort of observational studies with safety outcome(s) registered on ClinicalTrials.gov after October 1, 2007, and completed between October 1, 2007, and December 31, 2011. We systematically searched PubMed for a publication, as well as ClinicalTrials.gov and the sponsor website for results. The main outcomes were the time to the first publication in journals and to the first public availability of the study results (i.e. published or posted on ClinicalTrials.gov or the sponsor website). For all studies with results publicly available, we evaluated the completeness of reporting (i.e. reported with the number of events per arm) of safety outcomes. We identified 489 studies; 334 (68%) were partially or completely funded by industry. Results for only 189 (39%, i.e. 65% of the total target number of participants) were published at least 30 months after the study completion. When searching other data sources, we obtained the results for 53% (n = 158; i.e. 93% of the total target number of participants) of unpublished studies; 31% (n = 94) were posted on ClinicalTrials.gov and 21% (n = 64) on the sponsor website. As compared with non-industry-funded studies, industry-funded study results were less likely to be published but not less likely to be publicly available. Of the 242 studies with a primary outcome recorded as a safety issue, all these outcomes were adequately reported in 86% (114/133) when available in a publication, 91% (62/68) when available on ClinicalTrials.gov, and 80% (33/41) when available on the sponsor website. Only 39% of observational studies evaluating an intervention with safety outcome(s) registered at ClinicalTrials.gov had their results published at least 30 months after study completion. The registration of these observational studies allowed searching other sources (results posted at ClinicalTrials.gov and sponsor website) and obtaining results for half of unpublished studies and 93% of the total target number of participants.

Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk

PubMed Central

Raschi, Emanuel; De Ponti, Fabrizio

2015-01-01

Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent’s management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as “signals”), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of post-marketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies. In this context, ongoing European/United States research consortia and novel pharmaco-epidemiological tools (e.g., specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities. PMID:26167249

Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk.

PubMed

Raschi, Emanuel; De Ponti, Fabrizio

2015-07-08

Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent's management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as "signals"), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of post-marketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies. In this context, ongoing European/United States research consortia and novel pharmaco-epidemiological tools (e.g., specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities.

Breast milk sharing via the internet: the practice and health and safety considerations.

PubMed

Keim, Sarah A; McNamara, Kelly A; Jayadeva, Chenali M; Braun, Ashlea C; Dillon, Chelsea E; Geraghty, Sheela R

2014-08-01

To characterize the practice of breast milk sharing via the internet in the US and examine factors associated with participants' communication regarding potential health and safety risks. This cross-sectional study examined all original postings (n = 254) placed during 1 week in 2011 on four websites to facilitate the sharing of breast milk. Postings were characterized for intent and health and safety topics (i.e., selling vs. donating milk, hygiene/handling practices, infectious disease screening, diet/exercise habits, substance and pharmaceutical use, milk quality claims, price) communicated between milk providers and recipients. Approximately 69% of postings were providing milk and 31% were seeking milk; 47% included identifiers. Few provider postings reflected measures to potentially reduce risks to recipients: 20% mentioned using a healthy handling/hygiene practice, 11% offered specifics about infectious disease screening, 51% mentioned limiting/abstaining from 1+ substances. The presence of indications about handling/hygiene, diet/exercise, and abstaining from substances were strongly positively associated with each other (ORs 7.42-13.80), with the odds of selling (ORs 6.03-∞), and with making quality claims (ORs 3.14-13.54), but not with disease screening. One-fifth of recipients sought milk for a child with a medical condition or poor birth outcome. Most recipients (90%) did not specify any health and safety practices of a provider in their posting. Health behaviors and screening for diseases that may affect milk safety are not prominent topics in postings seeking to share milk. This lack of communication may exacerbate the health risks to recipient infants, especially infants at increased risk due to pre-existing health conditions.

Japanese study of tofogliflozin with type 2 diabetes mellitus patients in an observational study of the elderly (J-STEP/EL): A 12-week interim analysis.

PubMed

Utsunomiya, Kazunori; Shimmoto, Naoki; Senda, Masayuki; Kurihara, Yuji; Gunji, Ryoji; Kameda, Hiroyuki; Tamura, Masahiro; Mihara, Hanako; Kaku, Kohei

2016-09-01

Sodium-glucose co-transporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, but are associated with concerns about specific adverse drug reactions. We carried out a 1-year post-marketing surveillance of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus and here report the results of a 12-week interim analysis, focusing on adverse drug reactions of special interest. The present prospective observational study included all type 2 diabetes mellitus patients aged ≥65 years who started tofogliflozin during the first 3 months after its launch. Data on demographic and baseline characteristics, clinical course and adverse events were collected. Of 1,535 patients registered, 1,506 patients whose electronic case report forms were collected and who had at least one follow-up visit were included in the safety analysis at 12 weeks. A total of 178 of 1,506 patients (11.82%) had at least one adverse drug reaction to tofogliflozin. The incidence of adverse drug reactions of special interest (polyuria/pollakiuria, volume depletion-related events, urinary tract infection, genital infection, skin disorders and hypoglycemia) was 2.19, 2.32, 1.33, 1.13, 1.46 and 0.73%, respectively. No new safety concerns were identified. Among those evaluable for clinical effectiveness, the mean (standard deviation) glycated hemoglobin decreased from 7.65% (1.35%) at baseline to 7.25% (1.16%) at 12 weeks by 0.39% (0.94%; P < 0.0001). This interim analysis characterized the safety profile of tofogliflozin in Japanese elderly patients with type 2 diabetes mellitus during the early post-marketing period. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2-49years.

PubMed

Baxter, Roger; Eaton, Abigail; Hansen, John; Aukes, Laurie; Caspard, Herve; Ambrose, Christopher S

2017-03-01

Quadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013-2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2-49years. This was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell's palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients. A total of 62,040 eligible Q/LAIV recipients were identified during the 2013-2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2-4, 5-8, 9-17, and 18-49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV. In this large population study of individuals aged 2-49years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person-years. ClinicalTrials.gov NCT01985997. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study

PubMed Central

Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

2015-01-01

Purpose The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. Materials and methods The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1–4) in the tibio–femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. Main outcome measure(s) An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. Main results The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Conclusion Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce their required doses, and delay potential future surgical intervention. PMID:25897212

Transradial access: lessons learned from cardiology.

PubMed

Snelling, Brian M; Sur, Samir; Shah, Sumedh Subodh; Marlow, Megan M; Cohen, Mauricio G; Peterson, Eric C

2018-05-01

Innovations in interventional cardiology historically predate those in neuro-intervention. As such, studying trends in interventional cardiology can be useful in exploring avenues to optimise neuro-interventional techniques. One such cardiology innovation has been the steady conversion of arterial puncture sites from transfemoral access (TFA) to transradial access (TRA), a paradigm shift supported by safety benefits for patients. While neuro-intervention has unique anatomical challenges, the access itself is identical. As such, examining the extensive cardiology literature on the radial approach has the potential to offer valuable lessons for the neuro-interventionalist audience who may be unfamiliar with this body of work. Therefore, we present here a report, particularly for neuro-interventionalists, regarding the best practices for TRA by reviewing the relevant cardiology literature. We focused our review on the data most relevant to our audience, namely that surrounding the access itself. By reviewing the cardiology literature on metrics such as safety profiles, cost and patient satisfaction differences between TFA and TRA, as well as examining the technical nuances of the procedure and post-procedural care, we hope to give physicians treating complex cerebrovascular disease a broader data-driven understanding of TRA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A pre-marketing ALT signal predicts post-marketing liver safety.

PubMed

Moylan, Cynthia A; Suzuki, Ayako; Papay, Julie I; Yuen, Nancy A; Ames, Michael; Hunt, Christine M

2012-08-01

Drug induced liver injury during drug development is evidenced by a higher incidence of serum alanine aminotransferase (ALT) elevations in treated versus placebo populations and termed an "ALT signal". We sought to quantify whether an ALT signal in pre-marketing clinical trials predicted post-marketing hepatotoxicity. Incidence of ALT elevations (ALT ≥ 3 times upper limits normal [× ULN]) for drug and placebo of new chemical entities and approved drugs associated with hepatotoxicity was calculated using the Food and Drug Administration (FDA) website. Post-marketing liver safety events were identified using the FDA Adverse Event Reporting System (AERS). The association of FDA AERS signal score (EB05 ≥ 2) and excess risk of pre-marketing ALT elevation (difference in incidence of ALT ≥ 3× ULN in treated versus placebo) was examined. An ALT signal of ≥ 1.2% was significantly associated with a post-marketing liver safety signal (p ≤ 0.013) and a 71.4% positive predictive value. An absent ALT signal was associated with a high likelihood of post-marketing liver safety; negative predictive value of 89.7%. Daily drug dose information improved the prediction of post-marketing liver safety. A cut-off of 1.2% increase in ALT ≥ 3× ULN in treated versus placebo groups provides an easily calculated method for predicting post-marketing liver safety. Published by Elsevier Inc.

[Comparative study on four kinds of assessment methods of post-marketing safety of Danhong injection].

PubMed

Li, Xuelin; Tang, Jinfa; Meng, Fei; Li, Chunxiao; Xie, Yanming

2011-10-01

To study the adverse reaction of Danhong injection with four kinds of methods, central monitoring method, chart review method, literature study method and spontaneous reporting method, and to compare the differences between them, explore an appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection. Set down the adverse reactions' questionnaire of four kinds of methods, central monitoring method, chart review method, literature study method and collect the information on adverse reactions in a certain period. Danhong injection adverse reaction information from Henan Province spontaneous reporting system was collected with spontaneous reporting method. Carry on data summary and descriptive analysis. Study the adverse reaction of Danhong injection with four methods of central monitoring method, chart review method, literature study method and spontaneous reporting method, the rates of adverse events were 0.993%, 0.336%, 0.515%, 0.067%, respectively. Cyanosis, arrhythmia, hypotension, sweating, erythema, hemorrhage dermatitis, rash, irritability, bleeding gums, toothache, tinnitus, asthma, elevated aminotransferases, constipation, pain are new discovered adverse reactions. The central monitoring method is the appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection, which could objectively reflect the real world of clinical usage.

Globe rupture with post cataract-surgery safety sunglasses.

PubMed

Brooks, Clifford W; Howard, Robert C; Lyons, Robert A; Reilly, Charles D

2010-07-01

We report a case of globe rupture associated with the use of post cataract-surgery protective eyewear. The patient had routine cataract surgery 3 months before presentation and had adapted his post cataract-surgery glasses to use on the tennis court. He experienced a large posterior globe rupture after falling directly onto his face during a match. Spectacle torsion is the suspected biomechanical process that led to the rupture. We conclude that although the glasses given to many patients after cataract surgery are protective for most low-impact injuries, patients should be aware they are not designed for activities with a risk for significant impact. Patients should also be counseled to use protective eyewear specifically designed and approved for the sport or activity in which they participate. No author has a financial or proprietary interest in any material or method mentioned. Published by Elsevier Inc.

The role of the military in post-conflict situations.

PubMed

Court, Bruce V

2004-11-01

This article considers the possible role of the military in relation to 'post-conflict situations' and helping to improve the health of affected civilian populations. The opinions expressed are personal reflections which draw upon the author's recent military medical experience in southern Iraq in 2004. The perspective of humanitarian aid agencies that have strong reservations about any involvement with the military is recognised, as they seek to maintain neutrality and the safety of their staff. The environment itself, however, may represent an unacceptable level of threat to humanitarian aid agencies, if their personnel are at risk of serious intimidation, e.g. kidnap or murder. Where terrorist and insurgent para-military groups emerge in a post-war fighting phase, it may be that the military is best placed to help co-ordinate efforts to ensure public health and health care provision until a satisfactory level of security is attained and humanitarian aid agencies are able to operate with confidence.

Type I error probability spending for post-market drug and vaccine safety surveillance with binomial data.

PubMed

Silva, Ivair R

2018-01-15

Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near-continuous sequential analysis of post-market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post-market drug and vaccine safety surveillance, that is not important. In post-market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post-market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis. Copyright © 2017 John Wiley & Sons, Ltd.

Impacts of Health and Safety Education: Comparison of Worker Activities Before and After Training

PubMed Central

Becker, Paul; Morawetz, John

2014-01-01

Background The International Chemical Workers Union Council (ICWUC) Center for Worker Health and Safety Education in Cincinnati, Ohio, trains workers to protect themselves from hazards due to chemical spills and other chemical exposures. We evaluated whether the ICWUC Hazardous Waste Worker Training Program affects the attitudes and post-training activities, of trained union workers. Methods Detailed survey questionnaires were administered to 55 workers prior to and 14–18 months following training. Surveys queried trainees’ interest and involvement in safety and health, use of information resources, training activities at their worksite, and their attempts and successes at making worksite improvements. Results Post-training, the study population showed an increase in training of other workers, use of resources, attempts at improvements, success rates for those attempting change, and overall success at making improvements. Self-reported interest decreased, and self reported involvement in health and safety did not significantly change. Conclusion The study demonstrates that workers are more willing to attempt to change worksite conditions following training, and that their efficacy at making changes is substantially greater than before they were trained. The study confirms earlier work and strengthens these conclusions by using statistically tested comparisons of impact measures pre- and post-training. PMID:15202126

Teaching safety at a summer camp: evaluation of a fire safety curriculum in an urban community setting.

PubMed

Chavez, Audrie A; Duzinski, Sarah V; Wheeler, Tareka C; Lawson, Karla A

2014-09-01

To evaluate the effectiveness of the Danger Rangers Fire Safety Curriculum in increasing the fire safety knowledge of low-income, minority children in an urban community setting. Data was collected from child participants via teacher/researcher administered pre-, post-, and retention tests. A self-administered questionnaire was collected from parents pre- and post-intervention to assess fire/burn prevention practices. Paired t-tests were conducted to compare pre-, post-, and retention test mean scores by grade group. McNemar's test was used to determine if there was a change in parent-reported prevention practices following the intervention. The first/second grade group and the third grade group scored significantly higher on the post- and retention test as compared to the pre-test (p<0.0001 for all comparisons). There was no significant change in scores for the pre-k/k group after the intervention. There was a significant increase in 2 of 4 parent-reported fire/burn-related prevention practices after the intervention. Fire safety knowledge improved among first to third grade children, but not among pre-kinder and kindergarten children who participated in the intervention. This study also showed that a program targeted towards children and delivered in a classroom setting has the potential to influence familial prevention practices by proxy. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

The Drug Safety and Risk Management Advisory Committee: a case study of meeting frequency, content, and outcomes before and after FDAAA.

PubMed

Morrato, Elaine H; Ling, Sarah B

2012-11-01

The Food and Drug Administration Amendments Act (FDAAA) of 2007 granted FDA-expanded drug safety authority. We hypothesized that meetings involving the FDA Drug Safety and Risk Management (DSaRM) Advisory Committee might serve as a barometer for the impact of FDAAA on drug safety regulatory decision making. We conducted a case study analysis of 42 DSaRM advisory committee meetings held between 2002 and 2011. Publicly available sources (FDA meeting minutes and materials, safety alerts, and drug manufacturer Web sites) were reviewed to describe and compare DSaRM meeting frequency, content and outcomes between the pre-FDAAA (2002-2007) and post-FDAAA (2008-2011) periods. DSaRM meeting frequency increased after FDAAA (from 2.7 to 6.5 meetings per year). DSaRM meetings were more likely to be held jointly with other drug advisory committees after FDAAA (from 68% to 92% of meetings). DSaRM members were invited participants in 35 additional meetings of other drug advisory committees (2007-2011). DSaRM meetings were more likely to review issues of approvability (eg, new drugs, new indications, and new product formulations) after FDAAA. FDA questions to the committee were more likely to request an explicit drug safety assessment after FDAAA (from 31% to 76% of meetings). Content analysis of meeting outcomes and subsequent FDA regulatory decisions did not suggest a more or less risk aversive climate after FDAAA. Increased DSaRM advisory committee activity indicates its advice was being sought more broadly for drug regulatory decision making and at earlier stages of drug development after FDAAA was enacted.

Support for immunization registries among parents of vaccinated and unvaccinated school-aged children: a case control study.

PubMed

Linkins, Robert W; Salmon, Daniel A; Omer, Saad B; Pan, William Ky; Stokley, Shannon; Halsey, Neal A

2006-09-22

Immunizations have reduced childhood vaccine preventable disease incidence by 98-100%. Continued vaccine preventable disease control depends on high immunization coverage. Immunization registries help ensure high coverage by recording childhood immunizations administered, generating reminders when immunizations are due, calculating immunization coverage and identifying pockets needing immunization services, and improving vaccine safety by reducing over-immunization and providing data for post-licensure vaccine safety studies. Despite substantial resources directed towards registry development in the U.S., only 48% of children were enrolled in a registry in 2004. Parental attitudes likely impact child participation. Consequently, the purpose of this study was to assess the attitudes of parents of vaccinated and unvaccinated school-aged children regarding: support for immunization registries; laws authorizing registries and mandating provider reporting; opt-in versus opt-out registry participation; and financial worth and responsibility of registry development and implementation. A case control study of parents of 815 children exempt from school vaccination requirements and 1630 fully vaccinated children was conducted. Children were recruited from 112 elementary schools in Colorado, Massachusetts, Missouri, and Washington. Surveys administered to the parents, asked about views on registries and perceived utility and safety of vaccines. Parental views were summarized and logistic regression models compared differences between parents of exempt and vaccinated children. Surveys were completed by 56.1% of respondents. Fewer than 10% of parents were aware of immunization registries in their communities. Among parents aware of registries, exempt children were more likely to be enrolled (65.0%) than vaccinated children (26.5%) (p value = 0.01). A substantial proportion of parents of exempt children support immunization registries, particularly if registries offer choice for participation. Few parents of vaccinated (6.8%) and exempt children (6.7%) were aware of laws authorizing immunization registries. Support for laws authorizing registries and requiring health care providers to report to registries was more common among parents of vaccinated than exempt children. Most parents believed that the government, vaccine companies or insurance companies should pay for registries. Parental support for registries was relatively high. Parental support for immunization registries may increase with greater parental awareness of the risks of vaccine preventable diseases and utility of vaccination.

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

PubMed

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

2017-08-01

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

Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease.

PubMed

Bye, W A; Jairath, V; Travis, S P L

2017-07-01

Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression. To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged. A systematic bibliographic search identified six registration trials and nine cohort studies. Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure [PYs]) and 513 placebo patients. This reported lower exposure-adjusted incidence rates of infection (63.5/100 PYs; 95% CI: 59.6-67.3) and serious adverse events (20.0/100 PYs; 95% CI: 18.5-21.5) compared to placebo (82.9/100 PYs; 95% CI: 68.3-97.5) and (28.3/100 PYs 95% CI: 20.6-35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab-exposed patients (7.4/100 PYs; 95% CI: 6.6-8.3) compared to placebo (6.7 PYs; 95% CI: 3.2-10.1). Six post-marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited. Post-marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post-operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those pre-disposed to infection, malignancy or the elderly. © 2017 John Wiley & Sons Ltd.

Cardiovascular safety of vildagliptin in patients with type 2 diabetes: A European multi-database, non-interventional post-authorization safety study.

PubMed

Williams, Rachael; de Vries, Frank; Kothny, Wolfgang; Serban, Carmen; Lopez-Leon, Sandra; Chu, Changan; Schlienger, Raymond

2017-10-01

The aim of this non-interventional, multi-database, analytical cohort study was to assess the cardiovascular (CV) safety of vildagliptin vs other non-insulin antidiabetic drugs (NIADs) using real-world data from 5 European electronic healthcare databases. Patients with type 2 diabetes aged ≥18 years on NIAD treatment were enrolled. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the outcomes of interest (myocardial infarction [MI], acute coronary syndrome [ACS], stroke, congestive heart failure [CHF], individually and as a composite) were estimated using negative binomial regression. Approximately 2.8% of the enrolled patients (n = 738 054) used vildagliptin at any time during the study, with an average follow-up time of 1.4 years, resulting in a cumulative current vildagliptin exposure of 28 330 person-years. The adjusted IRRs (vildagliptin [±other NIADs] vs other NIADs) were in the range of 0.61 to 0.97 (MI), 0.55 to 1.60 (ACS), 0.02 to 0.77 (stroke), 0.49 to 1.03 (CHF), and 0.22 to 1.02 (composite CV outcomes). The IRRs and their 95% CIs were close to 1, demonstrating no increased risk of adverse CV events, including the risk of CHF, with vildagliptin vs other NIADs in real-world conditions. © 2017 Crown copyright. Diabetes, Obesity and Metabolism © 2017 John Wiley & Sons Ltd.

Institutional Response to Ohio's Campus Safety Initiatives: A Post-Virginia Tech Analysis

ERIC Educational Resources Information Center

Jackson, Natalie Jo

2009-01-01

The purpose of this study was to examine how institutions of higher education were responding to unprecedented state involvement in campus safety planning and policymaking in the aftermath of the Virginia Tech tragedy. Focused on Ohio, a state in which a state-level task force was convened and charged to promulgate campus safety recommendations…

75 FR 41531 - Brookwood-Sago Mine Safety Grants

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

... stated goals and current reporting period. objectives for improving safety. Conduct and report pre-test and post- test results of trainees. Course evaluations of trainer and training materials. The extent... pre-test and post- and improves safety. educational materials test results of the training materials...

The patient's safety and access to experimental drugs after the termination of clinical trials: regulations and trends.

PubMed

da Silva, Ricardo Eccard; Amato, Angélica Amorim; Sousa, Thiago do Rego; de Carvalho, Marta Rodrigues; Novaes, Maria Rita Carvalho Garbi

2018-05-12

Participants' rights and safety must be guaranteed not only while a clinical trial is being conducted but also when a clinical trial finishes. The criteria for post-trial access to experimental drugs, however, are unclear in various countries. The objectives of this study were (i) to ascertain if there were regulations or guidelines related to patients' access to drugs after the end of clinical trials in the countries selected in the study and (ii) to analyze trends in post-trial access in countries classified by their level of economic development. This study is a retrospective review. The data are from the records of clinical trials from 2014 registered in the World Health Organization's International Clinical Trials Registry Platform (ICTRP) database. Among the countries selected, provision of drugs post-trial is mandatory only in Argentina, Brazil, Chile, Finland, and Peru. The plans for post-trial access tend to be more present in low- and middle-income and upper middle-income countries, in comparison with high-income countries. Studies involving vulnerable populations are 2.53 times more likely to have plans for post-trial access than studies which do not. The guaranteeing of post-trial access remains mandatory in few countries. Considering that individuals seen as vulnerable have been included in clinical trials without plans for post-trial access, stakeholders must discuss the need to develop regulations mandating the guaranteeing of post-trial access in specified situations.

[Study on building index system of risk assessment of post-marketing Chinese patent medicine based on AHP-fuzzy neural network].

PubMed

Li, Yuanyuan; Xie, Yanming; Fu, Yingkun

2011-10-01

Currently massive researches have been launched about the safety, efficiency and economy of post-marketing Chinese patent medicine (CPM) proprietary Chinese medicine, but it was lack of a comprehensive interpretation. Establishing the risk evaluation index system and risk assessment model of CPM is the key to solve drug safety problems and protect people's health. The clinical risk factors of CPM exist similarities with the Western medicine, can draw lessons from foreign experience, but also have itself multi-factor multivariate multi-level complex features. Drug safety risk assessment for the uncertainty and complexity, using analytic hierarchy process (AHP) to empower the index weights, AHP-based fuzzy neural network to build post-marketing CPM risk evaluation index system and risk assessment model and constantly improving the application of traditional Chinese medicine characteristic is accord with the road and feasible beneficial exploration.

10 CFR 34.53 - Posting.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is being...

10 CFR 34.53 - Posting.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is being...

10 CFR 34.53 - Posting.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is being...

10 CFR 34.53 - Posting.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is being...

10 CFR 34.53 - Posting.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is being...

A Clinical Audit of Escorts' Awareness And Patients' Safety Following Intravenous Sedation In Adult Oral Surgery.

PubMed

Licheri, Luca; Erriu, Matteo; Bryant, Vincenzo; Piras, Vincenzo

2016-01-01

To evaluate current level of safety under the care of an escort following intravenous sedation, post-sedation arrangements and to identify potential risk levels. Information and post-sedation arrangements are important to patients'safety following surgery but although there is a general consensus over what is recommended for patients and their escorts, there is little, if any, literature on the escorts' awareness of sedation and accordance to post-sedation arrangement and recommendations. Escorts of 113 consecutive patients treated in oral surgery under sedation (midazolam) completed a questionnaire composed of 27 questions divided into seven sections including demographics, awareness of sedation, source of information and post-operative arrangement. From the data collected, two scores were calculated representative of the escorts' Safety and Reliability. Data were then analysed by ANOVA. Safety scores were statistically correlated with instruction source while Reliability correlated to a wider variety of parameters including gender, age as well as information source. Provision of clear written information to escorts is recommended as likely to improve patients' safety. Assessment of escorts' Safety and Reliability could provide a means for improving quality and safety of sedation service.

Safe Physical Activity Environments--To What Extent Are Local Government Authorities Auditing the Safety of Grassed Sporting Grounds?

ERIC Educational Resources Information Center

Otago, Leonie; Swan, Peter; Donaldson, Alex; Payne, Warren; Finch, Caroline

2009-01-01

Physical activity (PA) participation is influenced by the safety of the settings in which it is undertaken. This study describes the grounds assessment practices of Local Government Authorities (LGAs) in Victoria, Australia to ensure the safety of grassed sporting grounds. It also makes recommendations for improving these practices to maximise the…

Modeling and analyzing traffic safety perceptions: An application to the speed limit reduction pilot project in Edmonton, Alberta.

PubMed

El-Basyouny, Karim; El-Bassiouni, Mohamed Yahia

2013-03-01

To address the speeding problem in residential areas, the City of Edmonton initiated a pilot project to reduce the posted speed limit from 50km/h to 40km/h within six residential communities. This paper investigates the community perceptions of traffic safety within the six pilot communities in two phases: prior to project initiation (pre-pilot) and following the end of the project (post-pilot). This objective was accomplished by analyzing the results of two random dialing telephone surveys comprising 300 residents each. A preliminary analysis showed compatible demographic configurations for the two samples and confirmed that the residents were aware of both the posted speed limits and the adopted speed management controls. For the confirmatory factor analysis (CFA), a two-group (pre-pilot and post-pilot) three-factor model was used to assess the residents' perceptions of the speeding behavior (Speeding), their concerns about traffic safety issues (Concerns), and their perceptions of traffic safety (Safety). Comparing the CFA results of the post-pilot survey versus those of the pre-pilot survey, it was evident that there was a significant decrease in Speeding and Concerns accompanied by a significant increase in Safety. A structural equations model (SEM) was also fitted to the data in order to assess the impact of Speeding and Concerns on Safety. The results showed that Concerns increase significantly with Speeding, and that both factors have significant negative impacts on Safety. However, while the impact of Concerns on Safety was direct, that of Speeding on Safety was largely indirect (i.e., mediated through Concerns). Overall, the multivariate analysis has demonstrated that the pilot project was successful in improving the residents' perceptions of traffic safety in their community. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

The European post-marketing observational sertindole study: an investigation of the safety of antipsychotic drug treatment.

PubMed

Kasper, Siegfried; Möller, Hans-Jürgen; Hale, Anthony

2010-02-01

The objective of the European Post-marketing Observational Serdolect((R)) (EPOS) Study was to compare the safety of treatment with Serdolect (sertindole) with that of usual treatment in patients with schizophrenia, in normal European clinical practice. The EPOS was a multicentre, multinational, referenced, cohort study. Patients were enrolled at 226 centres in ten European countries. The study was prematurely terminated in 1998 as a result of the temporary market suspension of sertindole. Termination of the study reduced the number of patients recruited from the planned 12,000 to 2,321. While the power of the study was weakened, it did provide useful mortality information, which may be useful for future long-term studies. Crude mortality in the sertindole and non-sertindole groups was 1.45 (95% confidence interval, CI 0.53-3.16) and 1.50 (CI 0.72-2.76) deaths/100 patient-years exposed, respectively. There were no more cardiac deaths in the sertindole group than in the non-sertindole group. QT interval prolongation did not translate into an increased risk of death. Sertindole was well tolerated and caused few extrapyramidal symptoms. Although CIs remained large, this post-marketing study does not provide any evidence against the use of sertindole under normal conditions. Sertindole was well tolerated and posed no significant safety problems.

The rationale and design of the Micra Transcatheter Pacing Study: safety and efficacy of a novel miniaturized pacemaker.

PubMed

Ritter, Philippe; Duray, Gabor Z; Zhang, Shu; Narasimhan, Calambur; Soejima, Kyoko; Omar, Razali; Laager, Verla; Stromberg, Kurt; Williams, Eric; Reynolds, Dwight

2015-05-01

Recent advances in miniaturization technologies and battery chemistries have made it possible to develop a pacemaker small enough to implant within the heart while still aiming to provide similar battery longevity to conventional pacemakers. The Micra Transcatheter Pacing System is a miniaturized single-chamber pacemaker system that is delivered via catheter through the femoral vein. The pacemaker is implanted directly inside the right ventricle of the heart, eliminating the need for a device pocket and insertion of a pacing lead, thereby potentially avoiding some of the complications associated with traditional pacing systems. The Micra Transcatheter Pacing Study is currently undergoing evaluation in a prospective, multi-site, single-arm study. Approximately 720 patients will be implanted at up to 70 centres around the world. The study is designed to have a continuously growing body of evidence and data analyses are planned at various time points. The primary safety and efficacy objectives at 6-month post-implant are to demonstrate that (i) the percentage of Micra patients free from major complications related to the Micra system or implant procedure is significantly higher than 83% and (ii) the percentage of Micra patients with both low and stable thresholds is significantly higher than 80%. The safety performance benchmark is based on a reference dataset of 977 subjects from 6 recent pacemaker studies. The Micra Transcatheter Pacing Study will assess the safety and efficacy of a miniaturized, totally endocardial pacemaker in patients with an indication for implantation of a single-chamber ventricular pacemaker. NCT02004873. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Formation of the U.S. Air Force Aviator Post Traumatic Stress Disorder Study Group

DTIC Science & Technology

2016-11-15

to endorse PTSD during all four subsequent evaluations. Notably, they found that lingering symptoms of PTSD occurred frequently for both groups of...AFRL-SA-WP-TR-2016-0017 Formation of the U.S. Air Force Aviator Post-Traumatic Stress Disorder Study Group Joe D. Wood, III...Aviator Post-Traumatic Stress Disorder Study Group 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Joe D

Post-marketing surveillance in the published medical and grey literature for percutaneous transluminal coronary angioplasty catheters: a systematic review.

PubMed

Polisena, Julie; Forster, Alan J; Cimon, Karen; Rabb, Danielle

2013-10-10

Post-marketing surveillance (PMS) may identify rare serious incidents or adverse events due to the long-term use of a medical device, which was not captured in the pre-market process. Percutaneous transluminal coronary angioplasty (PTCA) is a non-surgical procedure that uses a balloon-tipped catheter to enlarge a narrowed artery. In 2011, 1,942 adverse event reports related to the use of PTCA catheters were submitted to the FDA by the manufacturers, an increase from the 883 reported in 2008. The primary research objective is to conduct a systematic review of the published and grey literature published between 2007 and 2012 for the frequency of incidents, adverse events and malfunctions associated with the use of PTCA catheters in patients with coronary artery disease (CAD). Grey literature has not been commercially published. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and PubMed for medical literature on PMS for PTCA catheters in patients with CAD published between January 2007 and July 2012. We also searched the grey literature. This review included 11 studies. The in-hospital adverse events reported were individual cases of myocardial infarction and hematoma. In studies of patients with coronary perforation, more patients with balloon angioplasty were identified compared with patients who required stenting. Our systematic review illustrates that the volume and quality of PMS studies associated with the use of PTCA catheters in patients with CAD are low in the published and grey literature, and may not be useful sources of information for decisions on safety. In most studies, the objectives were not to monitor the long-term safety of the use of PTCA catheters in clinical practice. Future studies can explore the strengths and limitations of PMS databases administered by regulatory authorities.

Challenges in conducting post-authorisation safety studies (PASS): A vaccine manufacturer's view.

PubMed

Cohet, Catherine; Rosillon, Dominique; Willame, Corinne; Haguinet, Francois; Marenne, Marie-Noëlle; Fontaine, Sandrine; Buyse, Hubert; Bauchau, Vincent; Baril, Laurence

2017-05-25

Post-authorisation safety studies (PASS) of vaccines assess or quantify the risk of adverse events following immunisation that were not identified or could not be estimated pre-licensure. The aim of this perspective paper is to describe the authors' experience in the design and conduct of twelve PASS that contributed to the evaluation of the benefit-risk of vaccines in real-world settings. We describe challenges and learnings from selected PASS of rotavirus, malaria, influenza, human papillomavirus and measles-mumps-rubella-varicella vaccines that assessed or identified potential or theoretical risks, which may lead to changes to risk management plans and/or to label updates. Study settings include the use of large healthcare databases and de novo data collection. PASS methodology is influenced by the background incidence of the outcome of interest, vaccine uptake, availability and quality of data sources, identification of the at-risk population and of suitable comparators, availability of validated case definitions, and the frequent need for case ascertainment in large databases. Challenges include the requirement for valid exposure and outcome data, identification of, and access to, adequate data sources, and mitigating limitations including bias and confounding. Assessing feasibility is becoming a key step to confirm that study objectives can be met in a timely manner. PASS provide critical information for regulators, public health agencies, vaccine manufacturers and ultimately, individuals. Collaborative approaches and synergistic efforts between vaccine manufacturers and key stakeholders, such as regulatory and public health agencies, are needed to facilitate access to data, and to drive optimal study design and implementation, with the aim of generating robust evidence. Copyright © 2017 GSK Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

[The significance of introducing registry study in the post-marketing safety research for Chinese medicine and pharmacy].

PubMed

Liao, Xing; Xie, Yan-Ming; Yang, Wei; Chang, Yan-Peng

2014-03-01

There is a new research model named 'registry study/patient registry' in Western medicine, which could be referred to by Chinese medicine researchers, such as active safety surveillance. This article will introduce registry study from different aspects as the developing history, features, and application in order to inform Chinese medicine researchers of future studies.

30 CFR 71.403 - Waiver of surface facilities requirements; posting of waiver.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Occupational Safety and Health, may, upon written application by the operator, and after consideration of any...; posting of waiver. 71.403 Section 71.403 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY HEALTH STANDARDS-SURFACE COAL MINES AND SURFACE...

30 CFR 57.19108 - Posting warning signs during shaft work.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Posting warning signs during shaft work. 57.19108 Section 57.19108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL...

30 CFR 77.1402-1 - Maximum load; posting.

Code of Federal Regulations, 2010 CFR

2010-07-01

....1402-1 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL... number of men permitted to ride on each hoist or elevator at one time; this limit shall be posted on each...

An observational study of rotigotine transdermal patch and other currently prescribed therapies in patients with Parkinson's disease.

PubMed

Müller, Thomas; Tolosa, Eduardo; Badea, Letitia; Asgharnejad, Mahnaz; Grieger, Frank; Markowitz, Michael; Nondonfaz, Xavier; Bauer, Lars; Timmermann, Lars

2018-06-01

Real-world data from large cohorts of patients with Parkinson's disease on the long-term effectiveness of different dopamine-substituting drug therapies are rare. The objective of this study was to obtain information on real-world management of PD with dopamine-substituting drugs. SP0854 (NCT00599339) was a prospective, multicenter, non-interventional, multiple-cohort, post-authorization safety study of rotigotine versus other dopaminergic therapies. The study was also part of a European Medicines Agency risk-management plan for the non-ergoline dopamine agonist rotigotine, focussing on cardiovalvular fibrosis. Eligible patients requiring monotherapy with a dopamine agonist, or levodopa in combination with a dopamine agonist were followed for ≤ 33 months; 1531 of 2195 patients completed the study. Mean motor scores improved for all dopamine-substituting treatments. Patients with more severe motor-symptoms/increased disability were more likely to receive levodopa alone or in combination with a DA at study onset. More patients who started on combination therapy with levodopa remained on this treatment versus those starting on dopaminergic monotherapy. This real-world study showed that the dopamine-substituting therapies were efficacious, with a safety profile consistent with that expected of dopaminergic treatments. Cardiovalvular pathology was rare and not found to be causally-related to rotigotine.

9 CFR 114.9 - Outline of Production guidelines.

Code of Federal Regulations, 2010 CFR

2010-01-01

... each satisfactory test. A. Purity. B. Safety. C. Potency. D. Other tests. VI. Post preparatory steps. A... test. A. Purity. B. Safety. C. Potency. D. Moisture, if desiccated. E. Any other tests. VI. Post.... Potency. D. Any other tests. E. Include any additional pertinent information. IV. Post preparatory steps...

9 CFR 114.9 - Outline of Production guidelines.

Code of Federal Regulations, 2012 CFR

2012-01-01

... each satisfactory test. A. Purity. B. Safety. C. Potency. D. Other tests. VI. Post preparatory steps. A... test. A. Purity. B. Safety. C. Potency. D. Moisture, if desiccated. E. Any other tests. VI. Post.... Potency. D. Any other tests. E. Include any additional pertinent information. IV. Post preparatory steps...

9 CFR 114.9 - Outline of Production guidelines.

Code of Federal Regulations, 2013 CFR

2013-01-01

... each satisfactory test. A. Purity. B. Safety. C. Potency. D. Other tests. VI. Post preparatory steps. A... test. A. Purity. B. Safety. C. Potency. D. Moisture, if desiccated. E. Any other tests. VI. Post.... Potency. D. Any other tests. E. Include any additional pertinent information. IV. Post preparatory steps...

9 CFR 114.9 - Outline of Production guidelines.

Code of Federal Regulations, 2011 CFR

2011-01-01

... each satisfactory test. A. Purity. B. Safety. C. Potency. D. Other tests. VI. Post preparatory steps. A... test. A. Purity. B. Safety. C. Potency. D. Moisture, if desiccated. E. Any other tests. VI. Post.... Potency. D. Any other tests. E. Include any additional pertinent information. IV. Post preparatory steps...

9 CFR 114.9 - Outline of Production guidelines.

Code of Federal Regulations, 2014 CFR

2014-01-01

... each satisfactory test. A. Purity. B. Safety. C. Potency. D. Other tests. VI. Post preparatory steps. A... test. A. Purity. B. Safety. C. Potency. D. Moisture, if desiccated. E. Any other tests. VI. Post.... Potency. D. Any other tests. E. Include any additional pertinent information. IV. Post preparatory steps...

Safe Schools Survey: Post-Secondary Survey Results.

ERIC Educational Resources Information Center

Mowery, Andrea

This report provides the results of a survey of safety and security at colleges and universities in Minnesota, along with policy recommendations to improve safety and security at Minnesota post-secondary institutions. It is based on campus security reports voluntarily submitted by 60 of the 110 Minnesota post-secondary institutions, personal…

Prototype CoolCup cryolipolysis applicator with over 40% reduced treatment time demonstrates equivalent safety and efficacy with greater patient preference.

PubMed

Kilmer, Suzanne L

2017-01-01

Cryolipolysis is a safe, effective non-surgical procedure to reduce fat. For most cryolipolysis treatments, tissue is pulled between parallel cooling plates with a treatment duration of 60 minutes. A novel contoured cup, medium-sized applicator was developed to increase tissue contact with reduced skin tension and reduced treatment time. This prototype contoured cup was investigated with a standard cryolipolysis applicator to evaluate safety, efficacy, and patient preference. A prototype CoolCup medium-sized vacuum applicator (CoolSculpting System, ZELTIQ Aesthetics) was used to treat n = 19 subjects in the flanks. Randomly assigned, one flank received standard treatment with the CoolCore applicator (-10°C for 60 minutes). The contralateral flank received treatment from the CoolCup (-11°C for 35 minutes). The clinical study primary efficacy endpoint was 70% correct identification of baseline photographs by independent physician review. Incidence of adverse device effects was monitored. Fat layer reduction was measured by ultrasound and subject surveys were administered 12 weeks post-treatment. Equivalent efficacy was demonstrated between the CoolCore standard treatment and the prototype CoolCup. Independent review from three blinded physicians found 81% correct identification of baseline photographs for the standard treatment and 79% for the CoolCup. Ultrasound measurements indicated mean fat layer reduction of 4.38 mm for the standard treatment and 4.40 mm for the CoolCup; no statistically significant difference was found when comparing treatment efficacy of the two applicators (P = 0.96). Patient questionnaires revealed 85% preferred CoolCup because of shorter treatment duration and greater comfort. Procedural assessments revealed 45% lower pain scores for CoolCup. Immediate post-treatment clinical assessments revealed 82% less bruising. Typical side effects, such as numbness and erythema, were similar. There were no adverse events. This clinical study of a prototype medium-sized vacuum applicator with a cooled contoured surface indicates that the CoolCup produces equivalent safety and efficacy to the standard CoolCore cryolipolysis applicator. With a 42% reduction in treatment time, the procedure was found to be more comfortable because of lower vacuum skin tension and shorter treatment duration. Lasers Surg. Med. 49:63-68, 2017. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Endoscopic non-technical skills team training: the next step in quality assurance of endoscopy training.

PubMed

Matharoo, Manmeet; Haycock, Adam; Sevdalis, Nick; Thomas-Gibson, Siwan

2014-12-14

To investigate whether novel, non-technical skills training for Bowel Cancer Screening (BCS) endoscopy teams enhanced patient safety knowledge and attitudes. A novel endoscopy team training intervention for BCS teams was developed and evaluated as a pre-post intervention study. Four multi-disciplinary BCS teams constituting BCS endoscopist(s), specialist screening practitioners, endoscopy nurses and administrative staff (A) from English BCS training centres participated. No patients were involved in this study. Expert multidisciplinary faculty delivered a single day's training utilising real clinical examples. Pre and post-course evaluation comprised participants' patient safety awareness, attitudes, and knowledge. Global course evaluations were also collected. Twenty-three participants attended and their patient safety knowledge improved significantly from 43%-55% (P ≤ 0.001) following the training intervention. 12/41 (29%) of the safety attitudes items significantly improved in the areas of perceived patient safety knowledge and awareness. The remaining safety attitude items: perceived influence on patient safety, attitudes towards error management, error management actions and personal views following an error were unchanged following training. Both qualitative and quantitative global course evaluations were positive: 21/23 (91%) participants strongly agreed/agreed that they were satisfied with the course. Qualitative evaluation included mandating such training for endoscopy teams outside BCS and incorporating team training within wider endoscopy training. Limitations of the study include no measure of increased patient safety in clinical practice following training. A novel comprehensive training package addressing patient safety, non-technical skills and adverse event analysis was successful in improving multi-disciplinary teams' knowledge and safety attitudes.

Endoscopic non-technical skills team training: The next step in quality assurance of endoscopy training

PubMed Central

Matharoo, Manmeet; Haycock, Adam; Sevdalis, Nick; Thomas-Gibson, Siwan

2014-01-01

AIM: To investigate whether novel, non-technical skills training for Bowel Cancer Screening (BCS) endoscopy teams enhanced patient safety knowledge and attitudes. METHODS: A novel endoscopy team training intervention for BCS teams was developed and evaluated as a pre-post intervention study. Four multi-disciplinary BCS teams constituting BCS endoscopist(s), specialist screening practitioners, endoscopy nurses and administrative staff (A) from English BCS training centres participated. No patients were involved in this study. Expert multidisciplinary faculty delivered a single day’s training utilising real clinical examples. Pre and post-course evaluation comprised participants’ patient safety awareness, attitudes, and knowledge. Global course evaluations were also collected. RESULTS: Twenty-three participants attended and their patient safety knowledge improved significantly from 43%-55% (P ≤ 0.001) following the training intervention. 12/41 (29%) of the safety attitudes items significantly improved in the areas of perceived patient safety knowledge and awareness. The remaining safety attitude items: perceived influence on patient safety, attitudes towards error management, error management actions and personal views following an error were unchanged following training. Both qualitative and quantitative global course evaluations were positive: 21/23 (91%) participants strongly agreed/agreed that they were satisfied with the course. Qualitative evaluation included mandating such training for endoscopy teams outside BCS and incorporating team training within wider endoscopy training. Limitations of the study include no measure of increased patient safety in clinical practice following training. CONCLUSION: A novel comprehensive training package addressing patient safety, non-technical skills and adverse event analysis was successful in improving multi-disciplinary teams’ knowledge and safety attitudes. PMID:25516665

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

PubMed Central

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

2013-01-01

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

Improving safety climate through a communication and recognition program for construction: a mixed-methods study

PubMed Central

Sparer, Emily H; Catalano, Paul J; Herrick, Robert F; Dennerlein, Jack T

2016-01-01

Objectives This study aimed to evaluate the efficacy of a safety communication and recognition program (B-SAFE), designed to encourage improvement of physical working conditions and hazard reduction in construction. Methods A matched pair cluster randomized controlled trial was conducted on eight worksites (four received the B-SAFE intervention, four served as control sites) for approximately five months per site. Pre- and post-exposure worker surveys were collected at all sites (N=615, pre-exposure response rate of 74%, post-exposure response rate of 88%). Multi-level mixed-effect regression models evaluated the effect of B-SAFE on safety climate as assessed from surveys. Focus groups (N=6–8 workers/site) were conducted following data collection. Transcripts were coded and analyzed for thematic content using Atlas.ti (version 6). Results The mean safety climate score at intervention sites, as measured on a 0–50 point scale, increased 0.5 points (1%) between pre- and post-B-SAFE exposure, compared to control sites that decreased 0.8 points (1.6%). The intervention effect size was 1.64 (3.28%) (P-value=0.01) when adjusted for month the worker started on-site, total length of time on-site, as well as individual characteristics (trade, title, age, and race/ethnicity). At intervention sites, workers noted increased levels of safety awareness, communication, and teamwork compared to control sites. Conclusions B-SAFE led to many positive changes, including an improvement in safety climate, awareness, teambuilding, and communication. B-SAFE was a simple intervention that engaged workers through effective communication infrastructures and had a significant, positive effect on worksite safety. PMID:27158914

Results from a Nationwide Cohort Temporary Utilization Authorization (ATU) survey of patients in france treated with Pheburane(®) (Sodium Phenylbutyrate) taste-masked granules.

PubMed

Kibleur, Yves; Dobbelaere, Dries; Barth, Magalie; Brassier, Anaïs; Guffon, Nathalie

2014-10-01

The aim of this study was to describe a nationwide system for pre-marketing follow-up (cohort temporary utilization authorization [ATU] protocol; i.e., 'therapeutic utilization') of a new taste-masked formulation of sodium phenylbutyrate (NaPB) granules (Pheburane(®)) in France and to analyze safety and efficacy in this treated cohort of patients with urea cycle disease (UCD). In October 2012, a cohort ATU was established in France to monitor the use of Pheburane(®) on a named-patient basis. All treated UCD patients were included in a follow-up protocol developed by the Laboratory (Lucane Pharma) and the French Medicines Agency (ANSM), which recorded demographics, dosing characteristics of NaPB, concomitant medications, adverse events, and clinical outcome during the period of treatment. Following the granting of the Marketing Authorization in Europe, the cohort ATU was terminated approximately 1 year after its initiation, as the product was launched on the French market. The ease of administration and acceptability were much better with the new taste-masked formulation than with the previous treatment. No episodes of metabolic decompensation were observed over a treatment period ranging from 3 to 11 months with Pheburane(®) and the range of ammonia and glutamine plasma levels improved and remained within the normal range. In all, no adverse events were reported with Pheburane(®) treatment. The recently developed taste-masked formulation of NaPB granules improved the quality of life for UCD patients. This may translate into improved compliance, efficacy, and safety, which may be demonstrated either in further studies or in the post-marketing use of the product.

Clinical feasibility of the Nintendo Wii™ for balance training post-stroke: a phase II randomized controlled trial in an inpatient setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2014-09-01

To investigate the feasibility and potential efficacy of the Nintendo Wii™ for balance rehabilitation after stroke. Phase II, single-blind, randomized controlled trial. Inpatient rehabilitation facility. Thirty adults (mean age 63.6 (14.7) years) undergoing inpatient rehabilitation who were less than three months post-stroke and able to stand unsupported. Participants were allocated to a Balance Group, using the 'Wii Fit Plus' in standing, or Upper Limb Group, using the 'Wii Sports/Sports Resort' in sitting. Both groups undertook three 45 minute sessions per week over two to four weeks in addition to standard care. The primary focus was feasibility, addressed by recruitment, retention, adherence, acceptability and safety. Efficacy was evaluated by balance, mobility and upper limb outcomes. Twenty-one percent of individuals screened were recruited and 86% (n = 30) of eligible people agreed to participate. Study retention and session adherence was 90% and > 99%, respectively, at two weeks; dropping to 70% and 87% at four weeks due to early discharge. All participants reported enjoying the sessions and most felt they were beneficial. No major adverse events occurred. Wii use by the Balance Group was associated with trends for improved balance, with significantly greater improvement in outcomes including the Step Test and Wii Balance Board-derived centre of pressure scores. The Upper Limb Group had larger, non-significant changes in arm function. A Wii-based approach appears feasible and promising for post-stroke balance rehabilitation. A larger randomized controlled trial is recommended to further investigate efficacy. © The Author(s) 2014.

Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal.

PubMed

Garfinkel, Sarah N; Abelson, James L; King, Anthony P; Sripada, Rebecca K; Wang, Xin; Gaines, Laura M; Liberzon, Israel

2014-10-01

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression. Copyright © 2014 the authors 0270-6474/14/3413435-09$15.00/0.

Management of post-LASIK dry eye: a multicenter randomized comparison of a new multi-ingredient artificial tear to carboxymethylcellulose

PubMed Central

Wallerstein, Avi; Jackson, W Bruce; Chambers, Jeffrey; Moezzi, Amir M; Lin, Hugh; Simmons, Peter A

2018-01-01

Purpose To compare the efficacy and safety of a preservative-free, multi-ingredient formulation of carboxymethylcellulose 0.5%, hyaluronic acid 0.1%, and organic osmolytes (CMC-HA), to preservative-free carboxymethylcellulose 0.5% (CMC) in the management of postoperative signs and symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK). Methods This was a double-masked, randomized, parallel-group study conducted in 14 clinical centers in Canada and Australia. Subjects with no more than mild dry eye instilled CMC-HA or CMC for 90 days post-LASIK. Ocular Surface Disease Index© (OSDI; primary efficacy measure), corneal staining, tear break-up time (TBUT), Schirmer’s test, acceptability/tolerability surveys, and visual acuity were assessed at screening and days 2, 10, 30, 60, and 90 post-surgery. Safety analyses included all enrolled. Results A total of 148 subjects (CMC-HA, n=75; CMC, n=73) were enrolled and assigned to receive treatment, and 126 subjects completed the study without any protocol violations. Post-LASIK, dry eye signs/symptoms peaked at 10 days. OSDI scores for both groups returned to normal with no differences between treatment groups at day 90 (P=0.775). Corneal staining, Schirmer’s test, TBUT, and survey results were comparable. Higher mean improvements in uncorrected visual acuity were observed in the CMC-HA group at all study visits, reaching statistical significance at day 30 (P=0.013). Both treatments were well tolerated. Conclusion CMC-HA-containing artificial tears relieved post-LASIK ocular dryness as well as CMC alone, and demonstrated incremental benefit in uncorrected vision, with a favorable safety profile. Results support use of CMC-HA eye drops to reduce signs and symptoms of ocular dryness post-LASIK. PMID:29765198

Selective resection of dorsal nerves of penis for premature ejaculation.

PubMed

Zhang, G-X; Yu, L-P; Bai, W-J; Wang, X-F

2012-12-01

Premature ejaculation (PE) is one of the most prevalent male sexual dysfunctions. Selective resection of the dorsal nerve (SRDN) of penis has recently been used for the treatment of PE and has shown some efficacy. To further clarify the efficacy and safety of SRDN on PE, we performed a preliminary, randomized, placebo-controlled clinical observational study. Persons with the complaints of rapid ejaculation, asking for circumcision because of redundant foreskin, intravaginal ejaculation latency time (IELT) within 2 min, not responding to antidepressant medication or disliking oral medication were randomly enrolled in two groups. From April 2007 to August 2010, a total of 101 eligible persons were enrolled, 40 of them received SRDN which dorsal nerves of the penis were selectively resected, and those (n = 61) enrolled in the control group were circumcised only. IELT and the Brief Male Sexual Function Inventory (BMSFI) questionnaire were implemented pre- and post-operatively for the evaluation of the effect and safety of the surgery. There are no statistically significant differences in the baseline data including mean ages, mean IELTs, perceived control abilities and the BMSFI mean scores between the two groups. With regard to the post-operative data of the surgery, both IELTs and perceived control abilities were significantly increased after SRDN (1.1 ± 0.9 min vs. 3.8 ± 3.1 min for pre- and post-operative IELT, respectively, p < 0.01),whereas the post-operative results were not significantly improved for the control group (1.2 ± 0.7 min vs. 1.5 ± 1.1 min, p > 0.05). Also, there were no statistically significant differences both in BMSFI composite and subscale scores between the two groups after surgery. Hence, we conclude that SRDN is effective in delaying ejaculation and improving ejaculatory control, whereas erectile function is not affected. The results imply that SRDN may be an alternative method for the treatment of PE for some patients. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

A qualitative study of factors influencing retention of doctors and nurses at rural healthcare facilities in Bangladesh.

PubMed

Darkwa, Emmanuel Kwame; Newman, M Sophia; Kawkab, Mahmud; Chowdhury, Mahbub Elahi

2015-08-27

Bangladesh is a highly populous country with three-quarters rural population. Pressing national shortages in health professionals has resulted in high vacancy rates in rural areas. These are compounded by excessive absenteeism and low retention among nurses and doctors posted to rural locations. This study attempts to ascertain reasons for providers' reluctance to work in rural and remote areas and to identify ways in which these barriers to appropriate staffing might be resolved. This is a qualitative study based on in-depth interviews with healthcare providers (n = 15) and facility managers (n = 4) posted in rural areas, and key informant interviews with health policymakers at the national level (n = 2). Interview guides were written in English and translated and administered in Bengali. The collected data were re-translated and analyzed in English. Braun and Clarke's thematic analysis approach (data familiarization, coding, identifying and reviewing themes, and producing a final report) was used. Participants reported poor living conditions in rural areas (e.g., poor housing facilities and unsafe drinking water); overwhelming workloads with poor safety and insufficient equipment; and a lack of opportunities for career development, and skill enhancement. They reported insufficient wages and inadequate opportunities for private practice in rural areas. Managers described their lack of sufficient authority to undertake disciplinary measures for absenteeism. They also pointed at the lack of fairness in promotion practices of the providers. Policymakers acknowledged unavailability or insufficient allowances for rural postings. There is also a lack of national policy on rural retention. The findings revealed a complex interplay of factors influencing doctors' and nurses' availability in rural and remote public health facilities from the perspective of different players in the healthcare delivery system of Bangladesh. In addition, the study generated several possibilities for improvement, including increased allowances and incentives for rural posting; a transparent and fair promotion system for serving in rural areas; enhanced authority of the local managers for reducing worker absenteeism; and improved national policies on rural retention.

[Post-marketing surveillance on Guizhi Fuling Jiaonang based on literature review].

PubMed

Wang, Gui-Qian; Gao, Yang; Liu, Fu-Mei; Wei, Rui-Li; Xie, Yan-Ming

2018-02-01

To systemically evaluate the post-marketing safety of Guizhi Fuling Jiaonang. Computer retrieval was conducted in Medline, EMbase, the Web of Science, Clinical Trials. Gov, the Cochrane Library, CNKI, VIP, WanFang Data and CBM to collect relevant information. The papers were then screened according to inclusion and exclusion criteria. A total of 234 papers were included in this study, including 164 randomized controlled trials, 7 quasi-randomized controlled trials, 8 non-randomized controls, 56 case series, and 1 cohort study. The patients were only treated with Guizhi Fuling Jiaonang in 56 studies, and Guizhi Fuling Jiaonang was combined with other drugs in 178 studies. The total ADRs/AEs incidence was 1.99% in single use of Guizhi Fuling Jiaonang, and 8.21% in combined use, but showing no severe adverse reactions. Gastrointestinal system damage was most common in mild ADRs. In this study, it was found that the overall safety of Guizhi Fuling Jiaonang was acceptable. The direct evidences of the drug's safety case reports were systematically analyzed in this study, but the mechanism study on the safety of the drug after marketing or the prospective long-term clinical observation study was not sufficient, so the further studies on the safety of drug use should be conducted in order to provide better guidance for clinical medication. Copyright© by the Chinese Pharmaceutical Association.

Social Media Listening for Routine Post-Marketing Safety Surveillance.

PubMed

Powell, Gregory E; Seifert, Harry A; Reblin, Tjark; Burstein, Phil J; Blowers, James; Menius, J Alan; Painter, Jeffery L; Thomas, Michele; Pierce, Carrie E; Rodriguez, Harold W; Brownstein, John S; Freifeld, Clark C; Bell, Heidi G; Dasgupta, Nabarun

2016-05-01

Post-marketing safety surveillance primarily relies on data from spontaneous adverse event reports, medical literature, and observational databases. Limitations of these data sources include potential under-reporting, lack of geographic diversity, and time lag between event occurrence and discovery. There is growing interest in exploring the use of social media ('social listening') to supplement established approaches for pharmacovigilance. Although social listening is commonly used for commercial purposes, there are only anecdotal reports of its use in pharmacovigilance. Health information posted online by patients is often publicly available, representing an untapped source of post-marketing safety data that could supplement data from existing sources. The objective of this paper is to describe one methodology that could help unlock the potential of social media for safety surveillance. A third-party vendor acquired 24 months of publicly available Facebook and Twitter data, then processed the data by standardizing drug names and vernacular symptoms, removing duplicates and noise, masking personally identifiable information, and adding supplemental data to facilitate the review process. The resulting dataset was analyzed for safety and benefit information. In Twitter, a total of 6,441,679 Medical Dictionary for Regulatory Activities (MedDRA(®)) Preferred Terms (PTs) representing 702 individual PTs were discussed in the same post as a drug compared with 15,650,108 total PTs representing 946 individual PTs in Facebook. Further analysis revealed that 26 % of posts also contained benefit information. Social media listening is an important tool to augment post-marketing safety surveillance. Much work remains to determine best practices for using this rapidly evolving data source.

A distributed research network model for post-marketing safety studies: the Meningococcal Vaccine Study.

PubMed

Velentgas, Priscilla; Bohn, Rhonda L; Brown, Jeffrey S; Chan, K Arnold; Gladowski, Patricia; Holick, Crystal N; Kramer, Judith M; Nakasato, Cynthia; Spettell, Claire M; Walker, Alexander M; Zhang, Fang; Platt, Richard

2008-12-01

We describe a multi-center post-marketing safety study that uses distributed data methods to minimize the need for covered entities to share protected health information (PHI). Implementation has addressed several issues relevant to creation of a large scale post-marketing drug safety surveillance system envisioned by the FDA's Sentinel Initiative. This retrospective cohort study of Guillain-Barré syndrome (GBS) following meningococcal conjugate vaccination incorporates the data and analytic expertise of five research organizations closely affiliated with US health insurers. The study uses administrative claims data, plus review of full text medical records to adjudicate the status of individuals with a diagnosis code for GBS (ICD9 357.0). A distributed network approach is used to create the analysis files and to perform most aspects of the analysis, allowing nearly all of the data to remain behind institutional firewalls. Pooled analysis files transferred to a central site will contain one record per person for approximately 0.2% of the study population, and contain PHI limited to the month and year of GBS onset for cases or the index date for matched controls. The first planned data extraction identified over 9 million eligible adolescents in the target age range of 11-21 years. They contributed an average of 14 months of eligible time on study over 27 months of calendar time. MCV4 vaccination coverage levels exceeded 20% among 17-18-year olds and 16% among 11-13 and 14-16-year-old age groups by the second quarter of 2007. This study demonstrates the feasibility of using a distributed data network approach to perform large scale post-marketing safety analyses and is scalable to include additional organizations and data sources. We believe these results can inform the development of a large national surveillance system. Copyright (c) 2008 John Wiley & Sons, Ltd.

Advising patients seeking stem cell interventions for multiple sclerosis.

PubMed

von Wunster, Beatrice; Bailey, Steven; Wilkins, Alastair; Marks, David I; Scolding, Neil J; Rice, Claire M

2018-05-30

Given the intuitive potential of stem cell therapy and limitations of current treatment options for progressive multiple sclerosis (MS), it is not surprising that patients consider undertaking significant clinical and financial risks to access stem cell transplantation. However, while increasing evidence supports autologous haematopoietic stem cell transplantation (AHSCT) in aggressive relapsing-remitting MS, interventions employing haematopoietic or other stem cells should otherwise be considered experimental and recommended only in the context of a properly regulated clinical study. Understandably, most neurologists are unfamiliar with AHSCT procedures and the specific requirements for quality assurance and safety standards, as well as post-procedure precautions and follow-up. Consequently they may feel ill-equipped to advise patients. Here, we highlight important points for discussion in consultations with patients considering stem cell 'tourism' for MS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Resident Aggression Toward Staff at a Center for the Developmentally Disabled

PubMed Central

West, Christine A.; Galloway, Ellen; Niemeier, Maureen T.

2015-01-01

Few studies have examined factors contributing to nonfatal assaults to staff working in residential care facilities. The authors evaluated resident assaults toward direct care/nursing staff at an Intermediate Care Facility for Individuals with Mental Retardation (ICF/MR), which included observations of work areas, employee interviews, calculation of injury and assault rates for 2004 to 2007 from Occupational Safety and Health Administration Logs, and review of state ICF/MR guidelines. Most staff interviewed reported having been injured during physical restraint of a resident and the average rate of injury from assault at the center evaluated was higher than the average national rates for the health care and social assistance sector for the same time period. The center lacked policies for a safe workplace. The authors recommended review and maintenance of workplace violence prevention policies and developing a post-incident response and evaluation program to assist staff in coping with the consequences of assault and/or occupational injury. PMID:24571051

The European "clinical trial" regulation; relationship with the Jardé Act: a Giens workshop.

PubMed

Lemaire, François; Marchenay, Brigitte; Chassany, Olivier; Barthélémy, Philippe; Bouzzagou, Mohamed; Comet, Denis; Delval, Cécile; Dubray, Claude; Fouret, Cécile; Frija-Orvoen, Elisabeth; Gambotti, Laetitia; Lamarque, Véronique; d'Orsay, Geneviève; Plattner, Valérie; Sibenaler, Claire; Roux, Jacques; Thoby, Frédérique

2015-01-01

In May 2014, the European Union Parliament and Council published a new regulation on clinical trials on medicinal products for human use, which is designed to replace Directive 2001/20/EC. It will not come into effect until 2016. Nevertheless, it is essential to examine its relationship with national legislation, i.e. the Jardé Act, whose implementation has been delayed pending publication of the European regulation. The Giens workshop identified and examined the various issues that this relationship is bound to raise. In particular, it looked at trial methodology assessment procedures, the working relationship between the French National Agency of Drug Safety and Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) and ethics committees during the authorization application evaluation phase, review of post-authorization/registration studies on medicinal products and medical devices, and data transparency. © 2015 Société Française de Pharmacologie et de Thérapeutique.

[Necessity of applying pharmacovigilance in post-marketing safety monitoring of traditional Chinese medicine injections].

PubMed

Wang, Hai-Nan; Chen, Wen; Fu, Zheng; Du, Wen-min; He, Jia

2008-03-01

Traditional Chinese medicine (TCM) injection has become one of the hotspots in the new TCM research and development. The serious adverse drug reactions happened in clinical have arosed attention widely in the whole society. It's very urgent to monitor the post-marketing safety of TCM injections. This paper elucidated the pharmacovigilance's necessity in the post-marketing safety monitoring of TCM injections, basing on the reason of safety problem of TCM injections and the future developing trend of adverse drug reaction monitoring. Also, this paper introduced the rapid signal detection method of spontaneous reporting system database by data mining technology.

[Post-marketing drug safety-risk management plan(RMP)].

PubMed

Ezaki, Asami; Hori, Akiko

2013-03-01

The Guidance for Risk Management Plan(RMP)was released by the Ministry of Health, Labour and Welfare in April 2012. The RMP consists of safety specifications, pharmacovigilance plans and risk minimization action plans. In this paper, we outline post-marketing drug safety operations in PMDA and the RMP, with examples of some anticancer drugs.

Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study.

PubMed

Necchi, A; Joseph, R W; Loriot, Y; Hoffman-Censits, J; Perez-Gracia, J L; Petrylak, D P; Derleth, C L; Tayama, D; Zhu, Q; Ding, B; Kaiser, C; Rosenberg, J E

2017-12-01

Conventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients. Patients were treated with atezolizumab 1200 mg i.v. every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively. In total, 220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% versus 31.3%), less likely to have had baseline liver metastases (27.0% versus 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% versus 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure-adjusted adverse event frequencies were generally similar before and following progression. In this single-arm study, patients who continued atezolizumab beyond RECIST v1.1 progression derived prolonged clinical benefit without additional safety signals. Identification of patients most likely to benefit from atezolizumab beyond progression remains an important challenge in the management of metastatic urothelial carcinoma. NCT02108652. © 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.

The effects of pre-slaughter restraint (for the purpose of cattle identification) on post-slaughter responses and carcass quality following the electrical stun/killing of cattle in a Jarvis Beef stunner.

PubMed

Mpamhanga, C J; Wotton, S B

2015-09-01

This study compared normal post-Jarvis stun/kill responses and carcass quality with those occurring when crush restraint was not used during pre-slaughter. The carcasses of 1065 cattle slaughtered during one week at a commercial abattoir were evaluated for quality. The post-stun/kill responses of 788 of these animals were also assessed. An additional study of data from the carcasses of 6061 cattle was further evaluated for quality findings. A significant reduction in post-stun/kill limb movement, muscle tone and the expression of brainstem functions was recorded when restraint was not used. Abolishing crush restraint pre-slaughter also produced a significant reduction in the incidence of blood splash. In addition, the study also showed that animal identification post-slaughter could be successfully implemented with no negative consequences to food safety or traceability. It is suggested that abolishing the use of pre-slaughter crush restraint of cattle would enhance animal welfare and operator safety in plants whether electrical, or mechanical stunning was employed. Copyright © 2015. Published by Elsevier Ltd.

A study of medical device regulation management model in Asia.

PubMed

Wu, Yi-Hui; Li, Fong-An; Fan, Yin-Ting; Tu, Pei-Weng

2016-06-01

With the aging of the post-war baby boomer generation, the increasing demands for healthcare are driving the growth of medical industry and development of new products in order to meet the immense needs from the aging population. However, medical devices are designed to maintain the health and safety of people, therefore, medical devices are undergoing rigorous management by competent health authorities in all countries. In recent years, Asian countries have been reforming their regulations and standards for medical devices with substantial changes. The study is a summary of the framework of medical device regulations in Asian countries, including Asian Harmonization Working Party (AHWP), Japan, China, Taiwan, South Korea, India and Singapore. Expert commentary: Asian countries are constantly reforming their medical device regulations. The emergence of brand-new technology and quality management issues arose by global manufacturing have imposed difficulties in harmonizing and reaching consensus between countries. The third-party conformity assessment system for medical devices can reduce the costs for competent health authorities and shorten the review time, which could facilitate the feasibility of harmonization of medical device regulations.

A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers.

PubMed

Agarwal, Suresh K; Kriel, Robert L; Cloyd, James C; Coles, Lisa D; Scherkenbach, Lisa A; Tobin, Michael H; Krach, Linda E

2015-01-01

Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P = .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three- and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures. © The Author(s) 2014.

Midwest guardrail system (MGS) with an omitted post.

DOT National Transportation Integrated Search

2016-02-22

The objective of this research study was to evaluate the MGS (31 tall W-beam guardrail) with an omitted post according to the safety performance criteria provided in MASH. A single full-scale crash test was conducted with the 2270P pickup truck in...

Evolution of safety-critical requirements post-launch

NASA Technical Reports Server (NTRS)

Lutz, R. R.; Mikulski, I. C.

2001-01-01

This paper reports the results of a small study of requirements changes to the onboard software of three spacecraft subsequent to launch. Only those requirement changes that resulted from post-launch anoma-lies (i.e., during operations) were of interest here, since the goal was to better understand the relation-ship between critical anomalies during operations and how safety-critical requirements evolve. The results of the study were surprising in that anomaly-driven, post-launch requirements changes were rarely due to previous requirements having been incorrect. Instead, changes involved new requirements (1) for the software to handle rare events or (2) for the software to compensate for hardware failures or limitations. The prevalence of new requirements as a result of post-launch anomalies suggests a need for increased requirements-engineering support of maintenance activities in these systems. The results also confirm both the difficulty and the benefits of pursuing requirements completeness, especially in terms of fault tolerance, during development of critical systems.

Erratum.

PubMed

2015-04-01

In issue 21.1 three of the DOIs were printed incorrectly, please see below for the correct information. Andrea Giorgianni, et al. Flow-diverter stenting of post-traumatic bilateral anterior cerebral artery pseudoaneurysm: A case report. Doi: 10.15274/INR-2014-10059 Correct: Doi: 10.1177/1591019915575441 Lee-Anne Slater, et al. Effect of flow diversion with silk on aneurysm size: A single center experience. Doi: 10.15274/INR-2014-10062 Correct DOI: 10.1177/1591019915576433 Robert J McDonald, et al. Periprocedural safety of Pipeline therapy for unruptured cerebral aneurysms: Analysis of 279 Patients in a multihospital database. Doi: 10.15274/INR-2014-10074 Correct DOI: 10.1177/1591019915576289. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Rutosides for prevention of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2013-04-30

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9). Clinical trials databases were searched for details of ongoing and unpublished studies. We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. Two authors independently assessed studies for inclusion and intended to extract information from the trials. No studies were identified comparing rutosides versus any alternative in the prevention of PTS. As there were no studies identified in this review it is not possible to support the use of rutosides in the prevention of PTS. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.

76 FR 53102 - Federal Motor Vehicle Safety Standards; Denial of Petition for Rulemaking; School Buses

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-25

... chronological order): Studies NTSB, 1987 In 1987, the NTSB reported on its investigation of forty-three post... seat belts by using the sled test data obtained from NHTSA's 2002 school bus safety study. For... incorporate test procedures to test lap/shoulder belts in small school buses and voluntarily-installed lap...

Fatal occupational accidents in Danish fishing vessels 1989-2005.

PubMed

Laursen, Lise H; Hansen, Henrik L; Jensen, Olaf C

2008-06-01

The purpose of the study was to study the circumstances and incidence rates of fatal accidents in inspection obligated and non-inspection obligated Danish fishing vessels to identify areas for prevention. Information about the fatalities came from maritime authority reports, including vessel disaster reports, post mortem reports, maritime inquiries and police reports. The person- and vessel years at risk came from the Danish Directorate of Fisheries. During the period 1989-2005, 114 fatalities occurred. Sixty-one of the fatalities occurred in 36 vessel disasters mainly caused by foundering/capsizing due to stability changes in rough weather and collisions; 39 fatal occupational accidents mainly occurred on the larger inspection obligated trawlers during fishing. In the remaining 14 other fatal accidents, the main causal factors were difficult embarking/disembarking conditions by darkness in foreign ports and alcohol intoxication. In the period 1995-2005, the overall incidence rate was 10 per 10,000 fishermen per year with no down-going trend during that period. The fatal accident rates are still too high, despite the efforts to reduce the risk. Increased focus on regular and repeated safety training for all fishermen and improved safety measures are needed, especially in the underscored areas of sea disasters concerning small vessels and occupational accidents on big vessels. Better registration of time at risk for fishermen is needed to validate the effect of the safety measures.

Prevention of Targeted School Violence by Responding to Students' Psychosocial Crises: The NETWASS Program.

PubMed

Leuschner, Vincenz; Fiedler, Nora; Schultze, Martin; Ahlig, Nadine; Göbel, Kristin; Sommer, Friederike; Scholl, Johanna; Cornell, Dewey; Scheithauer, Herbert

2017-01-01

The standardized, indicated school-based prevention program "Networks Against School Shootings" combines a threat assessment approach with a general model of prevention of emergency situations in schools through early intervention in student psychosocial crises and training teachers to recognize warning signs of targeted school violence. An evaluation study in 98 German schools with 3,473 school staff participants (M age  = 46.2 years) used a quasi-experimental comparison group design with three measurement points (pre, post, and 7 months followup) with schools randomly allocated to implementation conditions. The study found increases in teachers' expertise and evaluation skills, enhanced abilities to identify students experiencing a psychosocial crisis, and positive secondary effects (e.g., teacher-student interaction, feelings of safety). © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Changes in safety climate and teamwork in the operating room after implementation of a revised WHO checklist: a prospective interventional study.

PubMed

Erestam, Sofia; Haglind, Eva; Bock, David; Andersson, Annette Erichsen; Angenete, Eva

2017-01-01

Inter-professional teamwork in the operating room is important for patient safety. The World Health Organization (WHO) checklist was introduced to improve intraoperative teamwork. The aim of this study was to evaluate the safety climate in a Swedish operating room setting before and after an intervention, using a revised version of the WHO checklist to improve teamwork. This study is a single center prospective interventional study. Participants were personnel working in operating room teams including surgeons, anesthesiologists, scrub nurses, nurse anaesthetists and nurse assistants. The study started with pre-interventional observations of the WHO checklist use followed by education on safety climate, the WHO checklist, and non-technical skills in the operating room. Thereafter a revised version of the WHO checklist was introduced. Post-interventional observations regarding the performance of the WHO checklist were carried out. The Safety Attitude Questionnaire was used to assess safety climate at baseline and post-intervention. At baseline we discovered a need for improved teamwork and communication. The participants considered teamwork to be important for patient safety, but had different perceptions of good teamwork between professions. The intervention, a revised version of the WHO checklist, did not affect teamwork climate. Adherence to the revision of the checklist was insufficient, dominated by a lack of structure. There was no significant change in teamwork climate by use of the revised WHO checklist, which may be due to insufficient implementation, as a lack of adherence to the WHO checklist was detected. We found deficiencies in teamwork and communication. Further studies exploring how to improve safety climate are needed. NCT02329691.

Promotion of safety culture in Italian schools: effectiveness of interventions on student injuries.

PubMed

Bena, Antonella; Farina, Elena; Orengia, Manuela; Quarta, Denis

2016-08-01

Numerous safety promotion interventions in schools exist but these are rarely subject to impact evaluation. Few available studies are focused on intermediate outcomes. Our objective is to evaluate the impact of prevention interventions on school injuries in a number of schools in Italy. A pre-post-study with a control group was used. One hundred and three intervention units were selected; control units were selected randomly from those which did not implement safety projects. The general objective was to promote a safety culture by increasing expertise and knowledge, and by enabling the adoption of appropriate behavior. All projects combined various elements: training and educational, information and communication, as well as organizational. The projects evaluated in this article were specifically aimed at safety in indoor premises; they were implemented in 2009-10. Injury rates standardized by gender were calculated for 5 school years (from 2007/2008 to 2011/2012) stratified by type of school and place of occurrence. To assess the effectiveness the difference-in-differences method was used. Overall, 207 012 student-years and 2918 school injuries were considered. In all types of schools, the injury rates in indoor areas show a decreasing trend in the intervention units and an increasing trend in the control units. In high schools, there were no changes in the trend of injuries occurring in the gym and/or related to sports activities. The results suggest a positive short-term effect of the programs on injuries occurring in indoor premises. The quasi-experimental design has never been previously used to evaluate the effectiveness of a prevention program in schools. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Effect of safety education on knowledge of and compliance with road safety signs among commercial motorcyclists in Uyo, Southern Nigeria.

PubMed

Johnson, O E; Adebayo, A M

2011-09-01

Compliance with road safety signs is important in the reduction of motorcycle accidents. The aim of this study was to implement health education intervention and assess its impact on the knowledge of and compliance with road safety signs among commercial motorcyclists in Uyo, Southern Nigeria. This was an intervention study among motorcyclists in Uyo, Southern Nigeria, with a control group from a similar town. The instrument of data collection was a semi-structured interviewer administered questionnaire. Subjects were selected through multistage sampling method. Baseline data on compliance to road safety signs was collected from both groups. Motorcyclists in the intervention group were given education on the importance of compliance to road safety signs. Data was subsequently collected from both groups 3 months post intervention and analysed using the Statistical Package for the Social Sciences version 11. A total of 200 respondents participated in the study, 100 from each group. Following intervention, respondents with good knowledge score increased from 21% at baseline to 82% at 3 months post intervention in the intervention group (p<0.05) and from 19% to 21% in the control group. Compliance score in the intervention group increased from 15% to 70% (p<0.05) and from 12% to 18% in the control group. A significant increase in compliance to road safety signs was recorded among motorcyclists in the intervention group after safety education. All motorcyclists should therefore be given education on road safety signs as this will improve compliance and lead to safer road use among them.

Training in Post-authorization Pharmacovigilance.

PubMed

Ahuja, Vivek; Sharma, Varun

2010-04-01

Post-authorization pharmacovigilance refers to all the activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems, from the time a product gets the authorization to be marketed in a territory. The ultimate objective of pharmacovigilance is patient safety. To ensure this, any responsible pharmaceutical company will readily vouch for the importance of all these activities, each requiring specific training for efficient and effective execution. Having a well planned job specific training curriculum can help the organization realize its goals and objectives by covering the gaps between current and desired job performance levels and existing competencies of its employees. Apart from this, trainings can help in problem solving, increasing productivity and prepare for and respond to future changes in the organization or job duties. As the pharmaceutical business continues to grow, increasing numbers of skilled people are required to manage resultant increase in pharmacovigilance activities to remain compliant. Thus, the need for training qualified resources to develop into highly skilled pharmacovigilance professionals is the need of the hour. Currently, the supply-demand situation for skilled manpower is highly skewed in favor of the demand, as this field is relatively new in India and elsewhere. It is interesting to note that not many resources, be it internet, literature or books, are available specifically addressing the need of the industry to guide them on training requirements to set up and maintain a competent pharmacovigilance department. This article aims to present a comprehensive perspective on the trainings required in the post authorization scenario pertaining to pharmacovigilance activities and suggest ways to manage these in an efficient way so as to be compliant with the global norms and best practices.

Training in Post-authorization Pharmacovigilance

PubMed Central

Ahuja, Vivek; Sharma, Varun

2010-01-01

Post-authorization pharmacovigilance refers to all the activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems, from the time a product gets the authorization to be marketed in a territory. The ultimate objective of pharmacovigilance is patient safety. To ensure this, any responsible pharmaceutical company will readily vouch for the importance of all these activities, each requiring specific training for efficient and effective execution. Having a well planned job specific training curriculum can help the organization realize its goals and objectives by covering the gaps between current and desired job performance levels and existing competencies of its employees. Apart from this, trainings can help in problem solving, increasing productivity and prepare for and respond to future changes in the organization or job duties. As the pharmaceutical business continues to grow, increasing numbers of skilled people are required to manage resultant increase in pharmacovigilance activities to remain compliant. Thus, the need for training qualified resources to develop into highly skilled pharmacovigilance professionals is the need of the hour. Currently, the supply-demand situation for skilled manpower is highly skewed in favor of the demand, as this field is relatively new in India and elsewhere. It is interesting to note that not many resources, be it internet, literature or books, are available specifically addressing the need of the industry to guide them on training requirements to set up and maintain a competent pharmacovigilance department. This article aims to present a comprehensive perspective on the trainings required in the post authorization scenario pertaining to pharmacovigilance activities and suggest ways to manage these in an efficient way so as to be compliant with the global norms and best practices. PMID:21829787

Non-invasive fat reduction of the flanks using a new cryolipolysis applicator and overlapping, two-cycle treatments

PubMed Central

Bernstein, Eric F; Bloom, Jason D; Basilavecchio, Lisa D; Plugis, Jessica M

2014-01-01

Background and Objectives A sharply contoured cryolipolysis vacuum applicator was developed to improve fit and tissue draw in the abdomen and flanks to better accommodate a range of body types and a variety of treatment sites. This study was carried out to evaluate the safety and efficacy of the new applicator for treatment of flank fat (“love handles”). Study Design/Materials and Methods A cryolipolysis vacuum applicator with a sharply contoured cup and curved cooling plates was used to treat 20 flanks. Two treatment cycles were delivered sequentially to each flank (60-minute cycle at a Cooling Intensity Factor of 41.6). Efficacy was evaluated 12 weeks post-treatment by physicians performing blinded, independent review of clinical photographs. Safety was assessed by the treating physician monitoring subjects for side effects and adverse events. Results Four blinded, independent physician reviewers properly identified the pre- and post-treatment photographs 94.4% of the time. Improvement was scored from 0 (none) to 10 (complete) and showed an average 4.3 point (43%) improvement. Side-effects were limited to erythema, edema, bruising, and numbness or tingling at the treatment site, and resolved without treatment. Conclusions Multiple treatment cycles from a new improved-fit cryolipolysis applicator are safe and effective for reduction of flank fat bulges. A high degree of improvement was reported by blinded, physician evaluation of standardized photographs. Laser Surg. Med. 46:731–735, 2014. © 2014 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc. PMID:25395266

Hospital employee assault rates before and after enactment of the california hospital safety and security act.

PubMed

Casteel, Carri; Peek-Asa, Corinne; Nocera, Maryalice; Smith, Jamie B; Blando, James; Goldmacher, Suzi; O'Hagan, Emily; Valiante, David; Harrison, Robert

2009-02-01

This study examines changes in violent event rates to hospital employees before and after enactment of the California Hospital Safety and Security Act in 1995. We compared pre- and post-initiative employee assault rates in California (n = 116) emergency departments and psychiatric units with those in New Jersey (n = 50), where statewide workplace violence initiatives do not exist. Poisson regression with generalized estimating equations was used to compare assault rates between a 3-year pre-enactment period (1993-1995) and a 6-year post-enactment period (1996-2001) using New Jersey hospitals as a temporal control. Assault rates among emergency department employees decreased 48% in California post-enactment, compared with emergency department employee assault rates in New Jersey (rate ratio [RR] = 0.52, 95% confidence interval [CI]: 0.31, 0.90). Emergency department employee assault rates decreased in smaller facilities (RR = 0.46, 95% CI: 0.21, 0.96) and for-profit-controlled hospitals (RR = 0.39, 95% CI: 0.19, 0.79) post-enactment. Among psychiatric units, for-profit-controlled hospitals (RR = 0.41, 95% CI: 0.19, 0.85) and hospitals located in smaller communities (RR = 0.44, 95% CI: 0.21, 0.92) experienced decreased assault rates post-enactment. Policy may be an effective method to increase safety to health care workers.

Post-Disaster Safety Net: Instituting Leadership, Economic and Technological Arrangements

ERIC Educational Resources Information Center

Akaiso, Darlington

2013-01-01

This dissertation will present the findings of an in-depth study conducted on flood victims in Bangkok, Thailand. The objective of this study is to explore the feasibility of using modern technologies as a post-crisis remediation strategy to reconnect displaced families in the aftermath of a disaster. This will include investigating which modern…

A big data approach to the concordance of the toxicity of pharmaceuticals in animals and humans.

PubMed

Clark, Matthew; Steger-Hartmann, Thomas

2018-07-01

Although lack of efficacy is an important cause of late stage attrition in drug development the shortcomings in the translation of toxicities observed during the preclinical development to observations in clinical trials or post-approval is an ongoing topic of research. The concordance between preclinical and clinical safety observations has been analyzed only on relatively small data sets, mostly over short time periods of drug approvals. We therefore explored the feasibility of a big-data analysis on a set of 3,290 approved drugs and formulations for which 1,637,449 adverse events were reported for both humans animal species in regulatory submissions over a period of more than 70 years. The events reported in five species - rat, dog, mouse, rabbit, and cynomolgus monkey - were treated as diagnostic tests for human events and the diagnostic power was computed for each event/species pair using likelihood ratios. The animal-human translation of many key observations is confirmed as being predictive, such as QT prolongation and arrhythmias in dog. Our study confirmed the general predictivity of animal safety observations for humans, but also identified issues of such automated analyses which are on the one hand related to data curation and controlled vocabularies, on the other hand to methodological changes over the course of time. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

French policy for managing the post-accident phase of a nuclear accident.

PubMed

Gallay, F; Godet, J L; Niel, J C

2015-06-01

In 2005, at the request of the French Government, the Nuclear Safety Authority (ASN) established a Steering Committee for the Management of the Post-Accident Phase of a Nuclear Accident or a Radiological Emergency, with the objective of establishing a policy framework. Under the supervision of ASN, this Committee, involving several tens of experts from different backgrounds (e.g. relevant ministerial offices, expert agencies, local information commissions around nuclear installations, non-governmental organisations, elected officials, licensees, and international experts), developed a number of recommendations over a 7-year period. First published in November 2012, these recommendations cover the immediate post-emergency situation, and the transition and longer-term periods of the post-accident phase in the case of medium-scale nuclear accidents causing short-term radioactive release (less than 24 h) that might occur at French nuclear facilities. They also apply to actions to be undertaken in the event of accidents during the transportation of radioactive materials. These recommendations are an important first step in preparation for the management of a post-accident situation in France in the case of a nuclear accident. © The Chartered Institution of Building Services Engineers 2014.

A next-generation, serum-free, highly purified Vero cell rabies vaccine is safe and as immunogenic as the reference vaccine Verorab® when administered according to a post-exposure regimen in healthy children and adults in China.

PubMed

Li, Rongcheng; Huang, Lirong; Li, Jia; Mo, Zhaojun; He, Bin; Wang, Yunpeng; Wu, Xiaohong; Minutello, Maria; Guinet-Morlot, Françoise; Pichon, Sylvie

2013-12-05

As an evolution of its currently licensed rabies vaccine Verorab(®), Sanofi Pasteur has developed a next-generation, serum-free, highly purified Vero rabies vaccine (PVRV-NG). Through this Phase III clinical trial, we aimed to demonstrate the non-inferiority of PVRV-NG over Verorab when administered according to a post-exposure regimen and to assess its clinical safety. A total of 816 healthy subjects aged ≥10 years were randomized according to a 2:1 ratio to receive PVRV-NG or Verorab. Half of the subjects were aged 10-17 years, the other half were aged ≥18 years. All subjects were to receive 5 injections on days 0, 3, 7, 14 and 28. Three blood samples were taken for rabies virus neutralizing antibodies (RVNA) assessment, at baseline, on day 14 and day 42. Solicited adverse reactions (between injections 1, 2 and 3, and within 7 days post-injections 4 and 5) and adverse events (up to 28 days after the last injection) were collected for clinical safety assessment; serious adverse events were reported up to 6-months after the last injection. The proportion of subjects with an RVNA titer ≥0.5 IU/mL after the third injection of PVRV-NG was non-inferior to the proportion of those who received Verorab. PVRV-NG was shown to be as immunogenic as Verorab in each age range in the per-protocol and full analysis sets. PVRV-NG induced a strong immune response in both age ranges, with high RVNA levels and increased geometric mean titers compared to baseline after each measured time point. PVRV-NG had a satisfactory safety profile after each injection, similar to Verorab with regards to the nature, frequency, duration and severity of adverse events. Two serious adverse events were reported, none was related to vaccination. This trial demonstrated the immunogenic non-inferiority of PVRV-NG over Verorab and showed that both vaccines have similar safety profiles. This trial is registered at ClinicalTrials.gov (NCT01339312). This manuscript is the first full report of the study. An abstract of the study results was previously presented at the Rabies in the Americas (RITA) conference in October 2012 in São Paulo, Brazil. Sanofi Pasteur. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of safety issues with HIV drugs on the approval process of other drugs in the same class: an analysis of European Public Assessment Reports.

PubMed

Arnardottir, Arna H; Haaijer-Ruskamp, Flora M; Straus, Sabine M J; de Graeff, Pieter A; Mol, Peter G M

2011-11-01

Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required ≥1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval. The aim was to evaluate the extent to which regulators and industry have addressed the risk of safety issues for HIV drugs based on prior experience with other drugs in the same class and whether doing so impacts development time of these drugs. HIV drugs receiving ≥1 DHPC in the Netherlands between January 1999 and December 2008 were identified. Each drug with a DHPC ('index' drug) was paired with subsequently approved HIV drug(s) in the same class (Anatomical Therapeutic Chemical [ATC] 4th level) ['follow-on' drugs]. Characteristics of safety issues were extracted from the DHPCs of the 'index' drugs. European Public Assessment Reports (EPARs) were reviewed regarding whether the safety issues had been considered during development and approval. Consideration of previously identified safety issues in 'follow-on' drug applications was assessed regarding attention paid to adverse drug reaction (ADR) symptoms in pre-marketing studies, Summary of Product Characteristics (SmPC) and postmarketing commitments, and whether size of the safety population was in accordance with Regulatory guidelines. 'Index' drugs were also paired with drugs in the same class already on the market ('older' drugs). For 'older' drugs, we identified whether the safety issue led to appropriate changes in the current SmPC (January 2011) compared with the SmPC at the time of marketing authorization. Clinical development time was assessed using time from first patent application to market authorization as proxy, and comparison was made between 'index' and 'follow-on' drugs. For 9 (43%) of the 21 centrally authorized HIV drugs, 11 serious safety issues that required a DHPC were identified. Two drugs were excluded from our analysis (DHPCs related to contamination/medication error). Six 'index' drugs were paired, each with one to six 'follow-on' drugs. Three concerned drug-drug interactions (DDIs); the other three were intracranial haemorrhage, neuromuscular weakness and severe skin/hepatic reactions. All but one 'follow-on' drug had information in the EPAR on that specific ADR (i.e. attention was paid to the ADR). The DDIs were addressed in pre-marketing studies and/or the SmPC. Two of the other ADRs were addressed by postmarketing surveillance commitments; intracranial haemorrhage was not addressed. Three safety issues for two 'index' drugs could not be paired with a 'follow-on' drug as no drug in the same class was approved after the corresponding DHPCs were issued. Five of the nine safety issues were added to at least one of the current SmPCs for the 'older' drugs already on the market at the time of DHPC issue. Two safety issues were already in the SmPC of the 'older' drugs at time of market approval and two were not introduced into the SmPC of 'older' drugs. Population size to assess short-term safety complied with the guidelines for four 'index', seven 'follow-on' and three 'older' drugs; population size to assess long-term safety complied for one, three and two drugs, respectively. For five drugs, EPARs did not provide adequate information on population size. No statistically significant difference in development time between 'index' and 'follow-on' drugs was found. Generally, safety issues were taken into account in the approval process of other drugs in the class. The approaches were different and determined by the nature of the ADR. Taking safety issues into account in the approval process did not seem to impact on the time taken to perform the pre-approval clinical programme.

The effectiveness of insurer-supported safety and health engineering controls in reducing workers' compensation claims and costs.

PubMed

Wurzelbacher, Steven J; Bertke, Stephen J; Lampl, Michael P; Bushnell, P Timothy; Meyers, Alysha R; Robins, David C; Al-Tarawneh, Ibraheem S

2014-12-01

This study evaluated the effectiveness of a program in which a workers' compensation (WC) insurer provided matching funds to insured employers to implement safety/health engineering controls. Pre- and post-intervention WC metrics were compiled for the employees designated as affected by the interventions within 468 employers for interventions occurring from 2003 to 2009. Poisson, two-part, and linear regression models with repeated measures were used to evaluate differences in pre- and post-data, controlling for time trends independent of the interventions. For affected employees, total WC claim frequency rates (both medical-only and lost-time claims) decreased 66%, lost-time WC claim frequency rates decreased 78%, WC paid cost per employee decreased 81%, and WC geometric mean paid claim cost decreased 30% post-intervention. Reductions varied by employer size, specific industry, and intervention type. The insurer-supported safety/health engineering control program was effective in reducing WC claims and costs for affected employees. © 2014 Wiley Periodicals, Inc.

[Results of a post-marketing surveillance of meropenem for febrile neutropenia].

PubMed

Wakisaka, Koji; Tani, Shunsuke; Ishibashi, Kazuo; Nukui, Kazuhiko; Nagao, Munehiko

2015-08-01

The post-marketing surveillance of meropenem (Meropen) for febrile neutropenia (FN) was conducted between July 2010 and June 2012 to evaluate safety and efficacy under actual clinical use. There were 1191 and 1124 evaluable cases for safety and efficacy respectively, of 1207 case cards collected from 180 institutions. In safety analysis, the incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 15.7% (187/1191 cases), and the main ADRs were alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, hepatic function abnormal, and liver disorder, which were similar to these observed in the clinical study for FN or post marketing surveillances of meropenem conducted before. In efficacy analysis, the overall efficacy was 81.8% (919/1124 cases). Also, it was 79.2% (708/894 cases) for hematological malignancy and 91.8% (213/232 cases) for solid cancer. These results confirmed meropenem (Meropen) is one of the well-tolerated and potent antimicrobial agents for febrile neutropenia.

Driving Intervention for Returning Combat Veterans.

PubMed

Classen, Sherrilene; Winter, Sandra; Monahan, Miriam; Yarney, Abraham; Link Lutz, Amanda; Platek, Kyle; Levy, Charles

2017-04-01

Increased crash incidence following deployment and veterans' reports of driving difficulty spurred traffic safety research for this population. We conducted an interim analysis on the efficacy of a simulator-based occupational therapy driving intervention (OT-DI) compared with traffic safety education (TSE) in a randomized controlled trial. During baseline and post-testing, OT-Driver Rehabilitation Specialists and one OT-Certified Driver Rehabilitation Specialist measured driving performance errors on a DriveSafety CDS-250 high-fidelity simulator. The intervention group ( n = 13) received three OT-DI sessions addressing driving errors and visual-search retraining. The control group ( n = 13) received three TSE sessions addressing personal factors and defensive driving. Based on Wilcoxon rank-sum analysis, the OT-DI group's errors were significantly reduced when comparing baseline with Post-Test 1 ( p < .0001) and comparing the OT-DI group with the TSE group at Post-Test 1 ( p = .01). These findings provide support for the efficacy of the OT-DI and set the stage for a future effectiveness study.

The Effectiveness of Insurer-Supported Safety and Health Engineering Controls in Reducing Workers’ Compensation Claims and Costs

PubMed Central

Wurzelbacher, Steven J.; Bertke, Stephen J.; Lampl, Michael P.; Bushnell, P. Timothy; Meyers, Alysha R.; Robins, David C.; Al-Tarawneh, Ibraheem S.

2015-01-01

Background This study evaluated the effectiveness of a program in which a workers’ compensation (WC) insurer provided matching funds to insured employers to implement safety/health engineering controls. Methods Pre- and post-intervention WC metrics were compiled for the employees designated as affected by the interventions within 468 employers for interventions occurring from 2003 to 2009. Poisson, two-part, and linear regression models with repeated measures were used to evaluate differences in pre- and post-data, controlling for time trends independent of the interventions. Results For affected employees, total WC claim frequency rates (both medical-only and lost-time claims) decreased 66%, lost-time WC claim frequency rates decreased 78%, WC paid cost per employee decreased 81%, and WC geometric mean paid claim cost decreased 30% post-intervention. Reductions varied by employer size, specific industry, and intervention type. Conclusions The insurer-supported safety/health engineering control program was effective in reducing WC claims and costs for affected employees. PMID:25223846

Note on evaluating safety performance of road infrastructure to motivate safety competition.

PubMed

Han, Sangjin

2016-01-01

Road infrastructures are usually developed and maintained by governments or public sectors. There is no competitor in the market of their jurisdiction. This monopolic feature discourages road authorities from improving the level of safety with proactive motivation. This study suggests how to apply a principle of competition for roads, in particular by means of performance evaluation. It first discusses why road infrastructure has been slow in safety oriented development and management in respect of its business model. Then it suggests some practical ways of how to promote road safety between road authorities, particularly by evaluating safety performance of road infrastructure. These are summarized as decision of safety performance indicators, classification of spatial boundaries, data collection, evaluation, and reporting. Some consideration points are also discussed to make safety performance evaluation on road infrastructure lead to better road safety management.

Low-molecular-weight heparin biosimilars: potential implications for clinical practice. Australian Low-Molecular-Weight Heparin Biosimilar Working Group (ALBW).

PubMed

Nandurkar, H; Chong, B; Salem, H; Gallus, A; Ferro, V; McKinnon, R

2014-05-01

A working group of clinicians and scientists was formed to review the clinical considerations for use of low-molecular-weight heparin (LMWH) biosimilars. LMWH are biological molecules of significant complexity; the full complexity of chemical structure is still to be elucidated. LMWH biosimilars are products that are biologically similar to their reference product and rely on clinical data from a reference product to establish safety and efficacy. The complex nature of LMWH molecules means that it is uncertain whether a LMWH biosimilar is chemically identical to its reference product; this introduces the possibility of differences in activity and immunogenicity. The challenge for regulators and clinicians is to evaluate the level of evidence required to demonstrate that a LMWH is sufficiently similar to the reference product. The consensus opinion of the working group is that prior to clinical use a LMWH biosimilar should have proven efficacy and safety, similar to the reference product with prospective studies, which should be confirmed with a proactive post-marketing pharmacovigilance programme. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Engaging staff to improve quality and safety in an austere medical environment: a case-control study in two Sierra Leonean hospitals.

PubMed

Rosen, Michael A; Chima, Adaora M; Sampson, John B; Jackson, Eric V; Koka, Rahul; Marx, Megan K; Kamara, Thaim B; Ogbuagu, Onyebuchi U; Lee, Benjamin H

2015-08-01

Inadequate observance of basic processes in patient care such as patient monitoring and documentation practices are potential impediments to the timely diagnoses and management of patients. These gaps exist in low resource settings such as Sierra Leone and can be attributed to a myriad of factors such as workforce and technology deficiencies. In the study site, only 12.4% of four critical vital signs were documented in the pre-intervention period. Implement a failure mode and effects analysis (FMEA) to improve documentation of four patient vital signs: temperature, blood pressure, pulse rate and respiratory rate. FMEA was implemented among a subpopulation of health workers who are involved in monitoring and documenting patient vital signs. Pre- and post-FMEA monitoring and documentation practice were compared with a control site. Participants identified a four-step process to monitoring and documenting vital signs, three categories of failure modes and four potential solutions. Based on 2100 patient days of documentation compliance data from 147 patients between July and November 2012, staff members at the study site were 1.79 times more likely to document all four patient vital signs in the post-implementation period (95% CI [1.35, 2.38]). FMEA is a feasible and effective strategy for improving quality and safety in an austere medical environment. Documentation compliance improved at the intervention facility. To evaluate the scalability and sustainability of this approach, programs targeting the development of these types of process improvement skills in local staff should be evaluated. © The Author 2015. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

76 FR 12213 - Agency Information Collection Activities; Extension of an Approved Information Collection Request...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

...: Household Goods Consumer Information Program Assessment Study AGENCY: Federal Motor Carrier Safety... Notice. Note that DOT posts all comments received without change to http://www.regulations.gov... your comments, please include a self-addressed, stamped envelope or post card or print the...

How Safe and Innovative Are First-in-Class Drugs Approved by Health Canada: A Cohort Study

PubMed Central

2016-01-01

Introduction: First-in-class drugs use a unique mechanism of action. This study assessed the therapeutic innovativeness and safety of these drugs approved by Health Canada from 1997–2012. Methods: A list of new drugs was compiled and a database from the Food and Drug Administration was used to determine first-in-class status. Post-market safety warnings and drugs withdrawn for safety reasons were identified from the MedEffect Canada website. Therapeutic innovation evaluations came from the Patented Medicine Prices Review Board (PMPRB) and Prescrire International. The proportion of first-in-class drugs that were innovative was compared to the proportion of non-first-in-class drugs that were innovative. Kaplan–Meier survival curves assessed safety. Results: In all, 462 drugs were approved by Health Canada during the period under study. Among these, 345 were evaluated by PMPRB and/or Prescrire, and first-in-class data were available for 292. Ninety-eight of the 292 were first-in-class and 16 were innovative compared to 9 of 194 drugs that were not-first-in-class. There was no difference in safety between the two groups. Discussion: Overall, the benefit-to-harm ratio of first-in-class drugs, as measured by post-market safety warnings/withdrawals, is better than those that were not-first-in-class. PMID:28032825

Promoting young children's interpersonal safety knowledge, intentions, confidence, and protective behavior skills: Outcomes of a randomized controlled trial.

PubMed

White, Codi; Shanley, Dianne C; Zimmer-Gembeck, Melanie J; Walsh, Kerryann; Hawkins, Russell; Lines, Katrina; Webb, Haley

2018-06-11

Promoting young children's interpersonal safety knowledge, intentions confidence and skills is the goal of many child maltreatment prevention programs; however, evaluation of their effectiveness has been limited. In this study, a randomized controlled trial was conducted examining the effectiveness of the Australian protective behaviors program, Learn to be safe with Emmy and friends™ compared to a waitlist condition. In total, 611 Australian children in Grade 1 (5-7 years; 50% male) participated, with assessments at Pre-intervention, Post-intervention and a 6-month follow-up. This study also included a novel assessment of interpersonal safety skills through the Observed Protective Behaviors Test (OPBT). Analyses showed participating in Learn to be safe with Emmy and friends™ was effective post-program in improving interpersonal safety knowledge (child and parent-rated) and parent-rated interpersonal safety skills. These benefits were retained at the 6-month follow-up, with participating children also reporting increased disclosure confidence. However, Learn to be safe with Emmy and friends™ participation did not significantly impact children's disclosure intentions, safety identification skills, or interpersonal safety skills as measured by the OPBT. Future research may seek to evaluate the effect of further parent and teacher integration into training methods and increased use of behavioral rehearsal and modelling to more effectively target specific disclosure intentions and skills. Copyright © 2018 Elsevier Ltd. All rights reserved.

Improving multiple sclerosis management and collecting safety information in the real world: the MSDS3D software approach.

PubMed

Haase, Rocco; Wunderlich, Maria; Dillenseger, Anja; Kern, Raimar; Akgün, Katja; Ziemssen, Tjalf

2018-04-01

For safety evaluation, randomized controlled trials (RCTs) are not fully able to identify rare adverse events. The richest source of safety data lies in the post-marketing phase. Real-world evidence (RWE) and observational studies are becoming increasingly popular because they reflect usefulness of drugs in real life and have the ability to discover uncommon or rare adverse drug reactions. Areas covered: Adding the documentation of psychological symptoms and other medical disciplines, the necessity for a complex documentation becomes apparent. The collection of high-quality data sets in clinical practice requires the use of special documentation software as the quality of data in RWE studies can be an issue in contrast to the data obtained from RCTs. The MSDS3D software combines documentation of patient data with patient management of patients with multiple sclerosis. Following a continuous development over several treatment-specific modules, we improved and expanded the realization of safety management in MSDS3D with regard to the characteristics of different treatments and populations. Expert opinion: eHealth-enhanced post-authorisation safety study may complete the fundamental quest of RWE for individually improved treatment decisions and balanced therapeutic risk assessment. MSDS3D is carefully designed to contribute to every single objective in this process.

Effectiveness and Safety of Hyaluronic Acid Gel with Lidocaine for the Treatment of Nasolabial Folds: A Systematic Review and Meta-analysis.

PubMed

Wang, Chenglong; Luan, Sisi; Panayi, Adriana C; Xin, Minqiang; Mi, Bobin; Luan, Jie

2018-05-08

Hyaluronic acid (HA) gel is a widely used dermal filler for the correction facial volume loss. The incorporation of lidocaine with HA provides a pain-relieving alternative for individuals considering facial rejuvenation. The aim of this systematic review and meta-analysis is to compare the effectiveness and safety of HA with lidocaine (HAL) with that of HA without lidocaine for the treatment of nasolabial folds (NLFs). Studies were identified using the electronic databases PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science from inception up to January 2018. Randomized controlled trials (RCTs) were selected based on the inclusion criteria. Outcomes included 100-mm Visual Analogue Scale (VAS) score, Wrinkle Severity Rating Scale score and adverse events. A total of 908 patients from 12 RCTs were included in the meta-analysis. VAS score within 30 min after injection in the HAL group was much lower than that with just HA group (MD = - 28.83, 95% CI - 36.38 to - 21.28). There was no significant difference in effectiveness between the two products 24 months post-injection (MD = 0.13, 95% CI - 0.15 to 0.41). The main adverse events, such as swelling, erythema, bruising, itching and induration, also showed no significant difference. HAL is more effective for pain relief than HA alone, but both display similar effectiveness and safety for the correction of NLFs. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Can social media data lead to earlier detection of drug-related adverse events?

PubMed

Duh, Mei Sheng; Cremieux, Pierre; Audenrode, Marc Van; Vekeman, Francis; Karner, Paul; Zhang, Haimin; Greenberg, Paul

2016-12-01

To compare the patient characteristics and the inter-temporal reporting patterns of adverse events (AEs) for atorvastatin (Lipitor ® ) and sibutramine (Meridia ® ) in social media (AskaPatient.com) versus the FDA Adverse Event Reporting System (FAERS). We identified clinically important AEs associated with atorvastatin (muscle pain) and sibutramine (cardiovascular AEs), compared their patterns in social media postings versus FAERS and used Granger causality tests to assess whether social media postings were useful in forecasting FAERS reports. We analyzed 998 and 270 social media postings between 2001 and 2014, 69 003 and 7383 FAERS reports between 1997 and 2014 for atorvastatin and sibutramine, respectively. Social media reporters were younger (atorvastatin: 53.9 vs. 64.0 years, p < 0.001; sibutramine: 36.8 vs. 43.8 years, p < 0.001). Social media reviews contained fewer serious AEs (atorvastatin, pain: 2.5% vs. 38.2%; sibutramine, cardiovascular issues: 7.9% vs. 63.0%; p < 0.001 for both) and concentrated on fewer types of AEs (proportion comprising the top 20 AEs: atorvastatin, 88.7% vs. 55.4%; sibutramine, 86.3% vs. 65.4%) compared with FAERS. While social media sibutramine reviews mentioning cardiac issues helped predict those in FAERS 11 months later (p < 0.001), social media atorvastatin reviews did not help predict FAERS reports. Social media AE reporters were younger and focused on less-serious and fewer types of AEs than FAERS reporters. The potential for social media to provide earlier indications of AEs compared with FAERS is uncertain. Our findings highlight some of the promises and limitations of online social media versus conventional pharmacovigilance sources and the need for careful interpretation of the results. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Safety and efficacy of intensive intraoperative glycaemic control in cardiopulmonary bypass surgery: a randomised trial.

PubMed

Rujirojindakul, P; Liabsuetrakul, T; McNeil, E; Chanchayanon, T; Wasinwong, W; Oofuvong, M; Rergkliang, C; Chittithavorn, V

2014-05-01

This study aimed to determine the safety and efficacy of intraoperative intensive glycaemic treatment with modified glucose-insulin-potassium solution by hyperinsulinemic normoglycaemic clamp in cardiopulmonary bypass surgery patients. We hypothesised that the treatment would reduce infection rates in this group of patients. A prospective, randomised, double-blind trial was conducted in cardiopulmonary bypass surgery patients. A total of 199 adult patients (out of a planned 400) were randomly allocated to intensive or conventional treatment with target glucose levels of 4.4-8.3 mmol/l and < 13.8 mmol/l, respectively. The primary outcomes were clinical infection and cytokine levels, including interleukin (IL)-6 and IL-10. The secondary outcomes were morbidity and mortality. The study was terminated early because of safety concerns (hypoglycaemia). The clinical post-operative infection rate was 17% in the intensive group and 13% in the conventional group (P = 0.53). The proportion of patients with hypoglycaemia was significantly higher in the intensive group (23%) compared with the conventional group (3%) (P < 0.001). Morbidity and mortality rates were similar for both groups. Anaesthetic duration > 2 h (vs. ≤ 2 h), pre-operative IL-6 level > 15 pg/ml (vs. ≤ 15 pg/ml) and post-operative IL-6 level 56-110 pg/ml (vs. ≤ 55 pg/ml) were independent predictors for post-operative infection. Intraoperative intensive glycaemic treatment significantly increased the risk of hypoglycaemia, but its effect on post-operative infection by clinical assessment could not be determined. Anaesthetic duration, pre-operative and post-operative IL-6 levels can independently predict post-operative infection. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Is modified brief assertiveness training for nurses effective? A single-group study with long-term follow-up.

PubMed

Yoshinaga, Naoki; Nakamura, Yohei; Tanoue, Hiroki; MacLiam, Fionnula; Aoishi, Keiko; Shiraishi, Yuko

2018-01-01

To evaluate the long-term effectiveness of modified brief assertiveness training (with cognitive techniques) for nurses. Most assertiveness training takes a long time to conduct; thus, briefer training is required for universal on-the-job training in the workplace. In this single-group study, nurses received two 90-min training sessions with a 1-month interval between sessions. The degree of assertiveness was assessed by using the Rathus Assertiveness Schedule as the primary outcome, at four time points: pre- and post-training, 3-month follow-up and 6-month follow-up. A total of 33 nurses received the training, and the mean Rathus Assertiveness Schedule score improved from -14.2 (SD = 16.5) pre-training to -10.5 (SD = 18.0) post-training (p < .05). These improvements were maintained until the 6-month follow-up. The pre-post effect size of 0.22 (indicating small effect) was larger than the effect sizes ranging from -0.56 to 0.17 (no effect) reported in previous studies that used brief training. Modified brief assertiveness training seems feasible and may achieve long-term favourable outcomes in improving assertiveness among nurses. The ease of implementation of assertiveness training is important because creating an open environment for communication leads to improved job satisfaction, improved nursing care and increased patient safety. © 2017 The Authors. Journal of Nursing Management Published by John Wiley & Sons Ltd.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

PubMed

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-06-03

To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

A post-marketing safety and efficacy assessment of a monoclonal antibody purified high-purity factor VIII concentrate.

PubMed

Hay, C R; Lee, C A; Savidge, G

1996-01-01

The identification of infrequent side-effects of clotting factor concentrates, undetected by clinical trials, is facilitated by post-marketing surveillance. We present a post-marketing surveillance study in which 97 patients with haemophilia A, attending three haemophilia centres, were treated over a median follow-up period of 284 days (range 1-1074), and a total follow-up period of 30,080 days, with a pasteurized immunoaffinity purified factor VIII concentrate (Monoclate-P, Armour, Collegeville, USA). 5216 infusions, using 10,527,000 units of Monoclate-P, were carried out, mostly for routine haemarthroses or prophylaxis. No new inhibitors were observed during the study. At the start of the study 60/97 were HIV seropositive, 67/97 HBs antibody positive, 12 HbsAb negative and the remainder HBsAb positive before the study period. 13/14 tested were HAV seropositive at the beginning of the study. One patient became HAV seropositive during the study period, an infection thought to be community acquired. No other seroconversions were observed. Only one mild transfusion reaction was observed. This study confirms the safety and efficacy of Monoclate-P. Post-marketing surveillance or nationally organized pharmaco-vigilance should be practiced more widely to enable identification of low-frequency side-effects of treatment.

Post-marketing studies: the work of the Drug Safety Research Unit.

PubMed

Mackay, F J

1998-11-01

The Drug Safety Research Unit (DSRU) is the centre for prescription-event monitoring (PEM) in England. PEM studies are noninterventional observational cohort studies which monitor the safety of newly marketed drugs. The need for post-marketing surveillance is well recognised in the UK and general practice is an ideal source of data. PEM studies are general practitioner (community)-based and exposure is based on dispensed prescription data in England. To date, 65 PEM studies have been completed with a mean cohort size of 10 979 patients and the DSRU database has clinical information on over 700000 patients prescribed new drugs. Unlike spontaneous reporting schemes, PEM produces incidence rates for events reported during treatment. Comparative studies can be conducted for drugs in the same class. The DSRU aggregates outcome data for pregnancies exposed to new drugs. Data for children and the elderly can also be specifically examined. PEM data have a number of advantages over data from computerised general practice databases in the UK. PEM is the only technique within the UK capable of monitoring newly marketed drugs in such a comprehensive and systematic way.

[Post-authorization research, registries, and drug development].

PubMed

Patarnello, Francesca; Recchia, Giuseppe

2013-06-01

In the last decade regulators, payers and health care providers tried to react to three major problems in drug development and drug use in clinical practice: the pharmaceutical R&D productivity crisis, the immaturity of benefit-risk profile for several newly approved drugs and the overall impact on economic sustainability of reimbursing new high cost drugs in their systems. The potentiality of create a continuum between the evidence requirements relevant for registration, for reimbursement and for post authorization research is clear. All different parties involved, like regulators, HTA agencies, scientific communities and manufacturers, are working to improve the knowledge profile of new drugs in order to anticipate the patient access to innovation, limiting or preventing the clinical and economical risks deriving from an incomplete safety and effectiveness profile. The Italian example of "New Drugs AIFA Registries", with or without the application of risk sharing schemes (cost sharing, pay for performance, etc.), introduced a new process and increased the sensitivity on this topic. However this might probably represents only a partial answer to the problem of how to set up the governance of coverage with evidence, drug utilization monitoring, comparative effectiveness research, outcome research programs and may be how to link them to access, pricing and reimbursement. The step change in post authorization research could be to "integrate" different sources and stakeholders in a wider and continuous approach, in a well designed and inclusive "second generation" HTA approach, where all resources (competencies, data, funding) will concur to increase the evidence profile and reduce the risks, and where any "evidence generation approach" is really compliant with the standard and rules of best research practices.

Prediction of black box warning by mining patterns of Convergent Focus Shift in clinical trial study populations using linked public data.

PubMed

Ma, Handong; Weng, Chunhua

2016-04-01

To link public data resources for predicting post-marketing drug safety label changes by analyzing the Convergent Focus Shift patterns among drug testing trials. We identified 256 top-selling prescription drugs between 2003 and 2013 and divided them into 83 BBW drugs (drugs with at least one black box warning label) and 173 ROBUST drugs (drugs without any black box warning label) based on their FDA black box warning (BBW) records. We retrieved 7499 clinical trials that each had at least one of these drugs for intervention from the ClinicalTrials.gov. We stratified all the trials by pre-marketing or post-marketing status, study phase, and study start date. For each trial, we retrieved drug and disease concepts from clinical trial summaries to model its study population using medParser and SNOMED-CT. Convergent Focus Shift (CFS) pattern was calculated and used to assess the temporal changes in study populations from pre-marketing to post-marketing trials for each drug. Then we selected 68 candidate drugs, 18 with BBW warning and 50 without, that each had at least nine pre-marketing trials and nine post-marketing trials for predictive modeling. A random forest predictive model was developed to predict BBW acquisition incidents based on CFS patterns among these drugs. Pre- and post-marketing trials of BBW and ROBUST drugs were compared to look for their differences in CFS patterns. Among the 18 BBW drugs, we consistently observed that the post-marketing trials focused more on recruiting patients with medical conditions previously unconsidered in the pre-marketing trials. In contrast, among the 50 ROBUST drugs, the post-marketing trials involved a variety of medications for testing their associations with target intervention(s). We found it feasible to predict BBW acquisitions using different CFS patterns between the two groups of drugs. Our random forest predictor achieved an AUC of 0.77. We also demonstrated the feasibility of the predictor for identifying long-term BBW acquisition events without compromising prediction accuracy. This study contributes a method for post-marketing pharmacovigilance using Convergent Focus Shift (CFS) patterns in clinical trial study populations mined from linked public data resources. These signals are otherwise unavailable from individual data resources. We demonstrated the added value of linked public data and the feasibility of integrating ClinicalTrials.gov summaries and drug safety labels for post-marketing surveillance. Future research is needed to ensure better accessibility and linkage of heterogeneous drug safety data for efficient pharmacovigilance. Copyright © 2016 Elsevier Inc. All rights reserved.

Support for immunization registries among parents of vaccinated and unvaccinated school-aged children: a case control study

PubMed Central

Linkins, Robert W; Salmon, Daniel A; Omer, Saad B; Pan, William KY; Stokley, Shannon; Halsey, Neal A

2006-01-01

Background Immunizations have reduced childhood vaccine preventable disease incidence by 98–100%. Continued vaccine preventable disease control depends on high immunization coverage. Immunization registries help ensure high coverage by recording childhood immunizations administered, generating reminders when immunizations are due, calculating immunization coverage and identifying pockets needing immunization services, and improving vaccine safety by reducing over-immunization and providing data for post-licensure vaccine safety studies. Despite substantial resources directed towards registry development in the U.S., only 48% of children were enrolled in a registry in 2004. Parental attitudes likely impact child participation. Consequently, the purpose of this study was to assess the attitudes of parents of vaccinated and unvaccinated school-aged children regarding: support for immunization registries; laws authorizing registries and mandating provider reporting; opt-in versus opt-out registry participation; and financial worth and responsibility of registry development and implementation. Methods A case control study of parents of 815 children exempt from school vaccination requirements and 1630 fully vaccinated children was conducted. Children were recruited from 112 elementary schools in Colorado, Massachusetts, Missouri, and Washington. Surveys administered to the parents, asked about views on registries and perceived utility and safety of vaccines. Parental views were summarized and logistic regression models compared differences between parents of exempt and vaccinated children. Results Surveys were completed by 56.1% of respondents. Fewer than 10% of parents were aware of immunization registries in their communities. Among parents aware of registries, exempt children were more likely to be enrolled (65.0%) than vaccinated children (26.5%) (p value = 0.01). A substantial proportion of parents of exempt children support immunization registries, particularly if registries offer choice for participation. Few parents of vaccinated (6.8%) and exempt children (6.7%) were aware of laws authorizing immunization registries. Support for laws authorizing registries and requiring health care providers to report to registries was more common among parents of vaccinated than exempt children. Most parents believed that the government, vaccine companies or insurance companies should pay for registries. Conclusion Parental support for registries was relatively high. Parental support for immunization registries may increase with greater parental awareness of the risks of vaccine preventable diseases and utility of vaccination. PMID:16995946

Comparative Studies of Collaborative Team Depression Care Adoption in Safety Net Clinics

ERIC Educational Resources Information Center

Ell, Kathleen; Wu, Shinyi; Guterman, Jeffrey; Schulman, Sandra-Gross; Sklaroff, Laura; Lee, Pey-Jiuan

2018-01-01

Purpose: To evaluate three approaches adopting collaborative depression care model in Los Angeles County safety net clinics with predominantly Latino type 2 diabetes patients. Methods: Pre-post differences in treatment rates and symptom reductions were compared between baseline, 6-month, and 12-month follow-ups for each approach: (a) Multifaceted…

Post earthquake investigation field manual for the state of Kentucky.

DOT National Transportation Integrated Search

2006-09-01

The rapid assessment of a bridge structure's safety and functionality is an essential component to restoring vital lifeline routes after a major earthquake. Appropriate posting categories are used to assure the safety of the travelling public. The ob...

29 CFR 1926.1083 - Post-dive procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Diving General Operations Procedures § 1926.1083 Post-dive procedures. Note: The requirements applicable to construction work under this section are...

Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan.

PubMed

Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

2017-09-01

To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.

Safety Alerts: An Observational Study in Portugal.

PubMed

Soares, Sara; Roque, Fátima; Teixeira Rodrigues, António; Figueiras, Adolfo; Herdeiro, Maria Teresa

2015-09-01

The information that is available when marketing authorizations are approved is limited. Pharmacovigilance has an important role during the postauthorization period, and alerts published by national authorities allow health care professionals to be informed about new data on safety profiles. This study therefore sought to analyze all safety alerts published by the Portuguese National Authority of Medicines and Health Products I.P. (INFARMED). We conducted an observational study of all alerts published on the INFARMED website from January 2002 through December 2014. From the data included in the alerts, the following information was abstracted: active substance name (and trade name), event that led to the alert, and the resulting safety measures. Active substances were classified according to the Anatomical Therapeutic Chemical (ATC) code. A total of 562 alerts were published, and 304 were eligible for inclusion. The musculoskeletal system was the ATC code with more alerts (n = 53), followed by the nervous system (n = 42). Communication of the information and recommendations to the health care professionals and the public in general was the most frequent safety measure (n = 128), followed by changes in the Summary of the Product Characteristics and package information leaflet (n = 66). During the study period, 26 marketing authorizations were temporarily suspended and 10 were revoked. The knowledge of the alerts published during the postmarketing period is very useful to the health care professionals for improving prescription and use of medicines and to the scientific community for the development of new researches. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Foremen's intervention to prevent falls and increase safety communication at residential construction sites.

PubMed

Kaskutas, Vicki; Buckner-Petty, Skye; Dale, Ann Marie; Gaal, John; Evanoff, Bradley A

2016-10-01

This research aimed to improve residential construction foremen's communication skills and safety behaviors of their crewmembers when working at heights. Eighty-four residential construction foremen participated in the 8-hr fall prevention and safety communication training. We compared pre- and post-intervention surveys from foremen and their crewmembers to measure the effect of training. Foremen and crewmembers' ratings showed improvements in fall prevention knowledge, behaviors, and safety communication and were sustained 6-months post-training, with emphasized areas demonstrating larger increases. Ratings were similar between foremen and crewmembers, suggesting that the foremen effectively taught their crew and assigned accurate ratings. Based upon associations between safety behaviors and reported falls observed in prior research, we would expect a 16.6% decrease in the one year cumulative incidence of self-reported falls post-intervention. This intervention improved safety knowledge and behaviors of a large number of workers by training construction foremen in fall prevention and safety communication skills. Am. J. Ind. Med. 59:823-831, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Authorization basis supporting documentation for plutonium finishing plant

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

King, J.P., Fluor Daniel Hanford

1997-03-05

The identification and definition of the authorization basis for the Plutonium Finishing Plant (PFP) facility and operations are essential for compliance to DOE Order 5480.21, Unreviewed Safety Questions. The authorization basis, as defined in the Order, consists of those aspects of the facility design basis, i.e., the structures, systems and components (SSCS) and the operational requirements that are considered to be important to the safety of operations and are relied upon by DOE to authorize operation of the facility. These facility design features and their function in various accident scenarios are described in WHC-SD-CP-SAR-021, Plutonium Finishing Plant Final Safety Analysismore » Report (FSAR), Chapter 9, `Accident Analysis.` Figure 1 depicts the relationship of the Authorization Basis to its components and other information contained in safety documentation supporting the Authorization Basis. The PFP SSCs that are important to safety, collectively referred to as the `Safety Envelope` are discussed in various chapters of the FSAR and in WHC-SD-CP-OSR-010, Plutonium Finishing Plant Operational Safety Requirements. Other documents such as Criticality Safety Evaluation Reports (CSERS) address and support some portions of the Authorization Basis and Safety Envelope.« less

Safety and tolerability of dapagliflozin, saxagliptin and metformin in combination: Post-hoc analysis of concomitant add-on versus sequential add-on to metformin and of triple versus dual therapy with metformin.

PubMed

Del Prato, Stefano; Rosenstock, Julio; Garcia-Sanchez, Ricardo; Iqbal, Nayyar; Hansen, Lars; Johnsson, Eva; Chen, Hungta; Mathieu, Chantal

2018-06-01

The safety of triple oral therapy with dapagliflozin plus saxagliptin plus metformin versus dual therapy with dapagliflozin or saxagliptin plus metformin was compared in a post-hoc analysis of 3 randomized trials of sequential or concomitant add-on of dapagliflozin and saxagliptin to metformin. In the concomitant add-on trial, patients with type 2 diabetes on stable metformin received dapagliflozin 10 mg/d plus saxagliptin 5 mg/d. In sequential add-on trials, patients on metformin plus either saxagliptin 5 mg/d or dapagliflozin 10 mg/d received dapagliflozin 10 mg/d or saxagliptin 5 mg/d, respectively, as add-on therapy. After 24 weeks, incidences of adverse events and serious adverse events were similar between triple and dual therapy and between concomitant and sequential add-on regimens. Urinary tract infections were more common with sequential than with concomitant add-on therapy; genital infections were reported only with sequential add-on of dapagliflozin to saxagliptin plus metformin. Hypoglycaemia incidence was <2.0% across all analysis groups. In conclusion, the safety and tolerability of triple therapy with dapagliflozin, saxagliptin and metformin, as either concomitant or sequential add-on, were similar to dual therapy with either agent added to metformin. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

A post hoc evaluation of a sample size re-estimation in the Secondary Prevention of Small Subcortical Strokes study.

PubMed

McClure, Leslie A; Szychowski, Jeff M; Benavente, Oscar; Hart, Robert G; Coffey, Christopher S

2016-10-01

The use of adaptive designs has been increasing in randomized clinical trials. Sample size re-estimation is a type of adaptation in which nuisance parameters are estimated at an interim point in the trial and the sample size re-computed based on these estimates. The Secondary Prevention of Small Subcortical Strokes study was a randomized clinical trial assessing the impact of single- versus dual-antiplatelet therapy and control of systolic blood pressure to a higher (130-149 mmHg) versus lower (<130 mmHg) target on recurrent stroke risk in a two-by-two factorial design. A sample size re-estimation was performed during the Secondary Prevention of Small Subcortical Strokes study resulting in an increase from the planned sample size of 2500-3020, and we sought to determine the impact of the sample size re-estimation on the study results. We assessed the results of the primary efficacy and safety analyses with the full 3020 patients and compared them to the results that would have been observed had randomization ended with 2500 patients. The primary efficacy outcome considered was recurrent stroke, and the primary safety outcomes were major bleeds and death. We computed incidence rates for the efficacy and safety outcomes and used Cox proportional hazards models to examine the hazard ratios for each of the two treatment interventions (i.e. the antiplatelet and blood pressure interventions). In the antiplatelet intervention, the hazard ratio was not materially modified by increasing the sample size, nor did the conclusions regarding the efficacy of mono versus dual-therapy change: there was no difference in the effect of dual- versus monotherapy on the risk of recurrent stroke hazard ratios (n = 3020 HR (95% confidence interval): 0.92 (0.72, 1.2), p = 0.48; n = 2500 HR (95% confidence interval): 1.0 (0.78, 1.3), p = 0.85). With respect to the blood pressure intervention, increasing the sample size resulted in less certainty in the results, as the hazard ratio for higher versus lower systolic blood pressure target approached, but did not achieve, statistical significance with the larger sample (n = 3020 HR (95% confidence interval): 0.81 (0.63, 1.0), p = 0.089; n = 2500 HR (95% confidence interval): 0.89 (0.68, 1.17), p = 0.40). The results from the safety analyses were similar to 3020 and 2500 patients for both study interventions. Other trial-related factors, such as contracts, finances, and study management, were impacted as well. Adaptive designs can have benefits in randomized clinical trials, but do not always result in significant findings. The impact of adaptive designs should be measured in terms of both trial results, as well as practical issues related to trial management. More post hoc analyses of study adaptations will lead to better understanding of the balance between the benefits and the costs. © The Author(s) 2016.

Barriers to Safety Event Reporting in an Academic Radiology Department: Authority Gradients and Other Human Factors.

PubMed

Siewert, Bettina; Swedeen, Suzanne; Brook, Olga R; Eisenberg, Ronald L; Hochman, Mary

2018-05-15

Purpose To investigate barriers to reporting safety concerns in an academic radiology department and to evaluate the role of human factors, including authority gradients, as potential barriers to safety concern reporting. Materials and Methods In this institutional review board-approved, HIPAA-compliant retrospective study, an online questionnaire link was emailed four times to all radiology department staff members (n = 648) at a tertiary care institution. Survey questions included frequency of speaking up about safety concerns, perceived barriers to speaking up, and the annual number of safety concerns that respondents were unsuccessful in reporting. Respondents' sex, role in the department, and length of employment were recorded. Statistical analysis was performed with the Fisher exact test. Results The survey was completed by 363 of the 648 employees (56%). Of those 363 employees, 182 (50%) reported always speaking up about safety concerns, 134 (37%) reported speaking up most of the time, 36 (10%) reported speaking up sometimes, seven (2%) reported rarely speaking up, and four (1%) reported never speaking up. Thus, 50% of employees spoke up about safety concerns less than 100% of the time. The most frequently reported barriers to speaking up included high reporting threshold (69%), reluctance to challenge someone in authority (67%), fear of disrespect (53%), and lack of listening (52%). Conclusion Of employees in a large academic radiology department, 50% do not attain 100% reporting of safety events. The most common human barriers to speaking up are high reporting threshold, reluctance to challenge authority, fear of disrespect, and lack of listening, which suggests that existing authority gradients interfere with full reporting of safety concerns. © RSNA, 2018.

A post-market surveillance analysis of the safety of hydroxyapatite-derived products as bone graft extenders or substitutes for spine fusion.

PubMed

Barbanti Brodano, G; Griffoni, C; Zanotti, B; Gasbarrini, A; Bandiera, S; Ghermandi, R; Boriani, S

2015-10-01

Iliac crest bone graft (ICBG) is considered the gold standard for spine surgical procedures to achieve a successful fusion, because of its known osteoinductive and osteoconductive properties. Considering its autogenous origin, the use of ICBG has not been associated to an increase of intraoperative or postoperative complications directly related to the surgery. However, complications related to the harvesting procedure and to the donor site morbidity have been largely reported in the literature, favoring the development of a wide range of alternative products to be used as bone graft extenders or substitutes for spine fusion. The family of ceramic-based bone grafts has been widely used and studied during the last years for spine surgical procedures in order to reduce the need for iliac crest bone grafting and the consequent morbidity associated to the harvesting procedures. We report here the results of a post-market surveillance analysis performed on four independent cohorts of patients (115 patients) to evaluate the safety of three different formulations of hydroxyapatite-derived products used as bone graft extenders/substitutes for lumbar arthrodesis. No intraoperative or post-operative complications related to the use of hydroxyapatite-derived products were detected, during medium and long follow up period (minimum 12 months-maximum 5 years). This post-market surveillance analysis evidenced the safety of ceramic products as bone graft extenders or substitutes for spine fusion. Moreover, the evidence of the safety of hydroxyapatite-derived products allows to perform clinical studies aimed at evaluating the fusion rates and the clinical outcomes of these materials as bone graft extenders/substitutes, in order to support their use as an alternative to ICBG for spine fusion.

[Topics from "Overseas Drug Safety Information" in the past five years].

PubMed

Amanuma, Kimiko

2013-01-01

The Drug Safety Information Section of the Division of Safety Information on Drug, Food and Chemicals has been providing bulletins titled "Overseas Drug Safety Information" in Japanese since 2003. These bulletins comprise summarized and translated reports of important post-marketing drug safety information that are published by foreign regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medical Agency. A new issue of the bulletin is posted every two weeks on the website of the National Institute of Health Sciences, Japan; to date (May 2013), a total of 280 issues have been posted, covering approximately 2400 foreign news items and articles since its inception. Recently, visits to the bulletin website have been increasing: the number of hits for each issue totaled 570,000 in fiscal 2012. Among the "Overseas Drug Safety Information" issued in the past five years, I briefly describe here several topics which interested me: erythropoietin-stimulating agents in chronic kidney disease and their cardiovascular risk; bisphosphonates and atypical femur fracture; effectiveness of oral liquid cough medicines containing codeine in children; bevacizumab for metastatic breast cancer; and congenital abnormality associated with the use of antiepileptic drugs by pregnant women. I also describe the potential safety signals identified by FDA using its Adverse Event Reporting System, and their importance in ensuring the safe use of drugs in the post-marketing phase.

Pimecrolimus in atopic dermatitis: Consensus on safety and the need to allow use in infants

PubMed Central

Luger, Thomas; Boguniewicz, Mark; Carr, Warner; Cork, Michael; Deleuran, Mette; Eichenfield, Lawrence; Eigenmann, Philippe; Fölster-Holst, Regina; Gelmetti, Carlo; Gollnick, Harald; Hamelmann, Eckard; Hebert, Adelaide A; Muraro, Antonella; Oranje, Arnold P; Paller, Amy S; Paul, Carle; Puig, Luis; Ring, Johannes; Siegfried, Elaine; Spergel, Jonathan M; Stingl, Georg; Taieb, Alain; Torrelo, Antonio; Werfel, Thomas; Wahn, Ulrich

2015-01-01

Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered. PMID:25557211

Large Eddy Simulations of Transverse Combustion Instability in a Multi-Element Injector

DTIC Science & Technology

2016-07-27

Instability in a Multi- Element Injector 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Matthew Harvazinski, Yogin...Simulations of Transverse  Combustion Instability in a Multi‐ Element  Injector 2 History Damaged engine injector  faceplate caused by combustion...Clearance #16346 3 Single  Element  Studies Short Post Marginally Stable Intermediate Post Unstable Long Post Stable Long Post Unstable CVRC Experiment

Prevention of post-partum hemorrhage by rectal Misoprostol: A randomized clinical trial

PubMed Central

Firouzbakht, Mozhgan; Kiapour, Azadeh; Omidvar, Shabnam

2013-01-01

Background: Post-partum hemorrhage (PPH) is a common cause of maternal mortality in developing countries. This trial was conducted to study the effectiveness and safety of rectal misoprostol for PPH. Aim: To assess the effectiveness and safety of misoprostol and comparing with oxytocin for prevention of PPH. Materials and Methods: Women were randomized to receive either two 200 μg rectal misoprostol tablets (study group) or 20 units oxytocin in 1000 cc normal saline intravenously (control group). The outcomes were incidence of PPH, amount of blood loss, duration of labor, incidence of side effects, pre- and post-delivery hemoglobin, and use of additional uterotonics. Finding: The incidence of PPH was 12% in the study group and 10% in the control group (P > 0.05). No significant difference was observed between the groups hematocrit (P > 0.05). Other variables including severe PPH and duration of the third stage of labor were similar in both groups. Conclusion: Rectal misoprostol was as effective as intravenous oxytocin for preventing post-partum hemorrhage with the same incidence of side effects and is recommended to be use as an uterotonic agent to manage third stage of labor routinely. PMID:23633849

Efficacy and safety of endometrial ablation for treating abnormal uterine bleeding in pre- and postmenopausal women with liver cirrhosis.

PubMed

Liu, Qing; Li, Xiu-Lan; Liu, Ji-Juan; Song, Xiao-Hong; Jiang, Xiao-Ying; Li, Wei; Zhang, Hua; Pan, Calvin Q

2016-12-01

Abnormal uterine bleeding (AUB) occurs in 10-30% of women of reproductive age and up to 61% of cirrhotic women. We evaluated the efficacy and safety of endometrial ablation (NovaSure therapy) for AUB in cirrhotic women. This prospective, two-arm, observational study enrolled patients for NovaSure treatment, and they were followed for 12 months. Primary measurements were the amenorrhea rate and changes of pictorial blood loss assessment chart (PBLAC) scores at 1-month post-therapy. Key secondary end-points included the longevity of amenorrhea at 12 months, safety profile, and progression of cirrhosis. Among 88 women, 26 were cirrhotic and 62 were non-cirrhotic. At 1-month post-NovaSure treatment, a significant reduction of mean PBLAC scores was observed in cirrhotic patients compared to those at baseline (0.4 ± 1.3 vs 215.2 ± 410.9, P < 0.001), and the amenorrhea rate was 88.5%. The efficacy outcomes of the PBLAC scores and amenorrhea rate were maintained until the end of the 12-month follow-up. A significant improvement in quality of life scores was observed 1-month post-therapy compared to those at baseline (5.4 ± 3.1 vs 20.5 ± 5.5, P < 0.001). Patients' satisfaction rates were 100% and 92.31% at 6 and 12 months, respectively. The aforementioned outcomes were comparable with those in non-cirrhotic patients. No significant progression of cirrhosis or safety concern was reported. Cirrhotic patients on NovaSure therapy had a high rate of amenorrhea 1-month post-treatment, which maintained longevity for 12 months. The safety profile was similar to that in non-cirrhotic patients. © 2016 Japan Society of Obstetrics and Gynecology.

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

PubMed

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

2018-06-22

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

76 FR 47262 - Brookwood-Sago Mine Safety Grants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-04

... industry during the current reporting period. Pre-test and post- test results of trainees. Course... funding ends. 2. Agency creates training Increase number of Pre-test and post- materials and improves quality educational test results of the safety. materials developed. training materials. Provide quality...

Clinical safety of the ProMRI pacemaker system in patients subjected to head and lower lumbar 1.5-T magnetic resonance imaging scanning conditions.

PubMed

Bailey, William M; Rosenthal, Lawrence; Fananapazir, Lameh; Gleva, Marye; Mazur, Alexander; Rinaldi, C A; Kypta, Alexander; Merkely, Béla; Woodard, Pamela K

2015-06-01

Permanent cardiac pacemakers have historically been considered a contraindication to magnetic resonance imaging (MRI). The purpose of the ProMRI/ProMRI AFFIRM Study, which was a multicenter, prospective, single-arm, nonrandomized study, was to evaluate the clinical safety of the Biotronik ProMRI Pacemaker System under specific MRI conditions. The ProMRI Study (in the United States) and the ProMRI AFFIRM study (outside the United States) with identical design enrolled 272 patients with stable baseline pacing indices implanted with an Entovis or Evia pacemaker (DR-T or SR-T) and Setrox or Safio 53-cm or 60-cm lead. Device interrogation was performed at enrollment, pre-MRI and post-MRI scan, and 1 and 3 months post-MRI. End-points were (1) freedom from MRI- and pacing system-related serious adverse device effects (SADEs) through 1 month post-MRI, (2) freedom from atrial and ventricular MRI-induced pacing threshold increase (>0.5 V), and (3) freedom from P- and R-wave amplitude attenuation (<50%), or P wave <1.5 mV, or R wave <5.0 mV at 1 month post-MRI. Two hundred twenty-six patients completed the MRI and 1-month post-MRI follow-up. No adverse events related to the implanted system and the MRI procedure occurred, resulting in an SADE-free rate of 100.0% (229/229, P <.001). Freedom from atrial and ventricular pacing threshold increase was 99.0% (189/191, P = .003) and 100% (217/217, P <.001), respectively. Freedom from P- and R- wave amplitude attenuation was 99.4% (167/168, P <.001) and 99.5% (193/194, P <.001), respectively. The results of the ProMRI/ProMRI AFFIRM studies demonstrate the clinical safety and efficacy of the ProMRI pacemaker system in patients subjected to head and lower lumbar MRI conditions. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Long-Term Follow-Up on a Cohort Temporary Utilization Authorization (ATU) Survey of Patients Treated with Pheburane (Sodium Phenylbutyrate) Taste-Masked Granules.

PubMed

Kibleur, Yves; Guffon, Nathalie

2016-04-01

The aim was to describe the status of patients with urea cycle disorders (UCD) at the latest long-term clinical follow-up of treatment with a new taste-masked formulation of sodium phenylbutyrate (NaPB) granules (Pheburane). These patients are a subset of those treated under a cohort temporary utilisation study (ATU) previously reported and now followed for 2 years. From a French cohort temporary utilization authorization (ATU) set up to monitor the use of Pheburane on a named-patient basis in UCD patients in advance of its marketing authorization, a subset of patients were followed up in the long term. Data on demographics, dosing characteristics of NaPB, concomitant medications, adverse events and clinical outcomes were collected at a follow-up visit after 1-2 years of treatment with the drug administered under marketing conditions. This paper reports on the subset of patients who were included in further long-term follow-up at the principal recruiting metabolic reference center involved in the original cohort. No episode of metabolic decompensation was observed over a treatment period ranging from 8 to 30 months with Pheburane, and the range of ammonia and glutamine levels continued to improve and remained within the normal range, thus adding valuable longer-term feedback to the original ATU report. In all, no adverse events were reported with Pheburane treatment. These additional data demonstrate the maintenance of the safety and efficacy of Pheburane over time. The recently developed taste-masked formulation of NaPB granules (Pheburane) improved the quality of life for UCD patients. The present post-marketing report on the use of the product confirms the original observations of improved compliance, efficacy and safety with this taste-masked formulation of NaPB.

Safety and immunogenicity of an investigational meningococcal ACWY conjugate vaccine (MenACWY-CRM) in healthy Indian subjects aged 2 to 75 years.

PubMed

Lalwani, Sanjay; Agarkhedkar, Sharad; Gogtay, Nithya; Palkar, Sonali; Agarkhedkar, Shalaka; Thatte, Urmila; Vakil, Hoshang; Jonnalagedda, Rekha; Pedotti, Paola; Hoyle, Margaret; Bhusal, Chiranjiwi; Arora, Ashwani

2015-09-01

This phase 3, multi-center, open-label study evaluated the immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM, Menveo(®); Novartis Vaccines and Diagnostics S.r.l., Siena, Italy) in healthy Indian subjects aged 2-75 years, to provide data for licensure in India. A total of 180 subjects were enrolled (60 subjects 2-10 years, 60 subjects 11-18 years, and 60 subjects 19-75 years) and received one dose of MenACWY-CRM. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination. Adverse events were collected throughout the 29-day study period. Percentages of subjects with post-vaccination hSBA ≥8 were 72%, 95%, 94%, and 90% for serogroups A, C, W, and Y, respectively. Geometric mean titers rose 7-fold to 42-fold against the four serogroups. Similar immune responses were observed for the age subgroups 2-10 years, 11-18 years, and 19-75 years. Seroresponse rates at 1 month following vaccination were 72%, 88%, 55%, and 71% for serogroups A, C, W, and Y, respectively. The vaccine was well tolerated with no safety concerns. A single dose of MenACWY-CRM induced a robust immune response against all four meningococcal serogroups and was well tolerated in an Indian population 2-75 years of age. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

An Exploration of the Impact of Initial Timing of Physical Therapy on Safety and Outcomes After Concussion in Adolescents.

PubMed

Lennon, Anne; Hugentobler, Jason A; Sroka, Mary Claire; Nissen, Katharine S; Kurowski, Brad G; Gagnon, Isabelle; Quatman-Yates, Catherine C

2018-05-24

Physical therapy (PT) is a management strategy increasingly recognized to facilitate recovery after concussion. The purpose of this study was to investigate the safety and outcomes of multimodal impairment-based PT at varying time points after injury in youth diagnosed with concussion. Data were extracted retrospectively from medical records for patients who received PT for concussion-related impairments. Patient records were categorized into 3 cohorts on the basis of the timing of PT implementation: 0-20 days following injury (early intervention), 21 to 41 days following injury (middle intervention), and 42 or more days following injury (late intervention). The primary outcome measure was Post-Concussion Symptom Inventory score from the beginning to the end of the PT episode of care. Additional outcome measures included number of PT sessions, duration of PT episode of care (days), and occurrence of unplanned visits to a health care provider. A total of 120 patient records (mean age of 14.77 years) were analyzed. Thirty-three, 39, and 48 individuals were categorized into the early, middle, and late intervention cohorts, respectively. There were no significant differences between intervention cohorts with regard to symptom change on the Post-Concussion Symptom Inventory from the beginning to the end of the PT episode of care, unplanned health care visits, number of PT sessions, or duration of PT episode of care. Early initiation of PT may be safe and tolerable. Future prospective studies are needed to explore the efficacy of PT services administered early following injury to help characterize an optimal care plan for youth following concussion.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A210).

Full Bayesian evaluation of the safety effects of reducing the posted speed limit in urban residential area.

PubMed

Islam, Md Tazul; El-Basyouny, Karim

2015-07-01

Full Bayesian (FB) before-after evaluation is a newer approach than the empirical Bayesian (EB) evaluation in traffic safety research. While a number of earlier studies have conducted univariate and multivariate FB before-after safety evaluations and compared the results with the EB method, often contradictory conclusions have been drawn. To this end, the objectives of the current study were to (i) perform a before-after safety evaluation using both the univariate and multivariate FB methods in order to enhance our understanding of these methodologies, (ii) perform the EB evaluation and compare the results with those of the FB methods and (iii) apply the FB and EB methods to evaluate the safety effects of reducing the urban residential posted speed limit (PSL) for policy recommendation. In addition to three years of crash data for both the before and after periods, traffic volume, road geometry and other relevant data for both the treated and reference sites were collected and used. According to the model goodness-of-fit criteria, the current study found that the multivariate FB model for crash severities outperformed the univariate FB models. Moreover, in terms of statistical significance of the safety effects, the EB and FB methods led to opposite conclusions when the safety effects were relatively small with high standard deviation. Therefore, caution should be taken in drawing conclusions from the EB method. Based on the FB method, the PSL reduction was found effective in reducing crashes of all severities and thus is recommended for improving safety on urban residential collector roads. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of the Efficacy of Simulation Games in Traffic Safety Education of Kindergarten Children.

ERIC Educational Resources Information Center

Renaud, Lise; Suissa, Samy

1989-01-01

Uses a post-test-only control group study to evaluate the effect of three different types of simulation games used to teach traffic safety to kindergarten students. Results suggest that games including role-playing/group dynamics and modeling/training can change attitudes and modify behavior with this age group. (FMW)

Creation and preliminary validation of the screening for self-medication safety post-stroke scale (S-5).

PubMed

Kaizer, Franceen; Kim, Angela; Van, My Tram; Korner-Bitensky, Nicol

2010-03-01

Patients with stroke should be screened for safety prior to starting a self-medication regime. An extensive literature review revealed no standardized self-medication tool tailored to the multi-faceted needs of the stroke population. The aim of this study was to create and validate a condition-specific tool to be used in screening for self-medication safety in individuals with stroke. Items were generated using expert consultation and review of the existing tools. The draft tool was pilot-tested on expert stroke clinicians to receive feedback on content, clarity, optimal cueing and domain omissions. The final version was piloted on patients with stroke using a structured interviewer-administered interview. The tool was progressively refined and validated according to feedback from the 11 expert reviewers. The subsequent version was piloted on patients with stroke. The final version includes 16 questions designed to elicit information on 5 domains: cognition, communication, motor, visual-perception and, judgement/executive function/self-efficacy. The Screening for Safe Self-medication post-Stroke Scale (S-5) has been created and validated for use by health professionals to screen self-medication safety readiness of patients after stroke. Its use should also help to guide clinicians' recommendations and interventions aimed at enhancing self-medication post-stroke.

Nonfatal road traffic injuries: can road safety campaigns prevent hazardous behavior? An Italian experience.

PubMed

Zampetti, R; Messina, G; Quercioli, C; Vencia, F; Genco, L; Di Bartolomeo, L; Nante, N

2013-01-01

Road traffic injuries are a widespread problem and are very difficult to prevent. The purpose of this study was to verify whether intensive versus basic road safety education programs are associated with different incidence and severity of nonfatal road injuries. The study had an ecological design and involved Local Health Authority One (LHA1) in Salerno, Italy, which includes 20 municipalities. Data on nonfatal road injuries occurring in the periods June to August 2003 and June to August 2008 were obtained from trained operators through the information system of the emergency department. All 20 municipalities received a basic community road safety education program (publicity campaign using bill-posting, brochures, mass media communication with press conferences, articles in local papers, radio and television interviews, and a dedicated LHA1 web site), and 12 municipalities also received an intensive education campaign (in secondary schools, community conferences, and activities organized by police and firefighters). The incidence and severity of nonfatal road traffic injuries were compared between June to August 2003 (before the campaign) and June to August 2008. The total number of injuries in all 20 municipalities in 2003 and 2008 was 907 and 755, respectively. The incidence of injuries decreased in the study period both in the 8 municipalities where only the basic campaign was run (difference in incidence = -0.4; P = .053) and in the 12 municipalities where the intensive campaign was implemented (difference in incidence = -0.5; P < .001); focusing on severity, the incidence of severe injuries decreased or remained the same in the study period in the 2 studied group. The results are coherent with other European studies and show that an overall downward trend exists but is presumably not a direct consequence of road safety education. This does not mean that such campaigns are useless (they are important to raise awareness) but that they should be supplemented with complementary activities in order to be really effective.

The EXPAND study: Efficacy and safety of rivaroxaban in Japanese patients with non-valvular atrial fibrillation.

PubMed

Shimokawa, Hiroaki; Yamashita, Takeshi; Uchiyama, Shinichiro; Kitazono, Takanari; Shimizu, Wataru; Ikeda, Takanori; Kamouchi, Masahiro; Kaikita, Koichi; Fukuda, Koji; Origasa, Hideki; Sakuma, Ichiro; Saku, Keijiro; Okumura, Yasuo; Nakamura, Yuichiro; Morimoto, Hideo; Matsumoto, Naoki; Tsuchida, Akihito; Ako, Junya; Sugishita, Nobuyoshi; Shimizu, Shogo; Atarashi, Hirotsugu; Inoue, Hiroshi

2018-05-01

The EXPAND study examined the real-world efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism (SE) in Japanese patients with non-valvular atrial fibrillation (NVAF). This multicenter, prospective, non-interventional, observational, cohort study was conducted at 684 medical centers in Japan. A total of 7141 NVAF patients ≥20 years of age (mean, 71.6 ± 9.4 years) who were being or about to be treated with rivaroxaban (10 mg/day, 43.5%; 15 mg/day, 56.5%) were followed for an average of 897.1 (±206.8) days with a high follow-up rate (99.65%). The mean CHADS 2 score at baseline was 2.1 (1.3) (0-1, 37%; 2, 29%; ≥3, 34%). The total incidence rate of symptomatic stroke and SE (primary efficacy endpoint) was 1.0%/year, and 0.5%, 0.9%, and 1.7%/year for those with CHADS 2 scores of 0-1, 2, and ≥3, respectively. Cumulative incidence rates for major bleeding (primary safety endpoint) and non-major bleeding (secondary safety endpoint) were 1.2%/year and 4.9%/year, respectively. Differences were noted between new and current users only for major bleeding event rate (1.7% vs. 1.1%/year, P = 0.0024). Comparisons with previous studies suggested that rivaroxaban is effective and safe for low-risk patients (0-1 CHADS 2 ), as shown for warfarin in the XANTUS international prospective post-marketing study. The EXPAND study demonstrated that low dosages of rivaroxaban for Japanese NVAF patients in real-world clinical practice, including those with CHADS 2 scores 0-1, resulted in low rates of stroke and SE, and major and non-major bleeding. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Development of the Sanofi Pasteur tetravalent dengue vaccine: One more step forward.

PubMed

Guy, Bruno; Briand, Olivier; Lang, Jean; Saville, Melanie; Jackson, Nicholas

2015-12-10

Sanofi Pasteur has developed a recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) that is in late-stage development. The present review summarizes the different steps in the development of this dengue vaccine, with a particular focus on the clinical data from three efficacy trials, which includes one proof-of-concept phase IIb (NCT00842530) and two pivotal phase III efficacy trials (NCT01373281 and NCT01374516). Earlier studies showed that the CYD-TDV candidate had a satisfactory safety profile and was immunogenic across the four vaccine serotypes in both in vitro and in vivo preclinical tests, as well as in initial phase I to phase II clinical trials in both flavivirus-naïve and seropositive individuals. Data from the 25 months (after the first injection) active phase of the two pivotal phase III efficacy studies shows that CYD-TDV (administered at 0, 6, and 12 months) is efficacious against virologically-confirmed disease (primary endpoint) and has a good safety profile. Secondary analyses also showed efficacy against all four dengue serotypes and protection against severe disease and hospitalization. The end of the active phases in these studies completes more than a decade of development of CYD-TDV, but considerable activities and efforts remain to address outstanding scientific, clinical, and immunological questions, while preparing for the introduction and use of CYD-TDV. Additional safety observations were recently reported from the first complete year of hospital phase longer term surveillance for two phase 3 studies and the first and second completed years for one phase 2b study, demonstrating the optimal age for intervention from 9 years. Dengue is a complex disease, and both short-term and long-term safety and efficacy will continue to be addressed by ongoing long-term follow-up and future post-licensure studies. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Is the large simple trial design used for comparative, post-approval safety research? A review of a clinical trials registry and the published literature.

PubMed

Reynolds, Robert F; Lem, Joanna A; Gatto, Nicolle M; Eng, Sybil M

2011-10-01

Post-approval, observational drug safety studies face well known difficulties in controlling for confounding, particularly confounding by indication for drug use. A study design that addresses confounding by indication is the large simple trial (LST). LSTs are characterized by large sample sizes, often in the thousands; broad entry criteria consistent with the approved medication label; randomization based on equipoise, i.e. neither physician nor patient believes that one treatment option is superior; minimal, streamlined data collection requirements; objectively-measured endpoints (e.g. death, hospitalization); and follow-up that minimizes interventions or interference with normal clinical practice. In theory then, the LST is a preferred study design for drug and vaccine safety research because it controls for biases inherent to observational research while still providing results that are generalizable to 'real-world' use. To evaluate whether LSTs are used for comparative safety evaluation and if the design is, in fact, advantageous compared with other designs, we conducted a review of the published literature (1949 through 31 December 2010) and the ClinicalTrials.gov registry (2000 through 31 December 2010). Thirteen ongoing or completed safety LSTs were identified. The design has rarely been used in comparative drug safety research, which is due to the operational, financial and scientific hurdles of implementing the design. The studies that have been completed addressed important clinical questions and, in some cases, led to re-evaluation of medical practice. We conclude the design has demonstrated utility for comparative safety research of medicines and vaccines if the necessary scientific and operational conditions for its use are met.

Improving the Quality of Ward-based Surgical Care With a Human Factors Intervention Bundle.

PubMed

Johnston, Maximilian J; Arora, Sonal; King, Dominic; Darzi, Ara

2018-01-01

This study aimed to explore the impact of a human factors intervention bundle on the quality of ward-based surgical care in a UK hospital. Improving the culture of a surgical team is a difficult task. Engagement with stakeholders before intervention is key. Studies have shown that appropriate supervision can enhance surgical ward safety. A pre-post intervention study was conducted. The intervention bundle consisted of twice-daily attending ward rounds, a "chief resident of the week" available at all times on the ward, an escalation of care protocol and team contact cards. Twenty-seven junior and senior surgeons completed validated questionnaires assessing supervision, escalation of care, and safety culture pre and post-intervention along with interviews to further explore the impact of the intervention. Patient outcomes pre and postintervention were also analyzed. Questionnaires revealed significant improvements in supervision postintervention (senior median pre 5 vs post 7, P = 0.002 and junior 4 vs 6, P = 0.039) and senior surgeon approachability (junior 5 vs 6, P = 0.047). Both groups agreed that they would feel safer as a patient in their hospital postintervention (senior 3 vs 4.5, P = 0.021 and junior 3 vs 4, P = 0.034). The interviews confirmed that the safety culture of the department had improved. There were no differences in inpatient mortality, cardiac arrest, reoperation, or readmission rates pre and postintervention. Improving supervision and introducing clear protocols can improve safety culture on the surgical ward. Future work should evaluate the effect these measures have on patient outcomes in multiple institutions.

Design and analysis of post-marketing research.

PubMed

Zhou, Xiao-Hua Andrew; Yang, Wei

2013-07-01

A post-marketing study is an integral part of research that helps to ensure a favorable risk-benefit profile for approved drugs used in the market. Because most of post-marketing studies use observational designs, which are liable to confounding, estimation of the causal effect of a drug versus a comparative one is very challenging. This article focuses on methodological issues of importance in designing and analyzing studies to evaluate the safety of marketed drugs, especially marketed traditional Chinese medicine (TCM) products. Advantages and limitations of the current designs and analytic methods for postmarketing studies are discussed, and recommendations are given for improving the validity of postmarketing studies in TCM products.

Dabigatran – a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs

PubMed Central

Malmström, Rickard E.; Godman, Brian B.; Diogene, Eduard; Baumgärtel, Christoph; Bennie, Marion; Bishop, Iain; Brzezinska, Anna; Bucsics, Anna; Campbell, Stephen; Ferrario, Alessandra; Finlayson, Alexander E.; Fürst, Jurij; Garuoliene, Kristina; Gomes, Miguel; Gutiérrez-Ibarluzea, Iñaki; Haycox, Alan; Hviding, Krystyna; Herholz, Harald; Hoffmann, Mikael; Jan, Saira; Jones, Jan; Joppi, Roberta; Kalaba, Marija; Kvalheim, Christina; Laius, Ott; Langner, Irene; Lonsdale, Julie; Lööv, Sven-Äke; Malinowska, Kamila; McCullagh, Laura; Paterson, Ken; Markovic-Pekovic, Vanda; Martin, Andrew; Piessnegger, Jutta; Selke, Gisbert; Sermet, Catherine; Simoens, Steven; Tulunay, Cankat; Tomek, Dominik; Vončina, Luka; Vlahovic-Palcevski, Vera; Wale, Janet; Wilcock, Michael; Wladysiuk, Magdalena; van Woerkom, Menno; Zara, Corrine; Gustafsson, Lars L.

2013-01-01

Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use. Objective: To (i) review authority activities in over 30 countries and regions, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications for all major stakeholder groups. Methodology: Descriptive review and appraisal of activities regarding dabigatran and the development of guidance for groups through an iterative process. Results: There has been a plethora of activities among authorities to manage the prescribing of dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions, and monitoring of prescribing post-launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding. PMID:23717279

The Event Chain of Survival in the Context of Music Festivals: A Framework for Improving Outcomes at Major Planned Events.

PubMed

Lund, Adam; Turris, Sheila

2017-08-01

Despite the best efforts of event producers and on-site medical teams, there are sometimes serious illnesses, life-threatening injuries, and fatalities related to music festival attendance. Producers, clinicians, and researchers are actively seeking ways to reduce the mortality and morbidity associated with these events. After analyzing the available literature on music festival health and safety, several major themes emerged. Principally, stakeholder groups planning in isolation from one another (ie, in silos) create fragmentation, gaps, and overlap in plans for major planned events (MPEs). The authors hypothesized that one approach to minimizing this fragmentation may be to create a framework to "connect the dots," or join together the many silos of professionals responsible for safety, security, health, and emergency planning at MPEs. Adapted from the well-established literature regarding the management of cardiac arrests, both in and out of hospital, the "chain of survival" concept is applied to the disparate groups providing services that support event safety in the context of music festivals. The authors propose this framework for describing, understanding, coordinating and planning around the integration of safety, security, health, and emergency service for events. The adapted Event Chain of Survival contains six interdependent links, including: (1) event producers; (2) police and security; (3) festival health; (4) on-site medical services; (5) ambulance services; and (6) off-site medical services. The authors argue that adapting and applying this framework in the context of MPEs in general, and music festivals specifically, has the potential to break down the current disconnected approach to event safety, security, health, and emergency planning. It offers a means of shifting the focus from a purely reactive stance to a more proactive, collaborative, and integrated approach. Improving health outcomes for music festival attendees, reducing gaps in planning, promoting consistency, and improving efficiency by reducing duplication of services will ultimately require coordination and collaboration from the beginning of event production to post-event reporting. Lund A , Turris SA . The Event Chain of Survival in the context of music festivals: a framework for improving outcomes at major planned events. Prehosp Disaster Med. 2017;32(4):437-443.

An Exploratory Study on the Post-Implementation of Threat and Error Management Training in Australian General Aviation

ERIC Educational Resources Information Center

Lee, Seung Yong; Bates, Paul R.; Murray, Patrick S.; Martin, Wayne L.

2017-01-01

Threat and Error Management (TEM) training, endorsed and recommended by the International Civil Aviation Organisation (ICAO), was mandated in Australia with the aim of improving aviation safety. However, to date, there has been very limited, if any, formal post-implementation review, assessment or evaluation to examine the "after-state"…

Perioperative Mortality, 2010 to 2014: A Retrospective Cohort Study Using the National Anesthesia Clinical Outcomes Registry.

PubMed

Whitlock, Elizabeth L; Feiner, John R; Chen, Lee-Lynn

2015-12-01

The National Anesthesia Clinical Outcomes Registry collects demographic and outcome data from anesthesia cases, with the goal of improving safety and quality across the specialty. The authors present a preliminary analysis of the National Anesthesia Clinical Outcomes Registry database focusing on the rates of and associations with perioperative mortality (within 48 h of anesthesia induction). The authors retrospectively analyzed 2,948,842 cases performed between January 1, 2010, and May 31, 2014. Cases without procedure information and vaginal deliveries were excluded. Mortality and other outcomes were reported by the anesthesia provider. Hierarchical logistic regression was performed on cases with complete information for patient age group, sex, American Society of Anesthesiologists physical status, emergency case status, time of day, and surgery type, controlling for random effects within anesthesia practices. The final analysis included 2,866,141 cases and 944 deaths (crude mortality rate, 33 per 100,000). Increasing American Society of Anesthesiologists physical status, emergency case status, cases beginning between 4:00 PM and 6:59 AM, and patient age less than 1 yr or greater than or equal to 65 yr were independently associated with higher perioperative mortality. A post hoc subgroup analysis of 279,154 patients limited to 22 elective case types, post hoc models incorporating either more granular estimate of surgical risk or work relative value units, and a post hoc propensity score-matched cohort confirmed the association with time of day. Several factors were associated with increased perioperative mortality. A case start time after 4:00 PM was associated with an adjusted odds ratio of 1.64 (95% CI, 1.22 to 2.21) for perioperative death, which suggests a potentially modifiable target for perioperative risk reduction. Limitations of this study include nonstandardized mortality reporting and limited ability to adjust for missing data.

Adapting Dialectical Behavior Therapy for the Treatment of Dissociative Identity Disorder.

PubMed

Foote, Brad; Van Orden, Kim

2016-12-31

Dialectical Behavior Therapy (DBT), created by Marsha Linehan, has been shown to be an effective therapy for the treatment of borderline personality disorder (BPD) and for suicidal and self-harming behavior. Dissociative identity disorder (DID) is a complex post-traumatic disorder which is highly comorbid with BPD, shares a number of clinical features with BPD, and which like BPD features a high degree of suicidality. The DID treatment literature emphasizes the importance of a staged approach, beginning with the creation of a safe therapeutic frame prior to addressing traumatic material; DBT is also a staged treatment, in which behavioral and safety issues are addressed in Stage 1, and trauma work reserved for Stage 2. The authors describe adapting DBT, and especially its techniques for Stage 1 safety work, for work with DID patients. Basic theoretical principles are described and illustrated with a case example.

Adapting Dialectical Behavior Therapy for the Treatment of Dissociative Identity Disorder

PubMed Central

Foote, Brad; Van Orden, Kim

2017-01-01

Dialectical Behavior Therapy, created by Marsha Linehan, has been shown to be an effective therapy for the treatment of borderline personality disorder (BPD) and for suicidal and self-harming behavior. Dissociative identity disorder (DID) is a complex post-traumatic disorder which is highly comorbid with BPD, shares a number of clinical features with BPD, and which like BPD features a high degree of suicidality. The DID treatment literature emphasizes the importance of a staged approach, beginning with the creation of a safe therapeutic frame prior to addressing traumatic material; DBT is also a staged treatment, where behavioral and safety issues are addressed in Stage 1 and trauma work reserved for Stage 2. The authors describe adapting DBT, and especially its techniques for Stage 1 safety work, for work with DID patients. Basic theoretical principles are described and illustrated with a case example. PMID:28068498

Food Safety Instruction Improves Knowledge and Behavior Risk and Protection Factors for Foodborne Illnesses in Pregnant Populations.

PubMed

Kendall, Patricia; Scharff, Robert; Baker, Susan; LeJeune, Jeffrey; Sofos, John; Medeiros, Lydia

2017-08-01

Objective This study compared knowledge and food-handling behavior after pathogen-specific (experimental treatment) versus basic food safety instruction (active control) presented during nutrition education classes for low-income English- and Spanish-language pregnant women. Methods Subjects (n = 550) were randomly assigned to treatment groups in two different locations in the United States. Food safety instruction was part of an 8-lesson curriculum. Food safety knowledge and behavior were measured pre/post intervention. Descriptive data were analyzed by Chi-Square or ANOVA; changes after intervention were analyzed by regression analysis. Results Knowledge improved after intervention in the pathogen-specific treatment group compared to active control, especially among Spanish-language women. Behavior change after intervention for the pathogen-specific treatment group improved for thermometer usage, refrigeration and consumption of foods at high risk for safety; however, all other improvements in behavior were accounted for by intervention regardless of treatment group. As expected, higher pre-instruction behavioral competency limited potential gain in behavior post-instruction due to a ceiling effect. This effect was more dominant among English-language women. Improvements were also linked to formal education completed, a partner at home, and other children in the home. Conclusions for Practice This study demonstrated that pathogen-specific food safety instruction leads to enhance knowledge and food handling behaviors that may improve the public health of pregnant women and their unborn children, especially among Spanish-language women. More importantly, food safety instruction, even at the most basic level, benefited pregnant women's food safety knowledge and food-handling behavior after intervention.

Post market surveillance in the german medical device sector - current state and future perspectives.

PubMed

Zippel, Claus; Bohnet-Joschko, Sabine

2017-08-01

Medical devices play a central role in the diagnosis and treatment of diseases but also bring the potential for adverse events, hazards or malfunction with serious consequences for patients and users. Medical device manufacturers are therefore required by law to monitor the performance of medical devices that have been approved by the competent authorities (post market surveillance). Conducting a nationwide online-survey in the German medical device sector in Q2/2014 in order to explore the current status of the use of post market instruments we obtained a total of 118 complete data sets, for a return rate of 36%. The survey included manufacturers of different sizes, producing medical devices of all risk classes. The post market instruments most frequently reported covered the fields of production monitoring and quality management as well as literature observation, regulatory vigilance systems, customer knowledge management and market observation while Post Market Clinical Follow-up and health services research were being used less for product monitoring. We found significant differences between the different risk classes of medical devices produced and the intensity of use of post market instruments. Differences between company size and the intensity of instruments used were hardly detected. Results may well contribute to the development of device monitoring which is a crucial element of the policy and regulatory system to identify device-related safety issues. Copyright © 2017 Elsevier B.V. All rights reserved.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects

PubMed Central

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-01-01

ABSTRACT Aim: To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Methods: Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). Results: No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Conclusions: Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China. PMID:28121231

Hospital support services and the impacts of outsourcing on occupational health and safety.

PubMed

Siganporia, Pearl; Astrakianakis, George; Alamgir, Hasanat; Ostry, Aleck; Nicol, Anne-Marie; Koehoorn, Mieke

2016-10-01

Outsourcing labor is linked to negative impacts on occupational health and safety (OHS). In British Columbia, Canada, provincial health care service providers outsource support services such as cleaners and food service workers (CFSWs) to external contractors. This study investigates the impact of outsourcing on the occupational health safety of hospital CFSWs through a mixed methods approach. Worker's compensation data for hospital CFSWs were analyzed by negative binomial and multiple linear regressions supplemented by iterative thematic analysis of telephone interviews of the same job groups. Non-significant decreases in injury rates and days lost per injury were observed in outsourced CFSWs post outsourcing. Significant decreases (P < 0.05) were observed in average costs per injury for cleaners post outsourcing. Outsourced workers interviewed implied instances of underreporting workplace injuries. This mixed methods study describes the impact of outsourcing on OHS of healthcare workers in British Columbia. Results will be helpful for policy-makers and workplace regulators to assess program effectiveness for outsourced workers.

Hospital support services and the impacts of outsourcing on occupational health and safety

PubMed Central

Alamgir, Hasanat; Ostry, Aleck; Nicol, Anne-Marie; Koehoorn, Mieke

2016-01-01

Background Outsourcing labor is linked to negative impacts on occupational health and safety (OHS). In British Columbia, Canada, provincial health care service providers outsource support services such as cleaners and food service workers (CFSWs) to external contractors. Objectives This study investigates the impact of outsourcing on the occupational health safety of hospital CFSWs through a mixed methods approach. Methods Worker’s compensation data for hospital CFSWs were analyzed by negative binomial and multiple linear regressions supplemented by iterative thematic analysis of telephone interviews of the same job groups. Results Non-significant decreases in injury rates and days lost per injury were observed in outsourced CFSWs post outsourcing. Significant decreases (P < 0.05) were observed in average costs per injury for cleaners post outsourcing. Outsourced workers interviewed implied instances of underreporting workplace injuries. Conclusions This mixed methods study describes the impact of outsourcing on OHS of healthcare workers in British Columbia. Results will be helpful for policy-makers and workplace regulators to assess program effectiveness for outsourced workers. PMID:27696988

Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate.

PubMed

Batzloff, Michael R; Fane, Anne; Gorton, Davina; Pandey, Manisha; Rivera-Hernandez, Tania; Calcutt, Ainslie; Yeung, Grace; Hartas, Jon; Johnson, Linda; Rush, Catherine M; McCarthy, James; Ketheesan, Natkunam; Good, Michael F

2016-12-01

Streptococcus pyogenes (group A streptococcus, GAS) causes a wide range of clinical manifestations ranging from mild self-limiting pyoderma to invasive diseases such as sepsis. Also of concern are the post-infectious immune-mediated diseases including rheumatic heart disease. The development of a vaccine against GAS would have a large health impact on populations at risk of these diseases. However, there is a lack of suitable models for the safety evaluation of vaccines with respect to post-infectious complications. We have utilized the Lewis Rat model for cardiac valvulitis to evaluate the safety of the J8-DT vaccine formulation in parallel with a rabbit toxicology study. These studies demonstrated that the vaccine did not induce abnormal pathology. We also show that in mice the vaccine is highly immunogenic but that 3 doses are required to induce protection from a GAS skin challenge even though 2 doses are sufficient to induce a high antibody titer.

Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate

PubMed Central

Batzloff, Michael R.; Fane, Anne; Gorton, Davina; Pandey, Manisha; Rivera-Hernandez, Tania; Calcutt, Ainslie; Yeung, Grace; Hartas, Jon; Johnson, Linda; Rush, Catherine M.; McCarthy, James; Ketheesan, Natkunam; Good, Michael F.

2016-01-01

ABSTRACT Streptococcus pyogenes (group A streptococcus, GAS) causes a wide range of clinical manifestations ranging from mild self-limiting pyoderma to invasive diseases such as sepsis. Also of concern are the post-infectious immune-mediated diseases including rheumatic heart disease. The development of a vaccine against GAS would have a large health impact on populations at risk of these diseases. However, there is a lack of suitable models for the safety evaluation of vaccines with respect to post-infectious complications. We have utilized the Lewis Rat model for cardiac valvulitis to evaluate the safety of the J8-DT vaccine formulation in parallel with a rabbit toxicology study. These studies demonstrated that the vaccine did not induce abnormal pathology. We also show that in mice the vaccine is highly immunogenic but that 3 doses are required to induce protection from a GAS skin challenge even though 2 doses are sufficient to induce a high antibody titer. PMID:27541593

Reactogenicity and safety of the human rotavirus vaccine, Rotarix™ in The Philippines, Sri Lanka, and India: a post-marketing surveillance study.

PubMed

Bravo, Lulu; Chitraka, Amarjeet; Liu, Aixue; Choudhury, Jaydeep; Kumar, Kishore; Berezo, Lennie; Cimafranca, Leonard; Chatterjee, Pallab; Garg, Pankaj; Siriwardene, Prasanna; Bernardo, Rommel; Mehta, Shailesh; Balasubramanian, Sundaram; Karkada, Naveen; Htay Han, Htay

2014-01-01

Regulatory bodies in The Philippines, Sri Lanka, and India require post-marketing surveillance to provide additional safety data on Rotarix™ in real-life settings. In such studies conducted in The Philippines (November 2006 to July 2012; NCT00353366), Sri Lanka (November 2008 to August 2009; NCT00779779), and India (August 2009 to April 2010; NCT00938327), 2 doses of Rotarix™ were administered according to the local prescribing information (PI). The occurrence of at least Grade "2"/"3" solicited adverse event (AE) (fever, vomiting, or diarrhea), within 15 days in The Philippines or 8 days in Sri Lanka and India; unsolicited AEs within 31 days and serious adverse events (SAEs) throughout the study were recorded. Of the 1494, 522, and 332 infants enrolled in The Philippines, Sri Lanka, and India, 14.7% 14.9% and 12.7% infants, respectively recorded at least Grade "2"/"3" solicited AEs. The most commonly reported solicited AEs were irritability in The Philippines (32.2% post-Dose-1; 23.5% post-Dose-2) and India (23.0% post-Dose-1; 13.2% post-Dose-2), and fever (18.0% post-Dose-1; 20.2% post-Dose-2) in Sri Lanka. Unsolicited AEs were recorded in 24.5% (The Philippines), 4.8% (Sri Lanka), and 6.9% (India) of infants. Forty-one SAEs were recorded in the Philippines of which 6 (decreased oral intake with increased sleeping time and constipation; pneumonia, urinary tract infection, and intussusception) were considered by the investigators as causally related to vaccination. One vaccine-unrelated SAE occurred in a Sri Lankan infant. All SAEs resolved and the infants recovered. Two doses of Rotarix™, administered to healthy infants according to local PI, were well tolerated in The Philippines, Sri Lanka, and India.

Creating Safe Environments for Children with Post-Traumatic Stress Disorder.

ERIC Educational Resources Information Center

Demaree, Mary Ann

1995-01-01

Discusses development of Post-Traumatic Stress Disorder (PTSD) in children living in violent homes and communities. Discusses the role of teachers in creating classrooms that feel safe. Notes the importance of relearning safety to children who have PTSD. Describes strategies to create feeling of safety in the children. (BAC)

Clinical safety of the ProMRI pacemaker system in patients subjected to thoracic spine and cardiac 1.5-T magnetic resonance imaging scanning conditions.

PubMed

Bailey, William M; Mazur, Alexander; McCotter, Craig; Woodard, Pamela K; Rosenthal, Lawrence; Johnson, Whitney; Mela, Theofanie

2016-02-01

Permanent cardiac pacemakers have historically been considered a contraindication to magnetic resonance imaging (MRI). The purpose of the ProMRI Phase B Study, a multicenter, prospective, single-arm, nonrandomized study, was to evaluate the clinical safety of the Biotronik ProMRI pacemaker system in patients undergoing thoracic spine and cardiac MRI. The ProMRI Phase B study enrolled 245 patients with stable baseline pacing indices implanted with an Entovis pacemaker (DR-T or SR-T) and Setrox 53-cm and/or 60-cm lead(s). Device interrogation was performed at enrollment, pre- and post-MRI scan, and 1 and 3 months post-MRI. End-points were (1) freedom from MRI- and pacing system-related serious adverse device effects through 1 month post-MRI; (2) freedom from atrial and ventricular MRI-induced pacing threshold increase (>0.5 V); and (3) freedom from P- and R-wave amplitude attenuation (<50%), or P wave <1.5 mV, or R wave <5.0 mV at 1 month post-MRI. In total, 216 patients completed the MRI and 1-month post-MRI follow-up. One adverse event possibly related to the implanted system and the MRI procedure occurred, resulting in a serious adverse device effect-free rate of 99.6% (220/221; P < .0001. Freedom from atrial and ventricular pacing threshold increase was 100% (194/194, P < .001) and 100% (206/206, P < .001) respectively. Freedom from P- and R-wave amplitude attenuation was 98.2% (167/170, P < .001) and 100% (188/188, P < .001) respectively. The results of the ProMRI Phase B study demonstrate the clinical safety and efficacy of the ProMRI pacemaker system in patients subjected to thoracic spine and cardiac MRI conditions. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Local tolerability and effectiveness of Ketospray® 10% cutaneous spray solution.

PubMed

Fulga, I; Lupescu, O; Spircu, T

2012-12-01

Orally administrated nonsteroidal anti-inflammatory drugs are effective in the treatment of a variety of acute and chronic pain conditions but their use may be associated with serious systemic adverse effects which are correlated with the therapeutic plasma levels of the drug. In order to minimize the incidence of drug related systemic events, topical formulations of the nonsteroidal anti-inflammatory drugs have been developed. A recently performed review of the evidence from randomized, double-blind, placebo controlled trials with topically applied NSAIDs in the treatment of acute pain confirmed the previously described pain relief effectiveness. For all topical nonsteroidal anti-inflammatory drugs combined, in comparison to placebo, the number needed to treat (NNT) to achieve a clinically meaningful pain relief of 50 % was 4.5 (3.9 to 5.3) for treatment periods of 6 to 14 days. Local skin reactions were generally mild and transient, and did not differ from placebo. The present is an observational, multicenter, open-label, non-interventional, post-authorization safety study as it is defined by Article 21 of the European Clinical Trials Directive 2001/20/EC. The main objective of this study was to evaluate the local tolerability and the therapeutic efficacy of static and pain on movement intensity reduction of Ketospray® 10% cutaneous spray solution administered in accordance with the terms of the marketing authorization and last version of summary of product characteristics approved by National Medicines Agency of Romania. In compliance with the Post-marketing study type, the assignment of the patient to a particular therapeutic strategy fell within current practice. The prescription of the medicine was not subject to compliance with predefined patients' characteristics. No specific, out of the daily practice routine diagnostic, monitoring, instrumental or laboratory assessments were foreseen by the study protocol. Patients' data were collected into respective case report forms. Study medication, Ketoprofen 10% Cutaneous Spray Solution was administered to the affected area at the dose of 3-6 spray puffs, 2-3 times a day, for 7 days. According to the study type, descriptive statistical methods were applied. Since almost half of the patients were treated with combination of the pain relieving medications, sizing of the pain relieving effects, as NNT, between the two groups was made. There were 2020 study subjects in safety and ITT analysis population and 1802 (89%) in PP efficacy analysis population. There were 4 types of injuries: non-complicated strain-sprain (555), soft tissue contusion (323), low back pain (461) and osteoarthritis (681 patients). Ten patients reported 13 side effects of which 10 were recognized by investigators as adverse drug reactions. All side effects were non-serious, listed, application site skin changes. Remarkable reductions of static and pain on movement intensity were experienced by patients irrespective of the type of the injury and the type of the treatment. However, a clinically meaningful benefit of the concomitantly prescribed pain relieving medications was not observed for any type of pain. The lowest NNT (14) was obtained for the reduction of pain at rest in patients with strain-sprain or soft tissue contusions. The highest NNT (283) was for pain at rest in patients treated for the exacerbation of the chronic pain. The results of the current post-authorization study confirm beneficial pain intensity reducing efficacy of Ketospray 10% associated with good local tolerability of 7 days treatment course. Concomitant administration of systemic pain relieving medication did not substantially contribute neither to the relief of pain at rest nor of pain on movement among the subjects of respective study populations.

Eight-year follow-up data from the U.S. clinical trial for Sientra's FDA-approved round and shaped implants with high-strength cohesive silicone gel.

PubMed

Stevens, W Grant; Harrington, Jennifer; Alizadeh, Kaveh; Broadway, David; Zeidler, Kamakshi; Godinez, Tess B

2015-05-01

On March 9, 2012, the Food and Drug Administration (FDA) approved Sientra's premarket approval application for its portfolio of silicone gel breast implants based on their review of Sientra's 3-year study data from the largest pivotal silicone gel breast implant study to date. This included the first approval of shaped breast implants in the United States. The authors provide an update to the 8-year safety and effectiveness of the Sientra High-Strength silicone gel breast implants. The Sientra Core study is an ongoing 10 year open-label, prospective, multi-center clinical study, which includes 1788 patients implanted with 3506 Sientra implants across four indications (Primary Augmentation, Revision Augmentation, Primary Reconstruction, and Revision Reconstruction). For the safety analysis, the incidence of post-operative complications, including all breast implant-related adverse effects (eg, infection, asymmetry), was estimated based on Kaplan-Meier risk rates. The effectiveness analyses include surgeon and patient satisfaction and changes in bra/cup size. Through 8 years, the overall risk of rupture was 4.6%, the risk of capsular contracture was 11.8% (rates were lower when using True Texture™), and the risk of reoperation was 28.3%. Out of the 580 reoperations in 456 patients, over half of all reoperations were due to cosmetic reasons (n = 299). The most common reasons for reoperation were capsular contracture (19.0%), style and/or size change (18.4%), and asymmetry (8.8%). Patient satisfaction remains high through 8 years, with 87% indicating that their breast implants make them feel more feminine than prior to enrollment. Safety data from the FDA Core study continues to support a comprehensive safety and effectiveness profile of Sientra's portfolio of round and shaped implants through 8 years. 3 Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

40 CFR 170.135 - Posted pesticide safety information.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., pesticide safety information. (b) Pesticide safety poster. A safety poster must be displayed that conveys..., and telephone number of the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The agricultural employer shall inform workers promptly of any...

40 CFR 170.135 - Posted pesticide safety information.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., pesticide safety information. (b) Pesticide safety poster. A safety poster must be displayed that conveys..., and telephone number of the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The agricultural employer shall inform workers promptly of any...

40 CFR 170.135 - Posted pesticide safety information.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., pesticide safety information. (b) Pesticide safety poster. A safety poster must be displayed that conveys..., and telephone number of the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The agricultural employer shall inform workers promptly of any...

40 CFR 170.135 - Posted pesticide safety information.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., pesticide safety information. (b) Pesticide safety poster. A safety poster must be displayed that conveys..., and telephone number of the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The agricultural employer shall inform workers promptly of any...

40 CFR 170.135 - Posted pesticide safety information.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., pesticide safety information. (b) Pesticide safety poster. A safety poster must be displayed that conveys..., and telephone number of the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The agricultural employer shall inform workers promptly of any...

The Impact of Market Orientation on Patient Safety Climate Among Hospital Nurses.

PubMed

Weng, Rhay-Hung; Chen, Jung-Chien; Pong, Li-Jung; Chen, Li-Mei; Lin, Tzu-Chi

2016-03-01

Improving market orientation and patient safety have become the key concerns of nursing management. For nurses, establishing a patient safety climate is the key to enhancing nursing quality. This study explores how market orientation affects the climate of patient safety among hospital nurses. We proposed adopting a cross-sectional research design and using questionnaires to collect responses from nurses working in two Taiwanese hospitals. Three-hundred and forty-three valid samples were obtained. Multiple regression and path analyses were conducted to test the study. Market orientation was defined as the combination of customer orientation, competitor orientation, and interfunctional coordination. Customer orientation directly affects the climate of patient safety. Although the findings only supported Hypothesis 1, competitor orientation and interfunctional coordination positively affected the patient safety climate through the mediating effects of hospital support for staff. Health care managers could encourage nurses to adopt customer-oriented perspectives to enhance their nursing care. In addition, to enhance competitor orientation, interfunctional coordination, and the patient safety climate, hospital managers could strengthen their support for staff members. © The Author(s) 2014.

Incentivizing primary care providers to innovate: building medical homes in the post-Katrina New Orleans safety net.

PubMed

Rittenhouse, Diane R; Schmidt, Laura A; Wu, Kevin J; Wiley, James

2014-02-01

To evaluate safety-net clinics' responses to a novel community-wide Patient-Centered Medical Home (PCMH) financial incentive program in post-Katrina New Orleans. Between June 2008 and June 2010, we studied 50 primary care clinics in New Orleans receiving federal funds to expand services and improve care delivery. Multiwave, longitudinal, observational study of a local safety-net primary care system. Clinic-level data from a semiannual survey of clinic leaders (89.3 percent response rate), augmented by administrative records. Overall, 62 percent of the clinics responded to financial incentives by achieving PCMH recognition from the National Committee on Quality Assurance (NCQA). Higher patient volume, higher baseline PCMH scores, and type of ownership were significant predictors of achieving NCQA recognition. The steepest increase in adoption of PCMH processes occurred among clinics achieving the highest, Level 3, NCQA recognition. Following NCQA recognition, 88.9 percent stabilized or increased their use of PCMH processes, although several specific PCMH processes had very low rates of adoption overall. Findings demonstrate that widespread PCMH implementation is possible in a safety-net environment when external financial incentives are aligned with the goal of practice innovation. © Health Research and Educational Trust.

Monitoring safety in a phase III real-world effectiveness trial: use of novel methodology in the Salford Lung Study.

PubMed

Collier, Sue; Harvey, Catherine; Brewster, Jill; Bakerly, Nawar Diar; Elkhenini, Hanaa F; Stanciu, Roxana; Williams, Claire; Brereton, Jacqui; New, John P; McCrae, John; McCorkindale, Sheila; Leather, David

2017-03-01

The Salford Lung Study (SLS) programme, encompassing two phase III pragmatic randomised controlled trials, was designed to generate evidence on the effectiveness of a once-daily treatment for asthma and chronic obstructive pulmonary disease in routine primary care using electronic health records. The objective of this study was to describe and discuss the safety monitoring methodology and the challenges associated with ensuring patient safety in the SLS. Refinements to safety monitoring processes and infrastructure are also discussed. The study results are outside the remit of this paper. The results of the COPD study were published recently and a more in-depth exploration of the safety results will be the subject of future publications. The SLS used a linked database system to capture relevant data from primary care practices in Salford and South Manchester, two university hospitals and other national databases. Patient data were collated and analysed to create daily summaries that were used to alert a specialist safety team to potential safety events. Clinical research teams at participating general practitioner sites and pharmacies also captured safety events during routine consultations. Confidence in the safety monitoring processes over time allowed the methodology to be refined and streamlined without compromising patient safety or the timely collection of data. The information technology infrastructure also allowed additional details of safety information to be collected. Integration of multiple data sources in the SLS may provide more comprehensive safety information than usually collected in standard randomised controlled trials. Application of the principles of safety monitoring methodology from the SLS could facilitate safety monitoring processes for future pragmatic randomised controlled trials and yield important complementary safety and effectiveness data. © 2016 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. © 2016 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

Long-term risks of kidney living donation: review and position paper by the ERA-EDTA DESCARTES working group.

PubMed

Maggiore, Umberto; Budde, Klemens; Heemann, Uwe; Hilbrands, Luuk; Oberbauer, Rainer; Oniscu, Gabriel C; Pascual, Julio; Schwartz Sorensen, Soren; Viklicky, Ondrej; Abramowicz, Daniel

2017-02-01

Two recent matched cohort studies from the USA and Norway published in 2014 have raised some concerns related to the long-term safety of kidney living donation. Further studies on the long-term risks of living donation have since been published. In this position paper, Developing Education Science and Care for Renal Transplantation in European States (DESCARTES) board members critically review the literature in an effort to summarize the current knowledge concerning long-term risks of kidney living donation to help physicians for decision-making purposes and for providing information to the prospective live donors. Long-term risk of end-stage renal disease (ESRD) can be partially foreseen by trying to identify donors at risk of developing ‘de novo’ kidney diseases during life post-donation and by predicting lifetime ESRD risk. However, lifetime risk may be difficult to assess in young donors, especially in those having first-degree relatives with ESRD. The study from Norway also found an increased risk of death after living donor nephrectomy, which became visible only after >15 years of post-donation follow-up. However, these findings are likely to be largely the result of an overestimation due to the confounding effect related to a family history of renal disease. DESCARTES board members emphasize the importance of optimal risk–benefit assessment and proper information to the prospective donor, which should also include recommendations on health-promoting behaviour post-donation. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Biomonitoring at the UK Health and Safety Laboratory.

PubMed

Cocker, J; Jones, K; Morton, J; Mason, H J

2007-05-01

The UK Health and Safety Laboratory (HSL) provides research and analytical support to the Health and Safety Executive, other Government Departments and employers. In the area of biomonitoring HSL conducts research studies and provides an analytical service for regular surveillance of worker exposure to hazardous substances. This paper gives brief examples of how data from such studies can be used to develop biological monitoring guidance values for isocyanates, polycyclic aromatic hydrocarbons and hexavalent chromium. In addition, a study of occupational exposure to copper chrome arsenic wood preservatives is briefly described to show how biological monitoring can be used for post-approval surveillance of a biocide.

Patients as teachers: a randomised controlled trial on the use of personal stories of harm to raise awareness of patient safety for doctors in training.

PubMed

Jha, Vikram; Buckley, Hannah; Gabe, Rhian; Kanaan, Mona; Lawton, Rebecca; Melville, Colin; Quinton, Naomi; Symons, Jools; Thompson, Zoe; Watt, Ian; Wright, John

2015-01-01

Patient safety training often provides learners with a health professional's perspective rather than the patient's. Personal narratives of health-related harm allow patients to share their stories with health professionals to influence clinical behaviour by rousing emotions and improving attitudes to safety. This study measured the impact of patient narratives used to train junior doctors in patient safety. An open, multi-centre, two-arm, parallel design randomised controlled trial was conducted in the North Yorkshire East Coast Foundation School (NYECFS). The intervention consisted of 1-h-long patient narratives followed by discussion. The control arm received conventional faculty-delivered teaching. The Attitude to Patient Safety Questionnaire (APSQ) and the Positive and Negative Affect Schedule (PANAS) were used to measure the impact of the intervention. 142 trainees received the intervention; 141 the control teaching. There was no evidence of a difference in post-intervention APSQ scores between the groups. There was a statistically significant difference in the underlying distribution of both post PA (positive affect) and post NA (negative affect) scores between the groups on the PANAS (p<0.001) with indications of both higher PA and NA scores in the intervention group. Involving patients with experiences of safety incidents in training has an ideological appeal and seems an obvious choice in designing safety interventions. On the basis of our primary outcome measure, we were unable to demonstrate effectiveness of the intervention in changing general attitudes to safety compared to control. While the intervention may impact on emotional engagement and learning about communication, we remain uncertain whether this will translate into improved behaviours in the clinical context or indeed if there are any negative effects. Grant reference no. RP-PG-0108-10049. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Post-licensure safety surveillance of 23-valent pneumococcal polysaccharide vaccine in the Vaccine Adverse Event Reporting System (VAERS), 1990-2013.

PubMed

Miller, Elaine R; Moro, Pedro L; Cano, Maria; Lewis, Paige; Bryant-Genevier, Marthe; Shimabukuro, Tom T

2016-05-27

23-Valent pneumococcal polysaccharide vaccine, trade name Pneumovax(®)23 (PPSV23), has been used for decades in the Unites States and has an extensive clinical record. However, limited post-licensure safety assessment has been conducted. To analyze reports submitted to the Vaccine Adverse Event Reporting System (VAERS) following PPSV23 from 1990 to 2013 in order to characterize its safety profile. We searched the VAERS database for US reports following PPSV23 for persons vaccinated from 1990 to 2013. We assessed safety through: automated analysis of VAERS data, crude adverse event (AE) reporting rates based on PPSV23 doses distributed in the US market, clinical review of death reports and reports involving vaccine administered to pregnant women, and empirical Bayesian data mining to assess for disproportional reporting. During the study period, VAERS received 25,168 PPSV23 reports; 92% were non-serious, 67% were in females and 86% were in adults aged ≥19 years. When PPSV23 was administered alone, fever (43%), injection site erythema (28%) and injection site pain (25%) were the most commonly reported non-serious AEs in children. Injection site erythema (32%), injection site pain (27%) and injection site swelling (23%) were the most commonly reported non-serious AEs in adults. Of serious reports (2129, 8% of total), fever was most commonly reported in both children (69%) and adults (39%). There were 66 reports of death, four in children and 62 in adults. Clinical review of death reports did not reveal any concerning patterns that would suggest a causal association with PPSV23. No disproportional reporting of unexpected AEs was observed in empirical Bayesian data mining. We did not identify any new or unexpected safety concerns for PPSV23. The VAERS data are consistent with safety data from pre-licensure clinical trials and other post-licensure studies. Published by Elsevier Ltd.

Safety and efficacy of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice: interim results of the STELLA-LONG TERM post-marketing surveillance study.

PubMed

Nakamura, Ichiro; Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Uno, Satoshi

2018-02-01

Data regarding the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in the real-world setting in Japan are limited. The STELLA-LONG TERM study is an ongoing 3-year post-marketing surveillance study of ipragliflozin in type 2 diabetes (T2D) patients. Here, we report the interim results (including 3-, 12-, and 24-month data). All Japanese patients with T2D who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan were registered in STELLA-LONG TERM. At 3, 12, and 24 months, the safety analysis set comprised 11,053, 5475, and 138 patients, respectively; the efficacy analysis set comprised 8757 patients. Ipragliflozin treatment resulted in statistically significant improvements versus baseline in hemoglobin A1c, fasting plasma glucose concentration, body weight, blood pressure, heart rate, and serum concentrations of low-density lipoprotein cholesterol and triglycerides. The adverse drug reaction incidence rate was 10.71%, the most common reactions being renal and urinary disorders (5.06%), infections and infestations (1.24%), and skin and subcutaneous tissue disorders (1.14%). Ipragliflozin was well tolerated and effective in Japanese patients with T2D; no new safety issues were identified.

Citizen sensors for SHM: use of accelerometer data from smartphones.

PubMed

Feng, Maria; Fukuda, Yoshio; Mizuta, Masato; Ozer, Ekin

2015-01-29

Ubiquitous smartphones have created a significant opportunity to form a low-cost wireless Citizen Sensor network and produce big data for monitoring structural integrity and safety under operational and extreme loads. Such data are particularly useful for rapid assessment of structural damage in a large urban setting after a major event such as an earthquake. This study explores the utilization of smartphone accelerometers for measuring structural vibration, from which structural health and post-event damage can be diagnosed. Widely available smartphones are tested under sinusoidal wave excitations with frequencies in the range relevant to civil engineering structures. Large-scale seismic shaking table tests, observing input ground motion and response of a structural model, are carried out to evaluate the accuracy of smartphone accelerometers under operational, white-noise and earthquake excitations of different intensity. Finally, the smartphone accelerometers are tested on a dynamically loaded bridge. The extensive experiments show satisfactory agreements between the reference and smartphone sensor measurements in both time and frequency domains, demonstrating the capability of the smartphone sensors to measure structural responses ranging from low-amplitude ambient vibration to high-amplitude seismic response. Encouraged by the results of this study, the authors are developing a citizen-engaging and data-analytics crowdsourcing platform towards a smartphone-based Citizen Sensor network for structural health monitoring and post-event damage assessment applications.

Effectiveness of post-fire Burned Area Emergency Response (BAER) road treatments: Results from three wildfires

Treesearch

Randy B. Foltz; Peter Robichaud

2013-01-01

Wildland fires often cause extreme changes in the landscape that drastically influence surface runoff and soil erosion, which can impact forest resources, aquatic habitats, water supplies, public safety, and forest access infrastructure such as forest roads. Little information is available on the effectiveness of various post-fire road treatments, thus this study was...

Combined laser in-situ keratomileusis and accelerated corneal cross-linking: an update.

PubMed

Tomita, Minoru

2016-07-01

The purpose is to review the literature of combined laser in-situ keratomileusis (LASIK) and accelerated corneal collagen cross-linking (CXL) in context of its indications-contraindications, kerato-refractive, visual and safety outcomes, particularly with reference to preventing the development of post-LASIK ectasia. LASIK + accelerated CXL has been developed with the rationale that the addition of CXL after LASIK may strengthen the LASIK compromised corneal biomechanics and minimize the complications such as post-LASIK ectasia. Different clinical studies have documented the safety and efficacy of LASIK + accelerated CXL for the correction of myopia or hyperopia and in the patients with low predicted residual bed thickness. Available literature shows that refractive and keratometric outcomes of LASIK + accelerated CXL are comparable or better than LASIK alone. Less regression has been observed after LASIK + accelerated CXL compared with LASIK alone and no case of post-LASIK ectasia development has been reported among 673 eyes with the follow-up ranging from 3 months to 4.5 years. Future studies with large numbers of patients and longer postoperative follow-ups are needed to establish the efficacy of LASIK + accelerated CXL in preventing the development of post-LASIK ectasia.

Life cycle assessment of a road safety product made with virgin and recycled HDPE.

PubMed

Simões, Carla L; Xará, Susana M; Bernardo, C A

2011-04-01

The present study aims at evaluating the potential environmental impact of using recycled high-density polyethylene (HDPE) in the production of an anti-glare lamella (AGL), a road safety device currently manufactured from virgin (not recycled) polymer. The impact was evaluated using the life cycle assessment (LCA) technique and comparing two alternative systems: current AGL, manufactured from virgin HDPE, and optional AGL, made with recycled HDPE obtained from post-consumer packages. The AGL manufacturing phase was found to be responsible for most of the impacts in both systems, with the production of the raw material being the largest contributor for that phase. The present study makes a contribution to the problem of developing value-added products made from post-consumer polymeric recyclates.

10 CFR 35.50 - Training for Radiation Safety Officer.

Code of Federal Regulations, 2011 CFR

2011-01-01

... authorized nuclear pharmacist identified on the licensee's license and has experience with the radiation... Radiation Safety Officer, authorized medical physicist, authorized nuclear pharmacist, or authorized user...

10 CFR 35.50 - Training for Radiation Safety Officer.

Code of Federal Regulations, 2014 CFR

2014-01-01

... authorized nuclear pharmacist identified on the licensee's license and has experience with the radiation... Radiation Safety Officer, authorized medical physicist, authorized nuclear pharmacist, or authorized user...

10 CFR 35.50 - Training for Radiation Safety Officer.

Code of Federal Regulations, 2012 CFR

2012-01-01

... authorized nuclear pharmacist identified on the licensee's license and has experience with the radiation... Radiation Safety Officer, authorized medical physicist, authorized nuclear pharmacist, or authorized user...

10 CFR 35.50 - Training for Radiation Safety Officer.

Code of Federal Regulations, 2013 CFR

2013-01-01

... authorized nuclear pharmacist identified on the licensee's license and has experience with the radiation... Radiation Safety Officer, authorized medical physicist, authorized nuclear pharmacist, or authorized user...

Comparison of blogged and written reflections in two medicine clerkships.

PubMed

Fischer, Melissa A; Haley, Heather-Lyn; Saarinen, Carrie L; Chretien, Katherine C

2011-02-01

academic medical centres may adopt new learning technologies with little data on their effectiveness or on how they compare with traditional methodologies. We conducted a comparative study of student reflective writings produced using either an electronic (blog) format or a traditional written (essay) format to assess differences in content, depth of reflection and student preference. students in internal medicine clerkships at two US medical schools during the 2008-2009 academic year were quasi-randomly assigned to one of two study arms according to which they were asked to either write a traditional reflective essay and subsequently join in faculty-moderated, small-group discussion (n = 45), or post two writings to a faculty-moderated group blog and provide at least one comment on a peer's posts (n = 50). Examples from a pilot block were used to refine coding methods and determine inter-rater reliability. Writings were coded for theme and level of reflection by two blinded authors; these coding processes reached inter-rater reliabilities of 91% and 80%, respectively. Anonymous pre- and post-clerkship surveys assessed student perceptions and preferences. student writing addressed seven main themes: (i) being humanistic; (ii) professional behaviour; (iii) understanding caregiving relationships; (iv) being a student; (v) clinical learning; (vi) dealing with death and dying, and (vii) the health care system, quality, safety and public health. The distribution of themes was similar across institutions and study arms. The level of reflection did not differ between study arms. Post-clerkship surveys showed that student preferences for blogging or essay writing were predicted by experience, with the majority favouring the method they had used. our study suggests there is no significant difference in themes addressed or levels of reflection achieved when students complete a similar assignment via online blogging or traditional essay writing. Given this, faculty staff should feel comfortable in utilising the blog format for reflective exercises. Faculty members could consider the option of using either format to address different learning styles of students.

Efficacy, safety and tolerability of rasagiline as adjunctive therapy in elderly patients with Parkinson's disease.

PubMed

Tolosa, E; Stern, M B

2012-02-01

Rasagiline, an MAO-B inhibitor, is indicated for the treatment of Parkinson's disease (PD). In this post hoc analysis, the efficacy, safety and tolerability of rasagiline as an adjunct to levodopa were compared with placebo in elderly (≥70 years) and younger (<70 years) patients with PD. Data were pooled from the Parkinson's Rasagiline: Efficacy and Safety on the Treatment of 'OFF' and Lasting effect in Adjunct therapy with Rasagiline Given Once daily randomized, double-blind, placebo-controlled trials with the primary efficacy end-point being the reduction from baseline in daily OFF time. Secondary efficacy end-points included scores for Clinical Global Improvement (CGI)-Examiner during ON time, Unified Parkinson's Disease Rating Scale (UPDRS)-ADL during OFF time, UPDRS-Motor during ON time and total daily ON time with and without troublesome dyskinesia. Tolerability was evaluated from adverse events (AEs) in the two age groups. Rasagiline decreased daily OFF time versus placebo (P<0.01) and improved CGI-Examiner score (P=0.001) and UPDRS-Motor ON score (P<0.05). Changes in UPDRS-ADL OFF score and total daily ON time without dyskinesia also favoured rasagiline but were not significant. Between-group comparisons (≥70 vs. <70 years) showed that efficacy was unaffected by age for all end-points (P>0.1), and rasagiline was well tolerated amongst both groups of patients with a comparable incidence of total and dopaminergic AEs (P>0.1). Adjunct rasagiline is efficacious and well tolerated in elderly non-demented patients (≥70 years) with moderate to advanced PD. Confirmation of the efficacy and safety of rasagiline in the elderly patient subgroup is especially relevant because of the increasing number of elderly patients with PD. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Efficacy and Safety of the Over-the-Scope Clip (OTSC) System in the Management of Leak and Fistula After Laparoscopic Sleeve Gastrectomy: a Systematic Review.

PubMed

Shoar, Saeed; Poliakin, Lauren; Khorgami, Zhamak; Rubenstein, Rebecca; El-Matbouly, Moamena; Levin, Jun L; Saber, Alan A

2017-09-01

Endoscopic management of leaks/fistulas after laparoscopic sleeve gastrectomy (LSG) is gaining popularity in the bariatric surgery. This study aimed to review the efficacy and safety of over-the-scope-clip (OTSC) system in endoscopic closure of post-LSG leak/fistula. PubMed/Medline and major journals of the field were systematically reviewed for studies on endoscopic closure of post-LSG leaks/fistula by means of the OTSC system. A total of ten eligible studies including 195 patients with post-LSG leaks/fistula were identified. The time between LSG and leak/fistula ranged from 1 day to 803 days. Most of the leaks/fistula were located at the proximal staple line, and they sized from 3 to 20 mm. Time between leak diagnosis and OTSC clipping ranged from 0 to 271 days. Thirty-three out of 53 patients (63.5%) required one clip for closure of the lesion. Regarding the OTSC-related complications, a leak occurred in five patients (9.3%) and OTSC migration, stenosis, and tear each in one patient (1.8%). Of the 73 patients with post-LSG leak treated with OTSC, 63 patients had an overall successful closure (86.3%). OTSC system is a promising endoscopic approach for management of post-LSG leaks in appropriately selected patients. Unfortunately, most studies are series with a small sample size, short-term follow-up, and mixed data of concomitant procedures with OTSC. Further studies should distinguish the net efficacy of the OTSC system from other concomitant procedures in treatment of post-LSG leak.

Transient Peripheral Immune Activation follows Elective Sigmoidoscopy or Circumcision in a Cohort Study of MSM at Risk of HIV Infection.

PubMed

Lama, Javier R; Karuna, Shelly T; Grant, Shannon P; Swann, Edith M; Ganoza, Carmela; Segura, Patricia; Montano, Silvia M; Lacherre, Martin; De Rosa, Stephen C; Buchbinder, Susan; Sanchez, Jorge; McElrath, M Juliana; Lemos, Maria P

2016-01-01

Rectal and genital sampling in HIV prevention trials permits assessments at the site of HIV entry. Yet the safety and acceptability of circumcision and sigmoidoscopy (and associated abstinence recommendations) are unknown in uncircumcised men who have sex with men (MSM) at high risk of HIV infection. Twenty-nine HIV-seronegative high-risk Peruvian MSM agreed to elective sigmoidoscopy biopsy collections (weeks 2 and 27) and circumcision (week 4) in a 28-week cohort study designed to mimic an HIV vaccine study mucosal collection protocol. We monitored adherence to abstinence recommendations, procedure-related complications, HIV infections, peripheral immune activation, and retention. Twenty-three (79.3%) underwent a first sigmoidoscopy, 21 (72.4%) were circumcised, and 16 (55.2%) completed a second sigmoidoscopy during the study period. All who underwent procedures completed the associated follow-up safety visits. Those completing the procedures reported they were well tolerated, and complication rates were similar to those reported in the literature. Immune activation was detected during the healing period (1 week post-sigmoidoscopy, 6 weeks post-circumcision), including increases in CCR5+CD4+T cells and α4β7+CD4+T cells. Most participants adhered to post-circumcision abstinence recommendations whereas reduced adherence occurred post-sigmoidoscopy. Rectosigmoid mucosal and genital tissue collections were safe in high-risk MSM. Although the clinical implications of the post-procedure increase in peripheral immune activation markers are unknown, they reinforce the need to provide ongoing risk reduction counseling and support for post-procedure abstinence recommendations. Future HIV vaccine studies should also consider the effects of mucosal and tissue collections on peripheral blood endpoints in trial design and analysis. ClinicalTrials.gov NCT02630082.

Preventive medicines: vaccination, prophylaxis of infectious diseases, disinfectants.

PubMed

Heininger, Ulrich

2011-01-01

Immunizations belong to the most successful interventions in medicine. Like other drugs, vaccines undergo long periods of pre-clinical development, followed by careful clinical testing through study Phases I, II, and III before they receive licensure. A successful candidate vaccine will move on to be an investigational vaccine to undergo three phases of pre-licensure clinical trials in a stepwise fashion before it can be considered for approval, followed by an optional fourth phase of post-marketing assessment. The overall risk-benefit assessment of a candidate vaccine is very critical in making the licensure decision for regulatory authorities, supported by their scientific committees. It includes analyses of immunogenicity, efficacy, reactogenicity or tolerability, and safety of the vaccine. Public trust in vaccines is a key to the success of immunization programs worldwide. Maintaining this trust requires knowledge of the benefits and scientific understanding of real or perceived risks of immunizations. Under certain circumstances, pre- or post-exposure passive immunization can be achieved by administration of immunoglobulines. In terms of prevention of infectious diseases, disinfection can be applied to reduce the risk of transmission of pathogens from patient to patient, health-care workers to patients, patients to health-care workers, and objects or medical devices to patients.

Post-event debriefings during neonatal care: why are we not doing them, and how can we start?

PubMed

Sawyer, T; Loren, D; Halamek, L P

2016-06-01

Post-event debriefings are a foundational behavior of high performing teams. Despite the inherent value of post-event debriefings, the frequency with which they are used in neonatal care is extremely low. If post-event debriefings are so beneficial, why aren't they conducted more frequently? The reasons are many, but solutions are available. In this report, we provide practical advice on conducting post-event debriefing in neonatal care. In addition, we examine the perceived barriers to conducting post-event debriefings, and offer strategies to overcome them. Finally, we consider opportunities to foster a culture change within neonatal care which integrates debriefing as standard daily work. By establishing a safety culture in neonatal care that encourages and facilitates effective post-event debriefings, patient safety can be enhanced and clinical outcomes can be improved.

Intermediate clinical and radiological results of cervical TDR (Mobi-C®) with up to 2 years of follow-up

PubMed Central

Beaurain, J.; Bernard, P.; Dufour, T.; Fuentes, J. M.; Hovorka, I.; Huppert, J.; Steib, J. P.; Vital, J. M.; Aubourg, L.

2009-01-01

The interest in cervical total disc replacement (TDR) as an alternative to the so-far gold standard in the surgical treatment of degenerative disc disease (DDD), e.g anterior cervical discectomy and fusion (ACDF), is growing very rapidly. Many authors have established the fact that ACDF may result in progressive degeneration in adjacent segments. On the contrary, but still theoretically, preservation of motion with TDR at the surgically treated level may potentially reduce the occurrence of adjacent-level degeneration (ALD). The authors report the intermediate results of an undergoing multicentre prospective study of TDR with Mobi-C® prosthesis. The aim of the study was to assess the safety and efficacy of the device in the treatment of DDD and secondary to evaluate the radiological status of adjacent levels and the occurrence of ossifications, at 2-year follow-up (FU). 76 patients have performed their 2-year FU visit and have been analyzed clinically and radiologically. Clinical outcomes (NDI, VAS, SF-36) and ROM measurements were analyzed pre-operatively and at the different post-operative time-points. Complications and re-operations were also assessed. Occurrences of heterotopic ossifications (HOs) and of adjacent disc degeneration radiographic changes have been analyzed from 2-year FU X-rays. The mean NDI and VAS scores for arm and neck are reduced significantly at each post-operative time-point compared to pre-operative condition. Motion is preserved over the time at index levels (mean ROM = 9° at 2 years) and 85.5% of the segments are mobile at 2 years. HOs are responsible for the fusion of 6/76 levels at 2 years. However, presence of HO does not alter the clinical outcomes. The occurrence rate of radiological signs of ALD is very low at 2 years (9.1%). There has been no subsidence, no expulsion and no sub-luxation of the implant. Finally, after 2 years, 91% of the patients assume that they would undergo the procedure again. These intermediate results of TDR with Mobi-C® are very encouraging and seem to confirm the efficacy and the safety of the device. Regarding the preservation of the status of the adjacent levels, the results of this unconstrained device are encouraging, but longer FU studies are needed to prove it. PMID:19434431

Post-arrest therapeutic hypothermia in pediatric patients with congenital heart disease.

PubMed

Cheng, Henry H; Rajagopal, Satish K; Sansevere, Arnold J; McDavitt, Erica; Wigmore, Daniel; Mecklosky, Jessica; Andren, Kristofer; Williams, Kathryn A; Danehy, Amy; Soul, Janet S

2018-05-01

While therapeutic hypothermia (TH) is an effective neuroprotective therapy for neonatal hypoxic-ischemic encephalopathy, TH has not been demonstrated to improve outcome in other pediatric populations. Patients with acquired or congenital heart disease (CHD) are at high risk of both cardiac arrest and neurodevelopmental impairments, and therapies are needed to improve neurologic outcome. The primary goal of our study was to compare safety/efficacy outcomes in post-arrest CHD patients treated with TH versus controls not treated with TH. Patients with CHD treated during the first 18 months after initiation of a post-arrest TH protocol (temperature goal: 33.5 °C) were compared to historical and contemporary post-arrest controls not treated with TH. Post-arrest data, including temperature, safety measures (e.g. arrhythmia, bleeding), neurodiagnostic data (EEG, neuroimaging), and survival were compared. Thirty arrest episodes treated with TH and 51 control arrest episodes were included. The groups did not differ in age, duration of arrest, post-arrest lactate, or use of ECMO-CPR. The TH group's post-arrest temperature was significantly lower than control's (33.6 ± 0.2 °C vs 34.7 ± 0.5 °C, p < 0.001). There was no difference between the groups in safety/efficacy measures, including arrhythmia, infections, chest-tube output, or neuroimaging abnormalities, nor in hospital survival (TH 61.5% vs control 59.1%, p = NS). Significantly more controls had seizures than TH patients (26.1% vs. 4.0%, p = 0.04). Almost all seizures were subclinical and occurred more than 24 h post-arrest. Our data show that pediatric CHD patients who suffer cardiac arrest can be treated effectively and safely with TH, which may decrease the incidence of seizures. Copyright © 2018 Elsevier B.V. All rights reserved.

Fibrin Sealants in Dura Sealing: A Systematic Literature Review

PubMed Central

2016-01-01

Background Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. Methods A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. Results A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. Conclusions A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety. PMID:27119993

Fibrin Sealants in Dura Sealing: A Systematic Literature Review.

PubMed

Esposito, Felice; Angileri, Filippo Flavio; Kruse, Peter; Cavallo, Luigi Maria; Solari, Domenico; Esposito, Vincenzo; Tomasello, Francesco; Cappabianca, Paolo

2016-01-01

Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety.

A method for independent modelling in support of regulatory review of dose assessments.

PubMed

Dverstorp, Björn; Xu, Shulan

2017-11-01

Several countries consider geological disposal facilities as the preferred option for spent nuclear fuel due to their potential to provide isolation from the surface environment on very long timescales. In 2011 the Swedish Nuclear Fuel & Waste Management Co. (SKB) submitted a license application for construction of a spent nuclear fuel repository. The disposal method involves disposing spent fuel in copper canisters with a cast iron insert at about 500 m depth in crystalline basement rock, and each canister is surrounded by a buffer of swelling bentonite clay. SKB's license application is supported by a post-closure safety assessment, SR-Site. SR-Site has been reviewed by the Swedish Radiation Safety Authority (SSM) for five years. The main method for review of SKB's license application is document review, which is carried out by SSM's staff and supported by SSM's external experts. The review has proven a challenging task due to its broad scope, complexity and multidisciplinary nature. SSM and its predecessors have, for several decades, been developing independent models to support regulatory reviews of post-closure safety assessments for geological repositories. For the review of SR-Site, SSM has developed a modelling approach with a structured application of independent modelling activities, including replication modelling, use of alternative conceptual models and bounding calculations, to complement the traditional document review. This paper describes this scheme and its application to biosphere and dose assessment modelling. SSM's independent modelling has provided important insights regarding quality and reasonableness of SKB's rather complex biosphere modelling and has helped quantifying conservatisms and highlighting conceptual uncertainty. Copyright © 2017 Elsevier Ltd. All rights reserved.

Review of the Methods to Obtain Paediatric Drug Safety Information: Spontaneous Reporting and Healthcare Databases, Active Surveillance Programmes, Systematic Reviews and Meta-analyses

PubMed

Gentili, Marta; Pozzi, Marco; Peeters, Gabrielle; Radice, Sonia; Carnovale, Carla

2018-02-06

Knowledge of drugs safety collected during the pre-marketing phase is inevitably limited because the randomized clinical trials (RCTs) are rarely designed to evaluate safety. The small and selective groups of enrolled individuals and the limited duration of trials may hamper the ability to characterize fully the safety profiles of drugs. Additionally, information about rare adverse drug reactions (ADRs) in special groups is often incomplete or not available for most of the drugs commonly used in the daily clinical practice. In the paediatric setting several highimpact safety issues have emerged. Hence, in recent years, there has been a call for improved post-marketing pharmacoepidemiological studies, in which cohorts of patients are monitored for sufficient time in order to determine the precise risk-benefit ratio. In this review, we discuss the current available strategies enhancing the post-marketing monitoring activities of the drugs in the paediatric setting and define criteria whereby they can provide valuable information to improve the management of therapy in daily clinical practice including both safety and efficacy aspects. The strategies we cover include the signal detection using international pharmacovigilance and/or healthcare databases, the promotion of active surveillance initiatives which can generate complete, informative data sets for the signal detection and systematic review/meta-analysis. Together, these methods provide a comprehensive picture of causality and risk improving the management of therapy in a paediatric setting and they should be considered as a unique tool to be integrated with post-marketing activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

PubMed

Roger, Simon D; Gaillard, Carlo A; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Van Wyck, David B; Cronin, Maureen; Meier, Yvonne; Larroque, Sylvain; Macdougall, Iain C

2017-09-01

The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

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

Barkhouse, Darryll A.; Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107; Faber, Milosz

Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4more » RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.« less

Statewide Collaborative to Reduce Surgical Site Infections: Results of the Hawaii Surgical Unit-Based Safety Program.

PubMed

Lin, Della M; Carson, Kathryn A; Lubomski, Lisa H; Wick, Elizabeth C; Pham, Julius Cuong

2018-05-18

Surgical site infections (SSIs) after colorectal surgery are common, lead to patient harm, and are costly to the healthcare system. This study's purpose was to evaluate the effectiveness of the AHRQ Safety Program for Surgery in Hawaii. This pre-post cohort study involved 100% of 15 hospitals in Hawaii from January 2013 through June 2015. The intervention was a statewide implementation of the Comprehensive Unit-Based Safety Program and individualized bundles of interventions to reduce SSIs. Primary end point was colorectal SSIs. Secondary end point was safety culture measured by the AHRQ Hospital Survey on Patient Safety Culture. The most common interventions implemented were reliable chlorhexidine wash, wipe before operation, and surgical preparation; appropriate antibiotic choice, dose, and timing; standardized post-surgical debriefing; and differentiating clean-dirty-clean with anastomosis tray and closing tray. From January 2013 (quarter 1) through June 2015 (quarter 2), the collaborative colorectal SSI rate decreased (from 12.08% to 4.63%; p < 0.01). The SSI rate exhibited a linear decrease during the 10-quarter period (p = 0.005). Safety culture increased in 10 of 12 domains: Overall Perception/Patient Safety (from 49% to 53%); Teamwork Across Units (from 49% to 54%); Management-Support Patient Safety (from 53% to 60%); Nonpunitive Response to Error (from 36% to 40%); Communication Openness (from 50% to 55%); Frequency of Events Reported (from 51% to 60%); Feedback/Communication about Error (from 52% to 59%); Organizational Learning/Continuous Improvement (from 59% to 70%); Supervisor/Manager Expectations and Actions Promoting Safety (from 58% to 64%); and Teamwork Within Units (from 68% to 75%) (all p < 0.05). Participation in the national AHRQ Safety Program for Surgery in the state of Hawaii was associated with a 61.7% decrease in colorectal SSI rate and an increase in patient safety culture. Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

A web-based intervention for abused women: the New Zealand isafe randomised controlled trial protocol.

PubMed

Koziol-McLain, Jane; Vandal, Alain C; Nada-Raja, Shyamala; Wilson, Denise; Glass, Nancy E; Eden, Karen B; McLean, Christine; Dobbs, Terry; Case, James

2015-01-31

Intimate partner violence (IPV) and its associated negative mental health consequences are significant for women in New Zealand and internationally. One of the most widely recommended interventions is safety planning. However, few women experiencing violence access specialist services for safety planning. A safety decision aid, weighing the dangers of leaving or staying in an abusive relationship, gives women the opportunity to prioritise, plan and take action to increase safety for themselves and their children. This randomised controlled trial is testing the effectiveness of an innovative, interactive web-based safety decision aid. The trial is an international collaborative concurrent replication of a USA trial (IRIS study NCT01312103), regionalised for the Aotearoa New Zealand culture and offers fully automated online trial recruitment, eligibility screening and consent. In a fully automated web-based trial (isafe) 340 abused women will be randomly assigned in equal numbers to a safety decision aid intervention or usual safety planning control website. Intervention components include: (a) safety priority setting, (b) danger assessment and (c) an individually tailored safety action plan. Self-reported outcome measures are collected at baseline and 3, 6, and 12-months post-baseline. Primary outcomes are depression (measured by Center for Epidemiologic Studies Depression Scale, Revised) and IPV exposure (measured by Severity Violence Against Women Scale) at 12 months post-baseline. Secondary outcomes include PTSD, psychological abuse, decisional conflict, safety behaviors and danger in the relationship. This trial will provide much-needed information on the potential relationships among safety planning, improved mental health, reduced violence as well as decreased decisional conflict related to safety in the abusive relationship. The novel web-based safety decision aid intervention may provide a cost-effective, easily accessed safety-planning resource that can be translated into clinical and community practice by multiple health disciplines and advocates. The trial will also provide information about how women in abusive relationships safely access safety information and resources through the Internet. Finally, the trial will inform other research teams on the feasibility and acceptability of fully automated recruitment, eligibility screening, consent and retention procedures. Trial registered on 03 July 2012 on the Australian New Zealand Clinical Trials Registry ACTRN12612000708853 .

Pimecrolimus in atopic dermatitis: consensus on safety and the need to allow use in infants.

PubMed

Luger, Thomas; Boguniewicz, Mark; Carr, Warner; Cork, Michael; Deleuran, Mette; Eichenfield, Lawrence; Eigenmann, Philippe; Fölster-Holst, Regina; Gelmetti, Carlo; Gollnick, Harald; Hamelmann, Eckard; Hebert, Adelaide A; Muraro, Antonella; Oranje, Arnold P; Paller, Amy S; Paul, Carle; Puig, Luis; Ring, Johannes; Siegfried, Elaine; Spergel, Jonathan M; Stingl, Georg; Taieb, Alain; Torrelo, Antonio; Werfel, Thomas; Wahn, Ulrich

2015-06-01

Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Ten years experience with the first approved biosimilar recombinant human growth hormone drug in normal clinical practice].

PubMed

López-Siguero, Juan Pedro; Palla García, Margarida; Martínez Busto, Elena; Rebollo, Francisco José; Pombo, Manuel

2018-04-01

Recombinant human growth hormone (rhGH) is the first biosimilar drug approved by the European Medicines Agency in 2006, using the biosimilar registration process. It was authorised for the treatment of growth hormone deficiency, and growth disorders associated with Turner's syndrome, chronic renal failure, Prader-Willi syndrome, and growth disorders in children/adolescents born small for gestational age, and replacement therapy in adults with pronounced growth hormone deficiency. This review is focused on the scientific evidence published about this drug in the last ten years, including the clinical trials on which the approval of the regulatory authority is based, and the most relevant studies evaluating the clinical impact of the drug in clinical practice. The equivalence between biosimilar and original product has been confirmed in the clinical trials published by Romer et al. and López-Siguero et al. Furthermore, studies carried out in real-life conditions confirm its long-term efficacy and safety, as well as the absence of clinical impact by switching treatment from the original to the biosimilar product. The number of patients receiving this medication has continuously increased since its approval. Its equivalence with the original product has been verified. Preliminary data from the post-authorisation PATRO study confirm the efficacy and safety of the biosimilar product in comparison with data from clinical trials. However, final results must be evaluated at the end of the study, which will provide additional information about the long-term efficacy and safety of the biosimilar drug. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Teen worker safety training: methods used, lessons taught, and time spent.

PubMed

Zierold, Kristina M

2015-05-01

Safety training is strongly endorsed as one way to prevent teens from performing dangerous tasks at work. The objective of this mixed methods study was to characterize the safety training that teenagers receive on the job. From 2010 through 2012, focus groups and a cross-sectional survey were conducted with working teens. The top methods of safety training reported were safety videos (42 percent) and safety lectures (25 percent). The top lessons reported by teens were "how to do my job" and "ways to spot hazards." Males, who were more likely to do dangerous tasks, received less safety training than females. Although most teens are getting safety training, it is inadequate. Lessons addressing safety behaviors are missing, training methods used are minimal, and the time spent is insignificant. More research is needed to understand what training methods and lessons should be used, and the appropriate safety training length for effectively preventing injury in working teens. In addition, more research evaluating the impact of high-quality safety training compared to poor safety training is needed to determine the best training programs for teens. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Freeze-dried live attenuated smallpox vaccine prepared in cell culture "LC16-KAKETSUKEN": Post-marketing surveillance study on safety and efficacy compliant with Good Clinical Practice.

PubMed

Nishiyama, Yasumasa; Fujii, Tatsuya; Kanatani, Yasuhiro; Shinmura, Yasuhiko; Yokote, Hiroyuki; Hashizume, So

2015-11-09

In Japan, production of smallpox vaccine LC16m8 (named LC16-KAKETSUKEN) was restarted and was determined to be maintained as a national stockpile in March 2002. To conduct a post-marketing surveillance study of the vaccination of freeze-dried live attenuated smallpox vaccine prepared in cell culture LC16-KAKETSUKEN using attenuated vaccinia strain LC16m8. The study complied with Good Clinical Practice, focusing on a comparison between primary vaccinees and re-vaccinees. 268 personnel (261 males and 7 females) of the Japan Ground Self-Defense Force were inoculated with LC16-KAKETSUKEN and thereafter adverse events and efficacy were evaluated. Among 268 vaccinee participants, the following vaccinees showed adverse events, none serious: 53 of 196 primary vaccinees (without previous smallpox vaccination), 4 of 71 re-vaccinees (with previous smallpox vaccination) and 1 vaccinee with unknown previous vaccination history. A breakdown of adverse events observed in this study (total 268 vaccinees) showed the following minor or mild adverse events: 52 (19.4%) swelling of axillary lymph node, 4 (1.5%) fever, 2 (0.7%) fatigue, 1 (0.4%) of rash, 14 (5.2%) erythema at the inoculation site, 1 (0.4%) swelling at the inoculation site and 1 (0.4%) autoinoculation. The incidence of adverse events for primary vaccinees (53/196; 27.0%) was significantly higher than for re-vaccinees (4/71; 5.6%). However, the proportion of vaccine take was significantly higher for primary vaccinees (185/196; 94.4%) than for re-vaccinees (58/71; 81.7%). Although the proportion of vaccine take of re-vaccinees was significantly lower than for primary vaccinees due to preexisting immunity by previous vaccination, no significant difference was found in neutralizing antibody titers between primary vaccinees and re-vaccinees at 1, 4 and 7 months after LC16-KAKETSUKEN vaccination. The present post-marketing surveillance study compliant with Good Clinical Practice demonstrated the efficacy and safety of the smallpox vaccine LC16-KAKETSUKEN in an adult population. LC16-KAKETSUKEN is the sole currently available licensed smallpox vaccine for both adult and pediatric populations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

14 CFR 417.403 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Ground Safety § 417.403 General. (a) Public safety. A launch operator must... with launch processing and post-launch operations. (b) Ground safety analysis. A launch operator must...

Assessment of safety and efficacy of lamotrigine over the course of 1-year observation in Japanese patients with bipolar disorder: post-marketing surveillance study report

PubMed Central

Terao, Takeshi; Ishida, Atsuko; Kimura, Toshifumi; Yoshida, Mitsuhiro; Hara, Terufumi

2017-01-01

Background A post-marketing surveillance (PMS) study was conducted with a 1-year observation period to assess the safety and efficacy of lamotrigine in routine clinical practice in patients with bipolar disorder (BD). Patients and methods Central enrollment method was used to recruit patients diagnosed with BD who were being treated for the first time with lamotrigine to prevent the recurrence/relapse of BD mood episodes. Adverse drug reactions (ADRs) and recurrence/relapse were assessed. Improvement of mania and depression was also assessed using the Hamilton’s Rating Scale for Depression (HAM-D) and the Young Mania Rating Scale (YMRS) at treatment initiation, 4–6 months post treatment initiation, and 10–12 months post treatment initiation. Results A total of 237/989 patients (24.0%) reported ADRs, most commonly rash (9.1%), and the incidence of serious ADRs was 3.3% (33/989 patients). Skin disorders occurred in 130 patients (13.1%), mostly within 8 weeks post treatment. A total of 237/703 patients (33.7%) experienced recurrence/relapse of mood episodes. The 25th percentile of the time to recurrence/relapse of mood episodes was 105 days. Remission of depression symptoms (HAM-D ≤7) occurred in 147/697 patients (21.1%) at treatment initiation, rising to 361 patients (67.4%) at 10–12 months post treatment. Remission of manic symptoms (YMRS ≤13) occurred in 615/676 patients (91.0%) at treatment initiation, rising to 500 patients (97.3%) at 10–12 months post treatment. Conclusion The results of this PMS study suggest that lamotrigine is a well-tolerated and effective drug for preventing recurrence/relapse of BD in clinical practice. PMID:28652744

40 CFR 170.235 - Posted pesticide safety information.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... (b) Pesticide safety poster. A safety poster must be displayed that conveys, at a minimum, the... the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The handler employer shall inform handlers promptly of any change to the information...

40 CFR 170.235 - Posted pesticide safety information.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... (b) Pesticide safety poster. A safety poster must be displayed that conveys, at a minimum, the... the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The handler employer shall inform handlers promptly of any change to the information...

40 CFR 170.235 - Posted pesticide safety information.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (b) Pesticide safety poster. A safety poster must be displayed that conveys, at a minimum, the... the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The handler employer shall inform handlers promptly of any change to the information...

40 CFR 170.235 - Posted pesticide safety information.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... (b) Pesticide safety poster. A safety poster must be displayed that conveys, at a minimum, the... the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The handler employer shall inform handlers promptly of any change to the information...

40 CFR 170.235 - Posted pesticide safety information.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (b) Pesticide safety poster. A safety poster must be displayed that conveys, at a minimum, the... the nearest emergency medical care facility shall be on the safety poster or displayed close to the safety poster. (2) The handler employer shall inform handlers promptly of any change to the information...

A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain.

PubMed

Juan-Giner, Aitana; Domicent, Camille; Langendorf, Céline; Roper, Martha H; Baoundoh, Paul; Fermon, Florence; Gakima, Primitive; Zipursky, Simona; Tamadji, Mbaihol; Grais, Rebecca F

2014-10-29

In resource-poor settings, cold chain requirements present barriers for vaccine delivery. We evaluated the immunogenicity and safety of tetanus toxoid (TT) vaccine in "Controlled Temperature Chain" (CTC; up to 40 °C for <30 days before administration), compared to standard cold chain (SCC; 2-8 °C). Prior to the study, stability parameters of TT-CTC were shown to meet international requirements. A cluster randomized, non-inferiority trial was conducted in Moïssala district, Chad, December 2012-March 2013. Thirty-four included clusters were randomized to CTC or SCC. Women aged 14-49 years, eligible for TT vaccination and with a history of ≤1 TT dose, received two TT doses 4 weeks apart. Participants were blinded to allocation strategy. Tetanus antibody titers were measured using standard ELISA at inclusion and 4 weeks post-TT2. Primary outcome measures were post-vaccination seroconversion and fold-increase in geometric mean concentrations (GMC). Non-inferiority was by seroconversion difference (TTSCC-TTCTC) <5% and ratio of GMCs (TTSCC/TTCTC) <1.5. Adverse events were monitored at health centers and at next contact with participants. A total of 2128 women (CTC=1068; SCC=1060) were recruited. Primary intention to vaccinate analysis included 1830 participants; 272 of these were included in the seroconversion analysis. Seroconversion was reached by >95% of participants; upper 95%CI of the difference was 5.6%. Increases in GMC were over 4-fold; upper 95%CI of GMC ratio was 1.36 in the adjusted analysis. Few adverse events were recorded. This study demonstrates the immunogenicity and safety of TT in CTC at <40 °C for <30 days. The high proportion of participants protected at baseline results in a reduction of power to detect a 5% non-inferiority margin. However, results at a 10% non-inferiority margin, the comparable GMC increases and vaccine's stability demonstrated in the preliminary phase indicate that CTC can be an alternative strategy for TT delivery in situations where cold chain cannot be maintained. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.

PubMed

Ortiz, Justin R; Goswami, Doli; Lewis, Kristen D C; Sharmeen, Amina Tahia; Ahmed, Moshtaq; Rahman, Mustafizur; Rahman, Mohammed Z; Feser, Jodi; Neuzil, Kathleen M; Brooks, W Abdullah

2015-06-26

Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings. We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations. Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events. In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Comparative Study Between Modified Starch and Xanthan Gum Thickeners in Post-Stroke Oropharyngeal Dysphagia.

PubMed

Vilardell, N; Rofes, L; Arreola, V; Speyer, R; Clavé, P

2016-04-01

Thickeners are used in post-stroke oropharyngeal dysphagia (OD) as a compensatory therapeutic strategy against aspirations. To compare the therapeutic effects of modified starch (MS) and xanthan gum (XG) thickeners on swallow safety and efficacy in chronic post-stroke OD patients using clinical and videofluoroscopic (VFS) assessment. Patients were studied by clinical assessment (volume-viscosity swallow test, V-VST) and VFS using 3 volumes (5, 10, 20 mL) and 3 viscosities (liquid, nectar and spoon thick), comparing MS and XG. We studied 122 patients (46MS, 76XG). (A) V-VST showed that both thickeners similarly improved safety of swallow. Prevalence of safe swallowing significantly increased with enhanced viscosity (P < 0.001 vs liquid), MS: 47.83 % at liquid, 84.93 % at nectar and 92.96 % at spoon thick; XG: 55.31 % at liquid, 77.78 % at nectar and 97.84 % at spoon thick. Patients on MS reported higher prevalence of pharyngeal residue at spoon-thick viscosities. (B) VFS: increasing bolus viscosity with either thickener increased prevalence of safe swallows (P < 0.001 vs liquid), MS: 30.25 % liquid, 61.07 % nectar and 92.64 % spoon thick; XG: 29.12 % liquid, 71.30 % nectar and 89.91 % spoon thick. Penetration-aspiration scale score was significantly reduced with increased viscosity with both thickeners. MS increased oral and pharyngeal residues at nectar and spoon-thick viscosities but XG did not. Timing of airway protection mechanisms and bolus velocity were not affected by either thickener. Increasing bolus viscosity with MS and XG thickeners strongly and similarly improved safety of swallow in chronic post-stroke OD by a compensatory mechanism; in contrast only MS thickeners increased oropharyngeal residue.

Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis

PubMed Central

Sinha, Michael S; Freifeld, Clark C; Brownstein, John S; Donneyong, Macarius M; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Dal Pan, Gerald J; Pawar, Ajinkya M; Hwang, Thomas J; Avorn, Jerry

2018-01-01

Background The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. Objective The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. Methods We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between –0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes “Related queries” during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website’s editorial history, which lists all revisions to a given page and the editor’s identity. Results In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the first DSC. ITS analyses demonstrated variability but pointed to an increase in interest around the first DSC. Chow tests were significant (P<.0001) for both DSCs on Facebook and Twitter, but only the first DSC on Google Trends. Wikipedia edits occurred soon after each DSC release, citing news articles rather than the DSC itself and presenting content that needed subsequent revisions for accuracy. Conclusions Social media offers challenges and opportunities for dissemination of the DSC messages. The FDA could consider strategies for more actively disseminating DSC safety information through social media platforms, particularly when announcements require updating. The FDA may also benefit from directly contributing content to websites like Wikipedia that are frequently accessed for drug-related information. PMID:29305342

Safety and immunogenicity of a booster dose of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) in healthy adults: A randomized phase 1 study.

PubMed

Marshall, Helen; Nissen, Michael; Richmond, Peter; Shakib, Sepehr; Jiang, Qin; Cooper, David; Rill, Denise; Baber, James; Eiden, Joseph; Gruber, William C; Jansen, Kathrin U; Anderson, Annaliesa S; Zito, Edward T; Girgenti, Douglas

2016-11-01

A 2-stage, phase 1, randomized, placebo-controlled study in healthy adults to assess immunogenicity and safety of a booster dose at three dose levels of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) containing recombinant clumping factor A (ClfA) and capsular polysaccharides 5 and 8 (CP5 and CP8) conjugated to a diphtheria toxoid. Six months after initial single vaccination, in Stage 2, SA3Ag recipients were randomized (1:1) to booster vaccination or placebo, while Stage 1 placebo recipients received placebo again. Pre- and post-vaccination blood samples were analyzed. In Stage 2 (n = 345), pre-booster CP5 and CP8 titers remained high with no increase post-booster. ClfA titers remained high after initial vaccination and increased post-booster, approaching the peak response to the initial dose. Post-booster local reactions were more frequent and of greater severity than reported after the initial vaccination, particularly for the high-dose level recipients. Post hoc analysis showed no dose-response pattern and no obvious association between diphtheria toxoid titers and local reactions after initial or booster vaccination. Immune responses after the initial vaccination persisted for the 12 months studied, with little additional response after the booster dose at 6 months. Post-booster injection site reactions were more frequent and more severe but self-limiting. CLINICALTRIALS. NCT01018641. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

A study to assess the influence of interprofessional point of care simulation training on safety culture in the operating theatre environment of a university teaching hospital.

PubMed

Hinde, Theresa; Gale, Thomas; Anderson, Ian; Roberts, Martin; Sice, Paul

2016-01-01

Interprofessional point of care or in situ simulation is used as a training tool in our operating theatre directorate with the aim of improving crisis behaviours. This study aimed to assess the impact of interprofessional point of care simulation on the safety culture of operating theatres. A validated Safety Attitude Questionnaire was administered to staff members before each simulation scenario and then re-administered to the same staff members after 6-12 months. Pre- and post-training Safety Attitude Questionnaire-Operating Room (SAQ-OR) scores were compared using paired sample t-tests. Analysis revealed a statistically significant perceived improvement in both safety (p < 0.001) and teamwork (p = 0.013) climate scores (components of safety culture) 6-12 months after interprofessional simulation training. A growing body of literature suggests that a positive safety culture is associated with improved patient outcomes. Our study supports the implementation of point of care simulation as a useful intervention to improve safety culture in theatres.

All-case post-marketing surveillance of 1371 patients treated with pirfenidone for idiopathic pulmonary fibrosis.

PubMed

Ogura, Takashi; Azuma, Arata; Inoue, Yoshikazu; Taniguchi, Hiroyuki; Chida, Kingo; Bando, Masashi; Niimi, Yuka; Kakutani, Shinichi; Suga, Moritaka; Sugiyama, Yukihiko; Kudoh, Shoji; Nukiwa, Toshihiro

2015-09-01

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with a median survival of 2-5 years and limited treatment options. In 2008, pirfenidone became the first drug to be approved for IPF treatment in Japan. The aim of this study was to assess the safety of pirfenidone for IPF treatment in a clinical setting. We conducted a safety-oriented post-marketing surveillance of all patients with IPF who were administered pirfenidone in the first year after its launch in Japan. This was a prospective, non-interventional, observational study. Case report forms were used to collect survey data, comprising adverse events, acute exacerbations, patient demographics, concomitant drug use, and concurrent treatment data. Of the 1371 patients available for safety evaluation, two-thirds had stage III-IV disease. The incidence of total adverse drug reactions (ADRs) was 64.6%. ADRs with an incidence of ≥3% were decreased appetite, photosensitivity reaction, nausea, abdominal discomfort, malaise, somnolence, and hepatic function abnormal. This safety profile was consistent with the findings in phase II and III trials in Japan. The discontinuation rates due to adverse events at 12 months for each disease stage were similar; however, discontinuation caused by disease progression increased with disease severity. Treatment with pirfenidone stabilized both vital capacity and subjective symptoms in most patients (70-80%) treated for at least 6 months. This post-marketing surveillance in Japan showed that pirfenidone was generally well tolerated in patients with IPF, including those with severe lung function impairment. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

New challenges in assuring vaccine quality.

PubMed Central

Dellepiane, N.; Griffiths, E.; Milstien, J. B.

2000-01-01

In the past, quality control of vaccines depended on use of a variety of testing methods to ensure that the products were safe and potent. These methods were developed for vaccines whose safety and efficacy were based on several years worth of data. However, as vaccine production technologies have developed, so have the testing technologies. Tests are now able to detect potential hazards with a sensitivity not possible a few years ago, and an increasing array of physicochemical methods allows a much better characterization of the product. In addition to sophisticated tests, vaccine regulation entails a number of other procedures to ensure safety. These include characterization of starting materials by supplier audits, cell banking, seed lot systems, compliance with the principles of good manufacturing practices, independent release of vaccines on a lot-by-lot basis by national regulatory authorities, and enhanced pre- and post-marketing surveillance for possible adverse events following immunization. These procedures help assure vaccine efficacy and safety, and some examples are given in this article. However, some contaminants of vaccines that can be detected by newer assays raise theoretical safety concerns but their presence may be less hazardous than not giving the vaccines. Thus risk-benefit decisions must be well informed and based on scientific evidence. PMID:10743279

PIE on Safety-Tested Loose Particles from Irradiated Compact 4-4-2

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

Hunn, John D.; Gerczak, Tyler J.; Morris, Robert Noel

2016-04-01

Post-irradiation examination (PIE) is being performed in support of tristructural isotropic (TRISO) coated particle fuel development and qualification for High Temperature Gas-cooled Reactors (HTGRs). This work is sponsored by the Department of Energy Office of Nuclear Energy (DOE-NE) through the Advanced Reactor Technologies (ART) Office under the Advanced Gas Reactor Fuel Development and Qualification (AGR) Program. The AGR-1 experiment was the first in a series of TRISO fuel irradiation tests initiated in 2006. The AGR-1 TRISO particles and fuel compacts were fabricated at Oak Ridge National Laboratory (ORNL) in 2006 using laboratory-scale equipment and irradiated for 3 years in themore » Advanced Test Reactor (ATR) at Idaho National Laboratory (INL) to demonstrate and evaluate fuel performance under HTGR irradiation conditions. Post-irradiation examination was performed at INL and ORNL to study how the fuel behaved during irradiation, and to test fuel performance during exposure to elevated temperatures at or above temperatures that could occur during a depressurized conduction cooldown event. This report summarizes safety testing and post-safety testing PIE conducted at ORNL on loose particles extracted from irradiated AGR-1 Compact 4-4-2.« less

[Safety of reducing the recovery time after percutaneous and laparoscopic liver biopsy].

PubMed

Nodarse-Pérez, Pablo Orlando; Pérez-Menéndez, Roberto; Heredia-Andrade, Enkly Dennys; Noa-Pedroso, Guillermo; Araluce-Cordoví, Roberto; Fernández-Sotolongo, José

2016-01-01

Liver biopsy is the main diagnostic tool for the study of the liver, and as such, its inherent complications have been minimised as much as possible over the years, through the modification of several factors regarding its procedure, including post-biopsy recovery time. The aim of this study was to evaluate the safety in the reduction of post-liver biopsy recovery time. A non-blinded, randomised clinical trial was conducted in the "Hermanos Ameijeiras" Hospital from November 2011 to October 2012, on 128 patients in order to assess safety when reducing post-biopsy recovery times. The patients were randomised into 2 groups. Group A was allowed a 6-hour recovery time, while Group B was allowed a 2-hour recovery time after liver biopsy. Complications were fully recorded. The Chi squared test of homogeneity and Student t test was used as appropriate, in the statistical analysis, a significance level of 0.05 was set. The main biopsy indication was elevated plasma transaminases. Pain in the puncture site was the most recurrent complication (67.2%), and the most serious complication was subcapsular liver haematoma in two cases (1.6%). There were no differences regarding the liver biopsy technique that could have caused complications in any group. There were no significant differences between 2 hours and 6 hours post-liver biopsy recovery time in terms of complications, so it is considered that after two hours the patient is incorporated more quickly into their activities, and the institution spends less material and human resources. Copyright © 2016. Published by Masson Doyma México S.A.

Adverse event assessment and reporting in trials of newer treatments for post-operative pain.

PubMed

Hoffer, D; Smith, S M; Parlow, J; Allard, R; Gilron, I

2016-08-01

Assessment and reporting of adverse events (AEs) in studies of perioperative interventions is critical given the potential for unintended and preventable iatrogenic morbidity and mortality. This focused review evaluated the quality of AE assessment and reporting in acute post-operative pain treatment trials. Since older analgesics (e.g., opioids, NSAIDs) already have a well-characterized safety profile, we concentrated on trials of pregabalin and gabapentin as a representative sample of studies where the perioperative safety profile was relatively unknown. We reviewed primary reports of trials of pregabalin and gabapentin for treatment of acute post-operative pain for: (1) adherence to the 10 recommendations from the 'CONSORT Extension for Harms,' (2) AE assessment method, (3) timing of AE assessment and reporting, and (4) assessment and reporting of AE severity. We identified 31 trials of pregabalin and 59 of gabapentin. The median number of CONSORT harms recommendations that were satisfied was 7 of 10. The most common (41%) method of AE assessment was direct questioning about specific AEs by investigators. However, AE assessment method was not described in 18% of trials. AE assessments were reported for specified perioperative time points in only 24% of trials. Of greatest concern, no AE data were reported whatsoever in 8 of the included publications. Considerable widespread improvements are needed in AE reporting for post-operative pain treatment trials. In addition to heightened awareness among clinical investigators, mandatory journal editorial policies may further facilitate improvements in safety assessment and reporting. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Establish research model of post-marketing clinical safety evaluation for Chinese patent medicine].

PubMed

Zheng, Wen-ke; Liu, Zhi; Lei, Xiang; Tian, Ran; Zheng, Rui; Li, Nan; Ren, Jing-tian; Du, Xiao-xi; Shang, Hong-cai

2015-09-01

The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.

Ohio Department of Natural Resources

Science.gov Websites

Safety Tick & Tick Bite Prevention Outdoor Safety Tips Firewise Algae Advisories Swim Safe OhioMeansJobs Your Next Trail Adventure ODNR, working with multiple partners, has created a new trails website Ohioans to be Safe This Summer Posted on 5/25/2018 by East End of Buckeye Lake to be Dredged Posted on 5

Health Care Worker Fatigue.

PubMed

Gardner, Lea Anne; Dubeck, Deborah

2016-08-01

The Pennsylvania Patient Safety Reporting System is a confidential, statewide Internet reporting system to which all Pennsylvania hospitals, outpatient-surgery facilities, birthing centers, and abortion facilities must file information on incidents and serious events.Safety Monitor is a column from Pennsylvania's Patient Safety Authority, the authority that informs nurses on issues that can affect patient safety and presents strategies they can easily integrate into practice. For more information on the authority, visit www.patientsafetyauthority.org. For the original article discussed in this column or for other articles on patient safety, click on "Patient Safety Advisories" and then "Advisory Library" in the left-hand navigation menu.

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.

76 FR 63988 - Pilot Project on NAFTA Trucking Provisions; Pre-Authorization Safety Audits

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-14

...-0097] Pilot Project on NAFTA Trucking Provisions; Pre-Authorization Safety Audits AGENCY: Federal Motor... public comment on data and information concerning the Pre-Authorization Safety Audits (PASAs) for two motor carriers that applied to participate in the Agency's long-haul pilot program to test and...

Off-label use of vaccines.

PubMed

Neels, Pieter; Southern, James; Abramson, Jon; Duclos, Philippe; Hombach, Joachim; Marti, Melanie; Fitzgerald-Husek, Alanna; Fournier-Caruana, Jacqueline; Hanquet, Germaine

2017-04-25

This article reviews the off-label recommendations and use of vaccines, and focuses on the differences between the labelled instructions on how to use the vaccine as approved by the regulatory authorities (or "label" 1 ), and the recommendations for use issued by public health advisory bodies at national and international levels. Differences between public health recommendations and the product label regarding the vaccine use can lead to confusion at the level of vaccinators and vaccinees and possibly result in lower compliance with national vaccination schedules. In particular, in many countries, the label may contain regulatory restrictions and warnings against vaccination of specific population groups (e.g. pregnant women) due to a lack of evidence of safety from controlled trials at the time of initial licensure of the vaccine, while public health authorities may recommend the same vaccine for that group, based on additional post-marketing data and benefit risk analyses. We provide an overview of the different responsibilities between regulatory authorities and public health advisory bodies, and the rationale for off-label use 2 of vaccines, the challenges involved based on the impact of off-label use in real-life. We propose to reduce off-label use of vaccines by requiring the manufacturer to regularly adapt the label as much as possible to the public health needs as supported by new evidence. This would require manufacturers to collect and report post-marketing data, communicate them to all stakeholders and regulators to extrapolate existing evidence (when acceptable) to other groups or to other brands of a vaccine (class effect 3 ). Regulatory authorities have a key role to play by requesting additional post-marketing data, e.g. in specific target groups. When public health recommendations for vaccine use that are outside labelled indications are considered necessary, good communication between regulatory bodies, public health authorities, companies and health care providers or vaccinators is crucial. Recommendations as well as labels and label changes should be evidence-based. The rationale for the discrepancy and the recommended off-label use of a vaccine should be communicated to providers. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Safety of food additives from a German and European point of view].

PubMed

Gürtler, R

2010-06-01

There are about 300 food additives permitted in the EU for which a re-evaluation program was initiated recently. Occasionally, it is speculated that the use of single food additives might be of safety concern. First results of the re-evaluation could give an impression on how such concerns were taken into account by responsible authorities, such as the European Food Safety Authority (EFSA). For some of the food additives, the lowest dose resulting in adverse effects was lower in recent studies compared to previous studies. Thus, the acceptable daily intake (ADI) derived applying the common uncertainty factor was lower than the ADI derived using data from previous studies. Therefore, it has to be considered whether the conditions of use need to be modified for these food additives.

Post-marketing safety evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir: A drug-use investigation in patients with high risk factors.

PubMed

Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

2016-10-01

Peramivir, the only injectable anti-influenza neuraminidase inhibitor medically available in Japan at present, is considered first-line treatment in patients with high risk factors for influenza exacerbation. We conducted a drug-use investigation of peramivir in inpatients with high risk factors (old age, pregnancy, and underlying disease such as chronic respiratory disease) from January 2010 to March 2013. Data of 772 patients from 124 facilities across Japan were collected; peramivir's safety in 770 patients and effectiveness in 688 patients were examined. In total, 412 adverse events were observed in 219 patients (28.4%). Of these, 155 events were adverse drug reactions (ADRs) observed in 98 patients (12.7%). Major ADRs (≥2%) were increased aspartate aminotransferase (5.1%), increased alanine aminotransferase (3.8%) and decreased white blood cell count (2.5%). Fourteen serious ADRs were observed in 12 patients (1.6%). All serious ADRs were resolved or improved except for two events for which outcomes were unknown. Multivariate analyses revealed that ADR incidences were significantly associated with these four backgrounds of patients: medical history, no influenza vaccination, renal impairment and other infection(s). With regard to its effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration, which was the same as in other previous surveillance studies. This surveillance study indicated the safety of peramivir in the treatment of influenza inpatients with high risk factors under routine clinical settings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immunogenicity and safety of the candidate RTS,S/AS01 vaccine in young Nigerian children: a randomized, double-blind, lot-to-lot consistency trial.

PubMed

Umeh, Rich; Oguche, Stephen; Oguonu, Tagbo; Pitmang, Simon; Shu, Elvis; Onyia, Jude-Tony; Daniyam, Comfort A; Shwe, David; Ahmad, Abdullahi; Jongert, Erik; Catteau, Grégory; Lievens, Marc; Ofori-Anyinam, Opokua; Leach, Amanda

2014-11-12

For regulatory approval, consistency in manufacturing of vaccine lots is expected to be demonstrated in confirmatory immunogenicity studies using two-sided equivalence trials. This randomized, double-blind study (NCT01323972) assessed consistency of three RTS,S/AS01 malaria vaccine batches formulated from commercial-scale purified antigen bulk lots in terms of anti-CS-responses induced. Healthy children aged 5-17 months were randomized (1:1:1:1) to receive RTS,S/AS01 at 0-1-2 months from one of three commercial-scale purified antigen bulk lots (1600 litres-fermentation scale; commercial-scale lots), or a comparator vaccine batch made from pilot-scale purified antigen bulk lot (20 litres-fermentation scale; pilot-scale lot). The co-primary objectives were to first demonstrate consistency of antibody responses against circumsporozoite (CS) protein at one month post-dose 3 for the three commercial-scale lots and second demonstrate non-inferiority of anti-CS antibody responses at one month post-dose 3 for the commercial-scale lots compared to the pilot-scale lot. Safety and reactogenicity were evaluated as secondary endpoints. One month post-dose-3, anti-CS antibody geometric mean titres (GMT) for the 3 commercial scale lots were 319.6 EU/ml (95% confidence interval (CI): 268.9-379.8), 241.4 EU/ml (207.6-280.7), and 302.3 EU/ml (259.4-352.3). Consistency for the RTS,S/AS01 commercial-scale lots was demonstrated as the two-sided 95% CI of the anti-CS antibody GMT ratio between each pair of lots was within the range of 0.5-2.0. GMT of the pooled commercial-scale lots (285.8 EU/ml (260.7-313.3)) was non-inferior to the pilot-scale lot (271.7 EU/ml (228.5-323.1)). Each RTS,S/AS01 lot had an acceptable tolerability profile, with infrequent reports of grade 3 solicited symptoms. No safety signals were identified and no serious adverse events were considered related to vaccination. RTS,S/AS01 lots formulated from commercial-scale purified antigen bulk batches induced a consistent anti-CS antibody response, and the anti-CS GMT of pooled commercial-scale lots was non-inferior to that of a lot formulated from a pilot-scale antigen bulk batch. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Resident aggression toward staff at a center for the developmentally disabled.

PubMed

West, Christine A; Galloway, Ellen; Niemeier, Maureen T

2014-01-01

Few studies have examined factors contributing to nonfatal assaults to staff working in residential care facilities. The authors evaluated resident assaults toward direct care/nursing staff at an intermediate Care Facility for Individuals with Mental Retardation (ICF/MR), which included observations of work areas, employee interviews, calculation of injury and assault rates for 2004 to 2007 from Occupational Safety and Health Administration Logs, and review of state ICP/MR guidelines. Most staff interviewed reported having been injured during physical restraint of a resident and the average rate of injury from assault at the center evaluated was higher than the average national rates for the health care and social assistance sector for the same time period. The center lacked policies and developing a post-incident response and evaluation program to assist staff in coping with the consequences of assault and/or occupational injury.

Post-marketing surveillance of adverse events following immunization with inactivated quadrivalent and trivalent influenza vaccine in health care providers in Western Australia.

PubMed

Regan, Annette K; Tracey, Lauren; Gibbs, Robyn

2015-11-17

In 2015, inactivated quadrivalent influenza vaccine (QIV) was first introduced into the Australian market. A routine vaccine safety surveillance system in Western Australia was used to conduct post-licensure surveillance of adverse events following immunization with inactivated QIV and trivalent influenza vaccines (TIV) in a sample of 1685 healthcare providers (HCPs). A similar percentage of HCPs who received QIV reported having any reaction seven days post-vaccination as HCPs who received TIV (13.6 vs. 12.8%, respectively; p=0.66). However, a slightly higher percentage of HCPs who received QIV reported pain or swelling at the injection site as compared to HCPs who received TIV (6.9% vs. 4.2%, respectively; p=0.02). No serious vaccine-associated adverse events were detected during follow-up of either vaccine. Acknowledging the study limitations, the results of this post-marketing surveillance support the safety of QIV, suggesting there is little difference in the reactogenicity of QIV as compared to TIV. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Randomized, double-blind, active-controlled study evaluating the safety and immunogenicity of three vaccination schedules and two dose levels of AV7909 vaccine for anthrax post-exposure prophylaxis in healthy adults.

PubMed

Hopkins, Robert J; Kalsi, Gurdyal; Montalvo-Lugo, Victor M; Sharma, Mona; Wu, Yukun; Muse, Derek D; Sheldon, Eric A; Hampel, Frank C; Lemiale, Laurence

2016-04-19

AV7909 vaccine being developed for post-exposure prophylaxis of anthrax disease may require fewer vaccinations and reduced amount of antigen to achieve an accelerated immune response over BioThrax(®) (Anthrax Vaccine Adsorbed). A phase 2, randomized, double-blind, BioThrax vacccine-controlled study was conducted to evaluate the safety and immunogenicity of three intramuscular vaccination schedules and two dose levels of AV7909 in 168 healthy adults. Subjects were randomized at a 4:3:2:4:2 ratio to 5 groups: (1) AV7909 on Days 0/14; (2) AV7909 on Days 0/28; (3) AV7909 on Days 0/14/28; (4) half dose AV7909 on Days 0/14/28; and (5) BioThrax vaccine on Days 0/14/28. Vaccinations in all groups were well tolerated. The incidences of adverse events (AEs) were 79% for AV7909 subjects and 65% for BioThrax subjects; 92% of AV7909 subjects and 87% of BioThrax subjects having AEs reported Grade 1-2 AEs. No serious AEs were assessed as potentially vaccine-related, and no AEs of potential autoimmune etiology were reported. There was no discernible pattern indicative of a safety concern across groups in the incidence or severity of reactogenicity events. Groups 2-4 achieved success for the primary endpoint, demonstrated by a lower 95% confidence limit of the percentage of subjects with protective toxin neutralizing antibody NF50 values (≥0.56) to be ≥40% at Day 63. Group 1 marginally missed the criterion (lower bound 95% confidence limit of 39.5%). Immune responses were above this threshold for Groups 1, 3 and 4 at Day 28 and all groups at Day 42. Further study of an AV7909 two-dose schedule given 2 weeks apart is warranted in light of the favorable tolerability profile and immunogenicity response relative to three doses of BioThrax vaccine, as well as preliminary data from nonclinical studies indicating similar immune responses correlate with higher survival for AV7909 than BioThrax vaccine. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Navigating the fine line between benefit and risk in chronic atrial fibrillation: rationale and design of the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY).

PubMed

Carrington, Melinda J; Ball, Jocasta; Horowitz, John D; Marwick, Thomas H; Mahadevan, Gnanadevan; Wong, Chiew; Abhayaratna, Walter P; Haluska, Brian; Thompson, David R; Scuffham, Paul A; Stewart, Simon

2013-06-20

Health outcomes associated with atrial fibrillation (AF) continue to be poor and standard management often does not provide clinical stability. The Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY) compares the efficacy of a post-discharge, nurse-led, multi-disciplinary programme to optimise AF management with usual care. SAFETY is a prospective, multi-centre, randomised controlled trial with blinded-endpoint adjudication. A target of 320 hospitalised patients with a chronic form of AF will be randomised (stratified by "rate" versus "rhythm" control) to usual post-discharge care or the SAFETY Intervention (SI). The SI involves home-based assessment, extensive clinical profiling and the application of optimal gold-standard pharmacology which is individually tailored according to a "traffic light" framework based on clinical stability, risk profile and therapeutic management. The primary endpoint is event-free survival from all-cause death or unplanned readmission during 18-36 months follow-up. Secondary endpoints include rate of recurrent hospital stay, treatment success (i.e. maintenance of rhythm or rate control and/or application of anti-thrombotic therapy without a bleeding event) and cost-efficacy. With study recruitment to be completed in early 2012, the results of this study will be available in early 2014. If positive, SAFETY will represent a potentially cost-effective and readily applicable strategy to improve health outcomes in high risk individuals discharged from hospital with chronic AF. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Thermal stress in North Western Australian iron ore mining staff.

PubMed

Peiffer, Jeremiah J; Abbiss, Chris R

2013-05-01

Demand for Australian mined iron ore has increased employment within this sector, thus exposing increased numbers of workers to the harsh Australian climate. This study examined the influence of hot (>30°C wet bulb globe temperature) environmental temperatures, consistent with working in North Western Australia, on iron ore mining staff. Core temperature, hydration status, perceived exertion, mood, and fatigue state were measured in 77 participants at three time points (pre-, mid-, and post-shift) during a normal 12-h shift at an open-cut iron ore mining/processing site (n = 31; Site1) and an iron ore processing/shipping site (n = 46; Site2). A significant effect for time was observed for core temperature with greater mean core temperatures measured mid-shift (37.5±0.4°C) and post-shift (37.6±0.3°C) compared with pre-shift values (37.0±0.5°C). All mean core temperature measures were lower than ISO7933 thresholds (38°C) for thermal safety. Mean hydration measures [urine-specific gravity (USG)] were greater at Site1 (1.029±0.006) compared with those at Site2 (1.021±0.007). Furthermore, both pre- and post-shift measures from Site1 and the post-shift measures from Site2 were greater than the threshold for dehydration (USG = 1.020). No differences were observed for mood or perceived exertion over time; however, measures of fatigue state were greater post-shift compared with pre- and mid-shift values for both sites. Our findings indicate that the majority of mine workers in North Western Australia are able to regulate work rate in hot environments to maintain core temperatures below ISO safety guidelines; however, 22% of workers reached or exceeded the safety guidelines, warranting further investigation. Furthermore, hydration practices, especially when off-work, appear inadequate and could endanger health and safety.

Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey.

PubMed

Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

2015-01-01

In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA's pre-market approval (PMA) pathway. We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives.

Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey

PubMed Central

Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

2015-01-01

Background In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA’s pre-market approval (PMA) pathway. Methods and results We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Conclusion Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives. PMID:26060416

49 CFR 190.239 - Safety orders.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pipeline integrity risk to public safety, property, or the environment, the Associate Administrator may... existence of a condition that poses a pipeline integrity risk to public safety, property, or the environment... public safety, property, or the environment. (5) Post-hearing action. Following a hearing under this...

Laboratory safety and the WHO World Alliance for Patient Safety.

PubMed

McCay, Layla; Lemer, Claire; Wu, Albert W

2009-06-01

Laboratory medicine has been a pioneer in the field of patient safety; indeed, the College of American Pathology first called attention to the issue in 1946. Delivering reliable laboratory results has long been considered a priority, as the data produced in laboratory medicine have the potential to critically influence individual patients' diagnosis and management. Until recently, most attention on laboratory safety has focused on the analytic stage of laboratory medicine. Addressing this stage has led to significant and impressive improvements in the areas over which laboratories have direct control. However, recent data demonstrate that pre- and post-analytical phases are at least as vulnerable to errors; to further improve patient safety in laboratory medicine, attention must now be focused on the pre- and post-analytic phases, and the concept of patient safety as a multi-disciplinary, multi-stage and multi-system concept better understood. The World Alliance for Patient Safety (WAPS) supports improvement of patient safety globally and provides a potential framework for considering the total testing process.

Panitumumab in Japanese Patients with Unresectable Colorectal Cancer: A Post-marketing Surveillance Study of 3085 Patients†

PubMed Central

Boku, Narikazu; Sugihara, Kenichi; Kitagawa, Yuko; Hatake, Kiyohiko; Gemma, Akihiko; Yamazaki, Naoya; Muro, Kei; Hamaguchi, Tetsuya; Yoshino, Takayuki; Yana, Ikuo; Ueno, Hiroshi; Ohtsu, Atsushi

2014-01-01

Objective Panitumumab was approved in Japan in April 2010 for the treatment of Kirsten rat sarcoma-2 virus oncogene wild-type unresectable and recurrent colorectal cancer. We conducted a post-marketing surveillance study to evaluate the safety and effectiveness of panitumumab. Methods After panitumumab was commercially available in Japan, all patients to be treated with panitumumab were enrolled. Data on baseline characteristics, treatment outcome, and incidence and severity of adverse drug reactions were collected. Results In total, 3091 patients were registered. In the safety analysis set (n = 3085), panitumumab was administered as monotherapy (40.7%) or combination therapy (59.4%). The median treatment duration was 113 days (range: 1–559 days), and 451 (14.6%) patients received panitumumab for ≥10 months. The overall incidence rate of adverse drug reactions was 84.1%, and the most common adverse drug reaction was skin disorders (78.4%). The incidence rates (all grades) of interstitial lung disease, infusion reaction, electrolyte abnormalities and cardiac disorders were 1.3% (mortality rate: 0.6%), 1.5, 19.3 and 0.2%, respectively. The median survival time of patients treated with panitumumab monotherapy as the third-line, or later, therapy was 10.3 months. Conclusion This post-marketing survey in clinical practice confirmed the safety and effectiveness of panitumumab. The benefit/risk balance for panitumumab in Japanese patients with unresectable colorectal cancer remains favorable. PMID:24526771

Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

PubMed

Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Study of Aircraft Post-Crash Fuel Fire Mitigation

DTIC Science & Technology

1994-06-01

AD-A282. 208 A STUDY OF AIRCRAFT POST-CRASH FUEL FIRE MITIGATION INTERIM REPORT BFLRF No. 292 By D.W. Naegeli B.R. Wright Belvoir Fuels and...DAAK7D-S7-C4.004; WD 36 6. AUTHOR(S) DA7-2C0.W Naegeli D"i N. and Wrigl* Bomnd L sed Zabne, David bi (Zalle. Assoiaes) 7. PERFORMING ORGANIZATION NAME...Proceedings, December 3-5, 1991. 6. Weatherford, W.D., Jr. and Naegeli , D,W., "Study of Pool Burning Self-Extinguishment Mechanisms in Aqueous Diesel

Risk evaluation and monitoring in multiple sclerosis therapeutics.

PubMed

Clanet, Michel C; Wolinsky, Jerry S; Ashton, Raymond J; Hartung, Hans-Peter; Reingold, Stephen C

2014-09-01

Risk for multiple sclerosis (MS) disease-modifying therapies (DMT) must be assessed on an ongoing basis. Early concerns regarding the first-approved DMTs for MS have been mitigated, but recently licensed therapies have been linked to possibly greater risks. The objective of this review is to discuss risk assessment in MS therapeutics based on an international workshop and comprehensive literature search and recommend strategies for risk assessment/monitoring. Assessment and perception of therapeutic risks vary between patients, doctors and regulators. Acceptability of risk depends on the magnitude of risk and the demonstrated clinical benefits of any agent. Safety signals must be distinguishable from chance occurrences in a clinical trial and in long-term use of medications. Post-marketing research is crucial for assessing longer-term safety in large patient cohorts. Reporting of adverse events is becoming more proactive, allowing more rapid identification of risks. Communication about therapeutic risks and their relationship to clinical benefit must involve patients in shared decision making. It is difficult to produce a general risk-assessment algorithm for all MS therapies. Specific algorithms are required for each DMT in every treated-patient population. New and evolving risks must be evaluated and communicated rapidly to allow patients and physicians to be well informed and able to share treatment decisions. © The Author(s) 2013.

Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial

PubMed Central

Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.

2014-01-01

Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

Caring for class III obese patients.

PubMed

Gardner, Lea Anne

2013-11-01

The Pennsylvania Patient Safety Reporting System is a confidential, statewide Internet reporting system to which all Pennsylvania hospitals, outpatient-surgery facilities, and birthing centers, as well as some abortion facilities, must file information on medical errors.Safety Monitor is a column from Pennsylvania's Patient Safety Authority, the authority that informs nurses on issues that can affect patient safety and presents strategies they can easily integrate into practice. For more information on the authority, visit www.patientsafetyauthority.org. For the original article discussed in this column or for other articles on patient safety, click on "Patient Safety Advisories" and then "Advisory Library" in the left-hand navigation menu.

The Advocacy for Pedestrian Safety Study: Cluster Randomised Trial Evaluating a Political Advocacy Approach to Reduce Pedestrian Injuries in Deprived Communities

PubMed Central

Lyons, Ronan A.; Kendrick, Denise; Towner, Elizabeth M. L.; Coupland, Carol; Hayes, Mike; Christie, Nicola; Sleney, Judith; Jones, Sarah; Kimberlee, Richard; Rodgers, Sarah E.; Turner, Samantha; Brussoni, Mariana; Vinogradova, Yana; Sarvotham, Tinnu; Macey, Steven

2013-01-01

Objective To determine whether advocacy targeted at local politicians leads to action to reduce the risk of pedestrian injury in deprived areas. Design Cluster randomised controlled trial. Setting 239 electoral wards in 57 local authorities in England and Wales. Participants 617 elected local politicians. Interventions Intervention group politicians were provided with tailored information packs, including maps of casualty sites, numbers injured and a synopsis of effective interventions. Main outcome measures 25–30 months post intervention, primary outcomes included: electoral ward level: percentage of road traffic calmed; proportion with new interventions; school level: percentage with 20 mph zones, Safe Routes to School, pedestrian training or road safety education; politician level: percentage lobbying for safety measures. Secondary outcomes included politicians’ interest and involvement in injury prevention, and facilitators and barriers to implementation. Results Primary outcomes did not significantly differ: % difference in traffic calming (0.07, 95%CI: −0.07 to 0.20); proportion of schools with 20 mph zones (RR 1.47, 95%CI: 0.93 to 2.32), Safe Routes to School (RR 1.34, 95%CI: 0.83 to 2.17), pedestrian training (RR 1.23, 95%CI: 0.95 to 1.61) or other safety education (RR 1.16, 95%CI: 0.97 to 1.39). Intervention group politicians reported greater interest in child injury prevention (RR 1.09, 95%CI 1.03 to 1.16), belief in potential to help prevent injuries (RR 1.36, 95%CI 1.16 to 1.61), particularly pedestrian safety (RR 1.55, 95%CI 1.19 to 2.03). 63% of intervention politicians reported supporting new pedestrian safety schemes. The majority found the advocacy information surprising, interesting, effectively presented, and could identify suitable local interventions. Conclusions This study demonstrates the feasibility of an innovative approach to translational public health by targeting local politicians in a randomised controlled trial. The intervention package was positively viewed and raised interest but changes in interventions were not statistically significance. Longer term supported advocacy may be needed. Trial Registration Current Controlled Trials ISRCTN91381117 PMID:23577088

Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension.

PubMed

Worthley, Stephen G; Wilkins, Gerard T; Webster, Mark W; Montarello, Joseph K; Delacroix, Sinny; Whitbourn, Robert J; Warren, Roderic J

2017-07-01

Catheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and performance of the second generation EnligHTN™ Renal Denervation System. This first-in-human, prospective, multi-center, non-randomized study included 39 patients (62% male, mean age 63 years, and mean baseline office blood pressure 174/93 mmHg) with drug-resistant hypertension. The primary safety and performance objectives were to characterize, from baseline to 6 months post procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure. Renal artery denervation, using the second generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, 6, 12, 18 and 24 months by 19/7, 26/9, 25/7, 23/7, 25/8 and 27/9 mmHg, respectively (p ≤ 0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through 24 months of follow-up. Renal sympathetic denervation using the second generation EnligHTN Renal Denervation System resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 24 months. Future studies will need to address the utility of this system against an appropriate sham based comparator. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Dams and Levees: Safety Risks

NASA Astrophysics Data System (ADS)

Carter, N. T.

2017-12-01

The nation's flood risk is increasing. The condition of U.S. dams and levees contributes to that risk. Dams and levee owners are responsible for the safety, maintenance, and rehabilitation of their facilities. Dams-Of the more than 90,000 dams in the United States, about 4% are federally owned and operated; 96% are owned by state and local governments, public utilities, or private companies. States regulate dams that are not federally owned. The number of high-hazard dams (i.e., dams whose failure would likely result in the loss of human life) has increased in the past decade. Roughly 1,780 state-regulated, high-hazard facilities with structural ratings of poor or unsatisfactory need rehabilitation. Levees-There are approximately 100,000 miles of levees in the nation; most levees are owned and maintained by municipalities and agricultural districts. Few states have levee safety programs. The U.S. Army Corps of Engineers (Corps) inspects 15,000 miles of levees, including levees that it owns and local levees participating in a federal program to assist with certain post-flood repairs. Information is limited on how regularly other levees are inspected. The consequence of a breach or failure is another aspect of risk. State and local governments have significant authority over land use and development, which can shape the social and economic impacts of a breach or failure; they also lead on emergency planning and related outreach. To date, federal dam and levee safety efforts have consisted primarily of (1) support for state dam safety standards and programs, (2) investments at federally owned dams and levees, and (3) since 2007, creation of a national levee database and enhanced efforts and procedures for Corps levee inspections and assessments. In Public Law 113-121, enacted in 2014, Congress (1) directed the Corps to develop voluntary guidelines for levee safety and an associated hazard potential classification system for levees, and (2) authorized support for the development of state levee safety programs. As of 2017, federal funding for work pursuant to these provisions has been limited. Key policy considerations include (1) whether the status quo regarding investment and responsibilities in dam and levee safety results in a tolerable level of risk nationally and locally, and (2) who bears those risks.

2016 Traffic Safety Culture Index

MedlinePlus

... for Traffic Safety. For media inquiries, contact: Tamra Johnson 202-942-2079 TRJohnson@national.aaa.com Authors ... for Traffic Safety. For media inquiries, contact: Tamra Johnson 202-942-2079 TRJohnson@national.aaa.com Authors ...

The new structure and contents of employers' juridical responsibility for workers' health and safety in the post-industrial system.

PubMed

Ichino, P

2006-01-01

1. The enlargement of the labour law application area in the post-industrial system. 2. The enormous growth of differences in productivity between workers and its consequences on the employer's safety obligation. 3. Depressive disorders as a typical professional risk in the post-industrial system and the employer's prevention responsibility. 4. Harassment in the work-place as a typical pathologic consequence of the de-standardization of jobs. The specific employer's prevention responsibility in this field. 5. A conclusive remark.

In America’s Wake: A Comparison of Rising Power Foreign Policies

DTIC Science & Technology

2016-06-01

judgments or pronouncements as to the propriety or impropriety of any particular course of action. The author is unconvinced that ex post facto ...Expansion, 3rd ed, Cambridge Imperial and Post -Colonial Studies Series (Houndmills, Basingstoke, Hampshire ; New York: Palgrave/Macmillan, 2002), 14...Century, 1815-1914: A Study of Empire and Expansion, 3rd ed, Cambridge Imperial and Post -Colonial Studies Series (Houndmills, Basingstoke, Hampshire

Evaluating SafeClub: can risk management training improve the safety activities of community soccer clubs?

PubMed

Abbott, K; Klarenaar, P; Donaldson, A; Sherker, S

2008-06-01

To evaluate a sports safety-focused risk-management training programme. Controlled before and after test. Four community soccer associations in Sydney, Australia. 76 clubs (32 intervention, 44 control) at baseline, and 67 clubs (27 intervention, 40 control) at post-season and 12-month follow-ups. SafeClub, a sports safety-focused risk-management training programme (3x2 hour sessions) based on adult-learning principles and injury-prevention concepts and models. Changes in mean policy, infrastructure and overall safety scores as measured using a modified version of the Sports Safety Audit Tool. There was no significant difference in the mean policy, infrastructure and overall safety scores of intervention and control clubs at baseline. Intervention clubs achieved higher post-season mean policy (11.9 intervention vs 7.5 controls), infrastructure (15.2 vs 10.3) and overall safety (27.0 vs 17.8) scores than did controls. These differences were greater at the 12-month follow-up: policy (16.4 vs 7.6); infrastructure (24.7 vs 10.7); and overall safety (41.1 vs 18.3). General linear modelling indicated that intervention clubs achieved statistically significantly higher policy (p<0.001), infrastructure (p<0.001) and overall safety (p<0.001) scores compared with control clubs at the post-season and 12-month follow-ups. There was also a significant linear interaction of time and group for all three scores: policy (p<0.001), infrastructure (p<0.001) and overall safety (p<0.001). SafeClub effectively assisted community soccer clubs to improve their sports safety activities, particularly the foundations and processes for good risk-management practice, in a sustainable way.

Bodies as means for continuing post-death relationships.

PubMed

Leichtentritt, Ronit D; Mahat Shamir, Michal; Barak, Adi; Yerushalmi, Ayelet

2016-05-01

Secondary analysis of data from 30 people in three interview studies shows that bereaved people use their own and the deceased's body in their continuing efforts to maintain a relationship with the departed. Following the continuing bond perspective, the study reveals three body-associated strategies for maintaining post-death relationships: (a) the presence of the deceased in the bereaved's body, (b) body-associated actions and activities, and (c) sensing and caring for the deceased's body. The conceptual dimension of embodiment is used to interpret results. Attention is also given to the bereaved's sense of disembodiment due to social rejection of these strategies for maintaining post-death relationships. Implications for health psychologists are offered. © The Author(s) 2014.

Evaluation of aviation-based safety team training in a hospital in The Netherlands.

PubMed

De Korne, Dirk F; Van Wijngaarden, Jeroen D H; Van Dyck, Cathy; Hiddema, U Francis; Klazinga, Niek S

2014-01-01

The purpose of this paper is to evaluate the implementation of a broad-scale team resource management (TRM) program on safety culture in a Dutch eye hospital, detailing the program's content and procedures. Aviation-based TRM training is recognized as a useful approach to increase patient safety, but little is known about how it affects safety culture. Pre- and post-assessments of the hospitals' safety culture was based on interviews with ophthalmologists, anesthesiologists, residents, nurses, and support staff. Interim observations were made at training sessions and in daily hospital practice. The program consisted of safety audits of processes and (team) activities, interactive classroom training sessions by aviation experts, a flight simulator session, and video recording of team activities with subsequent feedback. Medical professionals considered aviation experts inspiring role models and respected their non-hierarchical external perspective and focus on medical-technical issues. The post-assessment showed that ophthalmologists and other hospital staff had become increasingly aware of safety issues. The multidisciplinary approach promoted social (team) orientation that replaced the former functionally-oriented culture. The number of reported near-incidents greatly increased; the number of wrong-side surgeries stabilized to a minimum after an initial substantial reduction. The study was observational and the hospital's variety of efforts to improve safety culture prevented us from establishing a causal relation between improvement and any one specific intervention. Aviation-based TRM training can be a useful to stimulate safety culture in hospitals. Safety and quality improvements are not single treatment interventions but complex socio-technical interventions. A multidisciplinary system approach and focus on "team" instead of "profession" seems both necessary and difficult in hospital care.

Professional and Personal Qualities of the Teacher in the Context of the Psychological Safety of Educational Environment

ERIC Educational Resources Information Center

Kulikova, Tatyana I.; Maliy, Dmitriy V.

2017-01-01

The article deals with the phenomenon of psychological safety of the educational environment (PSEE) in the modern school. Indicators of the educational process participants' psychological safety are revealed. The notion of the teacher's preparedness for the designing activity is defined. The authors have conducted a case study revealing integrated…

The Home Inventory of Dangers and Safety Precautions--2: Addressing Critical Needs for Prescriptive Assessment Devices in Child Maltreatment and in Healthcare.

ERIC Educational Resources Information Center

Tymchuk, Alexander J.; Lang, Cathy M.; Doylniuk, Chrystina A.; Berney-Ficklin, Karen; Spitz, Rebecca

1999-01-01

Describes a study involving 29 low-income parents with learning difficulties that validated a prescriptive home-danger and safety-precaution instrument containing 14 epidemiological categories to be used in the design and evaluation of family-tailored injury prevention and safety interventions. (Author/CR)

A Comprehensive Approach to Managing School Safety: Case Studies in Catalonia, Spain

ERIC Educational Resources Information Center

Díaz-Vicario, Anna; Gairín Sallán, Joaquín

2017-01-01

Background: Schools should be safe spaces for students, teaching staff and non-teaching staff. For the concept of "safety" to be meaningful, it must be interpreted broadly to encompass well-being in its widest sense. A common challenge for schools and educational authorities is, therefore, to manage school safety appropriately not only…

42 CFR 3.544 - Post hearing briefs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.544 Post hearing briefs. The ALJ may require the parties to file post-hearing briefs. In any event, any party may file a post-hearing brief... 42 Public Health 1 2010-10-01 2010-10-01 false Post hearing briefs. 3.544 Section 3.544 Public...

42 CFR 3.544 - Post hearing briefs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.544 Post hearing briefs. The ALJ may require the parties to file post-hearing briefs. In any event, any party may file a post-hearing brief... 42 Public Health 1 2014-10-01 2014-10-01 false Post hearing briefs. 3.544 Section 3.544 Public...

42 CFR 3.544 - Post hearing briefs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.544 Post hearing briefs. The ALJ may require the parties to file post-hearing briefs. In any event, any party may file a post-hearing brief... 42 Public Health 1 2012-10-01 2012-10-01 false Post hearing briefs. 3.544 Section 3.544 Public...

42 CFR 3.544 - Post hearing briefs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.544 Post hearing briefs. The ALJ may require the parties to file post-hearing briefs. In any event, any party may file a post-hearing brief... 42 Public Health 1 2011-10-01 2011-10-01 false Post hearing briefs. 3.544 Section 3.544 Public...

42 CFR 3.544 - Post hearing briefs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.544 Post hearing briefs. The ALJ may require the parties to file post-hearing briefs. In any event, any party may file a post-hearing brief... 42 Public Health 1 2013-10-01 2013-10-01 false Post hearing briefs. 3.544 Section 3.544 Public...

Community partnership to promote home fire safety in children with special needs.

PubMed

Lehna, Carlee; Janes, Erika G; Rengers, Sharon; Graviss, Jackie; Scrivener, Drane; Knabel, Tom; Carver, Elizabeth; Myers, John

2014-09-01

Parents of children with special needs are vigilant as their child may have difficulty independently escaping a burning home. The purpose of this study was to evaluate if providing home fire safety information via a digital video disc (DVD) increases families' knowledge, behavior and ability regarding home fire safety. A school based classroom intervention (using a home fire safety DVD) was provided to parents (n=40) of children with and without special needs to improve home fire safety knowledge, behavior and ability. In addition, parents seen at the Kentucky Commission for Children with Special Health Care Needs clinics (n=47) received the same intervention in cohorts of 1-2 children. For both groups, knowledge, and behavior were measured before and after intervention. Repeated measures ANOVA were used to test for differences between groups and over time. Significance was set at p<0.05. No difference in scores between pre- and post-test scores existed between groups (with special needs vs. without special needs, or classroom vs. individualized instruction). However, some differences were noted for some individual survey questions during post-hoc comparisons. Having a smoke alarm in the home (90% vs. 95%, p=0.029) and having a smoke alarm outside of where everyone sleeps (75% vs. 95%, p=0.005) increased over time and was retained. Having a fire escape plan increased at post intervention (58% vs. 79%, p=0.033), but returned to pre levels at follow-up (58%). Perceived knowledge (7.7 vs. 9.3, p<0.001) and ability (8.7 vs. 9.1, p=0.069) increased over time. Parents of children with special needs had a significant increase in knowledge and behavior over those parents of children without special needs. They also perceived having a high fire safety ability. Many of the post-test questions/behaviors (e.g., capable of exiting home during a fire, etc.) were reported at 100%. The intervention was well received, but may not necessarily be needed. Focus for home fire safety may need to look at younger children and smaller families. Parents of special needs children may have had frequent interaction with health care professionals. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

New York Metropolitan Transportation Authority safety investigation

DOT National Transportation Integrated Search

1993-06-01

The Federal Transit Administration (FTA) conducted an intensive investigation of passenger and employee safety on the New York Metropolitan Transportation Authority (MTA) and its operating elements. The investigation stressed the system safety concep...

Efficacy of Erbium:YAG laser treatment compared to topical estriol treatment for symptoms of genitourinary syndrome of menopause.

PubMed

Gaspar, Adrian; Brandi, Hugo; Gomez, Valentin; Luque, Daniel

2017-02-01

The objective of this prospective comparative cohort study was to establish the effectiveness and safety of Erbium:YAG (Er:YAG) laser treatment for genitourinary syndrome of menopause and to compare it with an established topical estriol treatment. Fifty patients with genitourinary syndrome of menopause were divided into two groups. The estriol group received a treatment of 0.5 mg estriol ovules for 8 weeks and the laser group was first treated for 2 weeks with 0.5 mg estriol ovules 3 times per week to hydrate the mucosa and then received three sessions with 2,940 nm Er:YAG laser in non-ablative mode. Biopsies were taken before and at 1, 3, 6, and 12 months post-treatment. Maturation index, maturation value and pH where recorded up to 12-months post-treatment, while the VAS analysis of symptoms was recorded up to 18 months post-treatment. Statistically significant (P < 0.05), reduction of all assessed symptoms was observed in the laser group at all follow-ups up to 18 months post-treatment. Significant improvement in maturation value and a decrease of pH in the laser group was detected up to 12 months after treatment. The improvement in all endpoints was more pronounced and longer lasting in the laser group. Histological examination showed changes in the tropism of the vaginal mucosa and also angiogenesis, congestion, and restructuring of the lamina propria in the laser group. Side effects were minimal and of transient nature in both groups, affecting 4% of patients in the laser group and 12% of patients in the estriol group. Our results show that Er:YAG laser treatment successfully relieves symptoms of genitourinary syndrome of menopause and that the results are more pronounced and longer lasting compared to topical estriol treatment. Lasers Surg. Med. 49:160-168, 2017. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Immunogenicity of live attenuated Japanese encephalitis SA 14-14-2 vaccine among Sri Lankan children with previous receipt of inactivated JE vaccine.

PubMed

Wijesinghe, Pushpa Ranjan; Abeysinghe, M R Nihal; Yoksan, Sutee; Yao, Yafu; Zhou, Benli; Zhang, Lei; Fleming, Jessica A; Marfin, Anthony A; Victor, John C

2016-11-21

The performance of live attenuated Japanese Encephalitis SA 14-14-2 vaccine (CD-JEV) among children previously given inactivated mouse brain-derived JE vaccine (IMBV) is unknown. We evaluated the safety and immunogenicity of CD-JEV administered to 2- and 5-year-old children in Sri Lanka. In this open-label, single arm trial in the Colombo District of Sri Lanka, generally healthy children 2 and 5years of age who had previously received two and three doses of IMBV, respectively, were administered one dose of CD-JEV subcutaneously. Participants were monitored for adverse events for one year post-vaccination. Serum neutralizing antibody responses were evaluated pre and 28 and 365days post-vaccination using JE plaque reduction neutralization test and characterized as the proportion of participants seroconverting. Seroconversion was defined as either reaching a titer considered seroprotective (⩾1:10) among participants with a baseline titer <1:10 or achieving at least a 4-fold rise in titer among participants with a baseline titer ⩾1:10. Of 305 children given CD-JEV, 294 were included in the primary analysis of immunogenicity. Prior to vaccination, 144/147 (98.0%) 2-year-olds and 146/147 (99.3%) 5-year-olds had seroprotective levels. 28days post-vaccination, 79/147 [53.7% (95% CI, 45.3-62.0)] 2-year olds and of 60/147 [40.8% (95% CI, 32.8-49.2)] 5-year olds achieved seroconversion. Among 2-year-olds, geometric mean titers (GMTs) rose from 697 to 3175 28days post-vaccination. Among 5-year-olds, GMTs rose from 926 to 2776. Most adverse reactions were mild, and no serious adverse events were related to study vaccination. Administration of CD-JEV to these children with pre-existing neutralizing JE antibody titers was safe and resulted in substantial boosting of antibody levels. These results may inform other countries in Asia considering switching from IMBV to now WHO-prequalified CD-JEV vaccine to combat this disease of public health importance. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Human pregnancy safety for agents used to treat rheumatoid arthritis: adequacy of available information and strategies for developing post-marketing data

PubMed Central

Chambers, Christina D; Tutuncu, Zuhre N; Johnson, Diana; Jones, Kenneth L

2006-01-01

For female patients with rheumatoid arthritis, the availability of a host of new disease modifying antirheumatic drugs has raised important questions about fetal safety if a woman becomes pregnant while she is being treated. In addition, there is limited safety information regarding many of the older medications commonly used to treat rheumatoid arthritis in women of reproductive age. Current summary pregnancy risk information for selected medications used to treat rheumatoid arthritis is reviewed in the context of the pregnancy label category. In addition, the strengths and weaknesses of post-marketing strategies for developing new pregnancy safety information are described. PMID:16774693

Outcomes With Transcatheter Mitral Valve Repair in the United States: An STS/ACC TVT Registry Report.

PubMed

Sorajja, Paul; Vemulapalli, Sreekanth; Feldman, Ted; Mack, Michael; Holmes, David R; Stebbins, Amanda; Kar, Saibal; Thourani, Vinod; Ailawadi, Gorav

2017-11-07

Post-market surveillance is needed to evaluate the real-world clinical effectiveness and safety of U.S. Food and Drug Administration-approved devices. The authors examined the commercial experience with transcatheter mitral valve repair for the treatment of mitral regurgitation. Data from the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry on patients commercially treated with transcatheter mitral valve repair were analyzed. The study population consisted of 2,952 patients treated at 145 hospitals between November 2013 and September 2015. In 1,867 patients, data were linked to patient-specific Centers for Medicare and Medicaid Services administrative claims for analyses. The median age was 82 years (55.8% men), with a median Society of Thoracic Surgery predicted risk of mortality of 6.1% (interquartile range: 3.7% to 9.9%) and 9.2% (interquartile range: 6.0% to 14.1%) for mitral repair and replacement, respectively. Overall, in-hospital mortality was 2.7%. Acute procedure success occurred in 91.8%. Among the patients with Centers for Medicare and Medicaid Services linkage data, the mortality at 30 days and at 1 year was 5.2% and 25.8%, respectively, and repeat hospitalization for heart failure at 1 year occurred in 20.2%. Variables associated with mortality or rehospitalization for heart failure after multivariate adjustment were increasing age, lower baseline left ventricular ejection fraction, worse post-procedural mitral regurgitation, moderate or severe lung disease, dialysis, and severe tricuspid regurgitation. Our findings demonstrate that commercial transcatheter mitral valve repair is being performed in the United States with acute effectiveness and safety. Our findings may help determine which patients have favorable long-term outcomes with this therapy. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Making a difference: using the safe surgery checklist to initiate continuing education for perioperative nurses in low-income settings.

PubMed

Leifso, Genelle

2014-03-01

The WHO Safe Surgery Checklist (2008) patient safety focus and communication prompts are widely accepted. In many low-income regions (as defined by the World Bank and accepted by the World Health Organization) perioperative nurses have little or no formal training; continuing and in-service education are virtually unknown; nor does an articulated "culture of safety" exist. In 2009 the Canadian Network for International Surgery (CNIS) piloted a two-day perioperative nursing course, in Addis Ababa, Ethiopia, using lectures, case studies, skills sessions, and role-play exercises based on the SSSL Checklist outline and protocols. Canadian instructors (who are certified after taking the Canadian Network for International Surgery-sponsored Instructor's Course) have since returned and taught at additional sites in Ethiopia and Uganda. Course participants now include perioperative nurses, anaesthetists, and junior surgical residents--mirroring the interdisciplinary teamwork that is crucial to safe perioperative patient care. The course's facilitated discussions focus on workplace and practice issues in order to allow for appropriate evaluation and planning of future educational initiatives. Participants complete pre- and post-course questionnaires, which evaluate baseline and post-course knowledge, and further follow-up is completed four months after course completion. This article explains the need for aiding in the expansion of perioperative nursing knowledge and skill in low-income settings and provides the author's personal perspective and experience in responding to this need. Her experience as facilitator in a pilot project and subsequent course development described. The objective is to discuss ways that other perioperative nurses can work to make a positive difference on professional practice and patient care in low-income regions.

Tracheal intubation in critically ill patients: a comprehensive systematic review of randomized trials.

PubMed

Cabrini, Luca; Landoni, Giovanni; Baiardo Radaelli, Martina; Saleh, Omar; Votta, Carmine D; Fominskiy, Evgeny; Putzu, Alessandro; Snak de Souza, Cézar Daniel; Antonelli, Massimo; Bellomo, Rinaldo; Pelosi, Paolo; Zangrillo, Alberto

2018-01-20

We performed a systematic review of randomized controlled studies evaluating any drug, technique or device aimed at improving the success rate or safety of tracheal intubation in the critically ill. We searched PubMed, BioMed Central, Embase and the Cochrane Central Register of Clinical Trials and references of retrieved articles. Finally, pertinent reviews were also scanned to detect further studies until May 2017. The following inclusion criteria were considered: tracheal intubation in adult critically ill patients; randomized controlled trial; study performed in Intensive Care Unit, Emergency Department or ordinary ward; and work published in the last 20 years. Exclusion criteria were pre-hospital or operating theatre settings and simulation-based studies. Two investigators selected studies for the final analysis. Extracted data included first author, publication year, characteristics of patients and clinical settings, intervention details, comparators and relevant outcomes. The risk of bias was assessed with the Cochrane Collaboration's Risk of Bias tool. We identified 22 trials on use of a pre-procedure check-list (1 study), pre-oxygenation or apneic oxygenation (6 studies), sedatives (3 studies), neuromuscular blocking agents (1 study), patient positioning (1 study), video laryngoscopy (9 studies), and post-intubation lung recruitment (1 study). Pre-oxygenation with non-invasive ventilation (NIV) and/or high-flow nasal cannula (HFNC) showed a possible beneficial role. Post-intubation recruitment improved oxygenation , while ramped position increased the number of intubation attempts and thiopental had negative hemodynamic effects. No effect was found for use of a checklist, apneic oxygenation (on oxygenation and hemodynamics), videolaryngoscopy (on number and length of intubation attempts), sedatives and neuromuscular blockers (on hemodynamics). Finally, videolaryngoscopy was associated with severe adverse effects in multiple trials. The limited available evidence supports a beneficial role of pre-oxygenation with NIV and HFNC before intubation of critically ill patients. Recruitment maneuvers may increase post-intubation oxygenation. Ramped position increased the number of intubation attempts; thiopental had negative hemodynamic effects and videolaryngoscopy might favor adverse events.

The Mental Health Consequences of Mass Shootings.

PubMed

Lowe, Sarah R; Galea, Sandro

2017-01-01

Mass shooting episodes have increased over recent decades and received substantial media coverage. Despite the potentially widespread and increasing mental health impact of mass shootings, no efforts to our knowledge have been made to review the empirical literature on this topic. We identified 49 peer-reviewed articles, comprised of 27 independent samples in the aftermath of 15 mass shooting incidents. Based on our review, we concluded that mass shootings are associated with a variety of adverse psychological outcomes in survivors and members of affected communities. Less is known about the psychological effects of mass shootings on indirectly exposed populations; however, there is evidence that such events lead to at least short-term increases in fears and declines in perceived safety. A variety of risk factors for adverse psychological outcomes have been identified, including demographic and pre-incident characteristics (e.g., female gender and pre-incident psychological symptoms), event exposure (e.g., greater proximity to the attack and acquaintance with the deceased), and fewer psychosocial resources (e.g., emotion regulation difficulties and lower social support). Further research that draws on pre-incident and longitudinal data will yield important insights into the processes that exacerbate or sustain post-incident psychological symptoms over time and provide important information for crisis preparedness and post-incident mental health interventions. © The Author(s) 2015.

Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea.

PubMed

Kim, Tae Heon; Lee, Sang Eun; Lee, Hahn-Ey; Lee, Kyu-Sung

2016-08-01

The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz ) in Korean patients with overactive bladder (OAB) in routine clinical practice. This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator's discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy. A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24 hours decreased by 4.0, 2.4, and 0.8, respectively (all p < 0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration. These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.

23 CFR 1200.4 - State Highway Safety Agency-Authority and functions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... is suitably equipped and organized to carry out the State's highway safety program. (b) Authority... safety and projects administered by other State and local agencies; (3) Maintain or have ready access to information contained in State highway safety data systems, including crash, citation, adjudication, emergency...

23 CFR 1200.4 - State Highway Safety Agency-Authority and functions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... is suitably equipped and organized to carry out the State's highway safety program. (b) Authority... safety and projects administered by other State and local agencies; (3) Maintain or have ready access to information contained in State highway safety data systems, including crash, citation, adjudication, emergency...

76 FR 52231 - Restrictions on Operators Employing Former Flight Standards Service Aviation Safety Inspectors

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-22

... Standards Service Aviation Safety Inspectors AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... responsible for the oversight of, a Flight Standards Service Aviation Safety Inspector, and had direct... . SUPPLEMENTARY INFORMATION: Authority for This Rulemaking The FAA's authority to issue rules on aviation safety...

76 FR 20807 - Pilot Program on NAFTA Long-Haul Trucking Provisions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

..., and procedures to protect the health and safety of study participants and the general public. A pilot.... Whether environmental post-treatment equipment or other emissions-related equipment has been installed on...

Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study.

PubMed

Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

2015-01-01

This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.

Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study

PubMed Central

Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

2015-01-01

This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3–4–5 months of age) and booster vaccination (17–19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children. PMID:25830489

Procedural and short-term safety of bronchial thermoplasty in clinical practice: evidence from a national registry and Hospital Episode Statistics.

PubMed

Burn, Julie; Sims, Andrew J; Keltie, Kim; Patrick, Hannah; Welham, Sally A; Heaney, Liam G; Niven, Robert M

2017-10-01

Bronchial thermoplasty (BT) is a novel treatment for severe asthma. Its mode of action and ideal target patient group remain poorly defined, though clinical trials provided some evidence on efficacy and safety. This study presents procedural and short-term safety evidence from routine UK clinical practice. Patient characteristics and safety outcomes (procedural complications, 30-day readmission and accident and emergency (A&E) attendance, length of stay) were assessed using two independent data sources, the British Thoracic Society UK Difficult Asthma Registry (DAR) and Hospital Episodes Statistics (HES) database. A matched cohort (with records in both) was used to estimate safety outcome event rates and compare them with clinical trials. Between June 2011 and January 2015, 215 procedure records (83 patients; 68 treated in England) were available from DAR and 203 (85 patients) from HES. 152 procedures matched (59 patients; 6 centres), and of these, 11.2% reported a procedural complication, 11.8% resulted in emergency respiratory readmission, 0.7% in respiratory A&E attendance within 30 days (20.4% had at least one event) and 46.1% involved a post-procedure stay. Compared with published clinical trials which found lower hospitalisation rates, BT patients in routine clinical practice were, on average, older, had worse baseline lung function and asthma quality of life. A higher proportion of patients experienced adverse events compared with clinical trials. The greater severity of disease amongst patients treated in clinical practice may explain the observed rate of post-procedural stay and readmission. Study of long-term safety and efficacy requires continuing data collection.

The TRIPOD e-learning Platform for the Training of Earthquake Safety Assessment

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

Coppari, S.; Di Pasquale, G.; Goretti, A.

2008-07-08

The paper summarizes the results of the in progress EU Project titled TRIPOD (Training Civil Engineers on Post-Earthquake Safety Assessment of Damaged Buildings), funded under the Leonardo Da Vinci program. The main theme of the project is the development of a methodology and a learning platform for the training of technicians involved in post-earthquake building safety inspections. In the event of a catastrophic earthquake, emergency building inspections constitute a major undertaking with severe social impact. Given the inevitable chaotic conditions and the urgent need of a great number of specialized individuals to carry out inspections, past experience indicates that inspectionmore » teams are often formed in an adhoc manner, under stressful conditions, at a varying levels of technical expertise and experience, sometime impairing the reliability and consistency of the inspection results. Furthermore each Country has its own building damage and safety assessment methodology, developed according to its experience, laws, building technology and seismicity. This holds also for the partners participating to the project (Greece, Italy, Turkey, Cyprus), that all come from seismically sensitive Mediterranean countries. The project aims at alleviating the above shortcomings by designing and developing a training methodology and e-platform, forming a complete training program targeted at inspection engineers, specialized personnel and civil protection agencies. The e-learning platform will provide flexible and friendly authoring mechanisms, self-teaching and assessment capabilities, course and trainee management, etc. Courses will be also made available as stand-alone multimedia applications on CD and in the form of a complete pocket handbook. Moreover the project will offer the possibility of upgrading different experiences and practices: a first step towards the harmonization of methodologies and tools of different Countries sharing similar problems. Finally, through wide dissemination activities, the final aim of the project is to ensure the deployment and the integration into existing earthquake mitigation policies and vocational training schemes.« less

The TRIPOD e-learning Platform for the Training of Earthquake Safety Assessment

NASA Astrophysics Data System (ADS)

Coppari, S.; Di Pasquale, G.; Goretti, A.; Papa, F.; Papa, S.; Paoli, G.; Pizza, A. G.; Severino, M.

2008-07-01

The paper summarizes the results of the in progress EU Project titled TRIPOD (Training Civil Engineers on Post-Earthquake Safety Assessment of Damaged Buildings), funded under the Leonardo Da Vinci program. The main theme of the project is the development of a methodology and a learning platform for the training of technicians involved in post-earthquake building safety inspections. In the event of a catastrophic earthquake, emergency building inspections constitute a major undertaking with severe social impact. Given the inevitable chaotic conditions and the urgent need of a great number of specialized individuals to carry out inspections, past experience indicates that inspection teams are often formed in an adhoc manner, under stressful conditions, at a varying levels of technical expertise and experience, sometime impairing the reliability and consistency of the inspection results. Furthermore each Country has its own building damage and safety assessment methodology, developed according to its experience, laws, building technology and seismicity. This holds also for the partners participating to the project (Greece, Italy, Turkey, Cyprus), that all come from seismically sensitive Mediterranean countries. The project aims at alleviating the above shortcomings by designing and developing a training methodology and e-platform, forming a complete training program targeted at inspection engineers, specialized personnel and civil protection agencies. The e-learning platform will provide flexible and friendly authoring mechanisms, self-teaching and assessment capabilities, course and trainee management, etc. Courses will be also made available as stand-alone multimedia applications on CD and in the form of a complete pocket handbook. Moreover the project will offer the possibility of upgrading different experiences and practices: a first step towards the harmonization of methodologies and tools of different Countries sharing similar problems. Finally, through wide dissemination activities, the final aim of the project is to ensure the deployment and the integration into existing earthquake mitigation policies and vocational training schemes.

10 CFR 35.57 - Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized...

Code of Federal Regulations, 2011 CFR

2011-01-01

..., teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist. 35.57 Section 35.57 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF... pharmacist, and authorized nuclear pharmacist. (a)(1) An individual identified as a Radiation Safety Officer...

10 CFR 35.57 - Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized...

Code of Federal Regulations, 2014 CFR

2014-01-01

..., teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist. 35.57 Section 35.57 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF... pharmacist, and authorized nuclear pharmacist. (a)(1) An individual identified as a Radiation Safety Officer...

10 CFR 35.57 - Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized...

Code of Federal Regulations, 2012 CFR

2012-01-01

..., teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist. 35.57 Section 35.57 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF... pharmacist, and authorized nuclear pharmacist. (a)(1) An individual identified as a Radiation Safety Officer...

10 CFR 35.57 - Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized...

Code of Federal Regulations, 2013 CFR

2013-01-01

..., teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist. 35.57 Section 35.57 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF... pharmacist, and authorized nuclear pharmacist. (a)(1) An individual identified as a Radiation Safety Officer...

10 CFR 35.57 - Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized...

Code of Federal Regulations, 2010 CFR

2010-01-01

..., teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist. 35.57 Section 35.57 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF... pharmacist, and authorized nuclear pharmacist. (a)(1) An individual identified as a Radiation Safety Officer...

[Basic requirements on post-marketing clinical re-evaluation of chinese medicine and phase IV clinical trials].

PubMed

Xie, Yanming; Wang, Yanping; Tian, Feng; Wang, Yongyan

2011-10-01

As information on safety and effectiveness is not comprehensive, gained from the researches for listing approval of Chinese medicine, it is very necessary to conduct post-marketing clinical re-evaluation of Chinese medicine. Effectiveness, safety and economic evaluation are three main aspects of post-marketing clinical re-evaluation. In this paper, the difference and relations between the post-marketing clinical re-evaluation and the phase IV clinical trials were discussed, and the basic requests and suggestions were proposed, according to the domestic and foreign relevant regulations and experts' suggestions, and discussed the requirements of the phase IV clinical trials on indications, design methods, inclusion and exclusion criteria, sample size, etc.

Psychological mechanism linking abusive supervision and compulsory citizenship behavior: a moderated mediation study.

PubMed

Zhao, Hongdan; Peng, Zhenglong; Han, Yong; Sheard, Geoff; Hudson, Alan

2013-01-01

This study seeks to examine the effect of abusive supervision on the "dark side" of organizational citizenship behavior (OCB) and, specifically, compulsory citizenship behavior (CCB). The study focuses on the mediating role of psychological safety underpinning the relationship between abusive supervision and CCB, and the moderating role of Chinese traditionality in influencing the mediation. The authors tested the model with data of 434 dyads (employee-coworker pairs) in a large Chinese service company. Results indicated that psychological safety fully mediated the relationship between abusive supervision and CCB. The authors also found that Chinese traditionality moderated the strength of the mediated relationship between abusive supervision and CCB via psychological safety, such that the mediated relationship is weaker under high Chinese traditionality than under low Chinese traditionality. The article also discusses the implications, limitations, and future research directions.

International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals; availability. Notice.

PubMed

2010-01-21

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.'' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance, which is a revision of an existing guidance, discusses the types of nonclinical studies, their scope and duration, and their relation to the conduct of human clinical trials and marketing authorization for pharmaceuticals. The guidance is intended to facilitate the timely conduct of clinical trials and reduce the unnecessary use of animals and other drug development resources.

Rationale and design of TRANSITION: a randomized trial of pre-discharge vs. post-discharge initiation of sacubitril/valsartan.

PubMed

Pascual-Figal, Domingo; Wachter, Rolf; Senni, Michele; Belohlavek, Jan; Noè, Adele; Carr, David; Butylin, Dmytro

2018-04-01

The prognosis after hospitalization for acute decompensated heart failure (ADHF) remains poor, especially <30 days post-discharge. Evidence-based medications with prognostic impact administered at discharge improve survival and hospital readmission, but robust studies comparing pre-discharge with post-discharge initiation are rare. The PARADIGM-HF trial established sacubitril/valsartan as a new evidence-based therapy in patients with heart failure (HF) and reduced left ventricular ejection fraction (<40%) (rEF). In common with other landmark studies, it enrolled patients who were ambulatory at the time of inclusion. In addition, there is also still limited knowledge of initiation and up-titration of sacubitril/valsartan in ACEi/ARB- naïve patients and in de novo HF with rEF patients. TRANSITION is a multicentre, open-label study in which ~1000 adults hospitalized for ADHF with rEF are randomized to start sacubitril/valsartan in a pre-discharge arm (initiated ≥24 h after haemodynamic stabilization) or a post-discharge arm (initiated within Days 1-14 after discharge). The protocol allows investigators to select the appropriate starting dose and dose adjustments according to clinical circumstances. Over a 10 week treatment period, the primary and secondary objectives assess the feasibility and safety of starting sacubitril/valsartan in-hospital, early after haemodynamic stabilization. Exploratory objectives also include assessment of HF signs and symptoms, readmissions, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T levels, and health resource utilization parameters. TRANSITION will provide new evidence about initiating sacubitril/valsartan following hospitalization for ADHF, occurring either as de novo ADHF or as deterioration of chronic HF, and in patients with or without prior ACEI/ARB therapy. The results of TRANSITION will thus be highly relevant to the management of patients hospitalized for ADHF with rEF. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Driving reaction times in patients with foot and ankle pathology before and after image-guided injection: pain relief without improved function.

PubMed

Talusan, Paul G; Miller, Christopher P; Save, Ameya V; Reach, John S

2015-04-01

Foot and ankle pathology is common in the driving population. Local anesthetic steroid injections are frequent ambulatory treatments. Brake reaction time (BRT) has validated importance in motor vehicle safety. There are no prior studies examining the effect of foot and ankle pathology and injection treatment on the safe operation of motor vehicles. We studied BRT in patients with foot and ankle musculoskeletal disease before and after image-guided injection treatment. A total of 37 participants were enrolled. Image-guided injections of local anesthetic and steroid were placed into the pathological anatomical location of the right or left foot and ankles. A driving reaction timer was used to measure BRTs before and after injection. Patients suffering right "driving" and left "nondriving" pathology as well as a healthy control group were studied. All patients reported >90% pain relief postinjection. All injections were confirmed to be accurate by imaging. Post hoc Bonferonni analysis demonstrated significant difference between the healthy group and the right-sided injection group (P = .008). Mean BRT for healthy controls was 0.57 ± 0.11 s. Patients suffering right foot and ankle disease displayed surprisingly high BRTs (0.80 ± 0.23 s preinjection and 0.78 ± 0.16 s postinjection, P > .99). Left nondriving foot and ankle pathology presented a driving hazard as well (BRT of 0.75 ± 0.12 s preinjection and 0.77 ± 0.12 s postinjection, P > .99). Injections relieved pain but did not significantly alter BRT (P > .99 for all). Patients suffering chronic foot and ankle pathology involving either the driving or nondriving side have impaired BRTs. This preexisting driving impairment has not previously been reported and exceeds recommended cutoff safety values in the United States. Despite symptom improvement, there was no statistically significant change in BRT following image-guided injection in either foot and ankle. Therapeutic, Level II: Prospective Comparative Study. © 2014 The Author(s).

Discussion map and cooking classes: testing the effectiveness of teaching food safety to immigrants and refugees.

PubMed

Gold, Abby; Yu, Nan; Buro, Brandy; Garden-Robinson, Julie

2014-01-01

To evaluate the effectiveness of a food safety map as an educational method with English language learners. English language learner community members (n = 73) were assigned randomly to participate in 1 of 3 experimental conditions: food safety map, cooking class, and control. Participants in the food safety map and cooking class conditions completed a pre-education demographic and cooking history questionnaire, a post-education knowledge and intention questionnaire, and a 2-week post-cooking and food safety habits assessment. Participants in the control group received no educational training but completed the pre- and 2-week post-education assessments. The cooking class and the map class were both effective in increasing food safety knowledge. Specifically, by comparing with the control group, they significantly increased participants' knowledge of safely cooking large meat (χ² [df = 2, n = 66] = 40.87; P < .001; V* = .79) and correctly refrigerating cooked food (χ² [df = 2, n = 73] = 24.87, P < .001; V* = .58). The two class types generated similar positive educational effects on boosting food safety behavioral intention (measured right after the class). The data collected 2 weeks after the classes suggested that individuals who took the classes followed the suggested food behaviors more closely than those in the control group (P < .01). The food safety map is simple to use and prepare, beneficial for oral and visual learners, and inexpensive. Compared with a food safety cooking class, the map produces similar learning and behavioral outcomes. Copyright © 2014 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Pediatric post-marketing safety systems in North America: assessment of the current status.

PubMed

McMahon, Ann W; Wharton, Gerold T; Bonnel, Renan; DeCelle, Mary; Swank, Kimberley; Testoni, Daniela; Cope, Judith U; Smith, Phillip Brian; Wu, Eileen; Murphy, Mary Dianne

2015-08-01

It is critical to have pediatric post-marketing safety systems that contain enough clinical and epidemiological detail to draw regulatory, public health, and clinical conclusions. The pediatric safety surveillance workshop (PSSW), coordinated by the Food and Drug Administration (FDA), identified these pediatric systems as of 2010. This manuscript aims to update the information from the PSSW and look critically at the systems currently in use. We reviewed North American pediatric post-marketing safety systems such as databases, networks, and research consortiums found in peer-reviewed journals and other online sources. We detail clinical examples from three systems that FDA used to assess pediatric medical product safety. Of the 59 systems reviewed for pediatric content, only nine were pediatric-focused and met the inclusion criteria. Brief descriptions are provided for these nine. The strengths and weaknesses of three systems (two of the nine pediatric-focused and one including both children and adults) are illustrated with clinical examples. Systems reviewed in this manuscript have strengths such as clinical detail, a large enough sample size to capture rare adverse events, and/or a patient denominator internal to the database. Few systems include all of these attributes. Pediatric drug safety would be better informed by utilizing multiple systems to take advantage of their individual characteristics. Copyright © 2015 John Wiley & Sons, Ltd.

Growth hormone deficiency: optimizing therapy and new issues.

PubMed

Rappaport, Raphaël

2012-02-01

Growth Hormone Deficiency (GHD) with low circulating IGF1 requires replacement therapy. Paradoxically, it remains a controversial issue in a large part of patients, those considered as having isolated GHD of the idiopathic milder form. Challenges remain in this area in spite of intensive and sometimes controversial studies. This is true for the diagnosis of the milder forms (also called partial GHD), for the assessment of the growth response and the evaluation of final height benefit. In addition the cost-benefit issue should not be ignored. Therefore, the author tried to review data relevant to the evaluation of GH secretion which even now remains largely arbitrary. The growth response, which is the primary therapeutic goal in these children should also be carefully discussed as reported in recent papers. Focusing on individual responses should help adjusting individual dosage within the standard recommended doses, but one should also remember that there are no long term safety data for non conventional high rhGH doses. More studies are needed. Response to treatment during the first year may in the future help select the patients who are prone to the benefit of long term rhGH therapy. Basic rules for indication and progression of treatment are proposed in children with various forms of GHD. It is also remarkable that the present safety data are all coming from several post-marketing studies. This means that long term independent studies are now required as recombinant growth hormone remains the most appropriate and efficient therapy when permanent GH deficiency is fully documented.

Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study.

PubMed

Szenborn, L; Osipova, I V; Czajka, H; Kharit, S M; Jackowska, T; François, N; Habib, M A; Borys, D

2017-09-25

Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. PHiD-CV was immunogenic and well tolerated in 2-17-year-old children with asplenia or splenic dysfunction. Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108. Copyright © 2017. Published by Elsevier Ltd.

National Machine Guarding Program: Part 1. Machine safeguarding practices in small metal fabrication businesses.

PubMed

Parker, David L; Yamin, Samuel C; Brosseau, Lisa M; Xi, Min; Gordon, Robert; Most, Ivan G; Stanley, Rodney

2015-11-01

Metal fabrication workers experience high rates of traumatic occupational injuries. Machine operators in particular face high risks, often stemming from the absence or improper use of machine safeguarding or the failure to implement lockout procedures. The National Machine Guarding Program (NMGP) was a translational research initiative implemented in conjunction with two workers' compensation insures. Insurance safety consultants trained in machine guarding used standardized checklists to conduct a baseline inspection of machine-related hazards in 221 business. Safeguards at the point of operation were missing or inadequate on 33% of machines. Safeguards for other mechanical hazards were missing on 28% of machines. Older machines were both widely used and less likely than newer machines to be properly guarded. Lockout/tagout procedures were posted at only 9% of machine workstations. The NMGP demonstrates a need for improvement in many aspects of machine safety and lockout in small metal fabrication businesses. © 2015 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals, Inc.

Foremen’s Intervention to Prevent Falls and Increase Safety Communication at Residential Construction Sites

PubMed Central

Kaskutas, Vicki; Buckner-Petty, Skye; Dale, Ann Marie; Gaal, John; Evanoff, Bradley A.

2017-01-01

Background This research aimed to improve residential construction foremen’s communication skills and safety behaviors of their crewmembers when working at heights. Methods Eighty-four residential construction foremen participated in the 8-hour fall prevention and safety communication training. We compared pre-intervention surveys from foremen and their crewmembers to measure the effect of training. Results Foremen and crewmembers’ ratings showed improvements in fall prevention knowledge, behaviors, and safety communication and were sustained 6-months post-training, with emphasized areas demonstrating larger increases. Ratings were similar between foremen and crewmembers, suggesting that the foremen effectively taught their crew and assigned accurate ratings. Based upon associations between safety behaviors and reported falls observed in prior research, we would expect a 16.6% decrease in the one year cumulative incidence of self-reported falls post-intervention. Conclusions This intervention improved safety knowledge and behaviors of a large number of workers by training construction foremen in fall prevention and safety communication skills. PMID:27345465

Safety Assessment of Talc as Used in Cosmetics.

PubMed

Fiume, Monice M; Boyer, Ivan; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2015-01-01

The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of talc for use in cosmetics. The safety of talc has been the subject of much debate through the years, partly because the relationship between talc and asbestos is commonly misunderstood. Industry specifications state that cosmetic-grade talc must contain no detectable fibrous, asbestos minerals. Therefore, the large amount of available animal and clinical data the Panel relied on in assessing the safety of talc only included those studies on talc that did not contain asbestos. The Panel concluded that talc is safe for use in cosmetics in the present practices of use and concentration (some cosmetic products are entirely composed of talc). Talc should not be applied to the skin when the epidermal barrier is missing or significantly disrupted. © The Author(s) 2015.

Maintenance of safety behaviors via response-produced stimuli.

PubMed

Angelakis, Ioannis; Austin, Jennifer L

2015-11-01

Animal studies suggest that safety behaviors may be maintained by internally or externally produced safety signals, which function as positive reinforcers. We designed two experiments to test this phenomenon with humans. Participants played a computerized game in which they could earn or lose treasures by clicking on a map. In baseline, losses could be postponed by pressing a pedal that also produced a blue bar at the bottom of the screen. During test conditions, no losses were programmed, and pedal presses turned the bar from yellow to blue (Test 1) or blue to yellow (Test 2). In Experiment 2, new participants were exposed to the same conditions but were given information about the safety of the test environment. In both experiments, participants engaged in high rates of pedal pressing when presses were followed by blue bars, suggesting the bar functioned as a safety signal. We discuss how these findings may relate to safety behaviors commonly observed in certain mental health disorders. © The Author(s) 2015.

Stakeholders' Perspectives About and Priorities for Economic Evaluation of Health and Safety Programs in Healthcare.

PubMed

Tompa, Emile; de Boer, Henriette; Macdonald, Sara; Alamgir, Hasanat; Koehoorn, Mieke; Guzman, Jaime

2016-04-01

This study identified and prioritized resources and outcomes that should be considered in more comprehensive and scientifically rigorous health and safety economic evaluations according to healthcare sector stakeholders. A literature review and stakeholder interviews identified candidate resources and outcomes and then a Delphi panel ranked them. According to the panel, the top five resources were (a) health and safety staff time; (b) training workers; (c) program planning, promotion, and evaluation costs; (d) equipment purchases and upgrades; and (e) administration costs. The top five outcomes were (a) number of injuries, illnesses, and general sickness absences; (b) safety climate; (c) days lost due to injuries, illnesses, and general sickness absences; (d) job satisfaction and engagement; and (e) quality of care and patient safety. These findings emphasize stakeholders' stated priorities and are useful as a benchmark for assessing the quality of health and safety economic evaluations and the comprehensiveness of these findings. © 2016 The Author(s).

Safety assessment of modified terephthalate polymers as used in cosmetics.

PubMed

Becker, Lillian C; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2014-01-01

The safety of 6 modified terephthalate polymers as cosmetic ingredients was assessed. These ingredients mostly function as exfoliants, bulking agents, hair fixatives, and viscosity-increasing agents-nonaqueous. Polyethylene terephthalate (PET) is used in leave-on products up to 100% and in rinse-off products up to 2%. The Cosmetic Ingredient Review Expert Panel (Panel) considered that the PET used in cosmetics is chemically equivalent to that used in medical devices. The Panel determined that the Food and Drug Administration's determination of safety of PET in several medical devices, which included human and animal safety data, can be used as the basis for the determination of safety of PET and related polymers used in cosmetics. Use studies of cosmetic eye products that contain PET demonstrated no ocular irritation or dermal sensitization. The Panel concluded that modified terephthalate polymers were safe as cosmetic ingredients in the practices of use and concentration described in this safety assessment. © The Author(s) 2014.

Microbial safety of fresh produce

USDA-ARS?s Scientific Manuscript database

The book entitled “Microbial Safety of Fresh Produce” with 23 chapters is divided into following six sections: Microbial contamination of fresh produce, Pre-harvest strategies, post-harvest interventions, Produce safety during processing and handling, Public, legal, and economic Perspectives, and Re...

30 CFR 56.4101 - Warning signs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Fire Prevention and Control... open flames shall be posted where a fire or explosion hazard exists. ...

30 CFR 57.4101 - Warning signs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Fire Prevention and Control... open flames shall be posted where a fire or explosion hazard exists. ...

MedWatch, the FDA Safety Information and Adverse Event Reporting Program

MedlinePlus

... Information and Adverse Event Reporting Program MedWatch: The FDA Safety Information and Adverse Event Reporting Program Share ... use. [Posted 06/01/2018] More What's New FDA Approved Safety Information DailyMed (National Library of Medicine) ...

Knowledge and attitude of health-care professionals in hospitals towards pharmacovigilance in Saudi Arabia.

PubMed

Alshammari, Thamir M; Alamri, Khaled K; Ghawa, Yazeed A; Alohali, Noura F; Abualkol, Shaza A; Aljadhey, Hisham S

2015-12-01

Drug safety has major implications for patients' lives. However, this concept is still considered new to some healthcare professionals. This study aims to investigate the knowledge and awareness of Saudi healthcare professionals to pharmacovigilance (PV). Setting Governmental and private hospitals at three main cities in Saudi Arabia (Riyadh, Jeddah, and Dammam). A cross-sectional survey among healthcare professionals (pharmacists, physicians, and nurses) within 12 Saudi hospitals was conducted between November and December 2012. The questionnaire consisted of 18 questions assessing the knowledge, awareness, and attitude of healthcare professionals (HCPs) towards science and the concept of PV. Descriptive statistics were used to analyze the data. The data were analyzed using Statistical Analysis Software (SAS 9.3). Main outcome measure Knowledge, attitude and practice of HCPs toward pharmacovigilance. Three-hundred and thirty-two healthcare professionals completed the survey (response rate 72 %), 110 (34 %) physicians, 106 (33 %) pharmacists, and 104 (32 %) nurses. More than half of the participants (55 %) did not know the correct definition of PV. Two-thirds of the respondents, 207 (65.5 %), had knowledge of the aim of post-marketing surveillance, yet only 113 (36.9 %) were aware that the National Pharmacovigilance and Drug Safety Center is the official body for monitoring adverse drug reaction in Saudi Arabia. In addition, 34.7 % agreed that lack of time could be a major barrier for reporting. The majority of the respondents (78.4 %) believed that reporting was a professional obligation and hospitals should have a drug safety department. There was a limited knowledge of pharmacovigilance that could have affected reporting incidence. Educational intervention and a practical training program need to be applied by the drug regulatory body as well as health authorities to enhance the pharmacovigilance and drug safety culture in Saudi Arabia.

Probabilistic design of fibre concrete structures

NASA Astrophysics Data System (ADS)

Pukl, R.; Novák, D.; Sajdlová, T.; Lehký, D.; Červenka, J.; Červenka, V.

2017-09-01

Advanced computer simulation is recently well-established methodology for evaluation of resistance of concrete engineering structures. The nonlinear finite element analysis enables to realistically predict structural damage, peak load, failure, post-peak response, development of cracks in concrete, yielding of reinforcement, concrete crushing or shear failure. The nonlinear material models can cover various types of concrete and reinforced concrete: ordinary concrete, plain or reinforced, without or with prestressing, fibre concrete, (ultra) high performance concrete, lightweight concrete, etc. Advanced material models taking into account fibre concrete properties such as shape of tensile softening branch, high toughness and ductility are described in the paper. Since the variability of the fibre concrete material properties is rather high, the probabilistic analysis seems to be the most appropriate format for structural design and evaluation of structural performance, reliability and safety. The presented combination of the nonlinear analysis with advanced probabilistic methods allows evaluation of structural safety characterized by failure probability or by reliability index respectively. Authors offer a methodology and computer tools for realistic safety assessment of concrete structures; the utilized approach is based on randomization of the nonlinear finite element analysis of the structural model. Uncertainty of the material properties or their randomness obtained from material tests are accounted in the random distribution. Furthermore, degradation of the reinforced concrete materials such as carbonation of concrete, corrosion of reinforcement, etc. can be accounted in order to analyze life-cycle structural performance and to enable prediction of the structural reliability and safety in time development. The results can serve as a rational basis for design of fibre concrete engineering structures based on advanced nonlinear computer analysis. The presented methodology is illustrated on results from two probabilistic studies with different types of concrete structures related to practical applications and made from various materials (with the parameters obtained from real material tests).

Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis.

PubMed

Sinha, Michael S; Freifeld, Clark C; Brownstein, John S; Donneyong, Macarius M; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Dal Pan, Gerald J; Pawar, Ajinkya M; Hwang, Thomas J; Avorn, Jerry; Kesselheim, Aaron S

2018-01-05

The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity. In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the first DSC. ITS analyses demonstrated variability but pointed to an increase in interest around the first DSC. Chow tests were significant (P<.0001) for both DSCs on Facebook and Twitter, but only the first DSC on Google Trends. Wikipedia edits occurred soon after each DSC release, citing news articles rather than the DSC itself and presenting content that needed subsequent revisions for accuracy. Social media offers challenges and opportunities for dissemination of the DSC messages. The FDA could consider strategies for more actively disseminating DSC safety information through social media platforms, particularly when announcements require updating. The FDA may also benefit from directly contributing content to websites like Wikipedia that are frequently accessed for drug-related information. ©Michael S Sinha, Clark C Freifeld, John S Brownstein, Macarius M Donneyong, Paula Rausch, Brian M Lappin, Esther H Zhou, Gerald J Dal Pan, Ajinkya M Pawar, Thomas J Hwang, Jerry Avorn, Aaron S Kesselheim. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 05.01.2018.

Safety of the HyperSound® Audio System in Subjects with Normal Hearing.

PubMed

Mehta, Ritvik P; Mattson, Sara L; Kappus, Brian A; Seitzman, Robin L

2015-06-11

The objective of the study was to assess the safety of the HyperSound® Audio System (HSS), a novel audio system using ultrasound technology, in normal hearing subjects under normal use conditions; we considered pre-exposure and post-exposure test design. We investigated primary and secondary outcome measures: i) temporary threshold shift (TTS), defined as >10 dB shift in pure tone air conduction thresholds and/or a decrement in distortion product otoacoustic emissions (DPOAEs) >10 dB at two or more frequencies; ii) presence of new-onset otologic symptoms after exposure. Twenty adult subjects with normal hearing underwent a pre-exposure assessment (pure tone air conduction audiometry, tympanometry, DPOAEs and otologic symptoms questionnaire) followed by exposure to a 2-h movie with sound delivered through the HSS emitter followed by a post-exposure assessment. No TTS or new-onset otological symptoms were identified. HSS demonstrates excellent safety in normal hearing subjects under normal use conditions.

Safety of the HyperSound® Audio System in Subjects with Normal Hearing

PubMed Central

Mattson, Sara L.; Kappus, Brian A.; Seitzman, Robin L.

2015-01-01

The objective of the study was to assess the safety of the HyperSound® Audio System (HSS), a novel audio system using ultrasound technology, in normal hearing subjects under normal use conditions; we considered pre-exposure and post-exposure test design. We investigated primary and secondary outcome measures: i) temporary threshold shift (TTS), defined as >10 dB shift in pure tone air conduction thresholds and/or a decrement in distortion product otoacoustic emissions (DPOAEs) >10 dB at two or more frequencies; ii) presence of new-onset otologic symptoms after exposure. Twenty adult subjects with normal hearing underwent a pre-exposure assessment (pure tone air conduction audiometry, tympanometry, DPOAEs and otologic symptoms questionnaire) followed by exposure to a 2-h movie with sound delivered through the HSS emitter followed by a post-exposure assessment. No TTS or new-onset otological symptoms were identified. HSS demonstrates excellent safety in normal hearing subjects under normal use conditions. PMID:26779330

Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

PubMed

Uhara, H; Kiyohara, Y; Tsuda, A; Takata, M; Yamazaki, N

2018-02-01

Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

47 CFR 0.392 - Authority delegated.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Authority delegated. 0.392 Section 0.392 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMISSION ORGANIZATION Delegations of Authority Public Safety and Homeland Security Bureau § 0.392 Authority delegated. The Chief, Public Safety and Homeland...

47 CFR 0.392 - Authority delegated.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Authority delegated. 0.392 Section 0.392 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMISSION ORGANIZATION Delegations of Authority Public Safety and Homeland Security Bureau § 0.392 Authority delegated. The Chief, Public Safety and Homeland...

Long-term follow-up of HIV-1-infected adults who received the F4/AS01B HIV-1 vaccine candidate in two randomised controlled trials.

PubMed

Harrer, Thomas; Dinges, Warren; Roman, François

2018-05-03

This Phase I/II, open, long-term follow-up study was conducted in antiretroviral therapy (ART)-naïve (N = 212) and ART-treated (N = 19) human immunodeficiency virus 1 (HIV-1)-infected adults, who received an HIV-1 investigational vaccine (F4/AS01 B ) or placebo in two previous studies (NCT00814762 and NCT01218113). After a minimum of two years and a maximum of four years of follow-up post-vaccination per patient, no significant differences were observed between F4/AS01 B and placebo groups in terms of viral load, CD4 + T-cell count and incidence of specific clinical events. Vaccine-induced polyfunctional CD4 + T-cells persisted up to study end and no relevant vaccine-related safety events were reported in F4/AS01 B groups. This study has been registered at ClinicalTrials.gov (NCT01092611). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

77 FR 10666 - Pipeline Safety: Post Accident Drug and Alcohol Testing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-23

... operators of Liquefied Natural Gas (LNG) facilities to conduct post- accident drug and alcohol tests of... reviewed, along with other applicable sections of Part 199: Under Sec. 199.105, post-accident drug tests of... administering the test. Covered employees must remain available for post-accident testing, but emergency...

Effectiveness of Occupational Health and Safety Training: A Systematic Review with Meta-Analysis

ERIC Educational Resources Information Center

Ricci, Federico; Chiesi, Andrea; Bisio, Carlo; Panari, Chiara; Pelosi, Annalisa

2016-01-01

Purpose: This meta-analysis aims to verify the efficacy of occupational health and safety (OHS) training in terms of knowledge, attitude and beliefs, behavior and health. Design/methodology/approach: The authors included studies published in English (2007-2014) selected from ten databases. Eligibility criteria were studies concerned with the…

An assessment of drinking-water quality post-Haiyan.

PubMed

Magtibay, Bonifacio; Anarna, Maria Sonabel; Fernando, Arturo

2015-01-01

Access to safe drinking-water is one of the most important public health concerns in an emergency setting. This descriptive study reports on an assessment of water quality in drinking-water supply systems in areas affected by Typhoon Haiyan immediately following and 10 months after the typhoon. Water quality testing and risk assessments of the drinking-water systems were conducted three weeks and 10 months post-Haiyan. Portable test kits were used to determine the presence of Escherichia coli and the level of residual chlorine in water samples. The level of risk was fed back to the water operators for their action. Of the 121 water samples collected three weeks post-Haiyan, 44% were contaminated, while 65% (244/373) of samples were found positive for E. coli 10 months post-Haiyan. For the three components of drinking-water systems - source, storage and distribution - the proportions of contaminated systems were 70%, 67% and 57%, respectively, 10 months after Haiyan. Vulnerability to faecal contamination was attributed to weak water safety programmes in the drinking-water supply systems. Poor water quality can be prevented or reduced by developing and implementing a water safety plan for the systems. This, in turn, will help prevent waterborne disease outbreaks caused by contaminated water post-disaster.

An assessment of drinking-water quality post-Haiyan

PubMed Central

Anarna, Maria Sonabel; Fernando, Arturo

2015-01-01

Introduction Access to safe drinking-water is one of the most important public health concerns in an emergency setting. This descriptive study reports on an assessment of water quality in drinking-water supply systems in areas affected by Typhoon Haiyan immediately following and 10 months after the typhoon. Methods Water quality testing and risk assessments of the drinking-water systems were conducted three weeks and 10 months post-Haiyan. Portable test kits were used to determine the presence of Escherichia coli and the level of residual chlorine in water samples. The level of risk was fed back to the water operators for their action. Results Of the 121 water samples collected three weeks post-Haiyan, 44% were contaminated, while 65% (244/373) of samples were found positive for E. coli 10 months post-Haiyan. For the three components of drinking-water systems – source, storage and distribution – the proportions of contaminated systems were 70%, 67% and 57%, respectively, 10 months after Haiyan. Discussion Vulnerability to faecal contamination was attributed to weak water safety programmes in the drinking-water supply systems. Poor water quality can be prevented or reduced by developing and implementing a water safety plan for the systems. This, in turn, will help prevent waterborne disease outbreaks caused by contaminated water post-disaster. PMID:26767136

Predictors of Safety Training Transfer Support as In-Role Behavior of Occupational Health and Safety Professionals

ERIC Educational Resources Information Center

Freitas, Ana Cristina; Silva, Sílvia Agostinho; Santos, Catarina Marques

2017-01-01

Purpose: The purpose of this study is to identify individual and contextual influences on in-house safety trainers' role orientation toward the transfer of training (TT). Design/methodology/approach: The authors tested a model where felt-responsibility for TT mediates the influence of job resources (i.e. autonomy, access to resources, access to…

Legislating child restraint usage -Its effect on self-reported child restraint use rates in a central city.

PubMed

Brixey, Suzanne; Ravindran, Karthik; Guse, Clare E

2010-02-01

To assess the effect of the newly enacted child passenger safety law, Wisconsin Act 106, on self-report of proper restraint usage of children in Milwaukee's central city population. A prospective, non-randomized study design was used. The settings used were (a) a pediatric urban health center, and (b) two Women, Infants and Children offices in Milwaukee, Wisconsin. Participants included 11,566 surveys collected over 18 months that spanned the pre-legislation and post-legislation time periods from February 2006 through August 2008. The study set out to assess appropriate child passenger restraint. The results showed that the changes in adjusted proper restraint usage rates for infants between the pre-law, grace period, and post-fine periods were 94%, 94%, and 94% respectively. For children 1-3years old, the adjusted proper usage rates were 65%, 63%, and 59%, respectively. And for children 4-7years old, the rates were 43%, 44% and 42%, respectively. There was a significant increase in premature booster seat use in children who should have been restrained in a rear- or forward-facing car seat (10% pre-law, 12% grace period, 20% post-fine; p<0.0005). There was no statistically significant change over time in unrestrained children (2.1%, 1.7%, 1.7%, p=0.7, respectively). The passage of a strengthened child passenger safety law with fines did not significantly improve appropriate restraint use for 0-7year olds, and appropriate use in 1-7year olds remained suboptimal with a majority of urban children inappropriately restrained. Although the number of unrestrained children decreased, we identified an unintended consequence of the legislation - a significant increase in the rate of premature belt-positioning booster seat use among poor, urban children. The design of child restraint systems maximizes protection of the child. Increasing reports of misuse is a call to those who manufacture these child passenger restraints to improve advertising and marketing to the correct age group, ease of installation, and mechanisms to prevent incorrect safety strap and harness placement. To ensure accurate and consistent use on every trip, car seat manufacturers must ensure that best practice recommendations for use as well as age, weight, and height be clearly specified on each child restraint. The authors support the United States Department of Transportation's new consumer program that will assist caregivers in identifying the child seat that will fit in their vehicle. In addition, due to the increase in premature graduation of children into belt-positioning booster seats noted as a result of legislation, promoting and marketing booster seat use for children less than 40 pounds should not be accepted. Child passenger safety technicians must continue to promote best practice recommendations for child passenger restraint use and encourage other community leaders to do the same. Copyright 2010 Elsevier Ltd. All rights reserved.

A decade of marketing approval of gene and cell-based therapies in the United States, European Union and Japan: An evaluation of regulatory decision-making.

PubMed

Coppens, D G M; de Wilde, S; Guchelaar, H J; De Bruin, M L; Leufkens, H G M; Meij, P; Hoekman, J

2018-05-02

There is a widely held expectation of clinical advance with the development of gene and cell-based therapies (GCTs). Yet, establishing benefits and risks is highly uncertain. We examine differences in decision-making for GCT approval between jurisdictions by comparing regulatory assessment procedures in the United States (US), European Union (EU) and Japan. A cohort of 18 assessment procedures was analyzed by comparing product characteristics, evidentiary and non-evidentiary factors considered for approval and post-marketing risk management. Product characteristics are very heterogeneous and only three products are marketed in multiple jurisdictions. Almost half of all approved GCTs received an orphan designation. Overall, confirmatory evidence or indications of clinical benefit were evident in US and EU applications, whereas in Japan approval was solely granted based on non-confirmatory evidence. Due to scientific uncertainties and safety risks, substantial post-marketing risk management activities were requested in the EU and Japan. EU and Japanese authorities often took unmet medical needs into consideration in decision-making for approval. These observations underline the effects of implemented legislation in these two jurisdictions that facilitate an adaptive approach to licensing. In the US, the recent assessments of two chimeric antigen receptor-T cell (CAR-T) products are suggestive of a trend toward a more permissive approach for GCT approval under recent reforms, in contrast to a more binary decision-making approach for previous approvals. It indicates that all three regulatory agencies are currently willing to take risks by approving GCTs with scientific uncertainties and safety risks, urging them to pay accurate attention to post-marketing risk management. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Attention Deficit Hyperactivity Disorder Prevalence and Correlates Pre- and Post-Bariatric Surgery: A Comparative Cross-Sectional Study.

PubMed

Nielsen, Friedrich; Georgiadou, Ekaterini; Bartsch, Merle; Langenberg, Svenja; Müller, Astrid; de Zwaan, Martina

2017-01-01

Previous research shows an association between obesity and attention deficit hyperactivity disorder (ADHD). The present study compares pre- and post-bariatric surgery patients using the internationally used Conners' Adult ADHD Rating Scale (CAARS™) to screen for ADHD. Matched samples pre- (N = 120) and post-bariatric surgery (N = 128) were compared using self-rating instruments to assess ADHD-relevant symptomatology, depression, eating-related psychopathology, and BMI. Prevalence of probable ADHD did not differ between groups using the CAARS Index Scale T-scores; however, CAARS subscales Inattention/Memory and Self-Concept showed significantly lower scores in post-surgery patients. All CAARS subscales correlated significantly with each other, with depression and eating-related psychopathology. There was no correlation between ADHD and excess BMI loss in post-surgery patients. The findings suggest that a considerable number of patients before and after bariatric surgery screened positive for ADHD. It can be hypothesized that some core ADHD symptoms improve after surgery. Future studies are warranted to investigate the influence of ADHD on long-term surgery outcomes. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

An evaluation of The Great Escape: can an interactive computer game improve young children's fire safety knowledge and behaviors?

PubMed

Morrongiello, Barbara A; Schwebel, David C; Bell, Melissa; Stewart, Julia; Davis, Aaron L

2012-07-01

Fire is a leading cause of unintentional injury and, although young children are at particularly increased risk, there are very few evidence-based resources available to teach them fire safety knowledge and behaviors. Using a pre-post randomized design, the current study evaluated the effectiveness of a computer game (The Great Escape) for teaching fire safety information to young children (3.5-6 years). Using behavioral enactment procedures, children's knowledge and behaviors related to fire safety were compared to a control group of children before and after receiving the intervention. The results indicated significant improvements in knowledge and fire safety behaviors in the intervention group but not the control. Using computer games can be an effective way to promote young children's understanding of safety and how to react in different hazardous situations.

Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children and adults.

PubMed

Macartney, Kristine; Heywood, Anita; McIntyre, Peter

2014-06-23

The prevention of varicella (chickenpox) using live attenuated varicella vaccines has been demonstrated both in randomised controlled trials (RCTs) and in population-based immunisation programmes in countries such as the United States and Australia. Many countries do not routinely immunise children against varicella and exposures continue to occur. Although the disease is often mild, complications such as secondary bacterial infection, pneumonitis and encephalitis occur in about 1% of cases, usually leading to hospitalisation. The use of varicella vaccine in persons who have recently been exposed to the varicella zoster virus has been studied as a form of post-exposure prophylaxis (PEP). To assess the efficacy and safety of vaccines for use as PEP for the prevention of varicella in children and adults. We searched CENTRAL (2014, Issue 1), MEDLINE (1966 to March week 1, 2014), EMBASE (January 1990 to March 2014) and LILACS (1982 to March 2014). We searched for unpublished trials registered on the clinicaltrials.gov and WHO ICTRP websites. RCTs and quasi-RCTs of varicella vaccine for PEP compared with placebo or no intervention. The outcome measures were efficacy in prevention of clinical cases and/or laboratory-confirmed clinical cases and adverse events following vaccination. Two review authors independently extracted and analysed data using Review Manager software. We identified three trials involving 110 healthy children who were siblings of household contacts. The included trials varied in study quality, vaccine used, length of follow-up and outcomes measured and, as such, were not suitable for meta-analysis. We identified high or unclear risk of bias in two of the three included studies. Overall, 13 out of 56 vaccine recipients (23%) developed varicella compared with 42 out of 54 placebo (or no vaccine) recipients (78%). Of the vaccine recipients who developed varicella, the majority only had mild disease (with fewer than 50 skin lesions). In the three trials, most participants received PEP within three days following exposure; too few participants were vaccinated four to five days post-exposure to ascertain the efficacy of vaccine given more than three days after exposure. No included trial reported on adverse events following immunisation. These small trials suggest varicella vaccine administered within three days to children following household contact with a varicella case reduces infection rates and severity of cases. We identified no RCTs for adolescents or adults. Safety was not adequately addressed.

Effects of outside air temperature on the preparation of antineoplastic drug solutions in biological safety cabinets.

PubMed

Umemura, Masayuki; Itoh, Akio; Ando, Yuichi; Yamada, Kiyofumi; Wakiya, Yoshifumi; Nabeshima, Toshitaka

2015-08-01

In Japan, biological safety cabinets are commonly used by medical staff to prepare antineoplastic agents. At the Division of Chemotherapy for Outpatients, Nagoya University Hospital, a class II B2 biological safety cabinet is used. The temperature inside this biological safety cabinet decreases in winter. In this study, we investigated the effect of low outside air temperature on the biological safety cabinet temperature, time required to admix antineoplastic agents, and accuracy of epirubicin weight measurement. Studies were conducted from 1 January to 31 March 2008 (winter). The outside air temperature near the biological safety cabinet intake nozzle was compared with the biological safety cabinet temperature. The correlation between the outside air temperature and the biological safety cabinet temperature, time for cyclophosphamide and gemcitabine solubilization, and accuracy of epirubicin weight measurement were investigated at low and high biological safety cabinet temperatures. The biological safety cabinet temperature correlated with the outside air temperature of 5-20℃ (p < 0.0001). Compared to cyclophosphamide and gemcitabine solubilization in the biological safety cabinet at 25℃, solubilization at 10℃ was significantly delayed (p < 0.01 and p < 0.0001, respectively). Measurement of epirubicin weight by using a syringe lacked accuracy because of epirubicin's high viscosity at low temperatures (p < 0.01). These results suggest that the biological safety cabinet temperature decreases when cool winter air is drawn into the biological safety cabinet, affecting the solubilization of antineoplastic agents. We suggest that a decrease in biological safety cabinet temperature may increase the time required to admix antineoplastic agents, thereby increasing the time for which outpatients must wait for chemotherapy. © The Author(s) 2014.

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

PubMed

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

2018-01-01

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

Post-test analysis of dryout test 7B' of the W-1 Sodium Loop Safety Facility Experiment with the SABRE-2P code. [LMFBR

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

Rose, S.D.; Dearing, J.F.

An understanding of conditions that may cause sodium boiling and boiling propagation that may lead to dryout and fuel failure is crucial in liquid-metal fast-breeder reactor safety. In this study, the SABRE-2P subchannel analysis code has been used to analyze the ultimate transient of the in-core W-1 Sodium Loop Safety Facility experiment. This code has a 3-D simple nondynamic boiling model which is able to predict the flow instability which caused dryout. In other analyses dryout has been predicted for out-of-core test bundles and so this study provides additional confirmation of the model.

Fractional ablative and nonablative radiofrequency for skin resurfacing and rejuvenation of Thai patients.

PubMed

Thanasarnaksorn, Wilai; Siramangkhalanon, Vorapot; Duncan, Diane Irvine; Belenky, Inna

2018-04-01

Fractional radiofrequency (RF) technology is often the preferable skin resurfacing treatment, especially among Asian patients. Second generation fractional RF technology has exclusive capability to produce separate biological responses (ablation, coagulation, or a combination of both) with 3 distinguished penetration depth programs. The aim of this study was to evaluate the efficacy and safety of a fractional RF handpiece such as this, on the Thai population. Fifty-five Thai patients were treated with a fractional RF handpiece. The clinical assessment included a pain score, satisfaction survey, physician assessment, a combined patient and physician's assessment of skin condition, and clinical photographic assessments. The wound healing response was evaluated according to 5-time points: immediately after applying a pulse, post 24 hours, post 7 days, post 1 month and post 8 weeks. The obtained patient satisfaction score was "very satisfied" among 74% of the patients, post 3 sessions. Positive correlation was found between patient satisfaction and the physician's assessment. The skin condition assessment showed an increase from an average of 4.2 to 7.9. All treated symptoms improved after each treatment and the clinical outcome lasted at least up to 3-5 months. No significant adverse events were recorded. The in vivo prospective study showed a dose-related response in the deepness of the coagulation injury. In addition, there was evidence for a progressive healing process beginning shortly after exposure and completed within a week. This study clinically and histologically supports the efficacy of fractional RF handpiece in question with a high safety profile. © 2017 Wiley Periodicals, Inc.

The Regulatory Evaluation of Vaccines for Human Use.

PubMed

Baylor, Norman W

2016-01-01

A vaccine is an immunogen, the administration of which is intended to stimulate the immune system to result in the prevention, amelioration, or therapy of any disease or infection (US Food and Drug Administration. Guidance for Industry: content and format of chemistry, manufacturing, and controls information and establishment description information for a vaccine or related product). A vaccine may be a live attenuated preparation of microorganisms, inactivated (killed) whole organisms, living irradiated cells, crude fractions, or purified immunogens, including those derived from recombinant DNA in a host cell, conjugates formed by covalent linkage of components, synthetic antigens, polynucleotides (such as the plasmid DNA vaccines), living vectored cells expressing specific heterologous immunogens, or cells pulsed with immunogen. Vaccines are highly complex products that differ from small molecule drugs because of the biological nature of the source materials such as those derived from microorganisms as well as the various cell substrates from which some are derived. Regardless of the technology used, because of their complexities, vaccines must undergo extensive characterization and testing. Special expertise and procedures are needed for their manufacture, control, and regulation. The Food and Drug Administration (FDA) is the National Regulatory Authority (NRA) in the United States responsible for assuring quality, safety, and effectiveness of all human medical products, including vaccines for human use.The Center for Biologics Evaluation and Research (CBER) within the US FDA is responsible for overseeing the regulation of therapeutic and preventative vaccines against infectious diseases. Authority for the regulation of vaccines resides in Section 351 of the Public Health Service Act and specific sections of the Federal Food, Drug, and Cosmetic Act (FD&C). Vaccines are regulated as biologics and licensed based on the demonstration of safety and effectiveness. The vaccine development process can be divided into two major categories: those events that are not under the regulatory authority of the FDA and are exploratory in nature and those events that are subject to regulatory authority by the FDA. Exploratory events or research and development cover basic research drug discovery processes that occur before the sponsor submits an investigational new drug application (IND) to the FDA. There are four main stages of vaccine development under the purview of regulatory authorities: preclinical, clinical (IND), licensing, and post-licensure. Throughout their life cycle from preclinical evaluation to post-licensure lot release testing, vaccines are subject to rigorous testing and oversight by manufacturers and NRAs. In this chapter an overview of the regulatory evaluation and testing requirements for vaccines is presented.

A study on current risk assessments and guidelines on the use of food animal products derived from cloned animals.

PubMed

Hur, Sun Jin

2017-10-01

The author widely surveyed and analyzed the food safety issues, ethical issues, permits, and approval of animal products from animals cloned by somatic cell nuclear transfer worldwide. As a result of a 2-year survey, the author found that there is no evidence that meat and milk derived from cloned animals or their progeny pose a risk to food safety in terms of genotoxicity, adverse reproductive effects, or allergic reactions. Most countries have not approved meat and milk derived from cloned animals, and their progeny are entering the food supply. To establish the guidelines, the author suggests four principles of safety assessment for meat and milk derived from cloned animals. The four main principles for safety assessment are similarities of chemical composition, adverse reproductive effects, genotoxicity, and allergic reactions under the influence of meat and milk from cloned animals and noncloned counterparts. This principle means that meat and milk derived from a cloned animal are safe if there are no differences in the four safety assessments of meat and milk between cloned animal's progeny and noncloned counterparts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety Profile of Anticancer and Immune-Modulating Biotech Drugs Used in a Real World Setting in Campania Region (Italy): BIO-Cam Observational Study

PubMed Central

Scavone, Cristina; Sportiello, Liberata; Sullo, Maria G.; Ferrajolo, Carmen; Ruggiero, Rosanna; Sessa, Maurizio; Berrino, Pasquale M.; di Mauro, Gabriella; Berrino, Liberato; Rossi, Francesco; Rafaniello, Concetta; Capuano, Annalisa; Valentini, G.

2017-01-01

Objectives: To investigate the occurrence of adverse events (AEs) in naïve patients receiving biotech drugs. Design: A prospective observational study. Setting: Onco-hematology, Hepato-gastroenterology, Rheumatology, Dermatology, and Neurology Units in Campania Region (Italy). Participants: 775 patients (53.81% female) with mean age 56.0 (SD 15.2). The mean follow-up/patient was 3.48 (95% confidence interval 3.13–3.84). Main outcome measures: We collected all AEs associated to biotech drugs, including serious infections and malignancies. Serious AEs were defined according to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, clinical safety data management: definitions and standards for expedited reporting E2A guideline. Results: The majority of the study population was enrolled in Onco-hematology and Rheumatology Units and the most common diagnosis were hematological malignancies, followed by rheumatoid arthritis, colorectal cancer, breast cancer, and psoriatic arthritis. The most commonly prescribed biotech drugs were rituximab, bevacizumab, infliximab, trastuzumab, adalimumab, and cetuximab. Out of 775 patients, 320 experienced at least one AE. Most of patients experienced AEs to cetuximab therapy, rituximab and trastuzumab. Comparing female and male population, our findings highlighted a statistically significant difference in terms of AEs for adalimumab (35.90% vs. 7.41%, p < 0.001) and etanercept (27.59% vs. 10.00%, p = 0.023). Considering all biotech drugs, we observed a peak for all AEs occurrence at follow-up 91–180 days category. Bevacizumab, brentuximab, rituximab, trastuzumab and cetuximab were more commonly associated to serious adverse events; most of these were possibly related to biotech drugs, according to causality assessment. Three cases of serious infections occurred. Conclusions: The results of our study demonstrated that the majority of AEs were not serious and expected. Few cases of serious infections occurred, while no case of malignancy did. Overall, the safety profile of biotech drugs used in our population was similar to those observed in pivotal trials. Notwithstanding the positive results of our study, some safety concerns still remain unresolved. In order to collect more effectiveness and safety data on biotech drugs, the collection and analysis of real world data should be endorsed as well as the management of post-authorization studies. PMID:28932193

48 CFR 623.302-70 - Policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ENVIRONMENT, ENERGY AND WATER EFFICIENCY, RENEWABLE ENERGY TECHNOLOGIES, OCCUPATIONAL SAFETY, AND DRUG-FREE... affects the safety and/or health of post personnel, including the handling of hazardous materials, shall comply with the applicable requirements of the Department of State Safety/Health and Environmental...

48 CFR 623.302-70 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ENVIRONMENT, ENERGY AND WATER EFFICIENCY, RENEWABLE ENERGY TECHNOLOGIES, OCCUPATIONAL SAFETY, AND DRUG-FREE... affects the safety and/or health of post personnel, including the handling of hazardous materials, shall comply with the applicable requirements of the Department of State Safety/Health and Environmental...

Safety assurance and compliance program (SACP) : accomplishments for CY 2001

DOT National Transportation Integrated Search

2002-08-01

This recent research report by the Federal Railroad Administration (FRA), posted online, provides ease of access to information on the Safety Assurance and Compliance Program. The FRA promotes and helps ensure the safety of the nation's railroad indu...

29 CFR 1952.365 - Level of Federal enforcement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Mexico occupational health and safety plan, discretionary Federal enforcement authority under section 18... authority fully or effectively; (7) Enforcement of occupational safety and health standards at all Federal...

Citizen Sensors for SHM: Use of Accelerometer Data from Smartphones

PubMed Central

Feng, Maria; Fukuda, Yoshio; Mizuta, Masato; Ozer, Ekin

2015-01-01

Ubiquitous smartphones have created a significant opportunity to form a low-cost wireless Citizen Sensor network and produce big data for monitoring structural integrity and safety under operational and extreme loads. Such data are particularly useful for rapid assessment of structural damage in a large urban setting after a major event such as an earthquake. This study explores the utilization of smartphone accelerometers for measuring structural vibration, from which structural health and post-event damage can be diagnosed. Widely available smartphones are tested under sinusoidal wave excitations with frequencies in the range relevant to civil engineering structures. Large-scale seismic shaking table tests, observing input ground motion and response of a structural model, are carried out to evaluate the accuracy of smartphone accelerometers under operational, white-noise and earthquake excitations of different intensity. Finally, the smartphone accelerometers are tested on a dynamically loaded bridge. The extensive experiments show satisfactory agreements between the reference and smartphone sensor measurements in both time and frequency domains, demonstrating the capability of the smartphone sensors to measure structural responses ranging from low-amplitude ambient vibration to high-amplitude seismic response. Encouraged by the results of this study, the authors are developing a citizen-engaging and data-analytics crowdsourcing platform towards a smartphone-based Citizen Sensor network for structural health monitoring and post-event damage assessment applications. PMID:25643056

Exploring post-fall audit report data in an acute care setting.

PubMed

Tzeng, Huey-Ming; Yin, Chang-Yi

2015-06-01

This retrospective, descriptive, chart review study was done to demonstrate one strategy for communicating aggregated and actionable fall data to bedside nurses. It was conducted at a nonprofit acute care hospital in the northwestern United States to analyze the quantitative data captured in post-fall audit reports of patient falls (March 1-December 31, 2012, N = 107 falls). Descriptive and binary statistical analyses were used. The quarterly National Database of Nursing Quality Indicators 2011 and 2012 reports showed that implementation of post-fall audit reports can lead to a lower overall fall rate and a lower fall-injury rate. Increased nursing hours could be a confounding factor of the positive impact of conducting post-fall audits in this study. It is concluded that timely and systematic reporting, analysis, and interpretation of fall data in an electronic format can facilitate prevention of falls and fall injuries. © The Author(s) 2014.

Is post-marketing drug surveillance possible in the family practice setting? A collaborative study.

PubMed

Facklam, D P; Baker, M I; Gardner, J S; Herbert, C; Grava-Gubins, I

1988-04-01

Post-marketing surveillance is a mechanism to identify and quantify harmful, as well as beneficial, effects of drugs used under conditions different from those in which they were tested. The College of Family Physicians of Canada collaborated with the authors in a pilot, office-based, post-marketing, surveillance study. Target medications were selected from all prescriptions, written or authorized by participating physicians. The participants collected the prescriptions by using duplicate prescription pads. Follow-up data was collected from the patients by means of a self-administered questionnaire and from the physicians by means of a medical-chart review. This method of research allows the identification of a cohort of drug users in a systematic, non-biased fashion.

Thermal injury through intraradicular heat transfer using ultrasonic devices: precautions and practical preventive strategies.

PubMed

Gluskin, Alan H; Ruddle, Clifford J; Zinman, Edwin J

2005-09-01

The use of ultrasonic energy is a highly efficient method of removing obstructions and cements within the root canal space when re-treatment or rehabilitation of that ultrasonic energy dislodges and removes cemented objects from the bonded interface of the canal wall. When using this method, there is less potential for structural loss or root damage and significantly less operator stress than when using other methods. There is little evidence in published research of the considerable heat transfer that occurs during use of ultrasonic devices to remove posts, pastes and separated instruments in teeth. The authors present three cases of patients who experienced serious burn injuries during application of ultrasonic energy for restorative dentistry. The authors also offer techniques and strategies for safe and effective use of ultrasonic devices. On the basis of the best available evidence, the authors recommend strategies to provide safe and effective therapy while using ultrasonic devices in intraradicular obstruction removal. The intent of the suggested protocols is to provide advanced and sophisticated therapies in a safe and regulated manner with patient safety as an overriding priority.

77 FR 62466 - Airworthiness Directives; GA200 (Pty) Ltd Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-15

... Aviation Safety Authority (CASA), which is the aviation authority for the Commonwealth of Australia, has...) Related Information Refer to MCAI Civil Aviation Safety Authority (CASA) AD AD/ GA200/1, Amendment 1...

Blood pressure levels post mechanical thrombectomy and outcomes in non-recanalized large vessel occlusion patients.

PubMed

Goyal, Nitin; Tsivgoulis, Georgios; Pandhi, Abhi; Dillard, Kira; Alsbrook, Diana; Chang, Jason J; Krishnaiah, Balaji; Nickele, Christopher; Hoit, Daniel; Alsherbini, Khalid; Alexandrov, Andrei V; Arthur, Adam S; Elijovich, Lucas

2018-01-11

Permissive hypertension may benefit patients with non-recanalized large vessel occlusion (nrLVO) post mechanical thrombectomy (MT) by maintaining brain perfusion. Data evaluating the impact of post-MT blood pressure (BP) levels on outcomes in nrLVO patients are scarce. We investigated the association of the post-MT BP course with safety and efficacy outcomes in nrLVO. Hourly systolic BP (SBP) and diastolic BP (DBP) values were prospectively recorded for 24 hours following MT in consecutive nrLVO patients. Maximum, minimum, and mean BP levels were documented. Three-month functional independence (FI) was defined as modified Rankin Scale (mRS) scores of 0-2. A total of 88 nrLVO patients were evaluated post MT. Patients with FI had lower maximum SBP (160±19 mmHg vs 179±23 mmHg; P=0.001) and higher minimum SBP levels (119±12 mmHg vs 108±25 mmHg; P=0.008). Maximum SBP (183±20 mmHg vs 169±23 mmHg; P=0.008) and DBP levels (105±20 mmHg vs 89±18 mmHg; P=0.001) were higher in patients who died at 3 months while minimum SBP values were lower (102±28 mmHg vs 115±16 mmHg; P=0.007). On multivariable analyses, both maximum SBP (OR per 10 mmHg increase: 0.55, 95% CI 0.39 to 0.79; P=0.001) and minimum SBP (OR per 10 mmHg increase: 1.64, 95% CI 1.04 to 2.60; P=0.033) levels were independently associated with the odds of FI. Maximum DBP (OR per 10 mmHg increase: 1.61; 95% CI 1.10 to 2.36; P=0.014) and minimum SBP (OR per 10 mmHg increase: 0.65, 95% CI 0.47 to 0.90; P=0.009) values were independent predictors of 3-month mortality. Our study demonstrates that wide BP excursions from the mean during the first 24 hours post MT are associated with worse outcomes in patients with nrLVO. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

78 FR 28897 - Tennessee Valley Authority; Establishment of Atomic Safety and Licensing Board

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-16

...] Tennessee Valley Authority; Establishment of Atomic Safety and Licensing Board Pursuant to delegation by the... CFR 2.104, 2.105, 2.300, 2.309, 2.313, 2.318, and 2.321, notice is hereby given that an Atomic Safety... comprised of the following administrative judges: Alex S. Karlin, Chairman, Atomic Safety and Licensing...