WorldWideScience

Sample records for drug safety surveillance

  1. A primer of drug safety surveillance: an industry perspective. Part II: Product labeling and product knowledge.

    Science.gov (United States)

    Allan, M C

    1992-01-01

    To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part II of this series discusses specific issues regarding product labeling, such as developing the labeling, changing the labeling, and the legal as well as commercial ramifications of the contents of the labeling. An adverse event report scenario is further analyzed and suggestions are offered for maintaining the product labeling as an accurate reflection of the drug safety surveillance data. This article also emphasizes the necessity of product knowledge in adverse event database management. Both scientific and proprietary knowledge are required. Acquiring product knowledge is a part of the day-to-day activities of drug safety surveillance. A knowledge of the history of the product may forestall adverse publicity, as shown in the illustration. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction of the components of the process. Suggestions are offered

  2. A primer of drug safety surveillance: an industry perspective. Part I: Information flow, new drug development, and federal regulations.

    Science.gov (United States)

    Allan, M C

    1992-01-01

    To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part I of this series provides a background for the discussion of drug safety by defining the basic terms and showing the flow of safety information through a pharmaceutical company. The customers for adverse drug event data are identified to provide a basis for providing quality service. The development of a drug product is briefly reviewed to show the evolution of safety data. Drug development and safety are defined by federal regulations. These regulations are developed by the FDA with information from pharmaceutical manufacturers. The intent of the regulations and the accompanying guidelines is described. An illustration from the news media is cited to show an alternative, positive approach to handling an adverse event report. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text and additional readings are presented in an appendix. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction ;of the components

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

    Science.gov (United States)

    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.

  4. Evaluation of Electronic Healthcare Databases for Post-Marketing Drug Safety Surveillance and Pharmacoepidemiology in China.

    Science.gov (United States)

    Yang, Yu; Zhou, Xiaofeng; Gao, Shuangqing; Lin, Hongbo; Xie, Yanming; Feng, Yuji; Huang, Kui; Zhan, Siyan

    2018-01-01

    Electronic healthcare databases (EHDs) are used increasingly for post-marketing drug safety surveillance and pharmacoepidemiology in Europe and North America. However, few studies have examined the potential of these data sources in China. Three major types of EHDs in China (i.e., a regional community-based database, a national claims database, and an electronic medical records [EMR] database) were selected for evaluation. Forty core variables were derived based on the US Mini-Sentinel (MS) Common Data Model (CDM) as well as the data features in China that would be desirable to support drug safety surveillance. An email survey of these core variables and eight general questions as well as follow-up inquiries on additional variables was conducted. These 40 core variables across the three EHDs and all variables in each EHD along with those in the US MS CDM and Observational Medical Outcomes Partnership (OMOP) CDM were compared for availability and labeled based on specific standards. All of the EHDs' custodians confirmed their willingness to share their databases with academic institutions after appropriate approval was obtained. The regional community-based database contained 1.19 million people in 2015 with 85% of core variables. Resampled annually nationwide, the national claims database included 5.4 million people in 2014 with 55% of core variables, and the EMR database included 3 million inpatients from 60 hospitals in 2015 with 80% of core variables. Compared with MS CDM or OMOP CDM, the proportion of variables across the three EHDs available or able to be transformed/derived from the original sources are 24-83% or 45-73%, respectively. These EHDs provide potential value to post-marketing drug safety surveillance and pharmacoepidemiology in China. Future research is warranted to assess the quality and completeness of these EHDs or additional data sources in China.

  5. Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies.

    Science.gov (United States)

    Koutkias, Vassilis G; Lillo-Le Louët, Agnès; Jaulent, Marie-Christine

    2017-02-01

    Driven by the need of pharmacovigilance centres and companies to routinely collect and review all available data about adverse drug reactions (ADRs) and adverse events of interest, we introduce and validate a computational framework exploiting dominant as well as emerging publicly available data sources for drug safety surveillance. Our approach relies on appropriate query formulation for data acquisition and subsequent filtering, transformation and joint visualization of the obtained data. We acquired data from the FDA Adverse Event Reporting System (FAERS), PubMed and Twitter. In order to assess the validity and the robustness of the approach, we elaborated on two important case studies, namely, clozapine-induced cardiomyopathy/myocarditis versus haloperidol-induced cardiomyopathy/myocarditis, and apixaban-induced cerebral hemorrhage. The analysis of the obtained data provided interesting insights (identification of potential patient and health-care professional experiences regarding ADRs in Twitter, information/arguments against an ADR existence across all sources), while illustrating the benefits (complementing data from multiple sources to strengthen/confirm evidence) and the underlying challenges (selecting search terms, data presentation) of exploiting heterogeneous information sources, thereby advocating the need for the proposed framework. This work contributes in establishing a continuous learning system for drug safety surveillance by exploiting heterogeneous publicly available data sources via appropriate support tools.

  6. The role of electronic healthcare record databases in paediatric drug safety surveillance: A retrospective cohort study

    NARCIS (Netherlands)

    S. de Bie (Sandra); P.M. Coloma (Preciosa); C. Ferrajolo (Carmen); K.M.C. Verhamme (Katia); G. Trifirò (Gianluca); M.J. Schuemie (Martijn); S.M.J.M. Straus (Sabine); R. Gini (Rosa); R.M.C. Herings (Ron); G. Mazzaglia (Giampiero); G. Picelli (Gino); A. Ghirardi (Arianna); L. Pedersen (Lars); B.H.Ch. Stricker (Bruno); J. van der Lei (Johan); M.C.J.M. Sturkenboom (Miriam)

    2015-01-01

    textabstractAim Electronic healthcare record (EHR)-based surveillance systems are increasingly being developed to support early detection of safety signals. It is unknown what the power of such a system is for surveillance among children and adolescents. In this paper we provide estimates of the

  7. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  8. The potential of the European network of congenital anomaly registers (EUROCAT) for drug safety surveillance: a descriptive study.

    Science.gov (United States)

    Meijer, Willemijn M; Cornel, Martina C; Dolk, Helen; de Walle, Hermien E K; Armstrong, Nicola C; de Jong-van den Berg, Lolkje T W

    2006-09-01

    European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe surveying more than 1 million births per year, or 25% of the births in the European Union. This paper describes the potential of the EUROCAT collaboration for pharmacoepidemiology and drug safety surveillance. The 34 full members and 6 associate members of the EUROCAT network were sent a questionnaire about their data sources on drug exposure and on drug coding. Available data on drug exposure during the first trimester available in the central EUROCAT database for the years 1996-2000 was summarised for 15 out of 25 responding full members. Of the 40 registries, 29 returned questionnaires (25 full and 4 associate members). Four of these registries do not collect data on maternal drug use. Of the full members, 15 registries use the EUROCAT drug code, 4 use the international ATC drug code, 3 registries use another coding system and 7 use a combination of these coding systems. Obstetric records are the most frequently used sources of drug information for the registries, followed by interviews with the mother. Only one registry uses pharmacy data. Percentages of cases with drug exposure (excluding vitamins/minerals) varied from 4.4% to 26.0% among different registries. The categories of drugs recorded varied widely between registries. Practices vary widely between registries regarding recording drug exposure information. EUROCAT has the potential to be an effective collaborative framework to contribute to post-marketing drug surveillance in relation to teratogenic effects, but work is needed to implement ATC drug coding more widely, and to diversify the sources of information used to determine drug exposure in each registry.

  9. Clinical Relation Extraction Toward Drug Safety Surveillance Using Electronic Health Record Narratives: Classical Learning Versus Deep Learning.

    Science.gov (United States)

    Munkhdalai, Tsendsuren; Liu, Feifan; Yu, Hong

    2018-04-25

    Medication and adverse drug event (ADE) information extracted from electronic health record (EHR) notes can be a rich resource for drug safety surveillance. Existing observational studies have mainly relied on structured EHR data to obtain ADE information; however, ADEs are often buried in the EHR narratives and not recorded in structured data. To unlock ADE-related information from EHR narratives, there is a need to extract relevant entities and identify relations among them. In this study, we focus on relation identification. This study aimed to evaluate natural language processing and machine learning approaches using the expert-annotated medical entities and relations in the context of drug safety surveillance, and investigate how different learning approaches perform under different configurations. We have manually annotated 791 EHR notes with 9 named entities (eg, medication, indication, severity, and ADEs) and 7 different types of relations (eg, medication-dosage, medication-ADE, and severity-ADE). Then, we explored 3 supervised machine learning systems for relation identification: (1) a support vector machines (SVM) system, (2) an end-to-end deep neural network system, and (3) a supervised descriptive rule induction baseline system. For the neural network system, we exploited the state-of-the-art recurrent neural network (RNN) and attention models. We report the performance by macro-averaged precision, recall, and F1-score across the relation types. Our results show that the SVM model achieved the best average F1-score of 89.1% on test data, outperforming the long short-term memory (LSTM) model with attention (F1-score of 65.72%) as well as the rule induction baseline system (F1-score of 7.47%) by a large margin. The bidirectional LSTM model with attention achieved the best performance among different RNN models. With the inclusion of additional features in the LSTM model, its performance can be boosted to an average F1-score of 77.35%. It shows that

  10. Comparative study on drug safety surveillance between medical students of Malaysia and Nigeria.

    Science.gov (United States)

    Abubakar, Abdullahi Rabiu; Ismail, Salwani; Rahman, Nor Iza A; Haque, Mainul

    2015-01-01

    Internationally, there is a remarkable achievement in the areas of drug discovery, drug design, and clinical trials. New and efficient drug formulation techniques are widely available which have led to success in treatment of several diseases. Despite these achievements, large number of patients continue to experience adverse drug reactions (ADRs), and majority of them are yet to be on record. The purpose of this survey is to compare knowledge, attitude, and practice with respect to ADRs and pharmacovigilance (PV) between medical students of Malaysia and Nigeria and to determine if there is a relationship between their knowledge and practice. A cross-sectional, questionnaire-based survey involving year IV and year V medical students of the Department of Medicine, Universiti Sultan Zainal Abidin and Bayero University Kano was carried out. The questionnaire which comprised 25 questions on knowledge, attitude, and practice was adopted, modified, validated, and administered to them. The response was analyzed using SPSS version 20. The response rate from each country was 74%. There was a statistically significant difference in mean knowledge and practice score on ADRs and PV between medical students of Malaysia and Nigeria, both at PMalaysia, although they need improvement. Imparting knowledge of ADRs and PV among medical students will upgrade their practice and enhance health care delivery services in the future.

  11. Integrated cardiac safety: assessment methodologies for noncardiac drugs in discovery, development, and postmarketing surveillance

    National Research Council Canada - National Science Library

    Turner, J. Rick; Durham, Todd A

    2009-01-01

    ... PROTEOMICS AND TRANSCRIPTOMICS 2.8 GENE EXPRESSION 2.9 PROTEINS 2.10 CELLS 2.11 CELL MEMBRANES 2.12 PROTEINS IN CELL MEMBRANES 2.13 ION CHANNELS 2.14 RECEPTORS ADVERSE DRUG REACTIONS MELANOGASTER 25 ...

  12. Review of the Methods to Obtain Paediatric Drug Safety Information: Spontaneous Reporting and Healthcare Databases, Active Surveillance Programmes, Systematic Reviews and Meta-analyses

    Science.gov (United States)

    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.

  13. Microbiological Food Safety Surveillance in China

    Directory of Open Access Journals (Sweden)

    Xiaoyan Pei

    2015-08-01

    Full Text Available Microbiological food safety surveillance is a system that collects data regarding food contamination by foodborne pathogens, parasites, viruses, and other harmful microbiological factors. It helps to understand the spectrum of food safety, timely detect food safety hazards, and provide relevant data for food safety supervision, risk assessment, and standards-setting. The study discusses the microbiological surveillance of food safety in China, and introduces the policies and history of the national microbiological surveillance system. In addition, the function and duties of different organizations and institutions are provided in this work, as well as the generation and content of the surveillance plan, quality control, database, and achievement of the microbiological surveillance of food safety in China.

  14. The potential of the European network of congenital anomaly registers (EUROCAT) for drug safety surveillance : a descriptive study

    NARCIS (Netherlands)

    Meijer, Willemijn M.; Cornel, Martina C.; Dolk, Helen; de Walle, Hermien E. K.; Armstrong, Nicola C.; de Jong-van den Berg, Lolkje T. W.

    Background European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe surveying more than I million births per year, or 25% of the births in the European Union. This paper describes the potential of the EUROCAT collaboration for

  15. Drug overdose surveillance using hospital discharge data.

    Science.gov (United States)

    Slavova, Svetla; Bunn, Terry L; Talbert, Jeffery

    2014-01-01

    We compared three methods for identifying drug overdose cases in inpatient hospital discharge data on their ability to classify drug overdoses by intent and drug type(s) involved. We compared three International Classification of Diseases, Ninth Revision, Clinical Modification code-based case definitions using Kentucky hospital discharge data for 2000-2011. The first definition (Definition 1) was based on the external-cause-of-injury (E-code) matrix. The other two definitions were based on the Injury Surveillance Workgroup on Poisoning (ISW7) consensus recommendations for national and state poisoning surveillance using the principal diagnosis or first E-code (Definition 2) or any diagnosis/E-code (Definition 3). Definition 3 identified almost 50% more drug overdose cases than did Definition 1. The increase was largely due to cases with a first-listed E-code describing a drug overdose but a principal diagnosis that was different from drug overdose (e.g., mental disorders, or respiratory or circulatory system failure). Regardless of the definition, more than 53% of the hospitalizations were self-inflicted drug overdoses; benzodiazepines were involved in about 30% of the hospitalizations. The 2011 age-adjusted drug overdose hospitalization rate in Kentucky was 146/100,000 population using Definition 3 and 107/100,000 population using Definition 1. The ISW7 drug overdose definition using any drug poisoning diagnosis/E-code (Definition 3) is potentially the highest sensitivity definition for counting drug overdose hospitalizations, including by intent and drug type(s) involved. As the states enact policies and plan for adequate treatment resources, standardized drug overdose definitions are critical for accurate reporting, trend analysis, policy evaluation, and state-to-state comparison.

  16. Drug Overdose Surveillance Using Hospital Discharge Data

    Science.gov (United States)

    Bunn, Terry L.; Talbert, Jeffery

    2014-01-01

    Objectives We compared three methods for identifying drug overdose cases in inpatient hospital discharge data on their ability to classify drug overdoses by intent and drug type(s) involved. Methods We compared three International Classification of Diseases, Ninth Revision, Clinical Modification code-based case definitions using Kentucky hospital discharge data for 2000–2011. The first definition (Definition 1) was based on the external-cause-of-injury (E-code) matrix. The other two definitions were based on the Injury Surveillance Workgroup on Poisoning (ISW7) consensus recommendations for national and state poisoning surveillance using the principal diagnosis or first E-code (Definition 2) or any diagnosis/E-code (Definition 3). Results Definition 3 identified almost 50% more drug overdose cases than did Definition 1. The increase was largely due to cases with a first-listed E-code describing a drug overdose but a principal diagnosis that was different from drug overdose (e.g., mental disorders, or respiratory or circulatory system failure). Regardless of the definition, more than 53% of the hospitalizations were self-inflicted drug overdoses; benzodiazepines were involved in about 30% of the hospitalizations. The 2011 age-adjusted drug overdose hospitalization rate in Kentucky was 146/100,000 population using Definition 3 and 107/100,000 population using Definition 1. Conclusion The ISW7 drug overdose definition using any drug poisoning diagnosis/E-code (Definition 3) is potentially the highest sensitivity definition for counting drug overdose hospitalizations, including by intent and drug type(s) involved. As the states enact policies and plan for adequate treatment resources, standardized drug overdose definitions are critical for accurate reporting, trend analysis, policy evaluation, and state-to-state comparison. PMID:25177055

  17. The out-of-focus bias in drug surveillance.

    Science.gov (United States)

    Gnädinger, Markus; Mellinghoff, Hans-Ulrich

    2013-03-01

    Existing drug safety systems with phase II and III studies and post-marketing surveillance by principle do not allow for the recognition of an important class of adverse drug reactions (ADRs). ADRs that are resistant to being detected reliably may a) appear as if they are age-related chronic diseases, which also manifest themselves in a high degree without drug treatment, b) arise in "old" drugs, c) arise during long-term application, and d) arise with the administration to frail and aged populations. "Silent" and multi-factorial health problems evolving from long-term drug treatment must therefore be addressed with a systematic search strategy, as a third track along with the phase II and III studies and spontaneous reporting systems which still exist.

  18. Social Media Listening for Routine Post-Marketing Safety Surveillance.

    Science.gov (United States)

    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.

  19. ACP Facility Safety Surveillance System Installation

    International Nuclear Information System (INIS)

    You, Gil Sung; Kook, D. H.; Choung, W. M.; Ku, J. H.; Cho, I. J.; You, G. S.; Kwon, K. C.; Lee, W. K.; Lee, E. P.

    2006-10-01

    The Advanced spent fuel Conditioning Process is under development for effective management of spent fuel by converting UO 2 into U-metal. For demonstration of this process, α-γ type new hotcell was built in the IMEF basement. All facilities which treat radioactive materials must manage CCTV system which is under control of Health Physics department. Three main points (including hotcell rear door area) have each camera, but operators who are in charge of facility management need to check the safety of the facility immediately through the network in his office. This needs introduce additional network cameras installation and this new surveillance system is expected to update the whole safety control ability with existing system

  20. Automated Safety Incident Surveillance and Tracking System (ASISTS)

    Data.gov (United States)

    Department of Veterans Affairs — The Automated Safety Incident Surveillance and Tracking System (ASISTS) is a repository of Veterans Health Administration (VHA) employee accident data. Many types of...

  1. 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.

    Science.gov (United States)

    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.

  2. Drug Safety: Managing Multiple Drugs

    Science.gov (United States)

    ... This series is produced by Consumers Union and Consumer Reports Best Buy Drugs , a public information project sup- ported by grants from the Engelberg Foundation and the National Library of Medicine of ... Consumer and Prescriber Education Grant Program which is funded ...

  3. Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): Post-marketing surveillance in Japan.

    Science.gov (United States)

    Takeuchi, Tsutomu; Ishida, Kota; Shiraki, Katsuhisa; Yoshiyasu, Takashi

    2018-01-01

    Post-marketing surveillance (PMS) was conducted to assess the safety and effectiveness of tacrolimus (TAC) add-on therapy for patients with rheumatoid arthritis (RA) and an inadequate response to biological disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA from 180 medical sites across Japan were registered centrally with an electronic investigation system. The observational period was 24 weeks from the first day of TAC administration concomitantly with biological DMARDs. Safety and effectiveness populations included 624 and 566 patients, respectively. Patients were predominantly female (81.1%), with a mean age of 61.9 years. Overall, 125 adverse drug reactions (ADRs) occurred in 94 patients (15.1%), and 15 serious ADRs occurred in 11 patients (1.8%). These incidences were lower compared with previously reported incidences after TAC treatment in PMS, and all of the observed ADRs were already known. A statistically significant improvement was observed in the primary effectiveness variable of Simplified Disease Activity Index after TAC treatment; 62.7% of patients achieved remission or low disease activity at week 24. TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.

  4. Integrating animal health and food safety surveillance data from slaughterhouse control.

    Science.gov (United States)

    Lynch, J A; Silva, P

    2013-08-01

    Surveillance at the slaughterhouse level for animal health and food safety purposes encompasses examination for the presence of pathology, pathogens, drug residues, chemical contaminants and antimicrobial resistance. Government, industry and academia are the primary proponents of such surveillance. A variety of policies and policy instruments from voluntary to legislative may be applied to promote or obligate participation. Efforts to integrate data across such diverse organisations encounter significant legal, logistical and financial challenges. Enhancement of policies to encourage effective integration of animal health and food safety surveillance data from slaughterhouse control should promote: a long-term approach; collaboration among government, industry and academia; application of a risk-based scheme; and transparent public access to data, with generation of consumer-oriented communications derived from the data. A strong case can be made that the complementary pursuit of both sustainable animal health and food safety can continue to be aided by surveillance at the slaughterhouse level.

  5. Surveillance of Salmonella enteritidis in layer houses: a retrospective comparison of the Food and Drug Administration's egg safety rule (2010-2011) and the California Egg Quality Assurance Program (2007-2011).

    Science.gov (United States)

    Pitesky, Maurice; Charlton, Bruce; Bland, Mark; Rolfe, Dan

    2013-03-01

    Between July 2007 and December 2011, 2660 environmental drag swab samples were collected in total from California layer flocks on behalf of the California Egg Quality Assurance Program (CEQAP), the egg safety rule (21 CFR Parts 16 and 118) of the Food and Drug Administration (FDA), or both. The samples were processed by the California Animal Health and Food Safety Lab, and positive or negative results for Salmonella enterica serovar Enteritidis (SE) were recorded. This study retrospectively compares the differences between the FDA and CEQAP programs with respect to their SE environmental sampling surveillance results. To accomplish this comparison, two different CEQAP (new and old) data sets representing different SE environmental surveillance approaches in the life of the flock were compared against each other and against the FDA's SE environmental testing plan. Significant differences were noted between the CEQAP and FDA programs with respect to the prevalence of SE in the farm environment. Analyses of the prevalence of SE at different stages in the flock's life cycle (chick papers, preproduction, midproduction, postmolt, and premarket) found the highest prevalence of SE in premarket (11.9%), followed by postmolt (3.5%) and midproduction (3.4%), and there was a tie between chick papers and preproduction (2.1%). To assess the main effects of the presence of SE in the farm environment, backwards binary logistic regression was used. Of six independent variables examined (age of flock, year, season, owner, CEQAP membership, and analysis of pooled samples vs. individual swabs), only age of flock, owner, and year were determined to be significant factors in the final model. Although CEQAP membership and pooling vs. individuals swabs were not included in the final model, Pearson chi-square tests did show significantly higher odds of SE for non-CEQAP member farms and higher odds of SE in pooled samples vs. individual swabs.

  6. On some aspects of nuclear safety surveillance and review

    International Nuclear Information System (INIS)

    Li Ganjie; Zhu Hong; Zhou Shanyuan

    2004-01-01

    Five aspects of the nuclear safety surveillance and review are discussed: Strict implementation of nuclear safety regulation, making the nuclear safety surveillance and review more normalization, procedurization, scientific decision-making; Strictly requiring the applicant to comply with the requirements of codes, do not allowing the utilization of mixing of codes; Properly controlling the strictness for the review on significant non-conformance; Strengthening the co-operation between regional offices and technical support units, Properly treat the relations between administrational management unit and technical support units. (authors)

  7. Nuclear safety and radiation protection surveillance in different countries. Switzerland

    International Nuclear Information System (INIS)

    1993-01-01

    The information and historical review on the Nuclear Surveillance in Switzerland has been presented. Special attention has been paid on: general tasks and responsibility of the Nuclear Surveillance, its organization structures, legal aspects, regulations and recommendations governing all nuclear activities in Switzerland, licensing processes and their procedures, inspections and control functions as well as international cooperation in the field of nuclear safety and environment protection

  8. Diabetes Drugs and Cardiovascular Safety

    Directory of Open Access Journals (Sweden)

    Ji Cheol Bae

    2016-06-01

    Full Text Available Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

  9. [Active surveillance of adverse drug reaction in the era of big data: challenge and opportunity for control selection].

    Science.gov (United States)

    Wang, S F; Zhan, S Y

    2016-07-01

    Electronic healthcare databases have become an important source for active surveillance of drug safety in the era of big data. The traditional epidemiology research designs are needed to confirm the association between drug use and adverse events based on these datasets, and the selection of the comparative control is essential to each design. This article aims to explain the principle and application of each type of control selection, introduce the methods and parameters for method comparison, and describe the latest achievements in the batch processing of control selection, which would provide important methodological reference for the use of electronic healthcare databases to conduct post-marketing drug safety surveillance in China.

  10. Tenaga Nasional Berhad dam safety and surveillance program

    International Nuclear Information System (INIS)

    Jansen Luis; Zulkhairi Abd Talib

    2006-01-01

    This paper discusses the current practice of dam surveillance, which includes dam monitoring which is a process of visual inspections, measuring, processing, compiling and analyzing dam instrumentation data to determine the performance of a dam. The prime objective of the dam surveillance system is to ensure that any occurrence and development of safety deficiencies and problems are quickly detected, identified, analyzed and the required remedial actions are determined and consequently carried out in due time. In brief, the section is responsible to ensure that the dam monitoring and surveillance works are implemented as per scheduled and in accordance with the requirement and guidelines prepared by the dam designers and in accordance with international commission on large dams, ICOLD. The paper also illustrates and recommends an alternative approach for dam surveillance program using risk management approach, which is currently being actively adopted by some countries like USA, Canada, Australia and etc, towards improving the dam safety management and the decision making process. The approach provides a wider area of opportunity, improvements and benefits particular in the evaluation and modifications to the dam performance and safety. The process provides an effective and efficient tool for the decision makers and engineers through a comprehensive evaluation and a good understanding of the hazards, risks and consequences in relation to dam safety investigations. (Author)

  11. A Study on Drug Safety Monitoring Program in India

    Science.gov (United States)

    Ahmad, A.; Patel, Isha; Sanyal, Sudeepa; Balkrishnan, R.; Mohanta, G. P.

    2014-01-01

    Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers from their harmful effects. A number of single drugs as well as fixed dose combinations have been banned from manufacturing, marketing and distribution in India. An important issue about the availability of banned drugs over the counter in India is that sufficient adverse drug reactions data about these drugs have not been reported. The most common categories of drugs withdrawn in the last decade were nonsteroidal antiinflammatory drugs (28%), antidiabetics (14.28%), antiobesity (14.28%), antihistamines (14.28%), gastroprokinetic drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage (14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still available for sale in India. The present study compares the drug safety monitoring systems in the developed countries such as the USA and UK and provides implications for developing a system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard for a drug safety surveillance system, variations in culture and clinical practice across countries makes it difficult for India to completely adopt another country's practices. There should be a multidisciplinary approach towards drug safety that should be implemented throughout the entire duration spanning from drug discovery to usage by consumers. PMID:25425751

  12. SODAS: Surveillance of Drugs of Abuse Study.

    Science.gov (United States)

    Lowe, David J; Torrance, Hazel J; Ireland, Alastair J; Bloeck, Felix; Stevenson, Richard

    2017-04-01

    Novel psychoactive substance (NPS) as a form of recreational drug use has become increasingly popular. There is a paucity of information with regard to the prevalence and clinical sequelae of these drugs. The aim of this study was to detect NPS in patients presenting to the emergency department with suspected toxicological ingestion. The prospective study was performed in a large emergency department in the UK. During a 3-month period 80 patients were identified by clinicians as having potentially ingested a toxicological agent. Urine samples were analysed using liquid chromatography high-resolution mass spectrometry, and basic clinical data was gathered. Eighty patients with a history of illicit or recreational drug consumption had urine screenings performed. Forty-nine per cent (39) of the patients undergoing a screen had more than one illicit substance detected. Twenty per cent (16) of the patients tested positive for at least one NPS. Almost half of the presented patients revealed ingestion of multiple substances, which correlated poorly with self-reporting of patients. Developing enhanced strategies to monitor evolving drug trends is crucial to the ability of clinicians to deliver care to this challenging group of patients.

  13. The temporal relationship between drug supply indicators: an audit of international government surveillance systems

    Science.gov (United States)

    Werb, Dan; Kerr, Thomas; Nosyk, Bohdan; Strathdee, Steffanie; Montaner, Julio; Wood, Evan

    2013-01-01

    Objectives Illegal drug use continues to be a major threat to community health and safety. We used international drug surveillance databases to assess the relationship between multiple long-term estimates of illegal drug price and purity. Design We systematically searched for longitudinal measures of illegal drug supply indicators to assess the long-term impact of enforcement-based supply reduction interventions. Setting Data from identified illegal drug surveillance systems were analysed using an a priori defined protocol in which we sought to present annual estimates beginning in 1990. Data were then subjected to trend analyses. Main outcome measures Data were obtained from government surveillance systems assessing price, purity and/or seizure quantities of illegal drugs; systems with at least 10 years of longitudinal data assessing price, purity/potency or seizures were included. Results We identified seven regional/international metasurveillance systems with longitudinal measures of price or purity/potency that met eligibility criteria. In the USA, the average inflation-adjusted and purity-adjusted prices of heroin, cocaine and cannabis decreased by 81%, 80% and 86%, respectively, between 1990 and 2007, whereas average purity increased by 60%, 11% and 161%, respectively. Similar trends were observed in Europe, where during the same period the average inflation-adjusted price of opiates and cocaine decreased by 74% and 51%, respectively. In Australia, the average inflation-adjusted price of cocaine decreased 14%, while the inflation-adjusted price of heroin and cannabis both decreased 49% between 2000 and 2010. During this time, seizures of these drugs in major production regions and major domestic markets generally increased. Conclusions With few exceptions and despite increasing investments in enforcement-based supply reduction efforts aimed at disrupting global drug supply, illegal drug prices have generally decreased while drug purity has generally

  14. The temporal relationship between drug supply indicators: an audit of international government surveillance systems.

    Science.gov (United States)

    Werb, Dan; Kerr, Thomas; Nosyk, Bohdan; Strathdee, Steffanie; Montaner, Julio; Wood, Evan

    2013-09-30

    Illegal drug use continues to be a major threat to community health and safety. We used international drug surveillance databases to assess the relationship between multiple long-term estimates of illegal drug price and purity. We systematically searched for longitudinal measures of illegal drug supply indicators to assess the long-term impact of enforcement-based supply reduction interventions. Data from identified illegal drug surveillance systems were analysed using an a priori defined protocol in which we sought to present annual estimates beginning in 1990. Data were then subjected to trend analyses. Data were obtained from government surveillance systems assessing price, purity and/or seizure quantities of illegal drugs; systems with at least 10 years of longitudinal data assessing price, purity/potency or seizures were included. We identified seven regional/international metasurveillance systems with longitudinal measures of price or purity/potency that met eligibility criteria. In the USA, the average inflation-adjusted and purity-adjusted prices of heroin, cocaine and cannabis decreased by 81%, 80% and 86%, respectively, between 1990 and 2007, whereas average purity increased by 60%, 11% and 161%, respectively. Similar trends were observed in Europe, where during the same period the average inflation-adjusted price of opiates and cocaine decreased by 74% and 51%, respectively. In Australia, the average inflation-adjusted price of cocaine decreased 14%, while the inflation-adjusted price of heroin and cannabis both decreased 49% between 2000 and 2010. During this time, seizures of these drugs in major production regions and major domestic markets generally increased. With few exceptions and despite increasing investments in enforcement-based supply reduction efforts aimed at disrupting global drug supply, illegal drug prices have generally decreased while drug purity has generally increased since 1990. These findings suggest that expanding efforts at

  15. Doing the right things and doing things right : inpatient drug surveillance assisted by clinical decision support

    NARCIS (Netherlands)

    Helmons, Pieter J.; Suijkerbuijk, Bas O.; Nannan Panday, Prashant V.; Kosterink, Jos G. W.

    Increased budget constraints and a continuous focus on improved quality require an efficient inpatient drug surveillance process. We describe a hospital-wide drug surveillance strategy consisting of a multidisciplinary evaluation of drug surveillance activities and using clinical decision support to

  16. Surveillance of items important to safety in nuclear power plants

    International Nuclear Information System (INIS)

    1990-01-01

    The Guide was prepared as part of the IAEA's programme, referred to as the NUSS Programme, for establishing Codes and Safety Guides relating to nuclear power plants. THe Guide supplements the Code on the Safety of Nuclear Power Plants: Operation, IAEA Safety Series No. 50-C-O(Rev.1). The operating organization has overall responsibility for the safe operation of the nuclear power plant. Therefore, it shall ensure that adequate surveillance activities are carried out in order to verify that the plant is operated within the prescribed operational limits and conditions, and to detect in time any deterioration of structures, systems and components as well as any adverse trend that could lead to an unsafe condition. These activities can be classified as: Monitoring plant parameters and system status; Checking and calibrating instrumentation; Testing and inspecting structures, systems and components. This Safety Guide provides guidance and recommendations on surveillance activities to ensure that structures, systems and components important to safety are available to perform their functions in accordance with design intent and assumptions

  17. ISSUES OF FETUS DRUG SAFETY

    Directory of Open Access Journals (Sweden)

    A.V. Ostrovskaya

    2010-01-01

    Full Text Available The article is focused on the issue of fetus drug safety. Development of a child’s health depends both on hereditary information and environment factors. The reason for deviation from the process of normal prenatal development could be any xenobiotics, physical factors and some medications having a pathogenic effect during pregnancy on the embryo and fetus. Due to that, the physician’s preventive work based on the knowledge of embryogenesis processes and critical development periods. Key words: teratogenic action, medications, prenatal development, congenital malformation, newborns, children.(Pediatric Pharmacology. – 2010; 7(1:25-28

  18. Student Drug Testing and the Surveillance School Economy: An Analysis of Media Representation and Policy Transfer in Australian Schools

    Science.gov (United States)

    Taylor, Emmeline

    2018-01-01

    Anxieties relating to the health, safety and security of schoolchildren have been met with a variety of surveillance apparatus in schools internationally. Drawing on findings from a content analysis of newspaper reports relating to drug testing in Australian schools, this article seeks to excavate the ways in which the media shapes, informs,…

  19. Safety and Antihypertensive Effect of Selara® (Eplerenone: Results from a Postmarketing Surveillance in Japan

    Directory of Open Access Journals (Sweden)

    Shoko Takahashi

    2016-01-01

    Full Text Available Prospective postmarketing surveillance of Selara (eplerenone, a selective mineralocorticoid receptor antagonist, was performed to confirm its safety and efficacy for hypertension treatment in Japan. The change in blood pressure after initiation of eplerenone treatment was also examined. Patients with essential hypertension who were eplerenone-naïve were recruited regardless of the use of other antihypertensive drugs. For examination of changes in blood pressure, patients were excluded if eplerenone was contraindicated or used off-label. Patients received 50–100 mg of eplerenone once daily and were observed for 12 weeks. No treatments including antihypertensive drugs were restricted during the surveillance period. Across Japan, 3,166 patients were included for safety analysis. The incidence of adverse drug reactions was 2.4%. The major adverse drug reactions observed were hyperkalemia (0.6%, dizziness, renal impairment, and increased serum potassium (0.2% each. The mean systolic blood pressure decreased from 152.1±19.0 mmHg to 134.8±15.2 mmHg at week 12, and the mean diastolic blood pressure decreased from 85.8±13.7 mmHg to 77.7±11.4 mmHg. There were no significant new findings regarding the type or incidence of adverse reactions, and eplerenone had a clinically significant antihypertensive effect, leading to favorable blood pressure control.

  20. Safety surveillance of activities on nuclear pressure components in China

    International Nuclear Information System (INIS)

    Li Ganjie; Li Tianshu; Yan Tianwen

    2005-01-01

    The nuclear pressure components, which perform the nuclear safety functions, are one of the key physical barriers for nuclear safety. For the national strategy on further development of nuclear power and localization of nuclear pressure components, there still exist some problems in preparedness on the localization. As for the technical basis, what can not be overlooked is the management. Aiming at the current problems, National Nuclear Safety Administration (NNSA) has taken measures to strengthen the propagation and popularization of nuclear safety culture, adjust the review and approval policies for nuclear pressure components qualification license, establish more stringent management requirements, and enhance the surveillance of activities on nuclear pressure equipment. Meanwhile, NNSA has improved the internal management and the regulation efficiency on nuclear pressure components. At the same time, with the development and implementation of 'Rules on the Safety Regulation for Nuclear Safety Important Components' to be promulgated by the State Council of China, NNSA will complete and improve the regulation on nuclear pressure components and other nuclear equipment. (authors)

  1. Safety assessments using surveillance programmes and data base

    International Nuclear Information System (INIS)

    Njo, D.H.

    1998-01-01

    As a result of the popularity of the Agencies report 'Neutron Irradiation Embrittlement of Reactor Pressure Vessel Steels' of 1975, it was decided that another report on this broad subject would be of use. In this report, background and contemporary views on specially identified areas of the subject are considered as self-contained chapters, written by experts. Chapter 12 presents some aspects on safety assessments of RPV materials during the life of a NPP, using surveillance programmes and data bases. Specific criteria for the usefulness of data bases are developed

  2. Surveillance of gastrointestinal disease in France using drug sales data.

    Science.gov (United States)

    Pivette, Mathilde; Mueller, Judith E; Crépey, Pascal; Bar-Hen, Avner

    2014-09-01

    Drug sales data have increasingly been used for disease surveillance during recent years. Our objective was to assess the value of drug sales data as an operational early detection tool for gastroenteritis epidemics at national and regional level in France. For the period 2008-2013, we compared temporal trends of drug sales for the treatment of gastroenteritis with trends of cases reported by a Sentinel Network of general practitioners. We benchmarked detection models to select the one with the best sensitivity, false alert proportion and timeliness, and developed a prospective framework to assess the operational performance of the system. Drug sales data allowed the detection of seasonal gastrointestinal epidemics occurring in winter with a distinction between prescribed and non-prescribed drugs. Sales of non-prescribed drugs allowed epidemic detection on average 2.25 weeks earlier than Sentinel data. These results confirm the value of drug sales data for real-time monitoring of gastroenteritis epidemic activity. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Surveillance of drug resistance for tuberculosis control: why and how?

    Science.gov (United States)

    Chaulet, P; Boulahbal, F; Grosset, J

    1995-12-01

    The resistance of Mycobacterium tuberculosis to antibiotics, which reflects the quality of the chemotherapy applied in the community, is one of the elements of epidemiological surveillance used in national tuberculosis programmes. Measurement of drug resistance poses problems for biologists in standardization of laboratory methods and quality control. The definition of rates of acquired and primary drug resistance also necessitates standardization in the methods used to collect information transmitted by clinicians. Finally, the significance of the rates calculated depends on the choice of the patients sample on which sensitivity tests have been performed. National surveys of drug resistance therefore require multidisciplinary participation in order to select the only useful indicators: rates of primary resistance and of acquired resistance. These indicators, gathered in representative groups of patients over a long period, are a measurement of the impact of modern chemotherapy regimens on bacterial ecology.

  4. Safety aspects of core power distribution surveillance and control

    International Nuclear Information System (INIS)

    Beraha, D.; Grumbach, R.; Hoeld, A.; Werner, W.

    1978-01-01

    The incentives for improved core surveillance and core control systems are outlined. An efficient code for evaluating the power distribution is indispensable for designing and testing such a system. The characteristics of the core simulator QUABOX/CUBBOX and the features required for off-line and on-line applications are described. The important role of the simulator for the safety assessment of a digital core control system is underlined. With regard to the safety aspects of core control, possible disturbances are classified. Simulation results are given concerning the failure of a control actuator. It is shown that means can be devised to prevent unstable behaviour of the control system and, furthermore, to contribute to a safe reactor operation by accounting for process disturbances. (author)

  5. Assessment of pharmacovigilance approaches for monitoring the safety of antimalarial drugs in pregnancy

    NARCIS (Netherlands)

    Dellicour, S.O.M.C.

    2014-01-01

    Post-marketing surveillance of drugs used in pregnancy is challenging, especially in developing countries where resources for pharmacovigilance are rare. There is a need to establish simple but effective systems to monitor safety of drugs given during pregnancy in resource constrained countries.

  6. Drug safety alerts of pharmacovigilance programme of India: A scope for targeted spontaneous reporting in India

    Directory of Open Access Journals (Sweden)

    Prasad Thota

    2018-01-01

    Conclusion: In India, spontaneous reporting of ADRs existed since 1998 under passive surveillance method, but there is an urgent need to initiate TSR, which is a complementary method to spontaneous reporting on these drug safety alerts for further regulatory action by Central Drugs Standard Control Organization.

  7. Current French system of post-marketing drug surveillance.

    Science.gov (United States)

    Albengres, E; Gauthier, F; Tillement, J P

    1990-07-01

    The French system of drug surveillance is characterized by several original features: thirty regional centres are selected to cover all of France to collect, analyze and enter the adverse drug events in the national data bank. The system is based on a bank of well documented files submitted to a decision of imputation; the report of severe events by prescribers is mandatory; cases are collected either by spontaneous reporting (routine) or by direct request (intensive validation study); the system is being involved in studies of epidemiological type as carried out by the national system of health or a few societies of medicine as well as by the centres themselves in cooperative works on defined populations.

  8. Surveillance of veterinary drug residues in pork meat in Madagascar

    Directory of Open Access Journals (Sweden)

    M. V. Rakotoharinome

    2015-06-01

    Table I presents the results of the percentage of positive samples in the various regions of Madagascar. On average 37.2% sam­ples were contaminated by antimicrobial residues. A significant increase from 32 to 39% was observed between 2010 and 2011, respectively. No significant differences were found between samples according to sex, breed or age class in individual ani­mals. No differences between pig farm origins were found either (Figure 1. However, Amoron’i Mania Region, and particularly suburban Ambositra, was the most contaminated area in 2010 (67%; n = 9 and Melaky region (Western Madagascar in 2011. Pork meat samples originating from the same production area were less contaminated by drug residues when the animals were slaughtered in urban abattoirs compared to provincial abat­toirs. In this first step toward a national surveillance system, we confirm that drug residues in animal products are a serious public health concern for Madagascar.

  9. Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.

    Science.gov (United States)

    Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro

    2015-06-01

    All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Drug safety and the impact of drug warnings

    DEFF Research Database (Denmark)

    Hostenkamp, G.; Fischer, K. E.; Borch-Johnsen, K.

    2016-01-01

    Objective To analyse the impact of drug safety warnings from the European Medicines Agency (EMA) on drug utilisation and their interaction with information released through national reimbursement bodies. Methods Insurance claims data on anti-diabetic drug prescriptions in primary care in Germany...

  11. Risk management and post-marketing surveillance of CNS drugs.

    Science.gov (United States)

    Henningfield, Jack E; Schuster, Charles R

    2009-12-01

    Drugs affecting the central nervous system span a broad range of chemical entities, dosage forms, indications, and risks. Unintended consequences include potential abuse and overdose in non-patient drug abusers, deliberate tampering of drug dosage forms, and criminal behavior associated with diversion. Regulators must consider diverse factors to find the appropriate conditions of approval to minimize unintended consequences while enabling a level of access desired by health care providers and patients. This commentary appears as part of a special issue of Drug and Alcohol Dependence that focuses on risk management and post-marketing surveillance and addresses key issues that pose real-world challenges to pharmaceutical sponsors and regulators in particular. For example, in the U.S., Controlled Substances Act drug scheduling can be considered a risk management strategy but its legal authorities and administrative processes are independent from those of risk management (including Risk Evaluation and Mitigation Strategies or REMS); better harmonization of these approaches is vital from drug development and regulatory perspectives. Risk management would ideally be implemented on a strong science foundation demonstrating that the tools employed to mitigate risks and ensure safe use are effective. In reality, research and evaluation of tools in this area is in its infancy and will necessarily be an evolutionary process; furthermore, there is little precedent for linking interventions and program evolution to unintended consequences such as regional outbreaks of abuse and diversion. How such issues are resolved has the potential to stimulate or stifle innovations in drug development and advance or imperil health care.

  12. Predictive toxicology in drug safety

    National Research Council Canada - National Science Library

    Xu, Jinghai J; Urban, Laszlo

    2011-01-01

    .... It provides information on the present knowledge of drug side effects and their mitigation strategy during drug discovery, gives guidance for risk assessment, and promotes evidence-based toxicology...

  13. Drug Safety Crises Management in Pharmacovigilance

    Directory of Open Access Journals (Sweden)

    Gloria Shalviri

    2018-05-01

    Full Text Available Background: Adverse drug events can cause serious consequences including death. A published report by Lazarou et al in 1998 showed that adverse drug events were the 4th to 6th leading cause of death in the United States. These events may lead to drug safety crises in some issues, which need to take crises management process for solving the problem and/or preventing similar events.Objectives: To evaluate nature of drug safety crises based on adverse events reported to Iranian Pharmacovigilance Center from 1999 through 2012. To mention success and failure outcomes of crises management process taken against detected crises.Methods: All adverse drug events received by Iranian Pharmacovigilance Center from 1999 through 2012 were evaluated for reports with fatal outcome. All alerting letters and manuscripts published by the Center during the same period were reviewed for detailed information on detected crises. World Health Organization definition was used for detecting drug safety crises.Results: Among 42036 registered cases in our database, 463 deaths were recorded. The most frequent suspected drug for adverse events with fatal outcome was ceftriaxone (100 cases. Ten different drug safety crises issues were detected during the study period and their successful or failure outcomes were evaluated. There were 112 issued alerting letters and 17 published manuscript during the same period which was monitored for detailed information.  Conclusion: It is necessary for national pharmacovigilance centers to have prepared programs for crises management. This could be useful for reducing drug related mortality.

  14. [The senses of sanitary safety in the discourse of the National Health Surveillance Agency].

    Science.gov (United States)

    Barbosa, Ana de Oliveira; Costa, Ediná Alves

    2010-11-01

    The term sanitary safety (SS) appeared in the international debate mainly due to the emerging sanitary crisis, although its meaning has remained obscure. This paper aims to analyze the concept of SS brought into the Brazilian sanitary surveillance upon the creation of the National Health Surveillance Agency. An exploratory case study was undertaken with technical data analysis and semi-structured interviews with informants who had taken part in the process of formulating the body's institutional design. The following categories were analyzed: incorporation of the SS term into the institutional mission, the SS concept and SS mechanisms. The SS concept was analyzed in both institutional and technical discursive dimensions. The former elicits the sense of strategy, a reliable relationship and legitimacy whereas the latter shows the sense of an acceptable risk-benefit relationship from the perspective of individual and collective health protection and promotion. The SS concept was found to encompass health-related products, technologies and services, especially those designed for medical diagnosis and treatment, but environmental issues received little mention. The scope of the SS concept was shown to be widening to include the surveillance of hospital infection, drugs and blood.

  15. A temporal interestingness measure for drug interaction signal detection in post-marketing surveillance.

    Science.gov (United States)

    Ji, Yanqing; Ying, Hao; Tran, John; Dews, Peter; Mansour, Ayman; Massanari, R Michael

    2014-01-01

    Drug-drug interactions (DDIs) can result in serious consequences, including death. Existing methods for identifying potential DDIs in post-marketing surveillance primarily rely on the FDA's (Food and Drug Administration) spontaneous reporting system. However, this system suffers from severe underreporting, which makes it difficult to timely collect enough valid cases for statistical analysis. In this paper, we study how to signal potential DDIs using patient electronic health data. Specifically, we focus on discovery of potential DDIs by analyzing the temporal relationships between the concurrent use of two drugs of interest and the occurrences of various symptoms using novel temporal association mining techniques we developed. A new interestingness measure called functional temporal interest was proposed to assess the degrees of temporal association between two drugs of interest and each symptom. The measure was employed to screen potential DDIs from 21,405 electronic patient cases retrieved from the Veterans Affairs Medical Center in Detroit, Michigan. The preliminary results indicate the usefulness of our method in finding potential DDIs for further analysis (e.g., epidemiology study) and investigation (e.g., case review) by drug safety professionals.

  16. Drug safety evaluation of defibrotide.

    Science.gov (United States)

    Richardson, Paul G; Corbacioglu, Selim; Ho, Vincent Trien-Vinh; Kernan, Nancy A; Lehmann, Leslie; Maguire, Craig; Maglio, Michelle; Hoyle, Margaret; Sardella, Marco; Giralt, Sergio; Holler, Ernst; Carreras, Enric; Niederwieser, Dietger; Soiffer, Robert

    2013-01-01

    Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions. This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with ≥ 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included. DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.

  17. Safety and efficacy of drugs in pregnancy.

    Science.gov (United States)

    Knoppert, David

    2011-01-01

    Although most drugs are used to treat chronic or pregnancy-induced conditions during pregnancy and lactation, very few are studied in pregnant or breastfeeding women. The information we have on drugs taken during pregnancy and lactation is usually obtained after market approval through published case reports or case series and from pregnancy exposure or retrospective birth defect registries. Furthermore, generic drugs approved for use in this vulnerable population may be approved based on results from a male trial population. This disregards the changes that can occur during pregnancy which can affect the pharmacokinetics of drugs. In an effort to improve the information provided to prescribers, in 2008 the United States Food and Drug Administration proposed a change in product labelling where information from pregnancy exposure registries would be required. As of 2009, European Medicines Agency requires additional statements on use during pregnancy within drug labelling information. In Canada, it is anticipated that the efficacy and safety of drugs in pregnancy will be included under the Drug Safety and Effectiveness Network initiative, and that this will offer a unified approach for such assessments. Pregmedic, a non-profit organization for the advancement of safe and effective use of drugs in pregnancy, has presented a number of proposals and draft guidelines to Health Canada on the inclusion of pregnant women in pharmacokinetic studies and the establishment of registries for women who take drugs during pregnancy. Pregmedic advocates for ensuring that drugs indicated for women are studied in women.

  18. Improving Patient Safety in Hospitals through Usage of Cloud Supported Video Surveillance

    Directory of Open Access Journals (Sweden)

    Predrag Dašić

    2017-03-01

    CONCLUSION: Patient safety is a growing issue which can be improved with the usage of high-end centralised surveillance systems allowing the staff to focus more on treating health issues rather that keeping a watchful eye on potential incidents.

  19. Global optimization of maintenance and surveillance testing based on reliability and probabilistic safety assessment. Research project

    International Nuclear Information System (INIS)

    Martorell, S.; Serradell, V.; Munoz, A.; Sanchez, A.

    1997-01-01

    Background, objective, scope, detailed working plan and follow-up and final product of the project ''Global optimization of maintenance and surveillance testing based on reliability and probabilistic safety assessment'' are described

  20. Computerized surveillance of opioid-related adverse drug events in perioperative care: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Gattis Katherine G

    2009-08-01

    Full Text Available Abstract Background Given the complexity of surgical care, perioperative patients are at high risk of opioid-related adverse drug events. Existing methods of detection, such as trigger tools and manual chart review, are time-intensive which makes sustainability challenging. Using strategic rule design, computerized surveillance may be an efficient, pharmacist-driven model for event detection that leverages existing staff resources. Methods Computerized adverse drug event surveillance uses a logic-based rules engine to identify potential adverse drug events or evolving unsafe clinical conditions. We extended an inpatient rule (administration of naloxone to detect opioid-related oversedation and respiratory depression to perioperative care at a large academic medical center. Our primary endpoint was the adverse drug event rate. For all patients with a naloxone alert, manual chart review was performed by a perioperative clinical pharmacist to assess patient harm. In patients with confirmed oversedation, other patient safety event databases were queried to determine if they could detect duplicate, prior, or subsequent opioid-related events. Results We identified 419 cases of perioperative naloxone administration. Of these, 101 were given postoperatively and 69 were confirmed as adverse drug events after chart review yielding a rate of 1.89 adverse drug events/1000 surgical encounters across both the inpatient and ambulatory settings. Our ability to detect inpatient opioid adverse drug events increased 22.7% by expanding surveillance into perioperative care. Analysis of historical surveillance data as well as a voluntary reporting database revealed that 11 of our perioperative patients had prior or subsequent harmful oversedation. Nine of these cases received intraoperative naloxone, and 2 had received naloxone in the post-anesthesia care unit. Pharmacist effort was approximately 3 hours per week to evaluate naloxone alerts and confirm adverse drug

  1. [The role of drug registries in the post-marketing surveillance].

    Science.gov (United States)

    Traversa, Giuseppe; Sagliocca, Luciano; Magrini, Nicola; Venegoni, Mauro

    2013-06-01

    The aim of this article is to provide an introduction to issue of Recenti Progressi in Medicina, devoted to the role of drug registries in the post-marketing surveillance. We first motivate the need to implement registries as a tool in promoting the appropriateness of drug use and acquiring additional information on the risk-benefit profile of drugs. Then, the different role that can be played by registries in comparison with prescription monitoring systems and observational studies is clarified. The presentation of some of the most relevant registries established in Italy since the end of the '90s, with the analysis of their strengths and weaknesses, helps to understand some of the crucial issues that should be taken into account before a new registry is adopted. Specifically, we deal with the relationship between objectives - of appropriateness, effectiveness and safety - and methods; the overlapping between drug-based registries and disease-based ones; the duration and extension of data collection, which may be either exhaustive or based on a sampling frame; the importance of ensuring the quality of the data and to minimize the number of subjects who are lost to follow-up; the importance of infrastructures, and of ad hoc funding, for the functioning of a registry; the independence in data analysis and publication of findings.

  2. Toxicophores: Investigations in drug safety

    International Nuclear Information System (INIS)

    Williams, Dominic P.

    2006-01-01

    Adverse drug reactions, such as hepatotoxicity, blood dyscrasias and hypersensitivity are a major obstacle for the use and the development of new medicines. Many forms of organ-directed toxicity can arise from the bioactivation of drugs to the so-called chemically reactive metabolites, which can modify tissue macromolecules. It is well established that the toxicities of model hepatotoxins, such as acetaminophen, furosemide, bromobenzene and methapyrilene can be correlated with the generation of chemically reactive metabolites, which can be detected by measurement of the irreversible binding of radiolabelled material to hepatic protein and/or the detection of stable phase II metabolites such as glutathione conjugates. The basic chemistry of the reaction of such metabolites with model nucleophiles is relatively well understood. A major challenge is to define how certain reactive intermediates may chemically modify critical proteins and how modification of specific amino acids may alter protein function which in turn may affect cell signalling, regulation, defence, function and viability. This in turn will determine whether or not bioactivation will result in a particular form of drug-induced injury. It is now clear that even relatively simple reactive intermediates can react in a discriminative manner with particular cellular proteins and even with specific amino acids within those proteins. Therefore, both non-covalent, as well as covalent bonds will be important determinants of the target protein for a particular reactive metabolite. Mammalian cells have evolved numerous defence systems against reactive intermediates. Sensitive redox proteins such as Nrf-2 recognise oxidative stress and electrophilic agents, through oxidation or covalent modification of thiol groups. Defence genes, such as epoxide hydrolase and glutamate cysteine ligase then become up-regulated in an attempt to reduce the oxidising environment. However, whether the liver receives mild or severe

  3. Surveillance

    DEFF Research Database (Denmark)

    Albrechtslund, Anders; Coeckelbergh, Mark; Matzner, Tobias

    Studying surveillance involves raising questions about the very nature of concepts such as information, technology, identity, space and power. Besides the maybe all too obvious ethical issues often discussed with regard to surveillance, there are several other angles and approaches that we should...... like to encourage. Therefore, our panel will focus on the philosophical, yet non-ethical issues of surveillance in order to stimulate an intense debate with the audience on the ethical implications of our enquiries. We also hope to provide a broader and deeper understanding of surveillance....

  4. Analyzing research trends on drug safety using topic modeling.

    Science.gov (United States)

    Zou, Chen

    2018-04-06

    Published drug safety data has evolved in the past decade due to scientific and technological advances in the relevant research fields. Considering that a vast amount of scientific literature has been published in this area, it is not easy to identify the key information. Topic modeling has emerged as a powerful tool to extract meaningful information from a large volume of unstructured texts. Areas covered: We analyzed the titles and abstracts of 4347 articles in four journals dedicated to drug safety from 2007 to 2016. We applied Latent Dirichlet allocation (LDA) model to extract 50 main topics, and conducted trend analysis to explore the temporal popularity of these topics over years. Expert Opinion/Commentary: We found that 'benefit-risk assessment and communication', 'diabetes' and 'biologic therapy for autoimmune diseases' are the top 3 most published topics. The topics relevant to the use of electronic health records/observational data for safety surveillance are becoming increasingly popular over time. Meanwhile, there is a slight decrease in research on signal detection based on spontaneous reporting, although spontaneous reporting still plays an important role in benefit-risk assessment. The topics related to medical conditions and treatment showed highly dynamic patterns over time.

  5. The State Surveillance over Nuclear Safety of Nuclear Facilities Act No. 28/1984

    International Nuclear Information System (INIS)

    1995-01-01

    The Act lays down responsibilities of the Czechoslovak Atomic Energy Commission in the field of state surveillance over nuclear safety of nuclear facilities; determines the responsibilities of nuclear safety inspectors in their inspection activities; specifies duties of bodies and corporations responsible for nuclear safety of nuclear facilities; stipulates the obligation to set up emergency plans; and specifies penalties imposed on corporations and individuals for noncompliance with nuclear safety provisions. The Act entered into force on 4 April 1984. (J.B.)

  6. Drug safety data mining with a tree-based scan statistic.

    Science.gov (United States)

    Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R; Chan, Arnold K; Davis, Robert L; Graham, David; Platt, Richard; Andrade, Susan E; Boudreau, Denise; Gunter, Margaret J; Herrinton, Lisa J; Pawloski, Pamala A; Raebel, Marsha A; Roblin, Douglas; Brown, Jeffrey S

    2013-05-01

    In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Independent body for surveillance over nuclear safety in the Slovak Republic established

    International Nuclear Information System (INIS)

    Zlatnansky, J.

    1994-01-01

    The position, role, tasks and organizational structure of the Nuclear Safety Authority of the Slovak Republic are outlined. The Authority is responsible for state surveillance over nuclear safety of nuclear facilities including surveillance over radioactive waste management, over spent fuel management and other stages of the fuel cycle, as well as over nuclear materials including their accountancy and recording. The body is also responsible for assessing projects within the nuclear energy use programme and the quality of selected nuclear technological facilities and instrumentation, as well as for Slovak commitments and obligations under international agreements concerned with nuclear safety of nuclear facilities and with radioactive wastes. (J.B.). 1 fig

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

    Science.gov (United States)

    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.

  9. Surveillance of extensively drug-resistant tuberculosis in Europe, 2003-2007.

    NARCIS (Netherlands)

    Devaux, I.; Manissero, D.; Fernandez de la Hoz, K.; Kremer, K.; Soolingen, D. van

    2010-01-01

    This paper describes the results of second-line drug (SLD) susceptibility tests among multidrug-resistant tuberculosis (MDR TB) cases reported in 20 European countries aiming to identify extensively drug-resistant tuberculosis (XDR TB) cases. A project on molecular surveillance of MDR TB cases was

  10. Surveillance of emerging drugs of abuse in Hong Kong: validation of an analytical tool.

    Science.gov (United States)

    Tang, Magdalene H Y; Ching, C K; Tse, M L; Ng, Carol; Lee, Caroline; Chong, Y K; Wong, Watson; Mak, Tony W L

    2015-04-01

    To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Cross-sectional study. Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.

  11. Occupational health and safety surveillance and research using workers' compensation data.

    Science.gov (United States)

    Utterback, David F; Schnorr, Teresa M; Silverstein, Barbara A; Spieler, Emily A; Leamon, Tom B; Amick, Benjamin C

    2012-02-01

    Examine uses of US workers' compensation (WC) data for occupational safety and health purposes. This article is a summary of the proceedings from an invitational workshop held in September 2009 to discuss the use of WC data for occupational safety and health prevention purposes. Workers' compensation data systems, although limited in many ways, contain information such as medical treatments, their costs and outcomes, and disability causes that are unavailable from national occupational surveillance sources. Despite their limitations, WC records are collected in a manner consistent with many occupational health and safety surveillance needs. Reports are available on the use of WC data for surveillance and research purposes such as estimating the frequency, magnitude, severity, and cost of compensated injuries. Inconsistencies in WC data can limit generalization of research results.

  12. Surveillance of adverse effects following vaccination and safety of immunization programs.

    Science.gov (United States)

    Waldman, Eliseu Alves; Luhm, Karin Regina; Monteiro, Sandra Aparecida Moreira Gomes; Freitas, Fabiana Ramos Martin de

    2011-02-01

    The aim of the review was to analyze conceptual and operational aspects of systems for surveillance of adverse events following immunization. Articles available in electronic format were included, published between 1985 and 2009, selected from the PubMed/Medline databases using the key words "adverse events following vaccine surveillance", "post-marketing surveillance", "safety vaccine" and "Phase IV clinical trials". Articles focusing on specific adverse events were excluded. The major aspects underlying the Public Health importance of adverse events following vaccination, the instruments aimed at ensuring vaccine safety, and the purpose, attributes, types, data interpretation issues, limitations, and further challenges in adverse events following immunization were describe, as well as strategies to improve sensitivity. The review was concluded by discussing the challenges to be faced in coming years with respect to ensuring the safety and reliability of vaccination programs.

  13. Drug safety: Pregnancy rating classifications and controversies.

    Science.gov (United States)

    Wilmer, Erin; Chai, Sandy; Kroumpouzos, George

    2016-01-01

    This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Tolerability and safety of antifungal drugs

    Directory of Open Access Journals (Sweden)

    Francesco Scaglione

    2013-08-01

    Full Text Available When treating critically ill patients, as those with fungal infections, attention should be focused on the appropriate use of drugs, especially in terms of dose, safety, and tolerability. The fungal infection itself and the concomitant physiological disorders concur to increase the risk of mortality in these patients, therefore the use of any antifungal agent should be carefully evaluated, considering both the direct action on the target fungus and the adverse effects eventually caused. Among antifungal drugs, echinocandins have the greatest tolerability. In fact, unlike amphotericin B, showing nephrotoxicity, and azoles, which are hepatotoxic, the use of echinocandins doesn’t result in major adverse events.http://dx.doi.org/10.7175/rhc.v4i2s.873

  15. High Throughput Screening Method for Systematic Surveillance of Drugs of Abuse by Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry.

    Science.gov (United States)

    DiBattista, Alicia; Rampersaud, Dianne; Lee, Howard; Kim, Marcus; Britz-McKibbin, Philip

    2017-11-07

    New technologies are urgently required for reliable drug screening given a worldwide epidemic of prescription drug abuse and its devastating socioeconomic impacts on public health. Primary screening of drugs of abuse (DoA) currently relies on immunoassays that are prone to bias and are not applicable to detect an alarming array of psychoactive stimulants, tranquilizers, and synthetic opioids. These limitations impact patient safety when monitoring for medication compliance, drug substitution, or misuse/abuse and require follow-up confirmatory testing by more specific yet lower throughput instrumental methods. Herein, we introduce a high throughput platform for nontargeted screening of a broad spectrum of DoA and their metabolites based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). We demonstrate that MSI-CE-MS enables serial injections of 10 samples within a single run (high resolution MS with full-scan data acquisition. Unambiguous drug identification was achieved by four or more independent parameters, including comigration with a deuterated internal standard or in silico prediction of electromigration behavior together with accurate mass, most likely molecular formula, as well as MS/MS as required for confirmation testing. Acceptable precision was demonstrated for over 50 DoA at 3 concentration levels over 4 days (median coefficient of variance = 13%, n = 117) with minimal ion suppression, isobaric interferences, and sample carry-over (screening cutoff levels in human urine while allowing for systematic surveillance, specimen verification, and retrospective testing of designer drugs that elude conventional drug tests.

  16. Safety, surveillance and policing in the night-time economy: a visitor perspective

    NARCIS (Netherlands)

    Brands, J.

    2014-01-01

    The current doctoral thesis takes particular interest in the city-centre night-time economy (NTE), against a background of literatures that link economic vitality of city-centres, consumption and safety to greater need for surveillance and policing. Increasingly, nightlife is being problematized in

  17. OPPIDUM surveillance program: 20 years of information on drug abuse in France.

    Science.gov (United States)

    Frauger, Elisabeth; Moracchini, Christophe; Le Boisselier, Reynald; Braunstein, David; Thirion, Xavier; Micallef, Joëlle

    2013-12-01

    It is important to assess drug abuse liability in 'real life' using different surveillance systems. Some are based on specific population surveys, such as individuals with drug abuse or dependence, or under opiate maintenance treatment, because this population is very familiar with drugs and is more likely to divert or abuse them. In France, an original surveillance system based on this specific population and called 'Observation of illegal drugs and misuse of psychotropic medications (OPPIDUM) survey' was set up in 1990 as the first of its kind. The aim of this article is to describe this precursor of French drug abuse surveillance using different examples, to demonstrate its ability to effectively give health authorities and physicians interesting data on drug abuse. OPPIDUM is an annual, cross-sectional survey that anonymously collects information on abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. From 1990 to 2010, a total of 50,734 patients were included with descriptions of 102,631 psychoactive substance consumptions. These data have outlined emergent behaviors such as the misuse of buprenorphine by intravenous or nasal administration. It has contributed to assess abuse liability of emergent drugs such as clonazepam or methylphenidate. This surveillance system was also able to detect the decrease of flunitrazepam abuse following implementation of regulatory measures. OPPIDUM's twenty years of experience clearly demonstrate that collection of valid and useful data on drug abuse is possible and can provide helpful information for physicians and health authorities. © 2013 The Authors Fundamental and Clinical Pharmacology © 2013 Société Française de Pharmacologie et de Thérapeutique.

  18. Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data.

    Science.gov (United States)

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

    2017-05-01

    To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography. Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement. This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

  19. Surveillance of drug use among young people attending a music festival in Australia, 2005-2008.

    Science.gov (United States)

    Lim, Megan S C; Hellard, Margaret E; Hocking, Jane S; Spelman, Tim D; Aitken, Campbell K

    2010-03-01

    In order to monitor trends in illicit drug use among youth, surveillance of drug use behaviours among a variety of populations in different settings is required. We monitored drug use among music festival attendees. Cross-sectional studies of young people's reported drug use were performed at a music festival in Melbourne from 2005 to 2008. Self-administered questionnaires collected information on drug use, demographics and other risk behaviour. From 2005 to 2008, over 5000 questionnaires were completed by people aged 16-29; 2273 men and 3011 women. Overall, use of any illicit drug in the past month was reported by 44%. After adjusting for demographic and behavioural characteristics, the prevalence of recent illicit drug use decreased significantly from 46% in 2005 to 43% in 2008 (OR 0.92, 95% CI 0.87-0.97). After adjusting for age and sex the downwards trend was repeated for amphetamines and cannabis, but a significant increase in prevalence was observed in hallucinogen, ecstasy and inhalant use. Drug use was more common among men, older participants and those engaging in high-risk sexual behaviour. Illicit drug use was much more common in this sample than in the National Drug Strategy Household survey, but the direction of trends in drug use were similar; drug use prevalences were much lower than in the Ecstasy and Related Drugs Reporting System, the Illicit Drug Reporting System or National Needle and Syringe Program Survey. Music festival attendees are a potentially useful group for monitoring trends in illicit drug use.

  20. Preparation of Act on State Surveillance of Nuclear Safety of Nuclear Installations

    International Nuclear Information System (INIS)

    Kyncl, J.

    1983-01-01

    The Czechoslovak Government Decree no. 179 of June 1982 approved the principles underlying the first Czechoslovak legal norm to complexly resolve the problem of State surveillance of nuclear safety of nuclear installations. In the introduction the law will define the concept of nuclear safety of nuclear installations and will justify the reasons for which it has to be assured. The individual parts of the law will deal with the establishment of State surveillance of nuclear safety, the tasks of the Czechoslovak Atomic Energy Commission in this area, the control activity of Commission personnel, the measures taken against responsible organizations and personnel for failing to observe their duties, the obligations of bodies and organizations, and the cooperation between inspection bodies. (A.K.)

  1. Systematic review of surveillance by social media platforms for illicit drug use.

    Science.gov (United States)

    Kazemi, Donna M; Borsari, Brian; Levine, Maureen J; Dooley, Beau

    2017-12-01

    The use of social media (SM) as a surveillance tool of global illicit drug use is limited. To address this limitation, a systematic review of literature focused on the ability of SM to better recognize illicit drug use trends was addressed. A search was conducted in databases: PubMed, CINAHL via Ebsco, PsychINFO via Ebsco, Medline via Ebsco, ERIC, Cochrane Library, Science Direct, ABI/INFORM Complete and Communication and Mass Media Complete. Included studies were original research published in peer-reviewed journals between January 2005 and June 2015 that primarily focused on collecting data from SM platforms to track trends in illicit drug use. Excluded were studies focused on purchasing prescription drugs from illicit online pharmacies. Selected studies used a range of SM tools/applications, including message boards, Twitter and blog/forums/platform discussions. Limitations included relevance, a lack of standardized surveillance systems and a lack of efficient algorithms to isolate relevant items. Illicit drug use is a worldwide problem, and the rise of global social networking sites has led to the evolution of a readily accessible surveillance tool. Systematic approaches need to be developed to efficiently extract and analyze illicit drug content from social networks to supplement effective prevention programs. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  2. Comparing non-safety with safety device sharps injury incidence data from two different occupational surveillance systems.

    Science.gov (United States)

    Mitchell, A H; Parker, G B; Kanamori, H; Rutala, W A; Weber, D J

    2017-06-01

    The United States Occupational Safety and Health Administration (OSHA) Bloodborne Pathogens Standard as amended by the Needlestick Safety and Prevention Act requiring the use of safety-engineered medical devices to prevent needlesticks and sharps injuries has been in place since 2001. Injury changes over time include differences between those from non-safety compared with safety-engineered medical devices. This research compares two US occupational incident surveillance systems to determine whether these data can be generalized to other facilities and other countries either with legislation in place or considering developing national policies for the prevention of sharps injuries among healthcare personnel. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-12-18

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

  4. Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system.

    Directory of Open Access Journals (Sweden)

    Preciosa M Coloma

    Full Text Available Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings.To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI from a large international healthcare data network.Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible.Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects': azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate.Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out.A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical

  5. Post-marketing surveillance of the safety and effectiveness of tacrolimus in 3,267 Japanese patients with rheumatoid arthritis.

    Science.gov (United States)

    Takeuchi, Tsutomu; Kawai, Shinichi; Yamamoto, Kazuhiko; Harigai, Masayoshi; Ishida, Kota; Miyasaka, Nobuyuki

    2014-01-01

    A post-marketing surveillance (PMS) program was implemented to assess the safety and effectiveness of tacrolimus (TAC) in Japanese rheumatoid arthritis (RA) patients and to identify risk factors related to adverse drug reactions (ADRs). Patients were registered centrally and monitored for all adverse events (AEs) for 24 weeks. Effectiveness was evaluated using the Disease Activity Score 28-CRP (DAS28-CRP). Data from 3,172 patients (mean age 62.2 years) were evaluated in the safety analysis. Of the safety population, 78.5 %were female and 25.9 % were in Steinbrocker's functional class 3 or 4. TAC was prescribed as monotherapy in 52.5 % and the most common concomitant disease modifying antirheumatic drug (DMARD) was methotrexate, used in 28.9 % of the patients. The incidence of AEs, serious AEs (SAEs), ADRs and serious ADRs were 41.2, 6.4, 36.0, and 4.9 %, respectively. The most frequent serious ADR category was infections and infestations. Age ≥ 65 years, concurrent renal dysfunction, and concurrent diabetes mellitus were identified as significant risk factors for ADR. Based on EULAR response criteria, 65.4 % of the patients showed moderate or good response. The results demonstrate that TAC is well tolerated by Japanese patients with active RA, including those receiving concomitant methotrexate, in the real world.

  6. Criteria Document for B-plant's Surveillance and Maintenance Phase Safety Basis Document

    International Nuclear Information System (INIS)

    SCHWEHR, B.A.

    1999-01-01

    This document is required by the Project Hanford Managing Contractor (PHMC) procedure, HNF-PRO-705, Safety Basis Planning, Documentation, Review, and Approval. This document specifies the criteria that shall be in the B Plant surveillance and maintenance phase safety basis in order to obtain approval of the DOE-RL. This CD describes the criteria to be addressed in the S and M Phase safety basis for the deactivated Waste Fractionization Facility (B Plant) on the Hanford Site in Washington state. This criteria document describes: the document type and format that will be used for the S and M Phase safety basis, the requirements documents that will be invoked for the document development, the deactivated condition of the B Plant facility, and the scope of issues to be addressed in the S and M Phase safety basis document

  7. The nuts and bolts of pills and portions: the functions of a drug safety working group.

    Science.gov (United States)

    Nath, Noleen S; Jones, Ellen H; Stride, Peter; Premaratne, Manuja; Thaker, Darshit; Lim, Ivan

    2011-11-01

    Hospitalised patients commonly experience adverse drug events (ADEs) and medication errors. Runciman reported that ADEs in hospitals account for 20% of reported adverse events and contribute to 27% of deaths where death followed an adverse event. Hughes recommends multidisciplinary hospital drug committees to assess performance and raise standards. The new Code of Conduct of the Medical Board of Australia recommends participation in systems for surveillance and monitoring of adverse events, and to improve patient safety. We describe the functions and role of a Drug Safety Working Group (DSWG) in a suburban hospital, which aims to audit and promote a culture of prescribing and medication administration that is prudent and cautious to minimise the risk of harm to patients. We believe that regular prescription monitoring and feedback to Resident Medical Officers (RMOs) improves medication management in our hospital.

  8. 76 FR 59142 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2011-09-23

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the...., [[Page 59143

  9. Safety assessment and surveillance of decommissioning operations at DOE's nuclear facilities

    International Nuclear Information System (INIS)

    Cowgill, M.G.; Prochnow, D.; Worthington, P.R.

    1995-01-01

    A description is provided of a systematic approach currently being developed and deployed at the Department of Energy to obtain assurance that post-operational activities at nuclear facilities will be conducted in a safe manner. Using this approach, personnel will have available a formalized set of safety principles and associated question sets to assist them in the conducting of safety assessments and surveillance. Information gathered through this means will also be analyzed to determine if there are any generic complex-wide strengths or deficiencies associated with decommissioning activities and to which attention should be drawn

  10. [Surveillance system on drug abuse: Interest of the French national OPPIDUM program of French addictovigilance network].

    Science.gov (United States)

    Frauger, Elisabeth; Pochard, Liselotte; Boucherie, Quentin; Giocanti, Adeline; Chevallier, Cécile; Daveluy, Amélie; Gibaja, Valérie; Caous, Anne-Sylvie; Eiden, Céline; Authier, Nicolas; Le Boisselier, Reynald; Guerlais, Marylène; Jouanjus, Émilie; Lepelley, Marion; Pizzoglio, Véronique; Pain, Stéphanie; Richard, Nathalie; Micallef, Joëlle

    2017-09-01

    It is important to assess drug abuse liability in 'real life' using different surveillance systems. OPPIDUM ('Observation of illegal drugs and misuse of psychotropic medications') surveillance system anonymously collects information on drug abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. The aim of this article is to demonstrate the utility of OPPIDUM system using 2015 data. OPPIDUM is a cross-sectional survey repeated each year since 1995. In 2015, 5003 patients described the modality of use of 10,159 psychoactive drugs. Among them, 77% received an opiate maintenance treatment: 68% methadone (half of them consumed capsule form) and 27% buprenorphine (39% consumed generic form). Brand-name buprenorphine is more often injected than generic buprenorphine (10% vs. 2%) and among methadone consumers 7% of methadone capsule consumers have illegally obtained methadone (vs. 9% for syrup form). The proportion of medications among psychoactive drugs injected is important (42%), with morphine representing 21% of the total psychoactive drugs injected and buprenorphine, 16%. OPPIDUM highlighted emergent behaviors of abuse with some analgesic opioids (like tramadol, oxycodone or fentanyl), pregabalin, or quetiapine. OPPIDUM highlighted variations of drugs use regarding geographic approaches or by drug dependence care centers (like in harm reduction centers). OPPIDUM clearly demonstrated that collection of valid and useful data on drug abuse is possible, these data have an interest at regional, national and international levels. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  11. Remote-Reading Safety and Safeguards Surveillance System for 3013 Containers

    International Nuclear Information System (INIS)

    Lechelt, W. M.; Skorpik, J. R.; Silvers, K. L.; Szempruch, R. W.; Douglas, D. G.; Fein, K. O.

    2002-01-01

    At Hanford's Plutonium Finishing Plant (PFP), plutonium oxide is being loaded into stainless steel containers for long-term storage on the Hanford Site. These containers consist of two weld-sealed stainless steel cylinders nested one within the other. A third container holds the plutonium within the inner cylinder. This design meets the U.S. Department of Energy (DOE) storage standard, DOE-STD- 3013-2000, which anticipates a 50-year storage lifetime. The 3013 standard also requires a container surveillance program to continuously monitor pressure and to assure safeguards are adequate. However, the configuration of the container system makes using conventional measurement and monitoring methods difficult. To better meet the 3013 monitoring requirements, a team from Fluor Hanford (who manages the PFP), Pacific Northwest National Laboratory (PNNL), and Vista Engineering Technologies, LLC, developed a safer, cost-efficient, remote PFP 3013 container surveillance system. This new surveillance system is a combination of two successfully deployed technologies: (1) a magnetically coupled pressure gauge developed by Vista Engineering and (2) a radio frequency (RF) tagging device developed by PNNL. This system provides continuous, 100% monitoring of critical parameters with the containers in place, as well as inventory controls. The 3013 container surveillance system consists of three main elements: (1) an internal magnetic pressure sensor package, (2) an instrument pod (external electronics package), and (3) a data acquisition storage and display computer. The surveillance system described in this paper has many benefits for PFP and DOE in terms of cost savings and reduced personnel exposure. In addition, continuous safety monitoring (i.e., internal container pressure and temperature) of every container is responsible nuclear material stewardship and fully meets and exceeds DOE's Integrated Surveillance Program requirements

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

    Science.gov (United States)

    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.

  13. Impact of biomarker development on drug safety assessment

    International Nuclear Information System (INIS)

    Marrer, Estelle; Dieterle, Frank

    2010-01-01

    Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

  14. Sources of Safety Data and Statistical Strategies for Design and Analysis: Postmarket Surveillance.

    Science.gov (United States)

    Izem, Rima; Sanchez-Kam, Matilde; Ma, Haijun; Zink, Richard; Zhao, Yueqin

    2018-03-01

    Safety data are continuously evaluated throughout the life cycle of a medical product to accurately assess and characterize the risks associated with the product. The knowledge about a medical product's safety profile continually evolves as safety data accumulate. This paper discusses data sources and analysis considerations for safety signal detection after a medical product is approved for marketing. This manuscript is the second in a series of papers from the American Statistical Association Biopharmaceutical Section Safety Working Group. We share our recommendations for the statistical and graphical methodologies necessary to appropriately analyze, report, and interpret safety outcomes, and we discuss the advantages and disadvantages of safety data obtained from passive postmarketing surveillance systems compared to other sources. Signal detection has traditionally relied on spontaneous reporting databases that have been available worldwide for decades. However, current regulatory guidelines and ease of reporting have increased the size of these databases exponentially over the last few years. With such large databases, data-mining tools using disproportionality analysis and helpful graphics are often used to detect potential signals. Although the data sources have many limitations, analyses of these data have been successful at identifying safety signals postmarketing. Experience analyzing these dynamic data is useful in understanding the potential and limitations of analyses with new data sources such as social media, claims, or electronic medical records data.

  15. Long-term post-marketing surveillance of mizoribine for the treatment of lupus nephritis: Safety and efficacy during a 3-year follow-up

    Directory of Open Access Journals (Sweden)

    Nobuyuki Yagi

    2014-05-01

    Full Text Available Objective: To determine the safety and efficacy of long-term use of mizoribine by undertaking a 3-year post-marketing surveillance study. Methods: Subjects were all lupus nephritis patients newly treated with mizoribine between 1 October 2003 and 30 September 2005 at contracted study sites. Results: Mizoribine was administered to 881 lupus nephritis patients in the safety analysis set consisting of 946 patients recruited from 281 contracted study sites after satisfying the eligibility criteria. There were 301 events of adverse drug reactions that were observed in 196 (20.7% of the 946 subjects. There were 34 events of serious adverse drug reactions in 31 patients (3.2%. No deterioration in hematological and biochemical test values was observed, but immunological testing showed significant improvements in C3, CH50, and anti-DNA antibody titers. The negative rate of proteinuria also increased over time. The median steroid dosage was 15 mg/day at the commencement of treatment, but was reduced to 10 mg/day at 12 months and 8 mg/day at 36 months. Conclusion: The findings of the 3-year long-term drug use surveillance study indicated that mizoribine can be used over the long term with relatively few adverse drug reactions, suggesting its suitability for use in maintenance drug therapy.

  16. Maintenance, surveillance and in-service inspection in nuclear power plants. Safety guide

    International Nuclear Information System (INIS)

    2002-01-01

    Effective maintenance, surveillance and in-service inspection (MS and I) are essential for the safe operation of a nuclear power plant. The objective of this Safety Guide is to provide recommendations and guidance for MS and I activities to ensure that SSCs important to safety are available to perform their functions in accordance with the assumptions and intent of the design. This Safety Guide covers the organizational and procedural aspects of MS and I. However, it does not give detailed technical advice in relation to particular items of plant equipment, nor does it cover inspections made for and/or by the regulatory body. This Safety Guide provides recommendations and guidance for preventive and remedial measures, including testing, surveillance and in-service inspection, that are necessary to ensure that all plant structures, systems and components (SSCs) important to safety are capable of performing as intended. This Safety Guide covers measures for fulfilling the organizational and administrative requirements for: establishing and implementing schedules for preventive and predictive maintenance, repairing defective plant items, selecting and training personnel, providing related facilities and equipment, procuring stores and spare parts, and generating, collecting and retaining maintenance records for establishing and implementing an adequate feedback system for information on maintenance. MS and I should be subject to quality assurance in relation to all aspects important to safety. Quality assurance has been dealt with in detail in other IAEA safety standards and is covered here only in specific instances, for emphasis. In Section 2, a concept of MS and I is presented and the interrelationship between maintenance, surveillance and inspection is discussed. Section 3 concerns the functions and responsibilities of different organizations involved in MS and I activities. Section 4 provides recommendations and guidance on such organizational aspects as

  17. Maintenance, surveillance and in-service inspection in nuclear power plants. Safety guide

    International Nuclear Information System (INIS)

    2005-01-01

    Effective maintenance, surveillance and in-service inspection (MS and I) are essential for the safe operation of a nuclear power plant. The objective of this Safety Guide is to provide recommendations and guidance for MS and I activities to ensure that SSCs important to safety are available to perform their functions in accordance with the assumptions and intent of the design. This Safety Guide covers the organizational and procedural aspects of MS and I. However, it does not give detailed technical advice in relation to particular items of plant equipment, nor does it cover inspections made for and/or by the regulatory body. This Safety Guide provides recommendations and guidance for preventive and remedial measures, including testing, surveillance and in-service inspection, that are necessary to ensure that all plant structures, systems and components (SSCs) important to safety are capable of performing as intended. This Safety Guide covers measures for fulfilling the organizational and administrative requirements for: establishing and implementing schedules for preventive and predictive maintenance, repairing defective plant items, selecting and training personnel, providing related facilities and equipment, procuring stores and spare parts, and generating, collecting and retaining maintenance records for establishing and implementing an adequate feedback system for information on maintenance. MS and I should be subject to quality assurance in relation to all aspects important to safety. Quality assurance has been dealt with in detail in other IAEA safety standards and is covered here only in specific instances, for emphasis. In Section 2, a concept of MS and I is presented and the interrelationship between maintenance, surveillance and inspection is discussed. Section 3 concerns the functions and responsibilities of different organizations involved in MS and I activities. Section 4 provides recommendations and guidance on such organizational aspects as

  18. Advancing Drug Safety Through Prospective Pharmacovigilance.

    Science.gov (United States)

    Pitts, Peter J; Le Louet, Hervé

    2018-01-01

    Much has changed in a relatively short period of time. There is a raging debate over the level of evidence expected to first introduce a treatment to patients based on smaller, more adaptive data sets. Some argue for less data followed by postapproval follow-up, others for more adaptive clinical trial designs and end-point modification driven by patient-focused drug development and use of real-world evidence. The transition in both the review and postmarketing regulatory framework is happening in front of our eyes in real time. To improve the ability of patients to receive high-quality, safe, effective, and timely care, better information via pharmacovigilance must be a priority as the world's many regulatory systems build the capacity to harness electronic health information to improve health, care quality, and safety. Globally, the widely variable ability of nations to build reliable regulatory systems (from precise review to robust pharmacovigilance) is a dangerous source of health care inequality. Developing validated tools and techniques for "predictive pharmacovigilance" will assist all health systems in better understanding the risks and benefits of the medicines they regulate by understanding what should be happening once a new medicine moves from risk-benefit regulatory efficacy to real-world risk-effectiveness. This will be of particular utility for smaller regulatory agencies with fewer resources. By comparing preapproval predictive pharmacovigilance data, developing regulatory authorities will be able to better understand the potential gap between what was predicted and what was actually measured (via more traditional pharmacovigilance methodologies). Predictive pharmacovigilance recognizes the value of understanding the imperfect reporting of real-world clinical use and that the absence of reporting is, in itself, an important postmarketing signal.

  19. Drug safety: withdrawn medications are only part of the picture.

    Science.gov (United States)

    Rawson, Nigel S B

    2016-02-13

    In a research article published in BMC Medicine, Onakpoya and colleagues provide a historical review of withdrawals of medications for safety reasons. However, withdrawn medications are only one part of the picture about how regulatory agencies manage drug risks. Moreover, medications introduced before the increased pre-marketing regulations and post-marketing monitoring systems instituted after the thalidomide tragedy have little relevance when considering the present drug safety picture because the circumstances under which they were introduced were completely different. To more fully understand drug safety management and regulatory agency actions, withdrawals should be evaluated within the setting and timeframe in which the medications are approved, which requires information about approvals and safety warnings. Studies are needed that provide a more comprehensive current picture of the identification and evaluation of drug safety risks as well as how regulatory agencies deal with them. Please see related research article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0553-2.

  20. Clinical safety and efficacy of "filgrastim biosimilar 2" in Japanese patients in a post-marketing surveillance study.

    Science.gov (United States)

    Tamura, Kazuo; Hashimoto, Kazue; Nishikawa, Kiyohiro

    2018-05-01

    We conducted a post-marketing surveillance to evaluate the safety and efficacy of TKN732, approved as "filgrastim biosimilar 2", in Japanese patients who developed neutropenia in the course of cancer chemotherapy or hematopoietic stem cell transplantation. A total of 653 patients were registered during the 2-year enrollment period starting from May 2013, and 627 and 614 patients were eligible for safety and efficacy analyses of the G-CSF biosimilar, respectively. Forty-three adverse drug reactions were reported in 33 patients (5.26%). Back pain was most frequently observed and reported in 20 patients (3.19%), followed by pyrexia (1.28%) and bone pain (0.96%). Risk factors for adverse reactions identified by logistic regression analyses were younger age, presence of past medical history, and lower total dose at the onset of adverse reactions. Among the 576 cancer patients who developed Grade 2-4 neutropenia after chemotherapy, recovery to Grade 1/0 was reported in 553 patients (96%) following filgrastim biosimilar 2 treatment. The median duration of neutrophil counts below 1500/μL was 5 days. In addition, all 11 patients who underwent hematopoietic stem cell transplantation had good responses to filgrastim biosimilar 2. In conclusion, this study showed that filgrastim biosimilar 2 has a similar safety profile and comparable effects to the original G-CSF product in the real world clinical setting. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Alcohol and prescription drug safety in older adults

    Directory of Open Access Journals (Sweden)

    Zanjani F

    2013-02-01

    Full Text Available Faika Zanjani,1,2 Aasha I Hoogland,1 Brian G Downer11Department of Gerontology, 2Building Interdisciplinary Research Careers in Women's Health University of Kentucky, Lexington, KY, USABackground: The objectives of this study were to investigate older adults' knowledge of prescription drug safety and interactions with alcohol, and to identify pharmacists' willingness to disseminate prescription drug safety information to older adults.Methods: The convenience sample consisted of 48 older adults aged 54–89 years who were recruited from a local pharmacy and who completed surveys addressing their alcohol consumption, understanding of alcohol and prescription drug interactions, and willingness to change habits regarding alcohol consumption and prescription drugs. To address pharmacist willingness, 90 pharmacists from local pharmacies volunteered and answered questions regarding their willingness to convey prescription drug safety information to older adults.Results: Older adults reported low knowledge of alcohol and prescription drug safety, with women tending to be slightly more knowledgeable. More importantly, those who drank in the previous few months were less willing to talk to family and friends about how alcohol can have harmful interactions with prescription drugs, or to be an advocate for safe alcohol and prescription drug use than those who had not had a drink recently. Pharmacists reported that they were willing to convey prescription drug safety information to older adults via a variety of formats, including displaying or distributing a flyer, and directly administering a brief intervention.Conclusion: In this study, older adults were found to have inadequate knowledge of prescription drug safety and interactions with alcohol, but pharmacists who regularly come in contact with older adults indicated that they were ready and willing to talk to older adults about prescription drug safety. Future research should focus on interventions

  2. Safety and Effectiveness of Natalizumab: First Report of Interim Results of Post-Marketing Surveillance in Japan.

    Science.gov (United States)

    Saida, Takahiko; Yokoyama, Kazumasa; Sato, Ryusuke; Makioka, Haruki; Iizuka, Yukihiko; Hase, Masakazu; Ling, Yan; Torii, Shinichi

    2017-12-01

    Natalizumab, a humanized anti-α4 integrin monoclonal antibody, received marketing approval in Japan in 2014 for the treatment of multiple sclerosis (MS). Because the previous large-scale clinical trials of natalizumab were mainly conducted in Europe and North American countries, and data in patients with MS from Japan were limited, we conducted an all-case post-marketing surveillance of natalizumab-treated MS patients from Japan to investigate the safety and effectiveness of natalizumab in a real-world clinical setting in Japan. Here, we report the results of an interim analysis. During the observation period of 2 years, all patients who were treated with natalizumab subsequent to its approval in Japan were followed. The effectiveness of natalizumab was assessed by examining the changes in expanded disability status scale (EDSS) score and annualized relapse rate (ARR) from baseline. Safety was assessed by analyzing the incidence of adverse drug reactions (ADRs). The safety analysis included 106 patients (mean age 39.3 years; women 62.3%) whose data were collected until the data lock point (February 7, 2016). The effectiveness analysis included 75 patients. The majority of patients had relapsing-remitting MS (93/106 patients; 87.7%). The mean length of treatment exposure in the present study was 6.6 months. During the 2-year observation period, no significant change in the EDSS was observed, while the ARR decreased significantly from baseline (72.9% reduction, p = 0.001). ADRs and serious ADRs were observed in 11.3% and 3.8% of patients, respectively; however, no new safety concerns were detected. No patient had progressive multifocal leukoencephalopathy (PML) during the present study period. The safety and effectiveness of natalizumab were confirmed in Japanese patients with MS in clinical practice. Nevertheless, potential risks including PML require continuous, careful observation. Biogen Japan Ltd (Tokyo, Japan).

  3. An exploration of counterfeit medicine surveillance strategies guided by geospatial analysis: lessons learned from counterfeit Avastin detection in the US drug supply chain.

    Science.gov (United States)

    Cuomo, Raphael E; Mackey, Tim K

    2014-12-02

    To explore healthcare policy and system improvements that would more proactively respond to future penetration of counterfeit cancer medications in the USA drug supply chain using geospatial analysis. A statistical and geospatial analysis of areas that received notices from the Food and Drug Administration (FDA) about the possibility of counterfeit Avastin penetrating the US drug supply chain. Data from FDA warning notices were compared to data from 44 demographic variables available from the US Census Bureau via correlation, means testing and geospatial visualisation. Results were interpreted in light of existing literature in order to recommend improvements to surveillance of counterfeit medicines. This study analysed 791 distinct healthcare provider addresses that received FDA warning notices across 30,431 zip codes in the USA. Statistical outputs were Pearson's correlation coefficients and t values. Geospatial outputs were cartographic visualisations. These data were used to generate the overarching study outcome, which was a recommendation for a strategy for drug safety surveillance congruent with existing literature on counterfeit medication. Zip codes with greater numbers of individuals age 65+ and greater numbers of ethnic white individuals were most correlated with receipt of a counterfeit Avastin notice. Geospatial visualisations designed in conjunction with statistical analysis of demographic variables appeared more capable of suggesting areas and populations that may be at risk for undetected counterfeit Avastin penetration. This study suggests that dual incorporation of statistical and geospatial analysis in surveillance of counterfeit medicine may be helpful in guiding efforts to prevent, detect and visualise counterfeit medicines penetrations in the US drug supply chain and other settings. Importantly, the information generated by these analyses could be utilised to identify at-risk populations associated with demographic characteristics

  4. Safety and effectiveness of rapid-acting intramuscular olanzapine for agitation associated with schizophrenia – Japan postmarketing surveillance study

    Directory of Open Access Journals (Sweden)

    Katagiri H

    2018-01-01

    Full Text Available Hideaki Katagiri,1 Masanori Taketsuna,2 Shinpei Kondo,3 Kenta Kajimoto,4 Etsuko Aoi,5 Yuka Tanji1 1Bio Medicine, 2Statistical Sciences, 3Post Marketing Study Management, 4Scientific Communications, Medicines Development Unit Japan, 5Global Patient Safety Japan, Quality and Patient Safety, Eli Lilly Japan K.K., Kobe, Japan Objective: The objective of this study was to evaluate the safety and effectiveness of rapid-acting intramuscular (IM olanzapine in the treatment of acute agitation associated with schizophrenia in real-world clinical settings in Japan.Methods: In this multicenter, postmarketing surveillance (PMS study, patients with acute agitation associated with schizophrenia were treated with IM olanzapine daily in a daily clinical setting. The observational period ranged from 1 to 7 days, including the day of initial administration. Safety was assessed by reporting treatment-emergent adverse events (TEAEs and adverse drug reactions (ADRs. The Positive and Negative Syndrome Scale – Excited Component (PANSS-EC score was used to evaluate effectiveness at baseline and at 2 hours (after each administration, 2 days, and 3 days (end of the observational period from the last administration of the IM olanzapine injection.Results: The safety analysis set included 999 patients, and the initial dose of 10 mg was administered to 955 patients. TEAEs were reported in 28 patients (36 events, the most common of which were dyslalia (5 patients, akathisia and somno­lence (4 patients each, hepatic function abnormal (3 patients, and constipation and dehydration (2 patients each. One serious adverse event of akathisia occurred during the observation period. The PANSS-EC score (mean ± standard deviation was 23.3±6.4 (n=625 at baseline, 16.9±7.0 (n=522 at 2 hours after initial injection, and 14.9±6.5 (n=650 at the last observation carried forward.Conclusion: The results of this Japanese PMS study demonstrated that IM olanzapine is safe and has a

  5. Clinical and molecular surveillance of drug resistant vivax malaria in Myanmar (2009-2016).

    Science.gov (United States)

    Nyunt, Myat Htut; Han, Jin-Hee; Wang, Bo; Aye, Khin Myo; Aye, Kyin Hla; Lee, Seong-Kyun; Htut, Ye; Kyaw, Myat Phone; Han, Kay Thwe; Han, Eun-Taek

    2017-03-16

    One of the major challenges for control and elimination of malaria is ongoing spread and emergence of drug resistance. While epidemiology and surveillance of the drug resistance in falciparum malaria is being explored globally, there are few studies on drug resistance vivax malaria. To assess the spread of drug-resistant vivax malaria in Myanmar, a multisite, prospective, longitudinal study with retrospective analysis of previous therapeutic efficacy studies, was conducted. A total of 906 from nine study sites were included in retrospective analysis and 208 from three study sites in prospective study. Uncomplicated vivax mono-infected patients were recruited and monitored with longitudinal follow-up until day 28 after treatment with chloroquine. Amplification and sequence analysis of molecular markers, such as mutations in pvcrt-O, pvmdr1, pvdhps and pvdhfr, were done in day-0 samples in prospective study. Clinical failure cases were found only in Kawthaung, southern Myanmar and western Myanmar sites within 2009-2016. Chloroquine resistance markers, pvcrt-O 'AAG' insertion and pvmdr1 mutation (Y976F) showed higher mutant rate in southern and central Myanmar than western site: 66.7, 72.7 vs 48.3% and 26.7, 17.0 vs 1.7%, respectively. A similar pattern of significantly higher mutant rate of antifolate resistance markers, pvdhps (S382A, K512M, A553G) and pvdhfr (F57L/I, S58R, T61M, S117T/N) were noted. Although clinical failure rate was low, widespread distribution of chloroquine and antifolate resistance molecular makers alert to the emergence and spread of drug resistance vivax malaria in Myanmar. Proper strategy and action plan to eliminate and contain the resistant strain strengthened together with clinical and molecular surveillance on drug resistance vivax is recommended.

  6. Enabling social listening for cardiac safety monitoring: Proceedings from a drug information association-cardiac safety research consortium cosponsored think tank.

    Science.gov (United States)

    Seifert, Harry A; Malik, Raleigh E; Bhattacharya, Mondira; Campbell, Kevin R; Okun, Sally; Pierce, Carrie; Terkowitz, Jeffrey; Turner, J Rick; Krucoff, Mitchell W; Powell, Gregory E

    2017-12-01

    This white paper provides a summary of the presentations and discussions from a think tank on "Enabling Social Listening for Cardiac Safety Monitoring" trials that was cosponsored by the Drug Information Association and the Cardiac Safety Research Consortium, and held at the White Oak headquarters of the US Food and Drug Administration on June 3, 2016. The meeting's goals were to explore current methods of collecting and evaluating social listening data and to consider their applicability to cardiac safety surveillance. Social listening is defined as the act of monitoring public postings on the Internet. It has several theoretical advantages for drug and device safety. First, these include the ability to detect adverse events that are "missed" by traditional sources and the ability to detect adverse events sooner than would be allowed by traditional sources, both by affording near-real-time access to data from culturally and geographically diverse sources. Social listening can also potentially introduce a novel patient voice into the conversation about drug safety, which could uniquely augment understanding of real-world medication use obtained from more traditional methodologies. Finally, it can allow for access to information about drug misuse and diversion. To date, the latter 2 of these have been realized. Although regulators from the Food and Drug Administration and the United Kingdom's Medicines and Healthcare Products Regulatory Agency participated in the think tank along with representatives from industry, academia, and patient groups, this article should not be construed to constitute regulatory guidance. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Laboratory-Based Surveillance of Extensively Drug-Resistant Tuberculosis in Eastern China.

    Science.gov (United States)

    Huang, Yu; Wu, Qingqing; Xu, Shuiyang; Zhong, Jieming; Chen, Songhua; Xu, Jinghang; Zhu, Liping; He, Haibo; Wang, Xiaomeng

    2017-03-01

    With 25% of the global burden, China has the highest incidence of drug-resistant tuberculosis (TB) in the world. However, surveillance data on extensively drug-resistant TB (XDR-TB) from China are scant. To estimate the prevalence of XDR-TB in Zhejiang, Eastern China, 30 of 90 TB treatment centers in Zhejiang were recruited. Patients with suspected TB who reported to the clinics for diagnosis were requested to undergo a smear sputum test. Positive sputum samples were tested for drug susceptibility. Data on anti-TB drug resistance from 1999 to 2008 were also collected to assess drug resistance trends. A total of 931 cases were recruited for drug susceptibility testing (DST). Among these, 23.6% (95% confidence interval [CI], 18.8-24.4) were resistant to any of the following drugs: isoniazid, rifampin, streptomycin, and ethambutol. Multidrug resistant (MDR) strains were identified in 5.1% of all cases (95% CI, 3.61-6.49). Among MDR-TB cases, 6.4% were XDR (95% CI, 1.7-18.6) and 8.9% (95% CI, 7.0-10.8) of all cases were resistant to either isoniazid or rifampin (but not both). Among MDR-TB cases, 23.4% (95% CI, 12.8-38.4) were resistant to either fluoroquinolones or a second-line anti-TB injectable drug, but not both. From 1999 to 2014, the percentage of MDR cases decreased significantly, from 8.6% to 5.1% (p = 0.00). The Global Fund to Fight TB program showed signs of success in Eastern China. However, drug-resistant TB, MDR-TB, and XDR-TB still pose a challenge for TB control in Eastern China. High-quality directly observed treatment, short-course, and universal DST for TB cases to determine appropriate treatment regimens are urgently needed to prevent acquired drug resistance.

  8. 77 FR 2606 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2012-01-18

    ... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID PHMSA-2012-0004] Pipeline Safety: Random Drug Testing Rate AGENCY: Pipeline and Hazardous Materials... pipelines and operators of liquefied natural gas facilities must select and test a percentage of covered...

  9. 75 FR 9018 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2010-02-26

    ... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID PHMSA-2010-0034] Pipeline Safety: Random Drug Testing Rate AGENCY: Pipeline and Hazardous Materials... pipelines and operators of liquefied natural gas facilities must select and test a percentage of covered...

  10. Enhancing Seasonal Influenza Surveillance: Topic Analysis of Widely Used Medicinal Drugs Using Twitter Data.

    Science.gov (United States)

    Kagashe, Ireneus; Yan, Zhijun; Suheryani, Imran

    2017-09-12

    Uptake of medicinal drugs (preventive or treatment) is among the approaches used to control disease outbreaks, and therefore, it is of vital importance to be aware of the counts or frequencies of most commonly used drugs and trending topics about these drugs from consumers for successful implementation of control measures. Traditional survey methods would have accomplished this study, but they are too costly in terms of resources needed, and they are subject to social desirability bias for topics discovery. Hence, there is a need to use alternative efficient means such as Twitter data and machine learning (ML) techniques. Using Twitter data, the aim of the study was to (1) provide a methodological extension for efficiently extracting widely consumed drugs during seasonal influenza and (2) extract topics from the tweets of these drugs and to infer how the insights provided by these topics can enhance seasonal influenza surveillance. From tweets collected during the 2012-13 flu season, we first identified tweets with mentions of drugs and then constructed an ML classifier using dependency words as features. The classifier was used to extract tweets that evidenced consumption of drugs, out of which we identified the mostly consumed drugs. Finally, we extracted trending topics from each of these widely used drugs' tweets using latent Dirichlet allocation (LDA). Our proposed classifier obtained an F 1 score of 0.82, which significantly outperformed the two benchmark classifiers (ie, Pstrategies for mitigating the severity of seasonal influenza outbreaks. The proposed methods can be extended to the outbreaks of other diseases. ©Ireneus Kagashe, Zhijun Yan, Imran Suheryani. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 12.09.2017.

  11. Safety and efficacy of adapalene gel 0.1% in acne vulgaris: Results of a post-marketing surveillance study

    Directory of Open Access Journals (Sweden)

    Percy S

    2003-07-01

    Full Text Available Introduction: Adapalene is a novel retinoid indicated for the topical treatment of acne vulgaris. The drug was introduced in India in 2001. Aims: A post-marketing surveillance study was conducted to assess the safety and efficacy of adapalene gel 0.1% when used as monotherapy or in combination with other anti-acne agents in Indian patients of acne vulgaris. Material and Methods: A 12-week, multicentre, open-label, non-comparative study involving 571 patients from 21 centers across India was conducted between January and September of 2002. Concomitant prescription of other anti-acne drugs was permitted, if needed. Results: Of the 571 patients, 441 completed the treatment as per protocol. At the end of therapy, 96.3% of patients showed an improvement in their acne from baseline, with greater than 75% improvement seen in two-thirds of patients. Adverse events were reported in 24% of the patients, none of which were serious. The tolerability of therapy was rated as excellent/good in 81% of patients by physicians and in 78% by the patients. Conclusion: Adapalene gel 0.1% is a safe and effective topical agent in the treatment of mild to moderate acne vulgaris in Indian patients. It may be safely combined with other topical and oral anti-acne agents.

  12. Determining animal drug combinations based on efficacy and safety.

    Science.gov (United States)

    Kratzer, D D; Geng, S

    1986-08-01

    A procedure for deriving drug combinations for animal health is used to derive an optimal combination of 200 mg of novobiocin and 650,000 IU of penicillin for nonlactating cow mastitis treatment. The procedure starts with an estimated second order polynomial response surface equation. That surface is translated into a probability surface with contours called isoprobs. The isoprobs show drug amounts that have equal probability to produce maximal efficacy. Safety factors are incorporated into the probability surface via a noncentrality parameter that causes the isoprobs to expand as safety decreases, resulting in lower amounts of drug being used.

  13. Drug-induced lung injury associated with sorafenib: analysis of all-patient post-marketing surveillance in Japan.

    Science.gov (United States)

    Horiuchi-Yamamoto, Yuka; Gemma, Akihiko; Taniguchi, Hiroyuki; Inoue, Yoshikazu; Sakai, Fumikazu; Johkoh, Takeshi; Fujimoto, Kiminori; Kudoh, Shoji

    2013-08-01

    Sorafenib is a multi-kinase inhibitor currently approved in Japan for unresectable and/or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma. Although drug-induced lung injury has recently been the focus of interest in Japanese patients treated with molecular targeting agents, the clinical features of patients receiving sorafenib remain to be completely investigated. All-patient post-marketing surveillance data was obtained within the frame of Special Drug Use Investigation; between April 2008 and March 2011, we summarized the clinical information of 62 cases with drug-induced lung injury among approximately 13,600 sorafenib-treated patients in Japan. In addition, we summarized the results of evaluation by a safety board of Japanese experts in 34 patients in whom pulmonary images were available. For the calculation of reporting frequency, interim results of Special Drug Use Investigation were used. In the sets of completed reports (2,407 in renal cell carcinoma and 647 in hepatocellular carcinoma), the reporting frequency was 0.33 % (8 patients; fatal, 4/8) and 0.62 % (4 patients; fatal, 2/4), respectively. Major clinical symptoms included dyspnea, cough, and fever. Evaluation of the images showed that 18 cases out of 34 patients had a pattern of diffuse alveolar damage. The patients with hepatocellular carcinoma showed a greater incidence and earlier onset of lung injury than those with renal cell carcinoma. Although the overall reporting frequency of sorafenib-induced lung injury is not considered high, the radiological diffuse alveolar damage pattern led to a fatal outcome. Therefore, early recognition of sorafenib-induced lung injury is crucial for physicians and patients.

  14. Adverse drug reaction and concepts of drug safety in Ayurveda: An overview

    Science.gov (United States)

    Ajanal, Manjunath; Nayak, Shradda; Prasad, Buduru Sreenivasa; Kadam, Avinash

    2013-01-01

    Drug safety is a very basic and fundamental concept in medical practice. ADRs play an important role in assessing patient safety in any system of medicine. Pharmacovigilance study is thus significant to understand treatment outcomes. Current raised issue with respect to complementary and alternative system medicine (CAM) like Ayurveda is increased in number of safety reports along with report misinterpretation; this generates the negative impact on system. Although, Ayurveda which is holistic system of medicine from India has elaborated the causes and methods of drug-induced consequences along with preventive measures the available data in classical texts is scattered. The compilation and analysis along with modern concept drug safety is need of the hour. Present literature review was conducted from various compendium of Ayurveda and electronic data base with search terms of ‘Vyapad’, ‘Viruddha’, ‘Ahita’, ‘herb–herb interaction’, ‘idiosyncrasy’, ‘Prakritiviruddha’ etc. The reported information was analysed for the possible correlation on concept of ADR and Pharmacovigilance of current science. Overall review demonstrated that drug interaction, iatrogenic, over dose, administration of unsuitable drugs, reprehensive drug administration with respect to disease, complication from five procedural therapies (Panchakarma) and reprehensible preparation of mineral drug are nearer to the modern causes of ADR. Thus, concept of drug safety and ADR is not new to the Ayurveda. The concept “Drug which is not appropriate to be used as medicine”(Abheshaja) of Ayurveda sounds similar as that of modern pharmacovigilance. PMID:24563588

  15. Probabilistic approaches to LCO's and surveillance requirements for standby safety systems

    International Nuclear Information System (INIS)

    Lofgren, E.V.; Varcolik, F.

    1982-11-01

    Results are presented for a comprehensive analysis of risk-based methods for establishing Limiting Conditions for Operation (LCO) and surveillance requirements for on-line test and repair of nuclear power plant safety system components. Limiting Conditions for Operation refers to the legal constraint on safety system component outage times that are imposed by the NRC as part of the reactor operating license. Generally, when a safety system component is removed for repair or test for a period of time there is a period of increased vulnerability concerning the probability that the affected safety system will be available to mitigate an accident. This period of increased vulnerability exists until the component is restored to service. The constraint on the duration of this period, the allowed outage time (AOT), is the aspect of LCOs that is of interest here. In particular, methods are reviewed and developed that relate measures of risk to the AOT. Only by explicitly relating risk to AOT can outage times be constrained by placing limits on risk. Methods developed for relating risk measures to outage times are presented. The review and analysis of risk related methods for establishing LCOs are described

  16. Drug safety in pregnancy - monitoring congenital anomalies

    NARCIS (Netherlands)

    Morgan, Margery; De Jong-Van Den Berg, Lolkje T. W.; Jordan, Sue

    Aim This paper outlines research into the causes of congenital anomalies, and introduces a pan-European study. The potential roles of nurses and midwives in this area are illustrated by a case report. Background Since the thalidomide disaster, use of drugs in pregnancy has been carefully monitored

  17. 78 FR 20327 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2013-04-04

    ... Management Advisory Committee; Amendment of Notice AGENCY: Food and Drug Administration, HHS. ACTION: Notice... of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management... Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee...

  18. [Drug surveillance and adverse reactions to drugs. The literature and importance of historical data].

    Science.gov (United States)

    Mariani, L; Minora, T; Ventresca, G P

    1996-12-01

    The authors highlight the essential role of pharmacovigilance and the need for a simple, efficient and low-cost system of adverse reaction (AR) reporting which could cover the whole population and all marketed drugs, and suggest that the only one presently viable is based on spontaneous reporting. To support their proposal the authors provide a definition of AR and of the different monitoring system, and list as many drugs as possible to find in the literature that have been associated with a specific AR, together with the active molecule, the therapeutic indication, the features of the AR and the regulatory actions (withdrawal from the market, restriction of use). Moreover, by describing the "history" behind some of these drugs the authors highlight the contribution that pharmacovigilance and spontaneous reporting have had to the development of regulations for approval and marketing of new drugs. It is also highlighted how some of these unexpected events (thalidomide, DES) have had a significant and important contribution to pharmacological and toxicological knowledge.

  19. Sentinel surveillance of HIV-1 transmitted drug resistance, acute infection and recent infection.

    Directory of Open Access Journals (Sweden)

    Hong-Ha M Truong

    Full Text Available HIV-1 acute infection, recent infection and transmitted drug resistance screening was integrated into voluntary HIV counseling and testing (VCT services to enhance the existing surveillance program in San Francisco. This study describes newly-diagnosed HIV cases and characterizes correlates associated with infection.A consecutive sample of persons presenting for HIV VCT at the municipal sexually transmitted infections (STI clinic from 2004 to 2006 (N = 9,868 were evaluated by standard enzyme-linked immunoassays (EIA. HIV antibody-positive specimens were characterized as recent infections using a less-sensitive EIA. HIV-RNA pooled testing was performed on HIV antibody-negative specimens to identify acute infections. HIV antibody-positive and acute infection specimens were evaluated for drug resistance by sequence analysis. Multivariable logistic regression was performed to evaluate associations. The 380 newly-diagnosed HIV cases included 29 acute infections, 128 recent infections, and 47 drug-resistant cases, with no significant increases or decreases in prevalence over the three years studied. HIV-1 transmitted drug resistance prevalence was 11.0% in 2004, 13.4% in 2005 and 14.9% in 2006 (p = 0.36. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI was the most common pattern detected, present in 28 cases of resistance (59.6%. Among MSM, recent infection was associated with amphetamine use (AOR = 2.67; p<0.001, unprotected anal intercourse (AOR = 2.27; p<0.001, sex with a known HIV-infected partner (AOR = 1.64; p = 0.02, and history of gonorrhea (AOR = 1.62; p = 0.03.New HIV diagnoses, recent infections, acute infections and transmitted drug resistance prevalence remained stable between 2004 and 2006. Resistance to NNRTI comprised more than half of the drug-resistant cases, a worrisome finding given its role as the backbone of first-line antiretroviral therapy in San Francisco as well as worldwide. The integration of HIV-1 drug

  20. Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP

    Directory of Open Access Journals (Sweden)

    Haeberle Anne

    2012-09-01

    Full Text Available Abstract Background For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used. Methods The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009 from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally. Results From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%, followed by valproic acid (23%, mirtazapine and venlafaxine (16% each, quetiapine (15%, lamotrigine (14% and olanzapine (13%. Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI, but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined was the most frequently prescribed drug (39%; aripiprazole was administered in 10%. Conclusion Combinations of antidepressants (SSRI, mirtazapine, venlafaxine with mood stabilizers (lithium, valproic acid, lamotrigine and / or atypical antipsychotics (quetiapine, olanzapine are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines.

  1. Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

    Science.gov (United States)

    Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

    2017-01-01

    Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Safety learning from drugs of the same class

    DEFF Research Database (Denmark)

    Stefansdottir, G; Knol, M J; Arnardottir, A H

    2012-01-01

    This study was aimed at assessing the extent of safety learning from data pertaining to other drugs of the same class. We studied drug classes for which the first and second drugs were centrally registered in the European Union from 1995 to 2008. We assessed whether adverse drug reactions (ADRs......) associated with one of the drugs also appeared in the Summary of Product Characteristics (SPC) of the other drug, either initially or during the postmarketing phase. We identified 977 ADRs from 19 drug pairs, of which 393 ADRs (40.2%) were listed in the SPCs of both drugs of a pair. Of these 393 that were...... present in both SPCs of a drug pair, 241 (61.3%) were present when the drug entered the market and 152 (30.7%) appeared in the postmarketing phase. The mention of ADRs in the SPCs of both same-class drugs in the postmarketing phase was associated with type A ADRs, marketing in the same regulator country...

  3. Trust in the pharmaceutical sector : Analysis of drug safety controversies by means of drug life cycles

    NARCIS (Netherlands)

    Hernández, J.F.

    2015-01-01

    Before obtaining a marketing approval, the efficacy and safety profile of drugs is studied in specific populations and under well-controlled circumstances. After marketing approval, the drug is made available and used in ‘real world conditions’, which are known to deviate from the trial setting.

  4. Drug research methodology. Volume 2, The identification of drugs of interest in highway safety

    Science.gov (United States)

    1980-03-01

    This report presents findings of a workshop on the identification of drugs that should be the focus of near-term highway safety research. Drugs of interest are those that have a potential to increase the likelihood of traffic crashes and their attend...

  5. Can surveillance systems identify and avert adverse drug events? A prospective evaluation of a commercial application.

    Science.gov (United States)

    Jha, Ashish K; Laguette, Julia; Seger, Andrew; Bates, David W

    2008-01-01

    Computerized monitors can effectively detect and potentially prevent adverse drug events (ADEs). Most monitors have been developed in large academic hospitals and are not readily usable in other settings. We assessed the ability of a commercial program to identify and prevent ADEs in a community hospital. and Measurement We prospectively evaluated the commercial application in a community-based hospital. We examined the frequency and types of alerts produced, how often they were associated with ADEs and potential ADEs, and the potential financial impact of monitoring for ADEs. Among 2,407 patients screened, the application generated 516 high priority alerts. We were able to review 266 alerts at the time they were generated and among these, 30 (11.3%) were considered substantially important to warrant contacting the physician caring for the patient. These 30 alerts were associated with 4 ADEs and 11 potential ADEs. In all 15 cases, the responsible physician was unaware of the event, leading to a change in clinical care in 14 cases. Overall, 23% of high priority alerts were associated with an ADE (95% confidence interval [CI] 12% to 34%) and another 15% were associated with a potential ADE (95% CI 6% to 24%). Active surveillance used approximately 1.5 hours of pharmacist time daily. A commercially available, computer-based ADE detection tool was effective at identifying ADEs. When used as part of an active surveillance program, it can have an impact on preventing or ameliorating ADEs.

  6. [Safety and efficacy of docetaxel in prostate cancer patients: based on the post-marketing surveillance in Japan].

    Science.gov (United States)

    Mera, Takeshi; Saijo, Nagahiro; Akaza, Hideyuki

    2012-04-01

    The safety and efficacy of docetaxel in prostate cancer were evaluated based on the results of post-marketing surveillance. 149 patients were enrolled between September 2008 and May 2010. The starting dose of docetaxel was 75 mg/m² in 53 patients(36%), 70 mg/m² in 55 (37%), and ≤ 60 mg/m² in 41(28%). The median number of treatment cycles was 8 (range, 1 to 10). There was no age difference observed in the starting doses and the treatment cycles. The most common ≥ grade 3 adverse drug reactions (ADRs) were neutropenia (71%)and leukocytopenia (51%), and they occurred more frequently in patients receiving ≥ 70 mg/m². However, the multi-variate analyses revealed that ≥ grade 3 ADRs did not correlate with the starting doses. Infection-related events (≥ grade 3) and interstitial pneumonia were observed in 15% and 1% of patients, respectively. Prostate-specific-antigen (PSA) flare appeared in 19% of 95 evaluable patients at median period of 26 days from treatment initiation. It continued with median duration of 39. 5 days. PSA response rate as defined ≥ 50% level decline was 37%(95%confidence interval: 27-47) in evaluable patients. It was low in patients receiving ≤ 60 mg/m² (18%). There was no notable difference between patients with initial dose of 75 and 70 mg/m². Further investigation for the longer term is warranted.

  7. Population Genetics and Drug Resistance Markers: An Essential for Malaria Surveillance in Pakistan

    International Nuclear Information System (INIS)

    Raza, A.; Beg, M.A.

    2013-01-01

    Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of malaria cases in Pakistan. However, baseline epidemiological data on P. vivax population structure and drug resistance are lacking from Pakistan. For population structure studies, molecular genetic markers, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play an important role in P. vivax survival under immune and environmental pressure. Furthermore, these genes have also been identified as suitable candidates for vaccine development. While efforts for effective vaccine are underway, anti-malarial agents remain the mainstay for control. Evidence of resistance against commonly used anti-malarial agents, particularly Sulphadoxine-Pyrimethamine (SP) is threatening to make this form of control defunct. Therefore, studies on drug resistance are necessary so that anti-malarial treatment strategies can be structured and implemented accordingly by the Malaria Control Program, Pakistan. This review aims to provide information on genetic markers of P. vivax population structure and drug resistance and comment on their usefulness in molecular surveillance and control. (author)

  8. Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

    Science.gov (United States)

    Swedberg, Michael D B

    2016-01-01

    Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

  9. Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study.

    Science.gov (United States)

    Zignol, Matteo; Cabibbe, Andrea Maurizio; Dean, Anna S; Glaziou, Philippe; Alikhanova, Natavan; Ama, Cecilia; Andres, Sönke; Barbova, Anna; Borbe-Reyes, Angeli; Chin, Daniel P; Cirillo, Daniela Maria; Colvin, Charlotte; Dadu, Andrei; Dreyer, Andries; Driesen, Michèle; Gilpin, Christopher; Hasan, Rumina; Hasan, Zahra; Hoffner, Sven; Hussain, Alamdar; Ismail, Nazir; Kamal, S M Mostofa; Khanzada, Faisal Masood; Kimerling, Michael; Kohl, Thomas Andreas; Mansjö, Mikael; Miotto, Paolo; Mukadi, Ya Diul; Mvusi, Lindiwe; Niemann, Stefan; Omar, Shaheed V; Rigouts, Leen; Schito, Marco; Sela, Ivita; Seyfaddinova, Mehriban; Skenders, Girts; Skrahina, Alena; Tahseen, Sabira; Wells, William A; Zhurilo, Alexander; Weyer, Karin; Floyd, Katherine; Raviglione, Mario C

    2018-03-21

    In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis. Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing. Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87-94) for rpoB (rifampicin resistance), 86% (74-93) for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA (pyrazinamide resistance), 85% (77-91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81-92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing. Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation. Bill & Melinda

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

    Science.gov (United States)

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

    2016-10-02

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

  11. 78 FR 16271 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2013-03-14

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably...

  12. 76 FR 40735 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2011-07-11

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... East, Adelphi, MD. The conference center telephone number is: 301 985-7300. Contact Person: Kalyani...

  13. 78 FR 2677 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2013-01-14

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... before February 7, 2013. Time allotted for each presentation may be limited. If the number of registrants...

  14. 76 FR 59143 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2011-09-23

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the..., Adelphi, MD. The conference center telephone number is 301-985-7300. Contact Person: Kalyani Bhatt, Center...

  15. 75 FR 10490 - Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management...

    Science.gov (United States)

    2010-03-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management Advisory... Drug Safety and Risk Management Advisory Committee. General Function of the Committees: To provide...

  16. Exploring Machine Learning Techniques Using Patient Interactions in Online Health Forums to Classify Drug Safety

    Science.gov (United States)

    Chee, Brant Wah Kwong

    2011-01-01

    This dissertation explores the use of personal health messages collected from online message forums to predict drug safety using natural language processing and machine learning techniques. Drug safety is defined as any drug with an active safety alert from the US Food and Drug Administration (FDA). It is believed that this is the first…

  17. 77 FR 65000 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-24

    ...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide... Use (ETASU) before CDER's Drug Safety and Risk Management Advisory Committee (DSaRM). The Agency plans...

  18. 78 FR 30929 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-05-23

    ...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide... (REMS) with elements to assure safe use (ETASU) before its Drug Safety and Risk Management Advisory...

  19. 77 FR 75176 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-12-19

    ...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug... being rescheduled due to the postponement of the October 29-30, 2012, Drug Safety and Risk Management... Committee: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide...

  20. Auditable safety analysis for the surveillance and maintenance of the REDOX complex

    International Nuclear Information System (INIS)

    Cuneo, V.J.

    1997-02-01

    The Reduction-Oxidation (REDOX) Complex is an inactive surplus facility that contains two former fuel processing facilities (the 202-S Canyon Building and the 233-S Plutonium Concentration Facility) and a number of ancillary support structures. Deactivation started in 1967 and was completed in 1969 when the plant was transferred to surveillance and maintenance (S ampersand M). This document provides the auditable safety analysis (ASA) for the post-deactivation, long-term S ampersand M phase of the above grade structures of the REDOX Complex. The S ampersand M phase is conducted for the following reasons: (1) Maintain confinement of residual inventories of radioactive materials and other contaminants until the facility is ultimately dispositioned, (2) Prevent deterioration of confinement structures, (3) Respond to potential accident conditions requiring response and mitigation, (4) Provide for the safety of workers involved in the S ampersand M phase, and (5) Provide the basis for evaluation and selection of ultimate disposal alternatives. The ability of the existing facilities to withstand the effects of natural phenomena hazard events is evaluated and the active support systems used to maintain ventilation and/or prevent the spread of contamination are described. This auditable safety analysis document evaluates the routinely required S ampersand M activities (i.e., the S ampersand M of facility barriers, equipment, structures, and postings [including repair and upgrade]; measures to identify, remove, or repair damaged asbestos; measures to identify, remove, or appropriately manage existing containers of hazardous substances; and the performance of spill response measures as needed). For the REDOX Complex, the movement of cell cover blocks is also evaluated, as D-cell cover block was removed a number of years ago and should be replaced. The type and nature of the hazards presented by the REDOX Complex and the REDOX-specific controls required to maintain these

  1. Pooling, meta-analysis, and the evaluation of drug safety

    Directory of Open Access Journals (Sweden)

    Leizorovicz Alain

    2002-03-01

    Full Text Available Abstract Background The "integrated safety report" of the drug registration files submitted to health authorities usually summarizes the rates of adverse events observed for a new drug, placebo or active control drugs by pooling the safety data across the trials. Pooling consists of adding the numbers of events observed in a given treatment group across the trials and dividing the results by the total number of patients included in this group. Because it considers treatment groups rather than studies, pooling ignores validity of the comparisons and is subject to a particular kind of bias, termed "Simpson's paradox." In contrast, meta-analysis and other stratified analyses are less susceptible to bias. Methods We use a hypothetical, but not atypical, application to demonstrate that the results of a meta-analysis can differ greatly from those obtained by pooling the same data. In our hypothetical model, a new drug is compared to 1 a placebo in 4 relatively small trials in patients at high risk for a certain adverse event and 2 an active reference drug in 2 larger trials of patients at low risk for this event. Results Using meta-analysis, the relative risk of experiencing the adverse event with the new drug was 1.78 (95% confidence interval [1.02; 3.12] compared to placebo and 2.20 [0.76; 6.32] compared to active control. By pooling the data, the results were, respectively, 1.00 [0.59; 1.70] and 5.20 [2.07; 13.08]. Conclusions Because these findings could mislead health authorities and doctors, regulatory agencies should require meta-analyses or stratified analyses of safety data in drug registration files.

  2. Spillover Effects of Drug Safety Warnings on Preventive Health Care Use

    DEFF Research Database (Denmark)

    Daysal, N. Meltem; Orsini, Chiara

    2015-01-01

    We examine how new medical information on drug safety impacts preventive health care use. We exploit the release of the findings of the Women’s Health Initiative Study (WHIS) – the largest randomized controlled trial of women’s health – which demonstrated in 2002 the health risks associated...... with the long-term use of hormone replacement therapy (HRT). We first show that, after the release of the WHIS findings, HRT use dropped sharply among post-menopausal women. We then estimate the spillover effects of the WHIS findings on preventive care by means of a difference-in-differences methodology...... comparing changes in preventive care use among 60 to 69 year-old women (who have high rates of HRT use) with the change among women aged 75 and above (who have much lower rates of HRT use). Using data from the Behavioral Risk Factor Surveillance System for the period 1998–2007, we find that women aged 60...

  3. Surveillance of transmitted HIV drug resistance in antiretroviral-naive patients aged less than 25 years, in Bangkok, Thailand.

    Science.gov (United States)

    Sungkanuparph, Somnuek; Pasomsub, Ekawat; Chantratita, Wasun

    2014-01-01

    Emergence of transmitted HIV drug resistance (TDR) is a concern after global scale-up of antiretroviral therapy (ART). World Health Organization had developed threshold survey method for surveillance of TDR in resource-limited countries. ART in Thailand has been scaling up for >10 years. To evaluate the current TDR in Thailand, a cross-sectional study was conducted among antiretroviral-naive HIV-infected patients aged Thailand after a decade of rapid scale-up of ART. Interventions to prevent TDR at the population level are essentially needed in Thailand. Surveillance for TDR in Thailand has to be regularly performed.

  4. [Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

    Science.gov (United States)

    Okubo, Sumiko; Kobayashi, Noriko; Taketsuna, Masanori; Kaneko, Naoya; Enatsu, Sotaro; Nishiuma, Shinichi

    2014-04-01

    The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

  5. Auditable safety analysis for the surveillance and maintenance of the 224-B building

    International Nuclear Information System (INIS)

    Cuneo, V.J.

    1997-02-01

    The Plutonium Concentration Facility (224-B Building) is an inactive, surplus facility that operated from 1945 until 1976. This document provides the auditable safety analysis (ASA) for the post-deactivation, long-term surveillance and maintenance phase of the abovegrade structures of the 224-B Building. In this ASA, the ability of the existing facilities to withstand the effects of natural phenomena hazard events is evaluated and the support systems used to maintain ventilation and/or prevent the spread of contamination are described. The purpose of the S ampersand M phase is as follows: Maintain confinement of residual inventories of radioactive materials and other contaminants until the facility is ultimately dispositioned; Prevent deterioration of confinement structures; Respond to potential accident conditions requiring response and mitigation; Provide for the safety of workers involved in the S ampersand M phase; and Provide the basis for evaluation and selection of ultimate disposal alternatives. In this ASA, the ability of the existing facilities to withstand the effects of natural phenomena hazard (NPH) events is evaluated and the support systems used to maintain ventilation and/or prevent the spread of contamination are described. This document also evaluates S ampersand M activities that are routinely required (i.e., the S ampersand M of facility barriers, equipment, structures, and postings [including repair and upgrade]; measures to identify, remove, or repair damaged asbestos; measures to identify, remove, or appropriately manage existing containers of hazardous substances; nondestructive assay, waste characterization and sampling; and the performance of spill response measures as needed). The type and nature of the hazards presented by the 224-B Building and specific controls that are required to maintain these hazards to acceptable levels are also identified

  6. Auditable safety analysis for the surveillance and maintenance of U plant

    International Nuclear Information System (INIS)

    Cuneo, V.J.

    1997-02-01

    This document provides the auditable safety analysis for the post-deactivation, long-term surveillance and maintenance (S ampersand amp;M) phase of the U Plant. The U Plant is an inactive, surplus facility constructed in 1944 as one of three original chemical separations plants. However, U-Plant was never used for its original purpose and was eventually transferred to S ampersand amp;M. In 1957 it was converted to the tributyl phosphate process to recover uranium from the bismuth phosphate process waste. In 1958 it was placed on standby and was used to store inoperable and contaminated equipment from other facilities.This document evaluates the ability of the U Plant to withstand the effects of natural phenomena hazard events and describes the active support systems used to maintain ventilation and/or prevent the spread of contamination. This document also evaluates S ampersand amp;M activities that are routinely required (i.e., the S ampersand amp;M of facility barriers, equipment, structures, and postings [including repair and upgrade]; measures to identify, remove, or repair damaged asbestos; measures to identify, remove, or appropriately manage existing containers of hazardous substances; the performance of spill response measures as needed; and perform nondestructive assaying, waste characterization, and sampling). This document identifies the type and nature of the hazards presented by the U Plant and the specific controls that are required to maintain these hazards at acceptable levels

  7. [Post-licensure passive safety surveillance of rotavirus vaccines: reporting sensitivity for intussusception].

    Science.gov (United States)

    Pérez-Vilar, S; Díez-Domingo, J; Gomar-Fayos, J; Pastor-Villalba, E; Sastre-Cantón, M; Puig-Barberà, J

    2014-08-01

    The aims of this study were to describe the reports of suspected adverse events due to rotavirus vaccines, and assess the reporting sensitivity for intussusception. Descriptive study performed using the reports of suspected adverse events following rotavirus vaccination in infants aged less than 10 months, as registered in the Pharmacovigilance Centre of the Valencian Community during 2007-2011. The reporting rate for intussusception was compared to the intussusception rate in vaccinated infants obtained using the hospital discharge database (CMBD), and the regional vaccine registry. The adverse event reporting rate was 20 per 100,000 administered doses, with the majority (74%) of the reports being classified as non-serious. Fever, vomiting, and diarrhea were the adverse events reported more frequently. Two intussusception cases, which occurred within the first seven days post-vaccination, were reported as temporarily associated to vaccination. The reporting sensitivity for intussusception at the Pharmacovigilance Centre in the 1-7 day interval following rotavirus vaccination was 50%. Our results suggest that rotavirus vaccines have, in general, a good safety profile. Intussusception reporting to the Pharmacovigilance Centre shows sensitivity similar to other passive surveillance systems. The intussusception risk should be further investigated using well-designed epidemiological studies, and evaluated in comparison with the well-known benefits provided by these vaccines. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  8. Surveillance on The Safety and Efficacy of Ambrisentan (Volibris Tablet 2.5 mg) in Patients with Pulmonary Arterial Hypertension in Real Clinical Practice: Post-marketing Surveillance (Interim Analysis Report).

    Science.gov (United States)

    Takahashi, Tomohiko; Hayata, Satoru; Kobayashi, Akihiro; Onaka, Yuna; Ebihara, Takeshi; Hara, Terufumi

    2018-03-01

    Pulmonary arterial hypertension (PAH) is an intractable and rare disease and the accumulation of clinical evidence under real-world setting is needed. A post-marketing surveillance for the endothelin receptor antagonist ambrisentan (Volibris tablet) has been conducted by all-case investigation since September 2010. This paper is an interim report on the safety and efficacy of ambrisentan in 702 patients with PAH. PAH patients aged 15 years or older were subjected to the analysis. The safety analysis by overall cases or stratification of patient backgrounds and the efficacy analysis were investigated. Regarding patient characteristics, the 702 patients subjected to safety analysis included 543 (77.4%) women and 546 (77.8%) patients at WHO functional class II/III. The mean observational time was 392.7 days. A total of 324 adverse drug reaction (ADR) occurred in 204 (29.1%) patients. Common ADRs (≥ 2%) included anemia (4.6%), peripheral edema (4.1%), headache (3.6%), edema and face edema (2.6% each), abnormal hepatic function (2.3%), and epistaxis (2.1%). There were 82 serious ADRs occurring in 44 (6.3%) patients (385 serious adverse events in 184 (26.2%) patients). Although 11 (1.6%) interstitial lung disease (ILD) cases were reported, all were observed in patients with disease that may contribute to ILD and therefore it is difficult to assess if ambrisentan was associated with these events. There was no difference in safety in relation to the presence/absence of connective tissue disease-related PAH (CTD-PAH) or combination therapy. Among 677 patients subjected to efficacy analysis, those in whom hemodynamic status was determined before and after treatment showed improvement in the mean pulmonary arterial pressure and pulmonary vascular resistance after treatment. The interim results showed safety consistent with the known profile of ambrisentan in terms of the types and frequencies of ADRs in patients with PAH in real clinical practice, in comparison with

  9. 78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

    Science.gov (United States)

    2013-06-19

    ... inspections, and drive safety and quality throughout the supply chain. Implementation of these authorities... authorities granted to FDA under Title VII and their importance in ensuring drug safety, effectiveness, and.... FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and...

  10. Global patient safety and antiretroviral drug-drug interactions in the resource-limited setting.

    Science.gov (United States)

    Seden, Kay; Khoo, Saye H; Back, David; Byakika-Kibwika, Pauline; Lamorde, Mohammed; Ryan, Mairin; Merry, Concepta

    2013-01-01

    Scale-up of HIV treatment services may have contributed to an increase in functional health facilities available in resource-limited settings and an increase in patient use of facilities and retention in care. As more patients are reached with medicines, monitoring patient safety is increasingly important. Limited data from resource-limited settings suggest that medication error and antiretroviral drug-drug interactions may pose a significant risk to patient safety. Commonly cited causes of medication error in the developed world include the speed and complexity of the medication use cycle combined with inadequate systems and processes. In resource-limited settings, specific factors may contribute, such as inadequate human resources and high disease burden. Management of drug-drug interactions may be complicated by limited access to alternative medicines or laboratory monitoring. Improving patient safety by addressing the issue of antiretroviral drug-drug interactions has the potential not just to improve healthcare for individuals, but also to strengthen health systems and improve vital communication among healthcare providers and with regulatory agencies.

  11. Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

    Directory of Open Access Journals (Sweden)

    Jinsoo Lee

    2016-01-01

    Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.

  12. Lessons learnt from 20 years surveillance of malaria drug resistance prior to the policy change in Burkina Faso.

    Science.gov (United States)

    Tinto, Halidou; Valea, Innocent; Ouédraogo, Jean-Bosco; Guiguemdé, Tinga Robert

    2016-01-01

    The history of drug resistance to the previous antimalarial drugs, and the potential for resistance to evolve to Artemisinin-based combination therapies, demonstrates the necessity to set-up a good surveillance system in order to provide early warning of the development of resistance. Here we report a review summarizing the history of the surveillance of drug resistance that led to the policy change in Burkina Faso. The first Plasmodium falciparum Chloroquine-Resistance strain identified in Burkina Faso was detected by an in vitro test carried out in Koudougou in 1983. Nevertheless, no further cases were reported until 1987, suggesting that resistant strains had been circulating at a low prevalence before the beginning of the systematic surveillance system from 1984. We observed a marked increase of Chloroquine-Resistance in 2002-2003 probably due to the length of follow-up as the follow-up duration was 7 or 14 days before 2002 and 28 days from 2002 onwards. Therefore, pre-2002 studies have probably under-estimated the real prevalence of Chloroquine-Resistance by not detecting the late recrudescence. With a rate of 8.2% treatment failure reported in 2003, Sulfadoxine-Pyrimethamine was still efficacious for the treatment of uncomplicated malaria in Burkina Faso but this rate might rapidly increase as the result of its spreading from neighboring countries and due to its current use for both the Intermittent Preventive Treatment in pregnant women and Seasonal Malaria Chemoprophylaxis. The current strategy for the surveillance of the Artemisinin-based combination treatments resistance should build on lessons learnt under the previous period of 20 years surveillance of Chloroquine and Sulfadoxine-Pyrimethamine resistance (1994-2004). The most important aspect being to extend the number of sentinel sites so that data would be less patchy and could help understanding the dynamic of the resistance.

  13. Safety and Efficacy of Teneligliptin in Patients with Type 2 Diabetes Mellitus and Impaired Renal Function: Interim Report from Post-marketing Surveillance.

    Science.gov (United States)

    Haneda, Masakazu; Kadowaki, Takashi; Ito, Hiroshi; Sasaki, Kazuyo; Hiraide, Sonoe; Ishii, Manabu; Matsukawa, Miyuki; Ueno, Makoto

    2018-06-01

    Teneligliptin is a novel oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). Safety and efficacy of teneligliptin have been demonstrated in clinical studies; however, data supporting its use in patients with moderate or severe renal impairment are limited. This interim analysis of a post-marketing surveillance of teneligliptin, exploRing the long-term efficacy and safety included cardiovascUlar events in patients with type 2 diaBetes treated bY teneligliptin in the real-world (RUBY), aims to verify the long-term safety and efficacy of teneligliptin in Japanese patients with T2DM and impaired renal function. For this analysis, we used the data from case report forms of the RUBY surveillance between May 2013 and June 2017. The patients were classified into G1-G5 stages of chronic kidney disease according to estimated glomerular filtration rate (eGFR) at initiation of teneligliptin treatment. Safety and efficacy were evaluated in these subgroups. Patients on dialysis were also assessed. Safety was assessed from adverse drug reactions (ADRs). Glycemic control was evaluated up to 2 years after teneligliptin initiation. A total of 11,677 patients were enrolled in the surveillance and 11,425 patient case-report forms were collected for the interim analysis. The incidence of ADRs in each subgroup was 2.98-6.98% of patients, with no differences in the ADR profile (including hypoglycemia and renal function ADRs) between subgroups. At 1 and 2 years after starting teneligliptin, the least-squares mean change in HbA1c adjusted to the baseline was - 0.68 to - 0.85% and - 0.71 to - 0.85% across the eGFR groups, respectively. Treatment with teneligliptin in patients on dialysis reduced or tended to reduce glycated albumin levels [- 2.29%, (p < 0.001) after 1 year; - 1.64%, (p = 0.064) after 2 years]. During long-term treatment, teneligliptin was generally well tolerated in patients with any stage of renal impairment from

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

    Science.gov (United States)

    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.

  15. Swiss regulatory use of databanks for nuclear power plant life management, surveillance and safety analyses

    International Nuclear Information System (INIS)

    Tipping, Ph.; Beutler, R.; Schoen, G.; Noeggerath, J.

    2002-01-01

    Full text: As operational time is accumulated, the overall safety and performance of nuclear power plants (NPPs) will tend to be characterised by those areas in which structures, systems and components (SSCs) have not performed as well, or as reliably, as expected. The reasons for non-availability of equipment in NPPs due to SSC material malfunction or unsatisfactory performance, leading to events or even accidents, are varied and they must be analysed in order to obtain the root causes. Once the root causes are identified, corresponding measures can be applied in order to improve reliability and therefore safety. The root cause information obtained, if brought into user-friendly databanks (DBs), can be used to follow NPP performance trends, to check whether a repair or replacement has been effective, to focus regulatory attention and NPP surveillance on known weak-spots and to serve as an advance indicator where potential problems may arise. Using the DBs, similar occurrences of failures or problems in other NPPs can be identified and generic issues recognised early on and preventative action taken. The following describes the Swiss Federal Nuclear Safety Inspectorate's (HSK) DB concepts for keeping track of NPP safety and lifetime management issues. Typical sources of data for the Inspectorate's DBs are, for example, the IAEA/NEA Incident Reporting System (IRS) reports, US-NRC Generic Letters, the Swiss NPP's own reports (monthly, annual and normal outage) and, more importantly, the document that these NPPs must issue to the Inspectorate whenever a reportable event takes place. Specifically, the reporting of events in the NPPs is laid down in the Inspectorate's Guideline (R-15 'Reporting Guideline Concerning The Operation of Nuclear Power Plants'). In this Guideline, reportable events are defined and the criteria for assessing the degree of importance or impact on nuclear safety are given. In this manner, a standard and consistent approach to data collection is

  16. Observational Pharmacoepidemiology in the Drug Safety and Effectiveness Evaluation

    Directory of Open Access Journals (Sweden)

    José Cabrita

    2017-04-01

    Full Text Available Observational epidemiological studies have been used in the medicines context for more than 40 years, contributing to characterize drug use patterns and safety, efficacy and effectiveness profiles. Its use has been increased in recognition of the clinical trials limitations to assess the therapeutic and iatrogenic potential of the medicines after its commercialization. The evolution of the regulatory framework for pharmacovigilance, requiring post-marketing studies, post-authorization safety studies (PASS and the post-authorization efficacy studies (PAES to approve certain drugs, reinforced the importance of observational pharmacoepidemiology for the characterization of the medicines safety and effectiveness profiles. Pharmacoepidemiological research can be carried out from field studies designed to obtain the necessary information or in databases with health records of population samples that already contain the information. This 2nd option is more efficient and more and more frequent. Although, observational research from field studies continues to have its space, the increasing availability of databases allowed a new development to observational pharmacoepidemiology. Indeed, access to automated records databases with up-to-date information on medical prescriptions and global health care to representative population samples with long follow-up periods is a valuable tool for the study of drug use patterns and therapeutic and iatrogenic potential in routine clinical practice. In this context, observational pharmacoepidemiology reinforces its role as a scientific area particularly suitable for evaluating the safety and the effectiveness of the medicines in the “real world”, making a relevant contribution to overcome the gap in translating the evidence from the clinical trials for clinical practice.

  17. 75 FR 23782 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-05-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide...

  18. Nursing assessment of continuous vital sign surveillance to improve patient safety on the medical/surgical unit.

    Science.gov (United States)

    Watkins, Terri; Whisman, Lynn; Booker, Pamela

    2016-01-01

    Evaluate continuous vital sign surveillance as a tool to improve patient safety in the medical/surgical unit. Failure-to-rescue is an important measure of hospital quality. Patient deterioration is often preceded by changes in vital signs. However, continuous multi-parameter vital sign monitoring may decrease patient safety with an abundance of unnecessary alarms. Prospective observational study at two geographically disperse hospitals in a single hospital system. A multi-parameter vital sign monitoring system was installed in a medical/surgical unit in Utah and one in Alabama providing continuous display of SpO2, heart rate, blood pressure and respiration rate on a central station. Alarm thresholds and time to alert annunciations were set based on prior analysis of the distribution of each vital sign. At the end of 4 weeks, nurses completed a survey on their experience. An average alert per patient, per day was determined retrospectively from the saved vital signs data and knowledge of the alarm settings. Ninety-two per cent of the nurses agreed that the number of alarms and alerts were appropriate; 54% strongly agreed. On average, both units experienced 10·8 alarms per patient, per day. One hundred per cent agreed the monitor provided valuable patient data that increased patient safety; 79% strongly agreed. Continuous, multi-parameter patient monitoring could be performed on medical/surgical units with a small and appropriate level of alarms. Continuous vital sign assessment may have initiated nursing interventions that prevented failure-to-rescue events. Nurses surveyed unanimously agreed that continuous vital sign surveillance will help enhance patient safety. Nursing response to abnormal vital signs is one of the most important levers in patient safety, by providing timely recognition of early clinical deterioration. This occurs through diligent nursing surveillance, involving assessment, interpretation of data, recognition of a problem and meaningful

  19. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

    Science.gov (United States)

    2010-09-29

    The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

  20. Safety of diabetes drugs in patients with heart failure.

    Science.gov (United States)

    Carrasco-Sánchez, F J; Ostos-Ruiz, A I; Soto-Martín, M

    2018-03-01

    Heart failure (HF) and diabetes mellitus are 2 clinical conditions that often coexist, particularly in patients older than 65 years. Diabetes mellitus promotes the development of HF and confers a poorer prognosis. Hypoglycaemic agents (either by their mechanism of action, hypoglycaemic action or adverse effects) can be potentially dangerous for patients with HF. In this study, we performed a review of the available evidence on the safety of diabetes drugs in HF, focused on the main observational and experimental studies. Recent studies on cardiovascular safety have evaluated, although as a secondary objective, the impact of new hypoglycaemic agents on HF, helping us understand the neutrality, risks and potential benefits of these agents. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  1. Low-cost ultra-wide genotyping using Roche/454 pyrosequencing for surveillance of HIV drug resistance.

    Directory of Open Access Journals (Sweden)

    Dawn M Dudley

    Full Text Available Great efforts have been made to increase accessibility of HIV antiretroviral therapy (ART in low and middle-income countries. The threat of wide-scale emergence of drug resistance could severely hamper ART scale-up efforts. Population-based surveillance of transmitted HIV drug resistance ensures the use of appropriate first-line regimens to maximize efficacy of ART programs where drug options are limited. However, traditional HIV genotyping is extremely expensive, providing a cost barrier to wide-scale and frequent HIV drug resistance surveillance.We have developed a low-cost laboratory-scale next-generation sequencing-based genotyping method to monitor drug resistance. We designed primers specifically to amplify protease and reverse transcriptase from Brazilian HIV subtypes and developed a multiplexing scheme using multiplex identifier tags to minimize cost while providing more robust data than traditional genotyping techniques. Using this approach, we characterized drug resistance from plasma in 81 HIV infected individuals collected in São Paulo, Brazil. We describe the complexities of analyzing next-generation sequencing data and present a simplified open-source workflow to analyze drug resistance data. From this data, we identified drug resistance mutations in 20% of treatment naïve individuals in our cohort, which is similar to frequencies identified using traditional genotyping in Brazilian patient samples.The developed ultra-wide sequencing approach described here allows multiplexing of at least 48 patient samples per sequencing run, 4 times more than the current genotyping method. This method is also 4-fold more sensitive (5% minimal detection frequency vs. 20% at a cost 3-5× less than the traditional Sanger-based genotyping method. Lastly, by using a benchtop next-generation sequencer (Roche/454 GS Junior, this approach can be more easily implemented in low-resource settings. This data provides proof-of-concept that next

  2. Patient Drug Safety Reporting: Diabetes Patients' Perceptions of Drug Safety and How to Improve Reporting of Adverse Events and Product Complaints.

    Science.gov (United States)

    Patel, Puja; Spears, David; Eriksen, Betina Østergaard; Lollike, Karsten; Sacco, Michael

    2018-03-01

    Global health care manufacturer Novo Nordisk commissioned research regarding awareness of drug safety department activities and potential to increase patient feedback. Objectives were to examine patients' knowledge of pharmaceutical manufacturers' responsibilities and efforts regarding drug safety, their perceptions and experiences related to these efforts, and how these factors influence their thoughts and behaviors. Data were collected before and after respondents read a description of a drug safety department and its practices. We conducted quantitative survey research across 608 health care consumers receiving treatment for diabetes in the United States, Germany, United Kingdom, and Italy. This research validated initial, exploratory qualitative research (across 40 comparable consumers from the same countries) which served to guide design of the larger study. Before reading a drug safety department description, 55% of respondents were unaware these departments collect safety information on products and patients. After reading the description, 34% reported the department does more than they expected to ensure drug safety, and 56% reported "more confidence" in the industry as a whole. Further, 66% reported themselves more likely to report an adverse event or product complaint, and 60% reported that they were more likely to contact a drug safety department with questions. The most preferred communication methods were websites/online forums (39%), email (27%), and telephone (25%). Learning about drug safety departments elevates consumers' confidence in manufacturers' safety efforts and establishes potential for patients to engage in increased self-monitoring and reporting. Study results reveal potentially actionable insights for the industry across patient and physician programs and communications.

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

    Science.gov (United States)

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

    2015-07-01

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

  4. Surveillance, Evaluation of Programmatic Management of Drug Resistant Tuberculosis (PMDT at DR-TB Centre, NITRD, New Delhi

    Directory of Open Access Journals (Sweden)

    Preeti Padda

    2018-03-01

    Full Text Available Background: PMDT was launched in 2007 in our country but drug resistant TB remains to be a public health problem. Effective surveillance is the backbone for success of any programme and true stands for PMDT. Aim & Objectives: To identify the strengths and constraints of the surveillance evaluation system. Material & Methods: A cross sectional study was conducted in January 2015 at DR-TB Centre of NITRD, New Delhi which caters to a population of 29 lacs. PMDT surveillance system was evaluated using attributes like simplicity, data quality, acceptability, positive predictive value, representativeness and timeliness defined by CDC, USA guidelines. Relevant information was collected using data abstraction form and interview with stakeholders. Data was analysed using EpiInfo 07 version. Results: Nodal officer and District TB officer are responsible for surveillance system activities of PMDT at DR-TB centre and district level, respectively. All the reports (100% were submitted on time and all the districts were reporting to DR-TB centre. 75% of TB-HIV coordinators found reporting formats to be simple but all the quarterly reports were found to be complete. Data quality was not found to be optimal. Conclusion: Private sector needs to be taken on board as they have no to minimal involvement in PMDT. For data quality improvement time to time training of medical officers and health workers should be organized.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    Aim: To assess the safety of gadobutrol administration in elderly patients (≥65 years) by comparing the incidence of adverse drug reactions (ADRs) following gadobutrol-enhanced magnetic resonance imaging (MRI) procedures in elderly patients with that in adults aged 18–64 years. Materials and methods: Safety data on gadobutrol administration from clinical trials, post-marketing surveillance (PMS) studies, and pharmacovigilance reports were collected in three databases. In each dataset, absolute and relative frequencies of ADRs between age groups were analysed, along with odds ratios and 95% confidence intervals. Logistic regression was used to identify significant influencing factors on ADRs in the PMS and pharmacovigilance data. Results: Rates of reported ADRs were lower in elderly patients versus adults aged <65 years due to a reduced incidence of non-serious ADRs; this was statistically significant for the clinical trials and pharmacovigilance populations, with a trend in the PMS database. Serious ADRs occurred infrequently in the clinical trials and PMS populations (too low for statistical comparison), and pharmacovigilance data demonstrated a low incidence (<0.005%) in both age groups. Conclusions: This evaluation involving three large databases demonstrated no greater incidence of ADRs following gadobutrol-enhanced MRI in elderly patients (≥65 years) compared with younger adults, with gadobutrol having a favourable safety profile in both age groups. -- Highlights: •First dedicated safety study of an extracellular contrast agent in the elderly. •Elderly patients experience fewer non-serious ADRs than younger adults. •Gadobutrol has a favourable safety profile in both age groups

  6. Drug research methodology. Volume 5, Experimentation in drugs and highway safety : the study of drug effects on skills related to driving

    Science.gov (United States)

    1980-06-01

    This report presents the findings of a workshop on experimental research in the area of drugs and highway safety. Complementing studies of drug use in different driving populations, experimentation here refers to studies performed under controlled co...

  7. Drug research methodology. Volume 4, Epidemiology in drugs and highway safety : the study of drug use among drivers and its role in traffic crashes

    Science.gov (United States)

    1980-06-01

    This report presents the findings of a workshop on epidemiology in drugs and highway safety. A cross-disciplinary panel of experts (1) identified methodological issues and constraints present in research to define the nature and magnitude of the drug...

  8. Radiological safety and environmental surveillance during the mining and milling of beach minerals and processing of monazite

    International Nuclear Information System (INIS)

    Pillai, P.M.B.; Khan, A.H.

    2003-01-01

    This paper highlights the occupational and environmental radiological safety aspects and surveillance activities associated with mining and milling of beach minerals and processing of monazite, based on the experience gained over more than three decades of operations of the plants of Indian Rare Earths Ltd, at Chavara (Kerala), Manavalakurichi (Tamilnadu) and Udyogamandal (Kerala). The mining of beach sands, mineral separation and chemical processing of monazite for the recovery of Th and U involve occupational radiation hazards and safety problems of varying magnitudes. This part of the front end of the nuclear fuel cycle involves average per-capita occupational exposures ranging from 1.0 mSv to 8 mSv per year. The collective doses involved work out to 4.5 to 5.4 Person Sieverts per year and involve nearly 1000 radiation workers. Internal exposure contributes to nearly half of the exposure. Mechanization of the operations, process modifications, administrative controls and constant safety surveillance have over the years helped to reduce the exposures and to maintain them at levels as low as reasonably achievable (ALARA). Environmental releases resulting from the operations are well within the limits stipulated by competent authorities and exposures to public from the mining, mineral separation and monazite processing are not significant. (author)

  9. Surveillance efforts after mass drug administration to validate elimination of lymphatic filariasis as a public health problem in Vanuatu.

    Science.gov (United States)

    Taleo, Fasihah; Taleo, George; Graves, Patricia M; Wood, Peter; Kim, Sung Hye; Ozaki, Masayo; Joseph, Hayley; Chu, Brian; Pavluck, Alex; Yajima, Aya; Melrose, Wayne; Ichimori, Kazuyo; Capuano, Corinne

    2017-01-01

    Vanuatu was formerly highly endemic for lymphatic filariasis (LF), caused by Wuchereria bancrofti and transmitted by Anopheles mosquitoes. After a baseline survey showing 4.8% antigen prevalence in 1998, the country conducted nationwide (in one implementation unit) annual mass drug administration (MDA) with albendazole and diethylcarbamazine citrate from 2000 to 2004 and achieved prevalence of 0.2% by 2006 in a representative nationwide cluster survey among all age groups. Post MDA surveillance was conducted from 2006 to 2012. After MDA, the country was divided for surveillance into three evaluation units (EUs) formed by grouping provinces according to baseline prevalence: EU1: Torba, Sanma and Malampa; EU2: Penama; EU3: Shefa and Tafea. The study compiled all past data and information on surveys in Vanuatu from the country programme. This paper reviews the surveillance activities done after stopping MDA to validate the interruption of transmission and elimination of LF as a public health problem. Post-MDA surveillance consisting of at least three transmission assessment surveys (TAS) in each of the three EUs was conducted between 2006 and 2012. Sentinel and spot check surveys identified a few villages with persistent high prevalence; all antigen positive cases in these sites were treated and additional targeted MDA conducted for 3 years in 13 villages in one area of concern. All three EUs passed all TAS in 2007, 2010 and 2012 respectively, with no positives found except in EU2 (Penama province) in 2012 when 2 children tested positive for circulating filariasis antigen. Assessment of the burden of chronic filariasis morbidity found 95 cases in 2003 and 32 remaining cases in 2007, all aged over 60 years. Vanuatu has achieved validation of elimination of LF as a public health problem. Post-validation surveillance is still recommended especially in formerly highly endemic areas.

  10. Monitoring Device Safety in Interventional Cardiology

    OpenAIRE

    Matheny, Michael E.; Ohno-Machado, Lucila; Resnic, Frederic S.

    2006-01-01

    Objective: A variety of postmarketing surveillance strategies to monitor the safety of medical devices have been supported by the U.S. Food and Drug Administration, but there are few systems to automate surveillance. Our objective was to develop a system to perform real-time monitoring of safety data using a variety of process control techniques.

  11. Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis.

    Science.gov (United States)

    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

    first DSC. ITS analyses demonstrated variability but pointed to an increase in interest around the first DSC. Chow tests were significant (PSocial 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.

  12. Prevention of prescription errors by computerized, on-line, individual patient related surveillance of drug order entry.

    Science.gov (United States)

    Oliven, A; Zalman, D; Shilankov, Y; Yeshurun, D; Odeh, M

    2002-01-01

    Computerized prescription of drugs is expected to reduce the number of many preventable drug ordering errors. In the present study we evaluated the usefullness of a computerized drug order entry (CDOE) system in reducing prescription errors. A department of internal medicine using a comprehensive CDOE, which included also patient-related drug-laboratory, drug-disease and drug-allergy on-line surveillance was compared to a similar department in which drug orders were handwritten. CDOE reduced prescription errors to 25-35%. The causes of errors remained similar, and most errors, on both departments, were associated with abnormal renal function and electrolyte balance. Residual errors remaining on the CDOE-using department were due to handwriting on the typed order, failure to feed patients' diseases, and system failures. The use of CDOE was associated with a significant reduction in mean hospital stay and in the number of changes performed in the prescription. The findings of this study both quantity the impact of comprehensive CDOE on prescription errors and delineate the causes for remaining errors.

  13. Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study).

    Science.gov (United States)

    Sakaida, Isao; Terai, Shuji; Kurosaki, Masayuki; Yasuda, Moriyoshi; Okada, Mitsuru; Bando, Kosuke; Fukuta, Yasuhiko

    2017-10-01

    Loop diuretics and spironolactone are used in patients with hepatic edema, but they are sometimes associated with insufficient responses as well as adverse events. Tolvaptan, a vasopressin type 2 receptor antagonist, was approved for hepatic edema in 2013. A large-scale post-marketing surveillance study has been carried out to evaluate the effectiveness and safety of tolvaptan in real-world clinical settings. Patients with hepatic cirrhosis with insufficient response to conventional diuretics were enrolled. The observational period was up to 6 months. Changes in body weight and clinical symptoms were measured to evaluate effectiveness. The incidence of adverse drug reactions was summarized as a safety measure. Of 970 patients enrolled, 463 were included in the safety analysis. Of this group, 340 were included in the effectiveness analysis. Decreases in body weight from baseline were -2.38 kg on day 7 and -3.52 kg on day 14. Ascites and bloated feeling was significantly improved within 14 days. The mean change in body weight depended on estimated glomerular filtration rate levels. The most frequently reported adverse drug reaction was thirst (6.9% of patients). Serum sodium level of ≥146 mEq/L was observed in 12 patients (2.7%). In the real-world clinical setting, tolvaptan showed aquaretic effectiveness in patients with cirrhosis. The mean change in body weight depended on renal function. We recommend tolvaptan use for hepatic cirrhosis at a stage in which the renal function is maintained. © 2016 The Japan Society of Hepatology.

  14. Final hazard classification and auditable safety analysis for the 308 Building Complex during post-deactivation surveillance and maintenance mode

    International Nuclear Information System (INIS)

    Dexheimer, D.

    1996-11-01

    This document summarizes the inventories of radioactive and hazardous materials present within the 308 Building Complex, and presents the hazard evaluation methodology used to prepare the hazard classification for the Complex. The complex includes the 308 Building (process area and office facilities) and the 308 Building Annex, which includes the former Neutron Radiography Facility containing a shutdown (and partially decommissioned) reactor. This document applies to the post-deactivation surveillance and maintenance mode only, and provides an authorization basis limited to surveillance and maintenance activities. This document does not authorize decommissioning and decontamination activities, movement of fissile materials, modification to facility confinement structures, nor the introduction or storage of additional radionuclides in the 308 Building Complex. This document established a final hazard classification and identifies appropriate and adequate safety functions and controls to reduce or mitigate the risk associated with the surveillance and maintenance mode. The most consequential hazard event scenario is a postulated unmitigated release from an earthquake event involving the entire complex. That release is equivalent to 30% of the Nuclear Category 3 threshold adjusted as allowed by DOE-STD-1027-92 (DOE 1992). The dominant isotopes are 239 Pu, 240 Pu, and 241 Am in the gloveboxes

  15. Principales resultados del sistema cubano de Farmacovigilancia en el año 2003 Main results of the Cuban System of Drug Surveillance in 2003

    Directory of Open Access Journals (Sweden)

    Francisco Debesa García

    2004-12-01

    Full Text Available Se describe el funcionamiento y principales resultados del sistema cubano de Farmacovigilancia durante el 2003 en todos los niveles de salud de Cuba. Durante 12 meses, los casos se identificaron mediante el sistema de notificación voluntaria de sospecha de reacciones adversas a medicamentos. Se recibieron en la Unidad Nacional Coordinadora de Farmacovilancia 12 601 notificaciones de reacciones adversas medicamentosas (RAM que contenían 25 348 sospechas de RAM, para una tasa de notificación de 1 119 reportes x 1 000 000 de habitantes. El 66 % de las RAM correspondió al sexo femenino y el 34 % al masculino. En cuanto al nivel de asistencia, la atención primaria es la que más notifica con 83,5 %. Fueron resultados alentadores que en este año la relación de reacciones leves con respecto a las moderadas y graves resultó del 55,3/44,7 %, que continúa con un balance bastante bueno en relación con el reporte por severidad. Se reportaron 54 reacciones con desenlace fatal, para el 0,2 %. Las notificaciones recibidas en nuestro unidad permitieron cuantificar y caracterizar las RAM, teniendo además un gran valor para generar alertas y vigilar la seguridad de los medicamentos que circulan en nuestro país.The functioning and the main results of the Cuban Drug Surveillance System at all the health levels, in 2003, are described. During 12 months, the cases were identified by the volunteer notification system of suspicion of adverse drug reactions. 12 601 notifications of adverse drug reactions (DAR containing 25 348 DAR suspicions were received at the National Coordinating Unit of Drug Surveillance for a notification rate of 1 119 reports x 1 000 000 inhabitants. 66 % of the ADRs corresponded to females and 34 % to males. As regards the assistance level, the primary care level notifies the most with 83.5 %. It was considered as encouraging the fact that the relation of mild adverse reactions with respect to the moderate and severe was 55.3 %/44

  16. Triangulating case-finding tools for patient safety surveillance: a cross-sectional case study of puncture/laceration.

    Science.gov (United States)

    Taylor, Jennifer A; Gerwin, Daniel; Morlock, Laura; Miller, Marlene R

    2011-12-01

    To evaluate the need for triangulating case-finding tools in patient safety surveillance. This study applied four case-finding tools to error-associated patient safety events to identify and characterise the spectrum of events captured by these tools, using puncture or laceration as an example for in-depth analysis. Retrospective hospital discharge data were collected for calendar year 2005 (n=48,418) from a large, urban medical centre in the USA. The study design was cross-sectional and used data linkage to identify the cases captured by each of four case-finding tools. Three case-finding tools (International Classification of Diseases external (E) and nature (N) of injury codes, Patient Safety Indicators (PSI)) were applied to the administrative discharge data to identify potential patient safety events. The fourth tool was Patient Safety Net, a web-based voluntary patient safety event reporting system. The degree of mutual exclusion among detection methods was substantial. For example, when linking puncture or laceration on unique identifiers, out of 447 potential events, 118 were identical between PSI and E-codes, 152 were identical between N-codes and E-codes and 188 were identical between PSI and N-codes. Only 100 events that were identified by PSI, E-codes and N-codes were identical. Triangulation of multiple tools through data linkage captures potential patient safety events most comprehensively. Existing detection tools target patient safety domains differently, and consequently capture different occurrences, necessitating the integration of data from a combination of tools to fully estimate the total burden.

  17. 'Next-Generation' Surveillance: An Epidemiologists' Perspective on the Use of Molecular Information in Food Safety and Animal Health Decision-Making.

    Science.gov (United States)

    Muellner, P; Stärk, K D C; Dufour, S; Zadoks, R N

    2016-08-01

    Advances in the availability and affordability of molecular and genomic data are transforming human health care. Surveillance aimed at supporting and improving food safety and animal health is likely to undergo a similar transformation. We propose a definition of 'molecular surveillance' in this context and argue that molecular data are an adjunct to rather than a substitute for sound epidemiological study and surveillance design. Specific considerations with regard to sample collection are raised, as is the importance of the relation between the molecular clock speed of genetic markers and the spatiotemporal scale of the surveillance activity, which can be control- or strategy-focused. Development of standards for study design and assessment of molecular surveillance system attributes is needed, together with development of an interdisciplinary skills base covering both molecular and epidemiological principles. © 2015 Blackwell Verlag GmbH.

  18. Health and Safety in Waste Collection: Towards Evidence-Based Worker Health Surveillance

    NARCIS (Netherlands)

    Kuijer, P. Paul F. M.; Sluiter, Judith K.; Frings-Dresen, Monique H. W.

    2010-01-01

    Background Waste collectors around the world are at risk for work-related disorders and injuries. The aim of this study was to assess work demands, acute physiologic responses, illnesses, and injuries as a starting point for worker health surveillance (WHS). Methods A systematic search was performed

  19. High Prevalence of HIV Drug Resistance Among Newly Diagnosed Infants Aged <18 Months: Results From a Nationwide Surveillance in Nigeria.

    Science.gov (United States)

    Inzaule, Seth C; Osi, Samuels J; Akinbiyi, Gbenga; Emeka, Asadu; Khamofu, Hadiza; Mpazanje, Rex; Ilesanmi, Oluwafunke; Ndembi, Nicaise; Odafe, Solomon; Sigaloff, Kim C E; Rinke de Wit, Tobias F; Akanmu, Sulaimon

    2018-01-01

    WHO recommends protease-inhibitor-based first-line regimen in infants because of risk of drug resistance from failed prophylaxis used in prevention of mother-to-child transmission (PMTCT). However, cost and logistics impede implementation in sub-Saharan Africa, and >75% of children still receive nonnucleoside reverse transcriptase inhibitor-based regimen (NNRTI) used in PMTCT. We assessed the national pretreatment drug resistance prevalence of HIV-infected children aged resistance surveillance protocol. We used remnant dried blood spots collected between June 2014 and July 2015 from 15 early infant diagnosis facilities spread across all the 6 geopolitical regions of Nigeria. Sampling was through a probability proportional-to-size approach. HIV drug resistance was determined by population-based sequencing. Overall, in 48% of infants (205 of 430) drug resistance mutations (DRM) were detected, conferring resistance to predominantly NNRTIs (45%). NRTI and multiclass NRTI/NNRTI resistance were present at 22% and 20%, respectively, while resistance to protease inhibitors was at 2%. Among 204 infants with exposure to drugs for PMTCT, 57% had DRMs, conferring NNRTI resistance in 54% and multiclass NRTI/NNRTI resistance in 29%. DRMs were also detected in 34% of 132 PMTCT unexposed infants. A high frequency of PDR, mainly NNRTI-associated, was observed in a nationwide surveillance among newly diagnosed HIV-infected children in Nigeria. PDR prevalence was equally high in PMTCT-unexposed infants. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected young children regardless of PMTCT history and underscore the need to accelerate implementation of the newly disseminated guideline in Nigeria.

  20. Integration of HIV testing in tuberculosis drug resistance surveillance in Kazakhstan and Kenya

    NARCIS (Netherlands)

    Klinkenberg, E.; van den Hof, S.; Tursynbayeva, A.; Kipruto, H.; Wahogo, J.; Pak, S.; Kutwa, A.; L'Herminez, R.

    2012-01-01

    In Kenya and Kazakhstan, integration of human immunodeficiency virus (HIV) testing results into the routine surveillance of multidrug-resistant tuberculosis (MDR-TB) proved feasible and useful. The integration process improved overall data quality and data validation capacity, and integrated data

  1. Epigenetics and cancer: implications for drug discovery and safety assessment

    International Nuclear Information System (INIS)

    Moggs, Jonathan G.; Goodman, Jay I.; Trosko, James E.; Roberts, Ruth A.

    2004-01-01

    It is necessary to determine whether chemicals or drugs have the potential to pose a threat to human health. Research conducted over the last two decades has led to the paradigm that chemicals can cause cancer either by damaging DNA or by altering cellular growth, probably via receptor-mediated changes in gene expression. However, recent evidence suggests that gene expression can be altered markedly via several diverse epigenetic mechanisms that can lead to permanent or reversible changes in cellular behavior. Key molecular events underlying these mechanisms include the alteration of DNA methylation and chromatin, and changes in the function of cell surface molecules. Thus, for example, DNA methyltransferase enzymes together with chromatin-associated proteins such as histone modifying enzymes and remodelling factors can modify the genetic code and contribute to the establishment and maintenance of altered epigenetic states. This is relevant to many types of toxicity including but not limited to cancer. In this paper, we describe the potential for interplay between genetic alteration and epigenetic changes in cell growth regulation and discuss the implications for drug discovery and safety assessment

  2. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

    Directory of Open Access Journals (Sweden)

    Roth SH

    2011-05-01

    Full Text Available Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.Keywords: NSAIDs, osteoarthritis, topical administration, synovial fluid, peptic ulcer, Helicobacter pylori

  3. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety.

    Science.gov (United States)

    Roth, Sanford H

    2011-01-01

    Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.

  4. Imported malaria in Finland 1995 to 2008: an overview of surveillance, travel trends, and antimalarial drug sales.

    Science.gov (United States)

    Guedes, Sandra; Siikamäki, Heli; Kantele, Anu; Lyytikäinen, Outi

    2010-01-01

    To improve pre-travel advice, we analyzed nationwide population-based surveillance data on malaria cases reported to the National Infectious Disease Register of Finland (population 5.3 million) during 1995 to 2008 and related it to data on traveling and antimalarial drug sales. Surveillance data comprised information on malaria cases reported to the National Infectious Disease Register during 1995 to 2008. Traveling data were obtained from Statistics Finland (SF) and the Association of Finnish Travel Agents (AFTA). SF data included information on overnight leisure trips to malaria-endemic countries during 2000 to 2008. AFTA data included annual number of organized trips during 1999 to 2007. Quarterly numbers of antimalarial drug sales were obtained from the Finnish Medicines Agency. Descriptive and time series analyses were performed. A total of 484 malaria cases (average annual incidence 0.7/100,000 population) were reported; 283 patients were Finnish- and 201 foreign-born. In all, 15% of all cases were children; 72% foreign- and 28% Finnish-born. Malaria infections were mostly acquired in Africa (76%). Among foreign-born cases, 89% of the infections were acquired in the region of birth. The most common species were Plasmodium falciparum (61%) and Plasmodium vivax (22%). Although traveling to malaria-endemic areas increased, no increase occurred in malaria cases, and a decreasing trend was present in antimalarial drug sales. Traveling to malaria-endemic countries and drug sales followed the same seasonal pattern, with peaks in the first and last quarter of the year. More efforts should be focused on disseminating pre-travel advice to immigrants planning to visit friends and relatives and travelers on self-organized trips. © 2010 International Society of Travel Medicine.

  5. Regulatory aspects of oncology drug safety evaluation: Past practice, current issues, and the challenge of new drugs

    International Nuclear Information System (INIS)

    Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M. Stacey; McGuinn, W. David; Verbois, S. Leigh

    2010-01-01

    The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

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

    Science.gov (United States)

    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.

  7. A data-capture system for post-marketing surveillance of drugs that integrates with hospital electronic health records

    Directory of Open Access Journals (Sweden)

    Yamamoto K

    2011-04-01

    Full Text Available Keiichi Yamamoto1, Shigemi Matsumoto2, Kazuhiro Yanagihara2, Satoshi Teramukai1, Masanori Fukushima1,2,31Department of Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, Japan; 2Outpatient Oncology Unit, Kyoto University Hospital, Kyoto, Japan; 3Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, JapanPurpose: In conventional clinical studies, the cost of data management for the purposes of quality control tend to be high and collecting paper-based case report forms (CRFs can be burdensome, because paper-based CRFs must be developed and filled out for each clinical study protocol. Use of electronic health records (EHRs for this purpose could reduce costs and improve data quality in clinical studies. Kyoto University Hospital launched an EHR system in January 2005. At the same time, a replicate of that database was established for other purposes. At the Outpatient Oncology Unit of Kyoto University Hospital we developed a data-capture system that includes a cancer clinical database system and a data warehouse for outcomes studies. This system allows us to accumulate data at low cost and apply it to various uses in clinical or outcomes studies. Here we report on the application of this system to the post-marketing surveillance of drugs.Methods: We evaluated the availability of this system and identified problems for future development. With this system investigators can register cases for post-marketing surveillance, and the registered cases are listed on a screen. When CRFs for a particular case are required, data can be extracted from the list and CRFs are produced in PDF format.Results and conclusion: In this study we confirmed the applicability of our new system to post-marketing surveillance in providing prompt and efficient data exchange. We expect it to reduce the cost of data management and analysis and to improve the quality of data in post

  8. The role of the Australian Adverse Drug Reactions Advisory Committee (ADRAC) in monitoring drug safety

    International Nuclear Information System (INIS)

    Boyd, Ian W.

    2002-01-01

    The Australian adverse drug reaction reporting system is acknowledged as one of the best in the world. Despite its small population of less than 20 million people, Australia's current ADR reporting rate of over 12000 reports per year places it in the top few nations in terms of reports per capita. The ADRAC program has been in operation for over 30 years. Australia was a founding member of the WHO International Drug Monitoring Programme which commenced in 1968 and currently there are about 153000 reports in the ADRAC database. Reports from health professionals have uncovered a number of significant safety problems over the years. Of particular importance are flucloxacillin-induced hepatitis, amoxycillin/clavulanate-induced hepatitis, and the association of cystitis with tiaprofenic acid. The number and quality of the reports has allowed an understanding of the characteristics of the reactions and, using ADRAC reporters as a major source of cases, case-control studies have been completed which have identified risk factors. ADRAC's review of Australian reports has highlighted many important associations that have been disseminated through the Australian Adverse Drug Reactions Bulletin

  9. From Drug Safety to Drug Security: A Contemporary Shift in the Policing of Health.

    Science.gov (United States)

    Hornberger, Julia

    2018-01-29

    The counterfeiting of medication is increasingly seen as a major threat to health, especially in the light of both the everyday reliance on and a broadening of world-wide access to pharmaceuticals. Exaggerated or real, this threat has inaugurated, this article argues, a shift from a drug safety regime to a drug security regime that governs the flow of pharmaceuticals and brings together markets, police, and health actors in new ways. This entails a shift from soft disciplinary means aimed at incremental and continued inclusion of defaulters, to one of drastically sovereign measures of exclusion and banishment aimed at fake goods and the people associated with them, in the name of health. Through a multi-sited ethnographic study, this article shows how such new drug security efforts play themselves out especially in (South) Africa, highlighting a modus operandi of spectacular performativity and of working through suspicion and association rather than factuality, producing value less so for those in need of health than for a petty security industry itself. © 2018 by the American Anthropological Association.

  10. Farmacovigilância: elementos para a discussão e perspectivas Drug surveillance: topics for discussion and prospects

    Directory of Open Access Journals (Sweden)

    Suely Rozenfeld

    1998-04-01

    Full Text Available A vigilância de medicamentos subdivide-se em dois grupos. O primeiro consiste nas ações de registro e fiscalização, que são as mais conhecidas da sociedade. O segundo grupo consiste nas ações de farmacovigilância, que são as de pesquisa e monitoramento de reações adversas. Essas últimas estão previstas na legislação federal do setor saúde que vigora desde a década de 70. Do mesmo modo, uma portaria recente prevê a criação do sistema nacional de monitoramento. O texto aborda de maneira panorâmica elementos da história, dos conceitos, das definições, da classificação, dos mecanismos de ação e do diagnóstico de reações adversas. São descritos os objetivos e as fontes de informação para os estudos de farmacovigilância, bem como a experiência nacional no campo.Drug surveillance can be grouped into two areas. The first includes registration and inspection, activities that are more familiar to society at large. The second involves research and monitoring of adverse effects. Brazilian legislation has regulated this subject since 1970. A recent directive also provides for a national pharmaceutical surveillance system. This current article provides an overview of the history, definitions, pharmacological concepts, classification, and diagnosis of the adverse effects of drugs. An analysis is presented of the goals and sources of information for drug monitoring as well as some Brazilian experience in this field.

  11. Prescription for antibiotics at drug shops and strategies to improve quality of care and patient safety

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Buregyeya, Esther; Rutebemberwa, Elizeus

    2016-01-01

    OBJECTIVES: The main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety......-line drug for treatment of pneumonia in children according to the guidelines. CONCLUSIONS: There is urgent need to regulate drug shop practices of prescribing and selling antibiotics, for the safety of patients seeking care at these outlets....

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

    Science.gov (United States)

    Day, Richard O; Williams, Kenneth M

    2007-01-01

    The number of open-label extension studies being performed has increased enormously in recent years. Often it is difficult to differentiate between these extension studies and the double-blind, controlled studies that preceded them. If undertaken primarily to gather more patient-years of exposure to the new drug in order to understand and gain confidence in its safety profile, open-label extension studies can play a useful and legitimate role in drug development and therapeutics. However, this can only occur if the open-label extension study is designed, executed, analysed and reported competently. Most of the value accrued in open-label extension studies is gained from a refinement in the perception of the expected incidence of adverse effects that have most likely already been identified as part of the preclinical and clinical trial programme. We still have to rely heavily on post-marketing safety surveillance systems to alert us to type B (unpredictable) adverse reactions because open-label extension studies are unlikely to provide useful information about these types of often serious and relatively rare adverse reactions. Random allocation into test and control groups is needed to produce precise incidence data on pharmacologically expected, or type A, adverse effects. Some increased confidence about incidence rates might result from the open-label extension study; however, as these studies are essentially uncontrolled and biased, the data are not of great value. Other benefits have been proposed to be gained from open-label extension studies. These include ongoing access to an effective but otherwise unobtainable medicine by the volunteers who participated in the phase III pivotal trials. However, there are unappreciated ethical issues about the appropriateness of enrolling patients whose response to previous treatment is uncertain, largely because treatment allocation in the preceding randomised, double-blind, controlled trial has not been revealed at the

  13. 77 FR 10666 - Pipeline Safety: Post Accident Drug and Alcohol Testing

    Science.gov (United States)

    2012-02-23

    ... 199 [Docket No. PHMSA-2011-0335] Pipeline Safety: Post Accident Drug and Alcohol Testing AGENCY... operators of Liquefied Natural Gas (LNG) facilities to conduct post- accident drug and alcohol tests of..., operators must drug and alcohol test each covered employee whose performance either contributed to the...

  14. Epidemiological Safety Surveillance of Cellular Telephones in the US (invited paper)

    International Nuclear Information System (INIS)

    Dreyer, N.A.; Loughlin, J.E.; Rothman, K.J.

    1999-01-01

    In 1994 a surveillance programme was initiated to monitor the effects of exposure to the human head from radiofrequency waves, such as those emitted from handheld cellular telephones. Cellular carriers contributed information about 1.5 million telephone account holders, their phones and two months of data on minutes used and number of calls. Cellular telephone manufacturers provided data that allowed classification of phones as analogue or digital and a handheld or mobile (car or bag) for 67% of the phones. Thus far 1,021,767 individuals have been identified who had at least one active cellular telephone account in 1994 and/or 1995 and who used either a handheld (41%) or a mobile (59%) phone during the study period, but not both. Seventy-four per cent of the cohort had used their cellular phone for ≥2 years, and 30% for ≥3 years. (author)

  15. Post-marketing surveillance study of the safety and efficacy of nalfurafine hydrochloride (Remitch® capsules 2.5 μg in 3,762 hemodialysis patients with intractable pruritus

    Directory of Open Access Journals (Sweden)

    Kozono H

    2018-01-01

    Full Text Available Hideki Kozono,* Hiroshi Yoshitani,* Ryoko Nakano* Pharmaceutical and Medical Device Vigilance Department, Toray Industries, Inc., Tokyo, Japan *The authors contributed equally to this work Background: Intractable pruritus in hemodialysis patients can significantly decrease their quality of life and is also associated with poor vital prognosis. Although combined multiple causes of intractable pruritus in these patients have been identified, no existing treatments are proven to be sufficiently effective. We conducted a post-marketing surveillance to follow-up and assess the safety and efficacy of nalfurafine, a selective κ-opioid receptor agonist, for the treatment of intractable pruritus in patients undergoing hemodialysis. Patients and methods: Hemodialysis patients with intractable pruritus from institutions in Japan who received oral nalfurafine hydrochloride between January 2010 and December 2013 were enrolled in the surveillance. Surveillance was completed in July 2015. Safety data during 1 year after nalfurafine treatment onset, and efficacy data of nalfurafine evaluating the first 12-week treatment period and the following period until 1 year after the initial dose of nalfurafine (using global assessment of the itch improvement by the physician, Visual Analog Scale, and the Shiratori’s severity scores were collected and analyzed. Results: In total, 3,762 patients were analyzed for safety. Adverse drug reactions were experienced by 402/3,762 (10.69% patients. The most frequent adverse drug reactions were insomnia (127/3,762 [3.38%] patients, constipation (34 [0.90%], somnolence (32 [0.85%], dizziness (23 [0.61%], nausea (13 [0.35%], and malaise (9 [0.24%]. No patients developed dependence on nalfurafine. Nalfurafine was effective in 82.50% (2,880/3,491 of patients during the first 12 weeks and in 84.95% (2,167/2,551 on treatment during the subsequent period until 1 year after nalfurafine treatment initiation. Statistically significant

  16. Best approaches to drug-resistance surveillance at the country level

    Directory of Open Access Journals (Sweden)

    A M Cabibbe

    2016-01-01

    Classical sequencing and NGS approaches have been successfully used in a recent study conducted in five countries with high burden of TB and multidrug resistant tuberculosis (MDR-TB and aimed at investigating levels of resistance to pyrazinamide among patients with TB by pncA sequencing [doi: 10.1016/S1473-3099(1630190-6]. This work innovatively demonstrated that the establishment of strong links between national (peripheral and reference laboratories and supranational laboratories, with the former possibly processing indirect or direct samples and generating sequencing data, and the latter supporting them for bioinformatics analysis and data interpretation, will soon make WGS and targeted NGS the preferred tools to conduct public health surveillances in TB field, thus helping the strategies adopted by TB control programs at local and national levels.

  17. Development and application of a living probabilistic safety assessment tool: Multi-objective multi-dimensional optimization of surveillance requirements in NPPs considering their ageing

    International Nuclear Information System (INIS)

    Kančev, Duško; Čepin, Marko; Gjorgiev, Blaže

    2014-01-01

    The benefits of utilizing the probabilistic safety assessment towards improvement of nuclear power plant safety are presented in this paper. Namely, a nuclear power plant risk reduction can be achieved by risk-informed optimization of the deterministically-determined surveillance requirements. A living probabilistic safety assessment tool for time-dependent risk analysis on component, system and plant level is developed. The study herein focuses on the application of this living probabilistic safety assessment tool as a computer platform for multi-objective multi-dimensional optimization of the surveillance requirements of selected safety equipment seen from the aspect of the risk-informed reasoning. The living probabilistic safety assessment tool is based on a newly developed model for calculating time-dependent unavailability of ageing safety equipment within nuclear power plants. By coupling the time-dependent unavailability model with a commercial software used for probabilistic safety assessment modelling on plant level, the frames of the new platform i.e. the living probabilistic safety assessment tool are established. In such way, the time-dependent core damage frequency is obtained and is further on utilized as first objective function within a multi-objective multi-dimensional optimization case study presented within this paper. The test and maintenance costs are designated as the second and the incurred dose due to performing the test and maintenance activities as the third objective function. The obtained results underline, in general, the usefulness and importance of a living probabilistic safety assessment, seen as a dynamic probabilistic safety assessment tool opposing the conventional, time-averaged unavailability-based, probabilistic safety assessment. The results of the optimization, in particular, indicate that test intervals derived as optimal differ from the deterministically-determined ones defined within the existing technical specifications

  18. A risk assessment approach to evaluating food safety based on product surveillance

    NARCIS (Netherlands)

    Notermans, S.; Nauta, M.J.; Jansen, J.; Jouve, J.L.; Mead, G.C.

    1998-01-01

    This paper outlines a risk assessment approach to food safety evaluation, which is based on testing a particular type of food, or group of similar foods, for relevant microbial pathogens. The results obtained are related to possible adverse effects on the health of consumers. The paper also gives an

  19. Probing cardiac repolarization reserve in drug safety assessment

    NARCIS (Netherlands)

    Nalos, L.

    2011-01-01

    Excessive prolongation of cardiac repolarization, manifested as QT prolongation on ECG, is common unwanted side effect of many drugs and drug candidates. Prolongation of QT interval may lead to life threatening cardiac arrhythmia – Torsade de Point (TdP). Number of drugs was withdrawn from the

  20. The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy.

    Science.gov (United States)

    Carnovale, Carla; Brusadelli, Tatiana; Zuccotti, GianVincenzo; Beretta, Silvia; Sullo, Maria Giuseppa; Capuano, Annalisa; Rossi, Francesco; Moschini, Martina; Mugelli, Alessandro; Vannacci, Alfredo; Laterza, Marcella; Clementi, Emilio; Radice, Sonia

    2014-09-01

    To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.

  1. Safety and effectiveness of certolizumab pegol in patients with rheumatoid arthritis: Interim analysis of post-marketing surveillance.

    Science.gov (United States)

    Kameda, Hideto; Nishida, Keiichiro; Nannki, Toshihiro; Watanabe, Akira; Oshima, Yukiya; Momohara, Shigaki

    2017-01-01

    Objective: To evaluate the safety and effectiveness of certolizumab pegol (CZP) in a real-world setting among Japanese patients with rheumatoid arthritis. Post-marketing surveillance data from 2,579 patients treated with CZP were analyzed. Adverse events (AEs) observed during the 24-week CZP treatment period were recorded. Disease activity was evaluated using DAS28-ESR and DAS28-CRP at baseline, Week 12, Week 24, or at withdrawal. The total period of exposure to CZP was 1313.8 patient-years (PY). AEs were reported in 658 (25.5%) patients, at an event rate (ER) of 73.68/100 PY. The most frequent serious AEs were pneumonia, herpes zoster, and interstitial lung disease, at ER per 100 PY of 2.06, 1.29, and 1.22, respectively. Mean disease activity scores at baseline, as measured by DAS28-ESR and DAS28-CRP, were 4.77 ± 1.34 and 4.21 ± 1.27, respectively. Mean changes from baseline at the last observation were -1.29 ± 1.46 and -1.30 ± 1.42, respectively. EULAR good or moderate responses were achieved in 65% of patients. Longer disease duration, prior biologics use, and treatment without MTX co-therapy were associated with EULAR no response. In this interim analysis, no new safety signals were observed. Clinical response to CZP was observed in approximately two thirds of patients.

  2. Safety and patient comfort with iodixanol: a postmarketing surveillance study in 9515 patients undergoing diagnostic CT examinations

    Energy Technology Data Exchange (ETDEWEB)

    Haeussler, Marc D. (Gemeinschaftspraxis fuer Radiologie und Neurologie, Praxis Mosbach, Mosbach (Germany)), e-mail: info@praxis-mosbach.de

    2010-10-15

    Background: Iodinated radiographic contrast media are considered safe diagnostic drugs with a low incidence of adverse drug reactions. Purpose: To determine prospectively the incidence and nature of immediate and delayed adverse drug reactions occurring after administration of iodixanol for contrast-enhanced computed tomography (CT) in routine practice in nonselected patients, and to assess patient comfort (pain and sensations of heat or coldness). Material and Methods: Patient characteristics (including demographics, risk factors, indication for CT, and status of the vein used to administer iodixanol) and aspects of iodixanol administration (including dose and volume) were documented on a standardized case report form. Patients were asked to report immediate (during the visit) or delayed (occurring up to 7 days after administration of iodixanol) adverse reactions; those deemed related or possibly related to iodixanol were documented on a standardized adverse drug reaction form. Discomfort was rated by patients on a scale of 0-10 for pain, heat, and coldness; individual scores were combined into a composite score (0-30). Results: Evaluable documentation was provided for 9515 patients in 77 centers across Germany. Adverse drug reactions were reported in 70 patients (0.74%), including hypersensitivity reactions in 55 patients. Thirty patients experienced immediate reactions and 40 experienced delayed reactions. Serious adverse drug reactions were evident in five patients (0.05%). Patients with allergic diathesis appeared to be at increased risk of immediate and delayed adverse drug reactions. Discomfort was generally mild, with 72% of patients reporting a composite score of 0-3. Conclusion: In the outpatient setting, where it is often difficult to properly assess patients for specific risk factors, it was reassuring that iodixanol demonstrated an excellent safety profile in over 9500 patients undergoing diagnostic CT examinations. There were no unexpected serious

  3. Safety and patient comfort with iodixanol: a postmarketing surveillance study in 9515 patients undergoing diagnostic CT examinations

    International Nuclear Information System (INIS)

    Haeussler, Marc D.

    2010-01-01

    Background: Iodinated radiographic contrast media are considered safe diagnostic drugs with a low incidence of adverse drug reactions. Purpose: To determine prospectively the incidence and nature of immediate and delayed adverse drug reactions occurring after administration of iodixanol for contrast-enhanced computed tomography (CT) in routine practice in nonselected patients, and to assess patient comfort (pain and sensations of heat or coldness). Material and Methods: Patient characteristics (including demographics, risk factors, indication for CT, and status of the vein used to administer iodixanol) and aspects of iodixanol administration (including dose and volume) were documented on a standardized case report form. Patients were asked to report immediate (during the visit) or delayed (occurring up to 7 days after administration of iodixanol) adverse reactions; those deemed related or possibly related to iodixanol were documented on a standardized adverse drug reaction form. Discomfort was rated by patients on a scale of 0-10 for pain, heat, and coldness; individual scores were combined into a composite score (0-30). Results: Evaluable documentation was provided for 9515 patients in 77 centers across Germany. Adverse drug reactions were reported in 70 patients (0.74%), including hypersensitivity reactions in 55 patients. Thirty patients experienced immediate reactions and 40 experienced delayed reactions. Serious adverse drug reactions were evident in five patients (0.05%). Patients with allergic diathesis appeared to be at increased risk of immediate and delayed adverse drug reactions. Discomfort was generally mild, with 72% of patients reporting a composite score of 0-3. Conclusion: In the outpatient setting, where it is often difficult to properly assess patients for specific risk factors, it was reassuring that iodixanol demonstrated an excellent safety profile in over 9500 patients undergoing diagnostic CT examinations. There were no unexpected serious

  4. 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

    Science.gov (United States)

    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

  5. Safety and effectiveness of gemcitabine in 260 patients with biliary tract cancer in a Japanese clinical practice based on post-marketing surveillance in Japan.

    Science.gov (United States)

    Okubo, Sumiko; Nishiuma, Shinichi; Kobayashi, Noriko; Taketsuna, Masanori; Taniai, Hisashi

    2012-11-01

    Gemcitabine was approved for the treatment of biliary tract cancer in 2006 in Japan. While biliary tract cancer is usually associated with patients 70 years of age or older and/or those who tend to have underlying liver dysfunction, data on this population were limited in the Japanese Phase II study of gemcitabine. Thus, further evaluation of safety and effectiveness in this population was planned. This special post-marketing surveillance was conducted as an observational study on the use of gemcitabine in a clinical practice setting. Gemcitabine-naïve patients with biliary tract cancer were enrolled from 2006 to 2008 and observed over 12 months; one or more doses of gemcitabine were administered during the period. Data such as patient background, treatment details, adverse events occurring during the observational period, laboratory values of liver enzyme and survival status were collected 3 and 12 months after the start of therapy. Of the 285 patients registered for the study, 260 were included in the analysis. The mean age was 66.9 years. There were 120 patients (46.2%) classified as elderly (70 years or older). Haematotoxicities were the most common adverse drug reactions. In the elderly and the non-elderly, adverse drug reactions (serious) occurred in 48.3% (20.8%) and 50.7% (12.9%), respectively. The overall estimated 1-year survival rate was 52.5% (95% confidence interval, 45.9-58.7%). In line with previous clinical and post-marketing studies conducted in Japan, the results of this study suggest that gemcitabine could be used safely and effectively for biliary tract cancer patients including the elderly.

  6. Innovations in Post-Marketing Safety Research

    NARCIS (Netherlands)

    Stefánsdóttir, G.

    2012-01-01

    Safety surveillance is important during the entire life cycle of a drug. Pre-marketing trials have been shown to be ineffective in establishing the full safety profile of the drug, mainly due to their relatively small sample size and characteristics of the patients, which are usually younger and

  7. Characterization of Adolescent Prescription Drug Abuse and Misuse Using the Researched Abuse Diversion and Addiction-Related Surveillance (RADARS[R]) System

    Science.gov (United States)

    Zosel, Amy; Bartelson, Becki Bucher; Bailey, Elise; Lowenstein, Steven; Dart, Rick

    2013-01-01

    Objective: To describe the characteristics and health effects of adolescent (age 13-19 years) prescription drug abuse and misuse using the Researched Abuse Diversion and Addiction-Related Surveillance (RADARS[R])) System. Method: Secondary analysis of data collected from RADARS System participating poison centers was performed. Data for all…

  8. Online availability and safety of drugs in shortage: a descriptive study of internet vendor characteristics.

    Science.gov (United States)

    Liang, Bryan A; Mackey, Tim K

    2012-02-09

    Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. We performed a descriptive study of the prevalence of online marketing for shortage drugs-that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing.

  9. VETSTAT - the Danish system for surveillance of the veterinary use of drugs for production animals

    DEFF Research Database (Denmark)

    Stege, H.; Bager, Flemming; Jacobsen, Erik

    2003-01-01

    The Danish Ministry of Food, Agriculture and Fisheries funds a monitoring system based on drug usage information collected at the herd level: VETSTAT. VETSTAT is constructed as a relational database and data originates from three sources: pharmacies, veterinarians and feed mills. All administration...... of drugs for use in animal production is reported on a monthly basis. Pharmacies provided 95% of the total weight antimicrobial compounds used in Denmark in 2001. More than 80% of the antimicrobial compounds reported by pharmacies were sold on prescription to end-users (owners) and included information...

  10. 76 FR 63929 - Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and...

    Science.gov (United States)

    2011-10-14

    ...] Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and... Administration (FDA). The meeting will be open to the public. Name of Committees: Drug Safety and Risk Management... Safe Use (ETASU) before its Drug Safety and Risk Management Advisory Committee (DSaRM). On December 1...

  11. 75 FR 17417 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

    Science.gov (United States)

    2010-04-06

    ...] Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory... Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee. This meeting was... Drug Safety and Risk Management Advisory Committee would be held on May 12, 2010. On page 10490, in the...

  12. The principles of measurement and of safety surveillance for the PCPV/helium-loop

    International Nuclear Information System (INIS)

    Zemann, H.

    1977-10-01

    The operating conditions of the PCVP/Helium-Loop are surveyed by gauges within the structural concrete, inside the vessel and at the auxiliary equipment Data are compared by the operator to the limits given by design and material properties. Under continuous operation the PCPV will be surveyed by an automatic safety system which will be able to detect the arise of unsafe operating conditions and initiate preventive reactions. (author)

  13. Tracking Ecstasy Trends in the United States with Data from Three National Drug Surveillance Systems

    Science.gov (United States)

    Yacoubian, George S., Jr.

    2003-01-01

    Anecdotal reports have suggested that the use of 3,4-methylenedioxymeth-amphetamine (MDMA or "ecstasy") is a prodigious problem across the United States. Unfortunately, no longitudinal evidence exists to support this contention. In the current study, data from the Drug Abuse Warning Network (DAWN), Monitoring the Future (MTF), and…

  14. Online Availability and Safety of Drugs in Shortage: A Descriptive Study of Internet Vendor Characteristics

    Science.gov (United States)

    Mackey, Tim K

    2012-01-01

    Background Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. Objective To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. Methods We performed a descriptive study of the prevalence of online marketing for shortage drugs—that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Results Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. Conclusions FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing. PMID:22321731

  15. Advice on drug safety in pregnancy: are there differences between commonly used sources of information?

    Science.gov (United States)

    Frost Widnes, Sofia K; Schjøtt, Jan

    2008-01-01

    Safety regarding use in pregnancy is not established for many drugs. Inconsistencies between sources providing drug information can give rise to confusion with possible therapeutic consequences. Therefore, it is important to measure clinically important differences between drug information sources. The objective of this study was to compare two easily accessible Norwegian sources providing advice on drug safety in pregnancy - the product monographs in the Felleskatalog (FK), published by the pharmaceutical companies, and the five regional Drug Information Centres (DICs) in Norway - in addition to assessing the frequency of questions regarding drug safety in pregnancy made to the DICs according to the Anatomical Therapeutic Chemical (ATC) classification system. Advice on drug use in pregnancy provided by the DICs in 2003 and 2005 were compared with advice in the product monographs for the respective drugs in the FK. Comparison of advice was based on categorization to one of four categories: can be used, benefit-risk assessment, should not be used, or no available information. A total of 443 drug advice were categorized. Seven out of ten of drugs frequently enquired about, according to the ATC system, were drugs acting on the nervous system (group N). For 208 (47%) of the drugs, advice differed between the DICs and FK. Advice from the FK was significantly (p drugs that were newly introduced and those that had been on the market for a longer time, advice regarding use of drugs in the first trimester and advice regarding use of drugs in the second or third trimester, or between advice provided during 2003 and during 2005. The results of this study show considerable differences between two Norwegian sources providing advice on the use of drugs in pregnancy. Based on the knowledge that healthcare providers choose sources of information in a random manner, our results may be of clinical importance. We believe that the problem with heterogeneous drug information on this

  16. HIV-1 drug resistance surveillance in antiretroviral treatment-naive individuals from a reference hospital in Guatemala, 2010-2013.

    Science.gov (United States)

    Avila-Ríos, Santiago; García-Morales, Claudia; Garrido-Rodríguez, Daniela; Tapia-Trejo, Daniela; Girón-Callejas, Amalia Carolina; Mendizábal-Burastero, Ricardo; Escobar-Urias, Ingrid Yessenia; García-González, Blanca Leticia; Navas-Castillo, Sabrina; Pinzón-Meza, Rodolfo; Mejía-Villatoro, Carlos Rodolfo; Reyes-Terán, Gustavo

    2015-04-01

    The recent expansion of antiretroviral treatment (ART) coverage in middle/low-income countries has been associated with increasing prevalence of HIV pre-ART drug resistance (PDR). We assessed PDR prevalence, patterns, and trends in Guatemala. Blood samples from 1,084 ART-naive individuals, enrolled from October 2010 to December 2013 at the Roosevelt Hospital in Guatemala City, were obtained. PDR was evaluated using the WHO mutation list for transmitted drug resistance (TDR) surveillance. An overall PDR prevalence of 7.3% (95% CI 5.8-9.0%) was observed for the whole study period. TDR to nonnucleoside reverse transcriptase inhibitors (NNRTI) was the highest (4.9%, p500 and 350-500 CD4(+) T cells/μl (7.4% and 8.7%, respectively) compared to individuals with Guatemala remains at an intermediate level. Nevertheless, we have shown evidence suggesting increasing trends in NNRTI PDR, which need to be taken into account in national HIV management policies.

  17. Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa.

    Science.gov (United States)

    Manasa, Justen; Danaviah, Siva; Lessells, Richard; Elshareef, Muna; Tanser, Frank; Wilkinson, Eduan; Pillay, Sureshnee; Mthiyane, Hloniphile; Mwambi, Henry; Pillay, Deenan; de Oliveira, Tulio

    2016-08-01

    As more human immunodeficiency virus (HIV)-infected patients access combination antiretroviral therapy (cART), higher proportions of newly infected patients may be infected with drug-resistant viruses. Regular surveillance of transmitted drug resistance (TDR) is required in southern Africa where high rates of transmission persist despite rapid expansion of ART. Dried blood spot samples from cART-naive participants from two rounds of an annual population-based HIV surveillance program in rural KwaZulu-Natal were tested for HIV RNA, and samples with HIV RNA >10,000 copies/ml were genotyped for drug resistance. The 2009 surveillance of drug resistance mutation (SDRM) list was used for drug resistance interpretation. The data were added to previously published data from the same program, and the χ(2) test for trend was used to test for trend in estimated prevalence of any TDR. Seven hundred and one participants' data were analyzed: 67 (2010), 381 (2011), and 253 (2012). No TDR was detected in 2010. Years 2011 and 2012 had 18 participants with SDRMs 4.7% and 7.1%, respectively (p = .02, χ(2) test for trend). The nonnucleoside reverse transcriptase inhibitor mutation, K103N, was the most common mutation, occurring in 27 (3.8%) of the participants, while nucleoside reverse transcriptase inhibitor (NRTI) SDRMs were detected in 10 (1.4%) of the participants, of whom eight had only a single NRTI SDRM. The increase in levels of drug resistance observed in this population could be a signal of increasing transmission of drug-resistant HIV. Thus, continued surveillance is critical to inform public health policies around HIV treatment and prevention.

  18. New York hazardous substances emergency events surveillance: learning from hazardous substances releases to improve safety

    International Nuclear Information System (INIS)

    Welles, Wanda Lizak; Wilburn, Rebecca E.; Ehrlich, Jenny K.; Floridia, Christina M.

    2004-01-01

    Since 1993, the New York State Department of Health, funded by the Agency for Toxic Substances and Disease Registry, has collected data about non-petroleum hazardous substances releases through the Hazardous Substances Emergency Events Surveillance (NYHSEES) project. This study investigates risk factors for hazardous substances releases that may result in public health consequences such as injury or reported health effects. The 6428 qualifying events that occurred during the 10-year-period of 1993-2002 involved 8838 hazardous substances, 842 evacuations, more than 75,419 people evacuated, and more than 3120 people decontaminated. These events occurred both at fixed facilities (79%) and during transport (21%). The causative factors most frequently contributing to reported events were equipment failure (39%) and human error (33%). Five of the 10 chemicals most frequently associated with injuries were also among the 10 chemicals most frequently involved in reported events: sulfuric acid, hydrochloric acid, ammonia, sodium hypochlorite, and carbon monoxide. The chemical categories most frequently associated with events, and with events with adverse health effects were volatile organic compounds (VOCs) and solvents, and acids. Events with releases of hazardous substances were associated with injuries to 3089 people including employees (37%), responders (12%), the general public (29%) and students (22%). The most frequently reported adverse health effects were respiratory irritation, headache, and nausea or vomiting. Most of the injured were transported to the hospital, treated, and released (55%) or treated at the scene (29%). These data have been used for emergency response training, planning, and prevention activities to reduce morbidity and mortality from future events

  19. Enhancing food safety: the role of the Food and Drug Administration

    National Research Council Canada - National Science Library

    Wallace, Robert B; Oria, Maria

    2010-01-01

    .... Food and Drug Administration's abilities to discover potential threats to food safety and prevent outbreaks of foodborne illness are hampered by impediments to efficient use of its limited resources...

  20. Safety of Etoricoxib, Celecoxib, and Nonselective Nonsteroidal Antiinflammatory Drugs in Ankylosing Spondylitis and Other Spondyloarthritis Patients

    DEFF Research Database (Denmark)

    Kristensen, L E; Jakobsen, A K; Askling, J

    2015-01-01

    OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardio......OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular...

  1. Drug and alcohol crash risk : traffic safety facts : research note.

    Science.gov (United States)

    2015-02-01

    While the extent of use of alcohol by drivers and the risks posed by alcohol use have been well known for many decades, relatively little has been known about the use of other drugs by drivers and the associated risks. However, drug-impaired driving ...

  2. Surveillance and Epidemiology of Drug Resistant Infections Consortium (SEDRIC: Supporting the transition from strategy to action [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Keiji Fukuda

    2018-05-01

    Full Text Available In recognition of the central importance of surveillance and epidemiology in the control of antimicrobial resistance and the need to strengthen surveillance at all levels, Wellcome has brought together a new international expert group SEDRIC (Surveillance and Epidemiology of Drug Resistant Infections Consortium. SEDRIC aims to advance and transform the ways of tracking, sharing and analysing rates of infection and drug resistance, burden of disease, information on antibiotic use, opportunities for preventative measures such as vaccines, and contamination of the environment. SEDRIC will strengthen the availability of information needed to monitor and track risks, including an evaluation of access to, and utility of data generated by pharma and research activities, and will support the translation of surveillance data into interventions, changes in policy and more effective practices. Ways of working will include the provision of independent scientific analysis, advocacy and expert advice to groups, such as the Wellcome Drug Resistant Infection Priority Programme. A priority for SEDRIC’s first Working Group is to review mechanisms to strengthen the generation, collection, collation and dissemination of high quality data, together with the need for creativity in the use of existing data and proxy measures, and linking to existing in-country networking infrastructure. SEDRIC will also promote the translation of technological innovations into public health solutions.

  3. The pharmacist and adverse drug reaction reporting.

    Science.gov (United States)

    Pearson, K

    1982-08-01

    During premarketing trials, the number of patients exposed to a drug and the length of exposure to a drug are both limited. After marketing, many thousands, frequently millions, of patients are exposed to the drug over considerably longer periods of time, and adverse drug reactions not previously recognized appear. Because of these factors, postmarketing surveillance is extremely important. Pharmacists can contribute to drug safety and improved patient care by understanding and actively participating in the Food and Drug Administration's Spontaneous Reporting Program.

  4. Drug resistant tuberculosis in Saudi Arabia: an analysis of surveillance data 2014-2015.

    Science.gov (United States)

    Al Ammari, Maha; Al Turaiki, Abdulrahman; Al Essa, Mohammed; Kashkary, Abdulhameed M; Eltigani, Sara A; Ahmed, Anwar E

    2018-01-01

    There is limited data that investigates the national rates of drug-resistant tuberculosis (TB) in Saudi Arabia.This study aimed to estimate the rates of multi-drug-resistant tuberculosis (MDR-TB), rifampicin-resistant tuberculosis (RR-TB), and monoresistance (MR) in Saudi Arabia. A retrospective cohort study was conducted on all TB cases reported to the National TB Control and Prevention Program (NTCPP) registry at the Saudi Ministry of Health between January 1, 2014 and December 31, 2015. A total of 2098 TB patients with positive TB cultures were included in the study. Subgroup analyses and multivariate binary logistic regression models were performed with IBM SPSS 23.0. Of the total TB cases, 4.4% (95% CI: 3.59%-5.40%) were found to have MDR-TB. The rates of MR were 3.8% (95% CI: 2.99%-4.67%) for ethambutol, 5.4% (95% CI: 4.50%-6.49%) for pyrazinamide, 10.2% (95% CI: 5.89%-11.52%) for isoniazid, 11% (95% CI: 9.70%-12.43%) for streptomycin, and 5.9% (95% CI: 4.90%-6.96%) for rifampicin. The high rates of MDR and RR-TB were found among the younger age group, female gender, and those who had a previous history of TB. We also discovered that renal failure tends to increase the risk of rifampicin resistance. National TB data in Saudi Arabia shows that the rate of MDR-TB was similar to the global rate reported by the World Health Organization (WHO). It is a relatively high rate as compared to Western countries. The proportion of MDR/RR-TB patients tends to be higher in the younger age group, female gender, and in patients with a previous history of TB treatment. Effective strategies for prevention of all multi-drug-resistant TB cases are warranted.

  5. Legacy data sharing to improve drug safety assessment: the eTOX project

    DEFF Research Database (Denmark)

    Sanz, Ferran; Pognan, François; Steger-Hartmann, Thomas

    2017-01-01

    The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through...

  6. Safety, efficacy, and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis

    DEFF Research Database (Denmark)

    Egeberg, A; Ottosen, M B; Gniadecki, R

    2018-01-01

    BACKGROUND: Real-life data on newer biologic and biosimilar agents for moderate-to-severe psoriasis are lacking. OBJECTIVES: To examine safety, efficacy, and time to discontinuation (drug survival) of biologics (adalimumab, etanercept, infliximab, secukinumab, and ustekinumab) and compare origina...... the long-term safety of novel biologics for psoriasis. This article is protected by copyright. All rights reserved....

  7. Safety and efficacy of lansoprazole injection in upper gastrointestinal bleeding: a postmarketing surveillance conducted in Indonesia.

    Science.gov (United States)

    Syam, Ari F; Setiawati, Arini

    2013-04-01

    to assess the safety and effectiveness of lansoprazole injection (Prosogan®) in patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis. this study was a multicenter observational postmarketing study of lansoprazole (Prosogan®) injection. Patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis were given intravenous lansoprazole for a maximum of 7 days or until the bleeding stopped and the patients were able to take oral doses of lansoprazole. Primary outcome of the study was cessation of bleeding. Some laboratory parameters were also measured. among a total of 204 patients evaluable for safety, there was no adverse event reported during the study. A total of 200 patients were eligible for efficacy evaluation, 125 patients (62.5%) were males. Among these patients, upper GI bleeding stopped in 20 patients (10.0%) on day 1, in 71 patients (35.5%) on day 2, 75 patients (37.5%) on day 3, 24 patients (12.0%) on day 4, and 7 patients (3.5%) on day 5, making a cumulative of 197 patients (98.5%) on day 5. The hemostatic effect was rated as 'excellent' if the bleeding stopped within 3 days, and 'good' if the bleeding stopped within 5 days. Thus, the results were 'excellent' in 166 patients (83.0%) and 'good' in 31 patients (15.5%). These results were not different between males and females, between age below 60 years and 60 years and above, and between baseline Hb below 10 g/dL and 10 g/dL and above. the results of this observational postmarketing study in 200 patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis demonstrated that intravenous lansoprazole twice a day was well tolerated and highly effective.

  8. Country-wide surveillance of molecular markers of antimalarial drug resistance in Senegal by use of positive Malaria Rapid Diagnostic Tests

    DEFF Research Database (Denmark)

    Ndiaye, Magatte; Sow, Doudou; Nag, Sidsel

    2017-01-01

    of drug resistance. Therefore, surveillance of drug resistance in the malaria parasites is essential. The objective of this pilot study was to test the feasibility of routinely sampled malaria rapid diagnostic tests (RDTs) at a national scale to assess the temporal changes in the molecular profiles...... of antimalarial drug resistance markers of Plasmodium falciparum parasites. Overall, 9,549 positive malaria RDTs were collected from 14 health facilities across the country. A limited random set of RDTs were analyzed regarding Pfcrt gene polymorphisms at codon 72-76. Overall, a high but varied prevalence (> 50...

  9. The Influence of Safety, Efficacy, and Medical Condition Severity on Natural versus Synthetic Drug Preference.

    Science.gov (United States)

    Meier, Brian P; Lappas, Courtney M

    2016-11-01

    Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as safer than the synthetic drug, and as that difference increased, the odds of choosing the natural over synthetic drug increased. In studies 2 and 3, approximately 20% of participants selected the natural drug even when they were informed that it was less safe (study 2) or less effective (study 3) than the synthetic drug. Finally, in study 4, approximately 65% of participants chose a natural over synthetic drug regardless of the severity of a specific medical condition (mild v. severe hypertension), and this choice was predicted by perceived safety and efficacy differences. Overall, these data indicate that there is a bias for natural over synthetic drugs. This bias could have implications for drug choice and usage. © The Author(s) 2015.

  10. HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy.

    Science.gov (United States)

    Avila-Ríos, Santiago; García-Morales, Claudia; Tapia-Trejo, Daniela; Meza, Rita I; Nuñez, Sandra M; Parham, Leda; Flores, Norma A; Valladares, Diana; Pineda, Luisa M; Flores, Dixiana; Motiño, Roxana; Umanzor, Víctor; Carbajal, Candy; Murillo, Wendy; Lorenzana, Ivette; Palou, Elsa Y; Reyes-Terán, Gustavo

    2015-01-01

    We assessed HIV drug resistance (DR) in individuals failing ART (acquired DR, ADR) and in ART-naïve individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART. 365 HIV-infected, ART-naïve, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIVDR mutation list and the Stanford algorithm. Recently infected (RI) individuals were identified using a multi-assay algorithm. PDR to any ARV drug was 11.5% (95% CI 8.4-15.2%). NNRTI PDR prevalence (8.2%) was higher than NRTI (2.2%) and PI (1.9%, p500 vs. Honduras remains at the intermediate level, after 10 years of widespread availability of ART. Evidence of ADR influencing the presence of PDR was observed by phylogenetic analyses and ADR/PDR mutation frequency correlations.

  11. The US Food and Drug Administration’s drug safety recommendations and long-acting beta2-agonist dispensing pattern changes in adult asthma patients: 2003–2012

    Directory of Open Access Journals (Sweden)

    Zhou EH

    2017-03-01

    Full Text Available Esther H Zhou,1 Sally Seymour,2 Margie R Goulding,1 Elizabeth M Kang,1 Jacqueline M Major,1 Solomon Iyasu1 1Division of Epidemiology, Office of Surveillance and Epidemiology, 2Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA Background: Emerging safety issues associated with long-acting beta2-agonist (LABA have led to multiple regulatory activities by the US Food and Drug Administration (FDA since 2003, including Drug Safety Communications (DSCs in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment. Methods: We examined the initiation of LABA-containing products for adult asthma treatment using an intermittent time series approach in a claims database from 2003 to 2012. We assessed the alignment of dispensing patterns with the following 2010 FDA recommendations: 1 contraindicated use of single-ingredient (SI-LABA without an asthma controller medication (ACM; 2 a LABA should only be used when asthma is not adequately controlled on inhaled corticosteroids (ICSs or ACM; and 3 step-down asthma therapy (e.g., discontinue LABA when asthma control is achieved. Results: There were 477,922 adults (18–64 years old dispensed a new LABA during 2003–2012. Among LABA initiators, patients who initiated an SI-LABA and who did “not” have an ACM dispensed on the same date decreased from >9% in 2003 (the initial labeling change to <2% post 2010 DSCs (p-value <0.0001 in the segmented regression model. The proportion of asthma patients dispensed an ICS in 6 months prior to initiating LABA treatment did not increase. The proportion of patients with longer than 4 months of continuous treatment did not decrease over the study period. Conclusion: Although the decrease in SI-LABA initiation is consistent with FDA’s recommendations, low ICS dispensing before initiating a LABA and LABA continuation practices require further efforts

  12. Safety of laboratory analyzers for infection testing - results of the market surveillance by the BfArM until end 2007

    Directory of Open Access Journals (Sweden)

    Siekmeier R

    2009-12-01

    Full Text Available Abstract The European Directive 98/79/EC on in vitro diagnostic medical devices (IVD stipulates the marketing and post market surveillance of IVD in the European Economic Area. In cases of issues and field corrective actions, the manufacturers have to inform the responsible Competent Authorities (CA. In Germany, the Federal Institute for Drugs and Medical Devices (BfArM is the responsible CA for most IVD, with a small subset of IVD for immune hematological and infectiological testing as well as tissue typing as specified in Annex II of the Directive, being within the responsibility of the Paul-Ehrlich-Institute (PEI. In this study, all issues regarding laboratory analyzers for infection testing and their consumables, but not reagents, kits and general culture media, reported to the BfArM between begin 1999 and end of 2007 were analyzed in respect to the sources of report, the underlying product failure and the performed corrective actions. Within the observation period a total of 1471 reports for IVD were received of which 73 related to the IVD for infection testing were included in our study. Reports were predominantly received from manufacturers (56 and competent authorities (15. Affected products were most frequently those for immunological analysis (42 whereas those based on culturing techniques (17 and molecular biological techniques (14 played only minor roles. In all these groups, laboratory analyzers (55 were more frequently affected than their consumables (18. Investigations of the manufacturers were able to identify the underlying root causes of product failures in 62 cases (84.9%. In 2 cases (2.7% the root cause remained unclear and in 9 cases (12.3% a product failure was excluded or a user error was the underlying cause. Product failures in laboratory analyzers were most frequently caused by software errors (31 and constructional faults (8 whereas the predominant cause of product failure in consumables were errors in production and

  13. Pancreatic Safety of Incretin-Based Drugs - FDA and EMA Assessment

    NARCIS (Netherlands)

    Egan, Amy G.; Blind, Eberhard; Dunder, Kristina; de Graeff, Pieter A.; Hummer, B. Timothy; Bourcier, Todd; Rosebraugh, Curtis

    2014-01-01

    After evaluating a safety signal regarding pancreatitis and pancreatic cancer in patients using incretin-based drugs, the Food and Drug Administration and the European Medicines Agency conclude that assertions of a causal association are inconsistent with the data. With approximately 25.8 million

  14. 78 FR 71036 - Pipeline Safety: Random Drug Testing Rate; Contractor Management Information System Reporting...

    Science.gov (United States)

    2013-11-27

    ... PHMSA-2013-0248] Pipeline Safety: Random Drug Testing Rate; Contractor Management Information System Reporting; and Obtaining Drug and Alcohol Management Information System Sign-In Information AGENCY: Pipeline... Management Information System (MIS) Data; and New Method for Operators to Obtain User Name and Password for...

  15. Drug Safety Monitoring in Children: Performance of Signal Detection Algorithms and Impact of Age Stratification

    NARCIS (Netherlands)

    O.U. Osokogu (Osemeke); C. Dodd (Caitlin); A.C. Pacurariu (Alexandra C.); F. Kaguelidou (Florentia); D.M. Weibel (Daniel); M.C.J.M. Sturkenboom (Miriam)

    2016-01-01

    textabstractIntroduction: Spontaneous reports of suspected adverse drug reactions (ADRs) can be analyzed to yield additional drug safety evidence for the pediatric population. Signal detection algorithms (SDAs) are required for these analyses; however, the performance of SDAs in the pediatric

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

    Science.gov (United States)

    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.

  17. Changes in the utilization of osteoporosis drugs after the 2010 FDA bisphosphonate drug safety communication

    Directory of Open Access Journals (Sweden)

    Bander Balkhi

    2018-02-01

    Conclusions: The 2010 FDA bisphosphonates safety communication appeared to have influenced Osteoporosis utilization in Medicaid recipients. The 2010 FDA bisphosphonates safety communication was associated with a significant reduction in the utilization of bisphosphonates in the Medicaid program.

  18. Regulatory surveillance of safety related maintenance at nuclear power plants. Report of a technical committee meeting

    International Nuclear Information System (INIS)

    1997-08-01

    The operational safety and reliability of a nuclear power plant as well as its availability for electricity generation depend on, among other things, its maintenance programme. Regulatory bodies therefore have considerable interest in maintenance activities. There are several approaches to maintenance, i.e. reliability centered maintenance or risk focused maintenance, aimed at optimizing maintenance by focusing on important components or systems. These approaches may result in significant changes to maintenance activities and therefore have to be considered for regulatory acceptance. In order to review and discuss the status of maintenance regulation in participating countries, the IAEA convened a Technical Committee Meeting on Regulatory Oversight of Maintenance Activities at Nuclear Power Plants in Vienna from 9 to 13 October 1995. The meeting was attended by 16 experts from 11 countries. In addition to the consideration of papers that were presented and which are reproduced here, extensive group and panel discussions took place during the meeting. These covered three main topics: general features and basic characteristics of maintenance regulation, regulatory acceptance of maintenance optimization and use of PSA for maintenance optimization. The discussion are summarized in Section 2. Section 3 discusses the following three additional topics: regulatory involvement in the maintenance programme, modifications to the maintenance programme and personnel related aspects of maintenance. The conclusions are presented in Section 4. Figs, tabs

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

    Science.gov (United States)

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

    2010-11-01

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

  20. Post-Marketing Safety Surveillance of the Salvia Miltiorrhiza Depside Salt for Infusion: A Real World Study.

    Directory of Open Access Journals (Sweden)

    Ying-Ying Yan

    Full Text Available Salvia Miltiorrhiza Depside Salt for Infusion (SMDS is made of a group of highly purified listed drugs. However, its safety data is still reported limitedly. Compared with the clinical trials, its safety in the real world setting is barely assessed.To investigate the safety issues, including adverse events (AEs, adverse events related to SMDS (ADEs, and adverse drug reactions (ADRs of the SMDS in the real world clinical practice.This is a prospective, multicenter, pharmacist-led, cohort study in the real world setting. Consecutive patients prescribed with SMDS were all included in 36 sites. Pharmacists were well trained to standardized collect the patients information, including demographics, medical history, prescribing patterns of SMDS, combined medications, adverse events, laboratory investigations, outcomes of the treatment when discharge, and interventions by pharmacists. Adverse events and adverse drug reactions were collected in details. Multivariate possion regression analysis was applied to identify risk factors associated with ADEs using the significance level (α 0.05. ClinicalTrials.gov Identifier: NCT01872520.Thirty six hospitals were participated in the study and 30180 consecutive inpatients were included. The median age was 62 (interquartile range [IQR], 50-73 years, and male was 17384 (57.60% among the 30180 patients. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. There were 9 kinds of new ADEs which were not on the approved label found in the present study. According to the multivariate analysis, male (RR = 1.381, P = 0.009, 95%CI [1.085~1.759], more concomitant medications (RR = 1.049, P<0.001, 95%CI [1.041~1.057], longer duration of SMDS therapy (RR = 1.027, P<0.001, 95%CI [1.013~1.041], higher drug concentration (RR = 1.003, P = 0.014, 95%CI [1.001~1.006], and resolvent unapproved (RR = 1.900, P = 0.002, 95%CI [1.260~2.866] were the independent risk factors of the ADEs. Moreover, following

  1. Application of the Pareto principle to identify and address drug-therapy safety issues.

    Science.gov (United States)

    Müller, Fabian; Dormann, Harald; Pfistermeister, Barbara; Sonst, Anja; Patapovas, Andrius; Vogler, Renate; Hartmann, Nina; Plank-Kiegele, Bettina; Kirchner, Melanie; Bürkle, Thomas; Maas, Renke

    2014-06-01

    Adverse drug events (ADE) and medication errors (ME) are common causes of morbidity in patients presenting at emergency departments (ED). Recognition of ADE as being drug related and prevention of ME are key to enhancing pharmacotherapy safety in ED. We assessed the applicability of the Pareto principle (~80 % of effects result from 20 % of causes) to address locally relevant problems of drug therapy. In 752 cases consecutively admitted to the nontraumatic ED of a major regional hospital, ADE, ME, contributing drugs, preventability, and detection rates of ADE by ED staff were investigated. Symptoms, errors, and drugs were sorted by frequency in order to apply the Pareto principle. In total, 242 ADE were observed, and 148 (61.2 %) were assessed as preventable. ADE contributed to 110 inpatient hospitalizations. The ten most frequent symptoms were causally involved in 88 (80.0 %) inpatient hospitalizations. Only 45 (18.6 %) ADE were recognized as drug-related problems until discharge from the ED. A limited set of 33 drugs accounted for 184 (76.0 %) ADE; ME contributed to 57 ADE. Frequency-based listing of ADE, ME, and drugs involved allowed identification of the most relevant problems and development of easily to implement safety measures, such as wall and pocket charts. The Pareto principle provides a method for identifying the locally most relevant ADE, ME, and involved drugs. This permits subsequent development of interventions to increase patient safety in the ED admission process that best suit local needs.

  2. [Drug supply chain safety in hospitals: current data and experience of the Grenoble university hospital].

    Science.gov (United States)

    Bedouch, P; Baudrant, M; Detavernier, M; Rey, C; Brudieu, E; Foroni, L; Allenet, B; Calop, J

    2009-01-01

    Drug supply chain safety has become a priority for public health which implies a collective process. This process associates all health professionals including the pharmacist who plays a major role. The objective of this present paper is to describe the several approaches proven effective in the reduction of drug-related problem in hospital, illustrated by the Grenoble University Hospital experience. The pharmacist gets involved first in the general strategy of hospital drug supply chain, second by his direct implication in clinical activities. The general strategy of drug supply chain combines risk management, coordination of the Pharmacy and Therapeutics Committee, selection and purchase of drugs and organisation of drug supply chain. Computer management of drug supply chain is a major evolution. Nominative drug delivering has to be a prior objective and its implementation modalities have to be defined: centralized or decentralized in wards, manual or automated. Also, new technologies allow the automation of overall drug distribution from central pharmacy and the implementation of automated drug dispensing systems into wards. The development of centralised drug preparation allows a safe compounding of high risk drugs, like cytotoxic drugs. The pharmacist should develop his clinical activities with patients and other health care professionals in order to optimise clinical decisions (medication review, drug order analysis) and patients follow-up (therapeutic monitoring, patient education, discharge consultation).

  3. Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

    Science.gov (United States)

    Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

    2018-01-01

    Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

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

    Science.gov (United States)

    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

  5. Discovering Cohorts of Pregnant Women From Social Media for Safety Surveillance and Analysis.

    Science.gov (United States)

    Sarker, Abeed; Chandrashekar, Pramod; Magge, Arjun; Cai, Haitao; Klein, Ari; Gonzalez, Graciela

    2017-10-30

    Pregnancy exposure registries are the primary sources of information about the safety of maternal usage of medications during pregnancy. Such registries enroll pregnant women in a voluntary fashion early on in pregnancy and follow them until the end of pregnancy or longer to systematically collect information regarding specific pregnancy outcomes. Although the model of pregnancy registries has distinct advantages over other study designs, they are faced with numerous challenges and limitations such as low enrollment rate, high cost, and selection bias. The primary objectives of this study were to systematically assess whether social media (Twitter) can be used to discover cohorts of pregnant women and to develop and deploy a natural language processing and machine learning pipeline for the automatic collection of cohort information. In addition, we also attempted to ascertain, in a preliminary fashion, what types of longitudinal information may potentially be mined from the collected cohort information. Our discovery of pregnant women relies on detecting pregnancy-indicating tweets (PITs), which are statements posted by pregnant women regarding their pregnancies. We used a set of 14 patterns to first detect potential PITs. We manually annotated a sample of 14,156 of the retrieved user posts to distinguish real PITs from false positives and trained a supervised classification system to detect real PITs. We optimized the classification system via cross validation, with features and settings targeted toward optimizing precision for the positive class. For users identified to be posting real PITs via automatic classification, our pipeline collected all their available past and future posts from which other information (eg, medication usage and fetal outcomes) may be mined. Our rule-based PIT detection approach retrieved over 200,000 posts over a period of 18 months. Manual annotation agreement for three annotators was very high at kappa (κ)=.79. On a blind test set

  6. Exploiting pluripotent stem cell technology for drug discovery, screening, safety, and toxicology assessments.

    Science.gov (United States)

    McGivern, Jered V; Ebert, Allison D

    2014-04-01

    In order for the pharmaceutical industry to maintain a constant flow of novel drugs and therapeutics into the clinic, compounds must be thoroughly validated for safety and efficacy in multiple biological and biochemical systems. Pluripotent stem cells, because of their ability to develop into any cell type in the body and recapitulate human disease, may be an important cellular system to add to the drug development repertoire. This review will discuss some of the benefits of using pluripotent stem cells for drug discovery and safety studies as well as some of the recent applications of stem cells in drug screening studies. We will also address some of the hurdles that need to be overcome in order to make stem cell-based approaches an efficient and effective tool in the quest to produce clinically successful drug compounds. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Transmitted antiretroviral drug resistance in New York State, 2006-2008: results from a new surveillance system.

    Directory of Open Access Journals (Sweden)

    Adam C Readhead

    Full Text Available HIV transmitted drug resistance (TDR is a public health concern because it has the potential to compromise antiretroviral therapy (ART at the population level. In New York State, high prevalence of TDR in a local cohort and a multiclass resistant case cluster led to the development and implementation of a statewide resistance surveillance system.We conducted a cross-sectional analysis of the 13,109 cases of HIV infection that were newly diagnosed and reported in New York State between 2006 and 2008, including 4,155 with HIV genotypes drawn within 3 months of initial diagnosis and electronically reported to the new resistance surveillance system. We assessed compliance with DHHS recommendations for genotypic resistance testing and estimated TDR among new HIV diagnoses.Of 13,109 new HIV diagnoses, 9,785 (75% had laboratory evidence of utilization of HIV-related medical care, and 4,155 (43% had a genotype performed within 3 months of initial diagnosis. Of these, 11.2% (95% confidence interval [CI], 10.2%-12.1% had any evidence of TDR. The proportion with mutations associated with any antiretroviral agent in the NNRTI, NRTI or PI class was 6.3% (5.5%-7.0%, 4.3% (3.6%-4.9% and 2.9% (2.4%-3.4%, respectively. Multiclass resistance was observed in <1%. TDR did not increase significantly over time (p for trend = 0.204. Men who have sex with men were not more likely to have TDR than persons with heterosexual risk factor (OR 1.0 (0.77-1.30. TDR to EFV+TDF+FTC and LPV/r+TDF+FTC regimens was 7.1% (6.3%-7.9% and 1.4% (1.0%-1.8%, respectively.TDR appears to be evenly distributed and stable among new HIV diagnoses in New York State; multiclass TDR is rare. Less than half of new diagnoses initiating care received a genotype per DHHS guidelines.

  8. Evaluation of a Broad-Spectrum Partially Automated Adverse Event Surveillance System: A Potential Tool for Patient Safety Improvement in Hospitals With Limited Resources.

    Science.gov (United States)

    Saikali, Melody; Tanios, Alain; Saab, Antoine

    2017-11-21

    The aim of the study was to evaluate the sensitivity and resource efficiency of a partially automated adverse event (AE) surveillance system for routine patient safety efforts in hospitals with limited resources. Twenty-eight automated triggers from the hospital information system's clinical and administrative databases identified cases that were then filtered by exclusion criteria per trigger and then reviewed by an interdisciplinary team. The system, developed and implemented using in-house resources, was applied for 45 days of surveillance, for all hospital inpatient admissions (N = 1107). Each trigger was evaluated for its positive predictive value (PPV). Furthermore, the sensitivity of the surveillance system (overall and by AE category) was estimated relative to incidence ranges in the literature. The surveillance system identified a total of 123 AEs among 283 reviewed medical records, yielding an overall PPV of 52%. The tool showed variable levels of sensitivity across and within AE categories when compared with the literature, with a relatively low overall sensitivity estimated between 21% and 44%. Adverse events were detected in 23 of the 36 AE categories defined by an established harm classification system. Furthermore, none of the detected AEs were voluntarily reported. The surveillance system showed variable sensitivity levels across a broad range of AE categories with an acceptable PPV, overcoming certain limitations associated with other harm detection methods. The number of cases captured was substantial, and none had been previously detected or voluntarily reported. For hospitals with limited resources, this methodology provides valuable safety information from which interventions for quality improvement can be formulated.

  9. Why trash don't pass? pharmaceutical licensing and safety performance of drugs.

    Science.gov (United States)

    Banerjee, Tannista; Nayak, Arnab

    2017-01-01

    This paper examines how asymmetric information in pharmaceutical licensing affects the safety standards of licensed drugs. Pharmaceutical companies often license potential drug molecules at different stages of drug development from other pharmaceutical or biotechnology companies and complete the remaining of research stages before submitting the new drug application(NDA) to the food and drug administration. The asymmetric information associated with the quality of licensed molecules might result in the molecules which are less likely to succeed to be licensed out, while those with greater potential of success being held internally for development. We identify the NDAs submitted between 1993 and 2004 where new molecular entities were acquired through licensing. Controlling for other drug area specific and applicant firm specific factors, we investigate whether drugs developed with licensed molecules face higher probability of safety based recall and ultimate withdrawal from the market than drugs developed internally. Results suggest the opposite of Akerlof's (Q J Econ 84:488-500, 1970) lemons problem. Licensed molecules rather have less probability of facing safety based recalls and ultimate withdrawal from the market comparing to internally developed drug molecules. This suggests that biotechnology and small pharmaceutical firms specializing in pharmaceutical research are more efficient in developing good potential molecules because of their concentrated research. Biotechnology firms license out good potential molecules because it increases their market value and reputation. In addition, results suggest that both the number of previous approved drugs in the disease area, and also the applicant firms' total number of previous approvals in all disease areas reduce the probability that an additional approved drug in the same drug area will potentially be harmful.

  10. Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

    OpenAIRE

    Castleden, C M; Pickles, H

    1988-01-01

    1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age grou...

  11. Context Is Everything: Harmonization of Critical Food Microbiology Descriptors and Metadata for Improved Food Safety and Surveillance

    Directory of Open Access Journals (Sweden)

    Emma Griffiths

    2017-06-01

    Full Text Available Globalization of food networks increases opportunities for the spread of foodborne pathogens beyond borders and jurisdictions. High resolution whole-genome sequencing (WGS subtyping of pathogens promises to vastly improve our ability to track and control foodborne disease, but to do so it must be combined with epidemiological, clinical, laboratory and other health care data (called “contextual data” to be meaningfully interpreted for regulatory and health interventions, outbreak investigation, and risk assessment. However, current multi-jurisdictional pathogen surveillance and investigation efforts are complicated by time-consuming data re-entry, curation and integration of contextual information owing to a lack of interoperable standards and inconsistent reporting. A solution to these challenges is the use of ‘ontologies’ - hierarchies of well-defined and standardized vocabularies interconnected by logical relationships. Terms are specified by universal IDs enabling integration into highly regulated areas and multi-sector sharing (e.g., food and water microbiology with the veterinary sector. Institution-specific terms can be mapped to a given standard at different levels of granularity, maximizing comparability of contextual information according to jurisdictional policies. Fit-for-purpose ontologies provide contextual information with the auditability required for food safety laboratory accreditation. Our research efforts include the development of a Genomic Epidemiology Ontology (GenEpiO, and Food Ontology (FoodOn that harmonize important laboratory, clinical and epidemiological data fields, as well as existing food resources. These efforts are supported by a global consortium of researchers and stakeholders worldwide. Since foodborne diseases do not respect international borders, uptake of such vocabularies will be crucial for multi-jurisdictional interpretation of WGS results and data sharing.

  12. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

    OpenAIRE

    Roth, Sandford

    2011-01-01

    Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less...

  13. Social safety and medical maintenance of the labour pool in surveillance areas of the nuclear power plants.

    Science.gov (United States)

    Prylipko, V A; Ozerova, Yu Yu; Kotsubinskij, O V; Morozova, M M; Petrychenko, O O; Bondarenko, I V

    2017-12-01

    To study the contentment of population of NPP surveillance areas i.e. monitoring zones with specific components of quality of life, namely the social security, medical care, and socio economic compensation of risk. A sociological study of public opinion about the specific components of quality of life has been conducted in population of the NPP monitoring zone. A questionnaire with independent question blocks was developed. A non repeatable probabilistic selection was applied in population opinion poll. The sampled population was calculated on the basis of the total population living in the NPP monitoring zone. Sample error not exceeded 7.0%. A comparative assessment of the responses of various groups of the able bodied population on issues of social security, medical care, socio economic compensation of risk and analysis of statistical data for 2011-2015 on the resource potential of medical facility of the nuclear power plant overspill town has been conducted. The safety and security status is rated at below the average. Documents regulating the life safety of pop ulation of NPP monitoring zone provide them no confidence in their security. Probability estimates of man made accidents are higher in urban population and depend on education level. The socialized health care is assessed on low and average levels according to the studied parameters. Among the types of medical care the providing of nec essary medical goods, preventive examinations, scheduled medical examination service, ambulance activity, and medical psychological aid need to be improved. There was no significant change in resource potential of special ized healthcare infirmary of NPP overspill town for the last 5 years. Low rating by the monitoring zone population of work efficiency of health facilities is determined by a set of factors, some of which lies in the plane of state socio economic problems. Choice priority of the direct sub ventions in population of monitoring zone depends on the place of

  14. Evaluation of Aryoseven Safety (Recombinant Activated Factor VII) in Patients with Bleeding Disorders (An Observational Post-Marketing Surveillance Study).

    Science.gov (United States)

    Toogeh, Gholamreza; Abolghasemi, Hassan; Eshghi, Peyman; Managhchi, Mohammadreza; Shaverdi-Niasari, Mohammadreza; Karimi, Katayoon; Roostaei, Samin; Emran, Neda; Abdollahi, Alireza

    2016-01-01

    Recombinant activated factor VII induces hemostasis in patients with coagulopathy disorders. AryoSeven™ as a safe Iranian Recombinant activated factor VII has been available on our market. This study was performed to establish the safety of AryoSeven on patients with coagulopathy disorder. This single-center, descriptive, cross sectional study was carried out in Thrombus and Homeostasis Research Center ValiAsr Hospital during 2013-2014. Fifty one patients with bleeding disorders who received at least one dose of Aryoseven were enrolled. Patients' demographic data and adverse effect of drug and reaction related to Aryoseven or previous usage of Recombinant activated FVII were recorded in questionnaires. Finally data were analyzed to compare side effects of Aryoseven and other Recombinant activated FVII brands. Aryoseven was prescribed for 51 Patients. Of all participants with mean age 57.18+21.38 yr, 31 cases were male and 26 subjects had past history of recombinant activated FVII usage. Glanzman was the most frequent disorder followed by congenital FVII deficiency, hemophilia with inhibitors, factor 5 deficiency, acquired hemophilia, hemophilia A with inhibitor, and hemophilia A or B with inhibitor. The majority of bleeding episodes had occurred in joints. Three patients (5.9%) complained about adverse effects of Aryoseven vs. 11.5 % about adverse effects of other brands. However this difference was not significant, statistically. Based on monitor patients closely for any adverse events, we concluded that Aryoseven administration under careful weighing of benefit versus potential harm may comparable with other counterpart drugs.

  15. Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

    Directory of Open Access Journals (Sweden)

    Giovanni Sotgiu

    2015-03-01

    Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

  16. Safety and problems in using radioactive drugs in hospitals

    International Nuclear Information System (INIS)

    Arimizu, Noboru

    1975-01-01

    The safety and the control problem of non-closed RI (radiopharmaceuticals) of which use has rapidly been increased, were studied. At present, the hospitals with an independent clinic for the nuclear medicine are very limited and many doctors, nurses and safety controllers who are working in the clinic belong to other clinics. As for the diagnosis using RI examination, the dangers of the persons who are working with radioimmunoassay, especially using Au-antigen kit were studied. Furthermore, the problems concerning the reduction of exposure dose by the use of a short half-life RI, such as sup(99m)Tc and the dangers of external exposure on the persons who use the isotope were studied. In addition, the control of RI ward for RI therapy was discussed. The author considered the specialization and fixation of doctors, nurses and technicians are becoming of necessity with the advancement of RI therapy. In addition, the necessity of training nurses for the nuclear medicine was insisted on. (Tsukamoto, Y.)

  17. Safety and problems in using radioactive drugs in hospitals

    Energy Technology Data Exchange (ETDEWEB)

    Arimizu, N [National Inst. of Radiological Sciences, Chiba (Japan)

    1975-01-01

    The safety and the control problem of non-closed RI (radiopharmaceuticals) of which use has rapidly been increased, were studied. At present, the hospitals with an independent clinic for the nuclear medicine are very limited and many doctors, nurses and safety controllers who are working in the clinic belong to other clinics. As for the diagnosis using RI examination, the dangers of the persons who are working with radioimmunoassay, especially using Au-antigen kit were studied. Furthermore, the problems concerning the reduction of exposure dose by the use of a short half-life RI, such as sup(99m)Tc and the dangers of external exposure on the persons who use the isotope were studied. In addition, the control of RI ward for RI therapy was discussed. The author considered the specialization and fixation of doctors, nurses and technicians are becoming of necessity with the advancement of RI therapy. In addition, the necessity of training nurses for the nuclear medicine was insisted on.

  18. Safety risks with investigational drugs: Pharmacy practices and perceptions in the veterans affairs health system.

    Science.gov (United States)

    Cruz, Jennifer L; Brown, Jamie N

    2015-06-01

    Rigorous practices for safe dispensing of investigational drugs are not standardized. This investigation sought to identify error-prevention processes utilized in the provision of investigational drug services (IDS) and to characterize pharmacists' perceptions about safety risks posed by investigational drugs. An electronic questionnaire was distributed to an audience of IDS pharmacists within the Veteran Affairs Health System. Multiple facets were examined including demographics, perceptions of medication safety, and standard processes used to support investigational drug protocols. Twenty-one respondents (32.8% response rate) from the Northeast, Midwest, South, West, and Non-contiguous United States participated. The mean number of pharmacist full-time equivalents (FTEs) dedicated to the IDS was 0.77 per site with 0.2 technician FTEs. The mean number of active protocols was 22. Seventeen respondents (81%) indicated some level of concern for safety risks. Concerns related to the packaging of medications were expressed, most notably lack of product differentiation, expiration dating, barcodes, and choice of font size or color. Regarding medication safety practices, the majority of sites had specific procedures in place for storing and securing drug supply, temperature monitoring, and prescription labeling. Repackaging bulk items and proactive error-identification strategies were less common. Sixty-seven percent of respondents reported that an independent double check was not routinely performed. Medication safety concerns exist among pharmacists in an investigational drug service; however, a variety of measures have been employed to improve medication safety practices. Best practices for the safe dispensing of investigational medications should be developed in order to standardize these error-prevention strategies.

  19. Integrated safety analysis of rolapitant with coadministered drugs from phase II/III trials

    DEFF Research Database (Denmark)

    Barbour, S; Smit, T.; Wang, X

    2017-01-01

    adverse events by use versus non-use of drug substrates of CYP2D6 or BCRP. Patients and methods: Patients were randomized to receive either 180 mg oral rolapitant or placebo approximately 1-2 hours before chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Data...... cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined...... for treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) during cycle 1 were pooled across the four studies and summarized in the overall population and by concomitant use/non-use of CYP2D6 or BCRP substrate drugs. Results: In the integrated safety population, 828...

  20. Preventing errors in administration of parenteral drugs: the results of a four-year national patient safety program.

    NARCIS (Netherlands)

    Blok, C. de; Schilp, J.; Wagner, C.

    2013-01-01

    Objectives: To evaluate the implementation of a four-year national patient safety program concerning the parenteral drug administration process in the Netherlands. Methods: Structuring the preparation and administration process of parenteral drugs reduces the number of medication errors. A

  1. 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.

    Science.gov (United States)

    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.

  2. The Patient's Voice in Pharmacovigilance: Pragmatic Approaches to Building a Patient-Centric Drug Safety Organization.

    Science.gov (United States)

    Smith, Meredith Y; Benattia, Isma

    2016-09-01

    Patient-centeredness has become an acknowledged hallmark of not only high-quality health care but also high-quality drug development. Biopharmaceutical companies are actively seeking to be more patient-centric in drug research and development by involving patients in identifying target disease conditions, participating in the design of, and recruitment for, clinical trials, and disseminating study results. Drug safety departments within the biopharmaceutical industry are at a similar inflection point. Rising rates of per capita prescription drug use underscore the importance of having robust pharmacovigilance systems in place to detect and assess adverse drug reactions (ADRs). At the same time, the practice of pharmacovigilance is being transformed by a host of recent regulatory guidances and related initiatives which emphasize the importance of the patient's perspective in drug safety. Collectively, these initiatives impact the full range of activities that fall within the remit of pharmacovigilance, including ADR reporting, signal detection and evaluation, risk management, medication error assessment, benefit-risk assessment and risk communication. Examples include the fact that manufacturing authorization holders are now expected to monitor all digital sources under their control for potential reports of ADRs, and the emergence of new methods for collecting, analysing and reporting patient-generated ADR reports for signal detection and evaluation purposes. A drug safety department's ability to transition successfully into a more patient-centric organization will depend on three defining attributes: (1) a patient-centered culture; (2) deployment of a framework to guide patient engagement activities; and (3) demonstrated proficiency in patient-centered competencies, including patient engagement, risk communication and patient preference assessment. Whether, and to what extent, drug safety departments embrace the new patient-centric imperative, and the methods and

  3. Safety and efficacy of generic drugs with respect to brand formulation

    OpenAIRE

    Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

    2013-01-01

    Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to gener...

  4. Diffuse large B-cell lymphoma associated with the use of biologic and other investigational agents: the importance of long-term post-marketing safety surveillance.

    Science.gov (United States)

    Goddard, Allison; Borovicka, Judy H; West, Dennis P; Evens, Andrew M; Laumann, Anne

    2011-01-01

    This case report describes a patient who developed diffuse large B-cell lymphoma (DLBCL) after receiving courses of two investigational biologic agents and cyclosporine followed by more than four years of subcutaneous efalizumab for the treatment of extensive chronic plaque psoriasis. Three years later, the patient remains free of lymphoma and his psoriasis is well controlled with thrice-weekly narrow-band ultraviolet phototherapy. This case emphasizes the importance of continued long-term post-marketing safety surveillance and the early reporting of all possible serious side effects, including cancers, related to the use of any newly available product. In particular, surveillance should focus on the immunomodulating biologic agents in order to identify possible dangerous sequelae.

  5. Pharmacovigilance in Crisis: Drug Safety at a Crossroads.

    Science.gov (United States)

    Price, John

    2018-05-01

    Pharmacovigilance (PV) is under unprecedented stress from fundamental changes in a booming pharmaceutical industry, from the challenges of creating and maintaining an increasingly complex PV system in a globally diverse regulatory environment, and from unpredicted consequences of historical PV cost-reduction strategies. At the same time, talent availability lags demand, and many PV professionals may no longer be finding personal fulfillment in their careers. The situation creates risks for companies. Advantages and disadvantages of potential strategies to address this increasing problem at a corporate and industry level and in collaboration with regulatory agencies are discussed, as well as opportunities to adopt new technologies, including artificial intelligence and machine-learning to automate pharmacovigilance operations. These approaches would address burdensome and wasteful effort assuring regulatory compliance and free up resources to support the original mission of PV as an important public health activity and to reinvest in the development of new drugs. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  6. What can nanosafety learn from drug development? The feasibility of “safety by design”

    DEFF Research Database (Denmark)

    Hjorth, Rune; van Hove, Lilian; Wickson, Fern

    2017-01-01

    Safety by design” (SbD) is an intuitively appealing concept that is on the rise within nanotoxicology and nanosafety research, as well as within nanotechnology research policy. It leans on principles established within drug discovery and development (DDD) and seeks to address safety early, as well...... as throughout product development. However, it remains unclear what the concept of SbD exactly entails for engineered nanomaterials (ENMs) or how it is envisioned to be implemented. Here, we review the concept as it is emerging in European research and compare its resemblance with the safety testing...

  7. Surveillance of transmitted HIV drug resistance using matched plasma and dried blood spot specimens from voluntary counseling and testing sites in Ho Chi Minh City, Vietnam, 2007-2008.

    Science.gov (United States)

    Duc, Nguyen Bui; Hien, Bui Thu; Wagar, Nick; Tram, Tran Hong; Giang, Le Truong; Yang, Chunfu; Wolfe, Mitchell I; Hien, Nguyen Tran; Tuan, Nguyen Anh

    2012-05-01

    During 2007-2008, surveillance of transmitted human immunodeficiency virus (HIV) drug resistance (TDR) was performed following World Health Organization guidance among clients with newly diagnosed HIV infection attending voluntary counseling and testing (VCT) sites in Ho Chi Minh City (HCMC), Vietnam. Moderate (5%-15%) TDR to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was observed among VCT clients aged 18-21 years. Follow-up surveillance of TDR in HCMC and other geographic regions of Vietnam is warranted. Data generated will guide the national HIV drug resistance surveillance strategy and support selection of current and future first-line antiretroviral therapy and HIV prevention programs.

  8. Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

    Science.gov (United States)

    Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

    2011-04-01

    Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2015-07-01

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

  10. Drug packaging in 2014: authorities should direct more efforts towards medication safety.

    Science.gov (United States)

    2015-05-01

    In 2014, Prescrire examined the packaging quality of about 250 drugs. A few advances stand out, mainly involving recent drugs, but on the whole, the situation is worrisome in terms of medication safety. Although pharmaceutical companies and drug regulatory agencies seem to be taking more account of the risk of accidental poisoning in children, the level of protection remains low overall in the absence of stringent measures on the part of the authorities. New drugs too often have poor-quality or even dangerous packaging at the time of their market introduction. And the packaging quality of older drugs is disturbing. Pharmaceutical companies no longer invest in the packaging of these products, and agencies often fail to take advantage of the opportunities provided by their reassessment to improve the situation. The inappropriate labelling of certain injectable drugs remains a source of medication errors, sometimes resulting in very serious consequences. In 2014, signs of progress in the packaging of several drugs show that its role in medication safety is better appreciated. But the persistence of dangers in the pharmaceuticals market, created by "unfinished", overly complex or poor-quality packaging, raises the question of the responsibility of pharmaceutical companies and agencies for past and present accidents.

  11. FDA drug safety communications: a narrative review and clinical considerations for older adults.

    Science.gov (United States)

    Marcum, Zachary A; Vande Griend, Joseph P; Linnebur, Sunny A

    2012-08-01

    The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public. To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern. FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older

  12. Use of nonsteroidal anti-inflammatory drugs among healthy people and specific cerebrovascular safety

    DEFF Research Database (Denmark)

    Fosbøl, Emil L; Olsen, Anne-Marie Schjerning; Olesen, Jonas Bjerring

    2014-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs can increase bleeding and thrombosis, but little is known about the cerebrovascular safety of these drugs, especially among healthy people. AIMS: The aim of this study was to examine the risk of ischemic and hemorrhagic stroke associated with the use...... stroke). RESULTS: We selected 1,028,437 healthy individuals (median age 39 years). At least one nonsteroidal anti-inflammatory drug was claimed by 44·7% of the study population, and the drugs were generally used for a short period of time and in low doses. High-dose ibuprofen and diclofenac were......·35-3·42)]. CONCLUSIONS: In healthy individuals, use of commonly available nonsteroidal anti-inflammatory drugs such as ibuprofen, diclofenac, and naproxen was associated with increased risk of stroke....

  13. Safety pharmacology of sibutramine mesylate, an anti-obesity drug.

    Science.gov (United States)

    Kim, Eun-Joo; Park, Eun-Kyung; Suh, Kwee-Hyun

    2005-03-01

    Sibutramine mesylate is a new anti-obesity drug. It is a crystalline salt of sibutramine developed to improve the solubility of sibutramine hydrochloride. Methanesulfonic acid was used as a salt-forming acid instead of hydrochloric acid, resulting in a greatly improved solubility of 1000 mg/mL in water. Sibutramine mesylate was administered orally to ICR mice, Sprague-Dawley rats, and beagle dogs at dose levels of 1.15, 3.45, and 11.50 mg/kg to measure its effects on the central nervous system (CNS), general behaviour, cardiovascular-respiratory system and the other organ systems. Following administration of sibutramine mesylate, spontaneous locomotor activity was significantly increased from 120 min to 24 hours at 3.45 mg/kg and from 30 min to 24 hours at 11.50 mg/kg. Furthermore, there were a decrease in hexobarbital-induced sleep time, an increase in respiratory rate at 120 min, increases in intestinal transport capacity and gastric pH at 11.50 mg/kg, and decreases in gastric volume and total acidity at 3.45 and 11.50 mg/kg. However sibutramine mesylate caused no effects on general behaviour, motor coordination, body temperature, analgesia, convulsion, blood pressure, heart rate, electrocardiogram, cardiac functions of the isolated rat heart, isolated smooth muscles and renal function. Based on the above results, it was concluded that sibutramine mesylate caused effects on the spontaneous locomotor activity, hexobarbital-induced sleep time, respiration, gastrointestinal transport, and gastric secretion at a dose level of 3.45 mg/kg or greater but caused no effects on other general pharmacological reactions.

  14. Trends in Drug Resistance of Acinetobacter baumannii over a 10-year Period: Nationwide Data from the China Surveillance of Antimicrobial Resistance Program.

    Science.gov (United States)

    Gao, Lei; Lyu, Yuan; Li, Yun

    2017-03-20

    Acinetobacter baumannii has emerged as an important pathogen causing a variety of infections. Using data from the China Surveillance of Antimicrobial Resistance Program conducted biennially, we investigated the secular changes in the resistance of 2917 isolates of A. baumannii from 2004 to 2014 to differ antimicrobial agents. Pathogen samples were collected from 17 to 20 hospitals located in the eastern, central, and western regions of China. Minimum inhibitory concentrations (MICs) were determined by a 2-fold agar dilution method, and antimicrobial susceptibility was established using the 2014 Clinical Laboratory Standards Institute-approved breakpoints. Isolates not susceptible to all the tested aminoglycosides, fluoroquinolones, β-lactams, β-lactam/β-lactam inhibitors and carbapenems were defined as extensively drug resistant. The rates of nonsusceptibility to common antimicrobial agents remained high (>65%) over the years with some fluctuations to certain agents. The prevalence of imipenem-resistant A. baumannii (IRAB) increased from 13.3% in 2004 to 70.5% in 2014 and that of extensively drug-resistant A. baumannii (XDRAB) increased from 11.1% in 2004 to 60.4% in 2014. The activity of tigecycline was stable with MIC90 ≤4 mg/L against A. baumannii from 2009 to 2014. Susceptibility to colistin remained high (97.0%) from 2009 to 2014. The prevalence of XDRAB increased in all the three surveillance regions over the years and was significantly higher in Intensive Care Unit (ICU) wards than non-ICU wards. This longitudinal multicenter surveillance program revealed the nationwide emergence of A. baumannii in China and showed a significant increase in prevalence from 2004 to 2014. High levels of bacterial resistance were detected among samples collected from clinical settings in China, with IRAB and XDRAB being especially prevalent. This study will help to guide empirical therapy and identify at-risk groups requiring more intense interventional infection control

  15. A randomised controlled trial to compare opt-in and opt-out parental consent for childhood vaccine safety surveillance using data linkage: study protocol

    OpenAIRE

    Berry, Jesia G; Ryan, Philip; Braunack-Mayer, Annette J; Duszynski, Katherine M; Xafis, Vicki; Gold, Michael S

    2011-01-01

    Abstract Background The Vaccine Assessment using Linked Data (VALiD) trial compared opt-in and opt-out parental consent for a population-based childhood vaccine safety surveillance program using data linkage. A subsequent telephone interview of all households enrolled in the trial elicited parental intent regarding the return or non-return of reply forms for opt-in and opt-out consent. This paper describes the rationale for the trial and provides an overview of the design and methods. Methods...

  16. Metabolic drug interactions - the impact of prescribed drug regimens on the medication safety.

    NARCIS (Netherlands)

    Fialova, D.; Vrbensky, K.; Topinkova, E.; Vlcek, J.; Soerbye, L.W.; Wagner, C.; Bernabei, R.

    2005-01-01

    Background and objective: Risk/benefit profile of prescribed drug regimens is unkown. Over 60% of commonly used medications interact on metabolic pathways (cytochrom P450 (CYP450), uridyl-glucuronyl tranferasis (UGT I, II) and P-glycoprotein (PGP) transport). Using an up-to-date knowledge on

  17. The practice of pre-marketing safety assessment in drug development.

    Science.gov (United States)

    Chuang-Stein, Christy; Xia, H Amy

    2013-01-01

    The last 15 years have seen a substantial increase in efforts devoted to safety assessment by statisticians in the pharmaceutical industry. While some of these efforts were driven by regulations and public demand for safer products, much of the motivation came from the realization that there is a strong need for a systematic approach to safety planning, evaluation, and reporting at the program level throughout the drug development life cycle. An efficient process can help us identify safety signals early and afford us the opportunity to develop effective risk minimization plan early in the development cycle. This awareness has led many pharmaceutical sponsors to set up internal systems and structures to effectively conduct safety assessment at all levels (patient, study, and program). In addition to process, tools have emerged that are designed to enhance data review and pattern recognition. In this paper, we describe advancements in the practice of safety assessment during the premarketing phase of drug development. In particular, we share examples of safety assessment practice at our respective companies, some of which are based on recommendations from industry-initiated working groups on best practice in recent years.

  18. 76 FR 64354 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

    Science.gov (United States)

    2011-10-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA). In particular...

  19. 76 FR 45818 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

    Science.gov (United States)

    2011-08-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... burden of fee amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA...

  20. Safety and efficacy of generic drugs with respect to brand formulation.

    Science.gov (United States)

    Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

    2013-12-01

    Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to generic formulations. In conclusion, the use of generic drugs could be related with an increased days of disease (time to relapse) or might lead to a therapeutic failure; on the other hand, a higher drug concentration might expose patients to an increased risk of dose-dependent side-effects.

  1. Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

    Directory of Open Access Journals (Sweden)

    Benjamin Hixon

    2017-02-01

    Full Text Available Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC. The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9% of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%. The three most frequently reported labeling changes were warnings (68.7%, precautions (58.6%, and patient package insert/medication guide (23.2%. Case reports resulted in the greatest number of documented literature types (n = 791, followed by randomized controlled trials (n = 76, and case control/cohort studies (n = 74. Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%, compared to LOE A (17.1%, and LOE C (14.1% (p = 0.007. Conclusions: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Original Research

  2. 76 FR 20686 - Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug...

    Science.gov (United States)

    2011-04-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0164] Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  3. 75 FR 36427 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

    Science.gov (United States)

    2010-06-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice...

  4. Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

    Science.gov (United States)

    DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

    2017-07-01

    Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

  5. The impact of medicinal drugs on traffic safety: a systematic review of epidemiological studies.

    Science.gov (United States)

    Orriols, Ludivine; Salmi, Louis-Rachid; Philip, Pierre; Moore, Nicholas; Delorme, Bernard; Castot, Anne; Lagarde, Emmanuel

    2009-08-01

    To evaluate the quality of epidemiological research into effects of medicinal drugs on traffic safety and the current knowledge in this area. The bibliographic search was done in Medline electronic database using the keywords: ((accident* or crash*) and traffic and drug*) leading to 1141 references. Additional references were retrieved from the Safetylit website and the reference lists of selected studies. Original articles published in English or French, between 1 April 1979 and 31 July 2008, were considered for inclusion. We excluded descriptive studies, studies limited to alcohol or illicit drug involvement and investigations of injuries other than from traffic crashes. Studies based on laboratory tests, driving simulators or on-the-road driving tests were also excluded. Eligible studies had to evaluate the causal relationship between the use of medicinal drugs and the risk of traffic crashes. Study quality was assessed by two independent experts, according to a grid adapted from the strengthening the reporting of observational studies in epidemiology (STROBE) statement. Twenty two studies of variable methodological quality were included. Definition of drug exposure varied across studies and depended on the data sources. Potential confounding due to the interaction between the effects of the medicinal drug and disease-related symptoms was often not controlled. The risk of motor-vehicle crashes related to benzodiazepines has been amply studied and demonstrated. Results for other medicinal drugs remain controversial. There is a need for large studies, investigating the role of individual substances in the risk of road traffic crashes. Copyright 2009 John Wiley & Sons, Ltd.

  6. Holes in the safety net: a case study of access to prescription drugs and specialty care.

    Science.gov (United States)

    Stanley, Ava; Cantor, Joel C; Guarnaccia, Peter

    2008-07-01

    The health care safety net in the United States is intended to fill gaps in health care services for uninsured and other vulnerable populations. This paper presents a case study of New Brunswick, NJ, a small city rich in safety net resources, to examine the adequacy of the American model of safety net care. We find substantial gaps in access to care despite the presence of a medical school, an abundance of primary care and specialty physicians, two major teaching hospitals, a large federally qualified health center and other safety net resources in this community of about 50,000 residents. Using a blend of random-digit-dial and area probability sampling, a survey of 595 households was conducted in 2001 generating detailed information about the health, access to care, demographic and other characteristics of 1,572 individuals. Confirming the great depth of the New Brunswick health care safety net, the survey showed that more than one quarter of local residents reported a hospital or community clinic as their usual source of care. Still, barriers to prescription drugs were reported for 11.0% of the area population and more than two in five (42.8%) local residents who perceived a need for specialty care reported difficulty getting those services. Bivariate analyses show significantly elevated risk of access problems among Hispanic and black residents, those in poor health, those relying on hospital and community clinics or with no usual source of care, and those living at or below poverty. In multivariate analysis, lack of health insurance was the greatest risk factor associated with both prescription drug and specialty access problems. Few local areas can claim the depth of safety net resources as New Brunswick, NJ, raising serious concerns about the adequacy of the American safety net model, especially for people with complex and chronic health care needs.

  7. Does the Early Adopter of Drugs Exist? A Population Based Study of General Practitioners’ Prescribing of New Drugs.20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158

    DEFF Research Database (Denmark)

    Dybdahl, Torben; Andersen, Morten; Søndergaard, Jens

    2004-01-01

    20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158......20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158...

  8. Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations.

    Science.gov (United States)

    Vega, Yolanda; Delgado, Elena; Fernández-García, Aurora; Cuevas, Maria Teresa; Thomson, Michael M; Montero, Vanessa; Sánchez, Monica; Sánchez, Ana Maria; Pérez-Álvarez, Lucia

    2015-01-01

    Our objectives were to carry out an epidemiological surveillance study on transmitted drug resistance (TDR) among individuals newly diagnosed of HIV-1 infection during a nine year period in Spain and to assess the role of transmission clusters (TC) in the propagation of resistant strains. An overall of 1614 newly diagnosed individuals were included in the study from January 2004 through December 2012. Individuals come from two different Spanish regions: Galicia and the Basque Country. Resistance mutations to reverse transcriptase inhibitors (RTI) and protease inhibitors (PI) were analyzed according to mutations included in the surveillance drug-resistance mutations list updated in 2009. TC were defined as those comprising viruses from five or more individuals whose sequences clustered in maximum likelihood phylogenetic trees with a bootstrap value ≥90%. The overall prevalence of TDR to any drug was 9.9%: 4.9% to nucleoside RTIs (NRTIs), 3.6% to non-nucleoside RTIs (NNRTIs), and 2.7% to PIs. A significant decrease of TDR to NRTIs over time was observed [from 10% in 2004 to 2% in 2012 (p=0.01)]. Sixty eight (42.2%) of 161 sequences with TDR were included in 25 TC composed of 5 or more individuals. Of them, 9 clusters harbored TDR associated with high level resistance to antiretroviral drugs. T215D revertant mutation was transmitted in a large cluster comprising 25 individuals. The impact of epidemiological networks on TDR frequency may explain its persistence in newly diagnosed individuals. The knowledge of the populations involved in TC would facilitate the design of prevention programs and public health interventions.

  9. Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations.

    Directory of Open Access Journals (Sweden)

    Yolanda Vega

    Full Text Available Our objectives were to carry out an epidemiological surveillance study on transmitted drug resistance (TDR among individuals newly diagnosed of HIV-1 infection during a nine year period in Spain and to assess the role of transmission clusters (TC in the propagation of resistant strains. An overall of 1614 newly diagnosed individuals were included in the study from January 2004 through December 2012. Individuals come from two different Spanish regions: Galicia and the Basque Country. Resistance mutations to reverse transcriptase inhibitors (RTI and protease inhibitors (PI were analyzed according to mutations included in the surveillance drug-resistance mutations list updated in 2009. TC were defined as those comprising viruses from five or more individuals whose sequences clustered in maximum likelihood phylogenetic trees with a bootstrap value ≥90%. The overall prevalence of TDR to any drug was 9.9%: 4.9% to nucleoside RTIs (NRTIs, 3.6% to non-nucleoside RTIs (NNRTIs, and 2.7% to PIs. A significant decrease of TDR to NRTIs over time was observed [from 10% in 2004 to 2% in 2012 (p=0.01]. Sixty eight (42.2% of 161 sequences with TDR were included in 25 TC composed of 5 or more individuals. Of them, 9 clusters harbored TDR associated with high level resistance to antiretroviral drugs. T215D revertant mutation was transmitted in a large cluster comprising 25 individuals. The impact of epidemiological networks on TDR frequency may explain its persistence in newly diagnosed individuals. The knowledge of the populations involved in TC would facilitate the design of prevention programs and public health interventions.

  10. Permitting product liability litigation for FDA-approved drugs and devices promotes patient safety.

    Science.gov (United States)

    Kesselheim, A S

    2010-06-01

    In 2008 and 2009, the Supreme Court reviewed the question of whether patients injured by dangerous prescription drugs or medical devices can bring tort lawsuits against pharmaceutical and device manufacturers. The Court ruled that claims against device manufacturers were preempted while claims against pharmaceutical manufacturers were not. The threat of product liability lawsuits promotes patient safety by encouraging manufacturers to take greater responsibility in providing clear warnings about known adverse effects of their products.

  11. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: myocardial and infectious adverse reactions as application cases.

    Science.gov (United States)

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-02-13

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure-activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. [Investigation of the cognition and behavior on drug safety in Beijing middle school students].

    Science.gov (United States)

    Cheng, Y C; Pan, Y P; Zhang, Y; Pan, Y T; Ding, C Y; Cao, Y; Zhuo, L; Fang, R F; Gao, A Y; Guo, J; Li, A J; Fu, Q; Ma, J; Zhan, S Y

    2017-12-18

    To understand the cognition and behavior of drug safety in Beijing middle school students and provide advice for relevant education. A cross-sectional survey using paper questionnaires was carried out on the student body of nine Beijing middle schools. Multi-stage proportionate stratified cluster sampling was adopted to enroll participants. In addition to demographic questions, the questionnaire included 17 questions assessing the cognition and behavior of safe drug use, prioritizing questions that aligned with the health education guideline for primary and secondary school students from Chinese Ministry of Education. Descriptive statistical methods were applied using the SAS 9.2 software. Of the 4 220 students investigated, 2 097(49.7%) were males and 2 123(50.3%) were females. The average age was (14.3±1.7) years. 2 030(48.1%) students were from downtown areas, 1 511(35.8%) were from urban-rural linking areas and 679(16.1%) were from rural areas. Half (51.5%) of the respondents were junior high school students, and the others were from senior high schools (34.2%) and vocational high schools (14.3%). Most of the students (89.6%) lived off campus. The awareness rate of drug safety knowledge was 74.4%, the median score of drug safety behavior was 4 points (full score was 5 points) and there was a statistically positive correlation between the two (Spearman's correlation coefficient was 0.156, Pmiddle school students is good, but problems still exist in medication adherence, the management of expired drugs and the antibiotics cognition, which need to be fixed through specific, pointed way of education. And more efforts should be made to improve the cognition in rural regions, vocational high schools and on campus students.

  13. The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety.

    Science.gov (United States)

    Carpenter, Daniel; Chattopadhyay, Jacqueline; Moffitt, Susan; Nall, Clayton

    2012-01-01

    Public agencies have discretion on the time domain, and politicians deploy numerous policy instruments to constrain it. Yet little is known about how administrative procedures that affect timing also affect the quality of agency decisions. We examine whether administrative deadlines shape decision timing and the observed quality of decisions. Using a unique and rich dataset of FDA drug approvals that allows us to examine decision timing and quality, we find that this administrative tool induces a piling of decisions before deadlines, and that these “just-before-deadline” approvals are linked with higher rates of postmarket safety problems (market withdrawals, severe safety warnings, safety alerts). Examination of data from FDA advisory committees suggests that the deadlines may impede quality by impairing late-stage deliberation and agency risk communication. Our results both support and challenge reigning theories about administrative procedures, suggesting they embody expected control-expertise trade-offs, but may also create unanticipated constituency losses.

  14. Adverse Drug Event Monitoring at the Food and Drug Administration: Your Report Can Make a Difference

    OpenAIRE

    Ahmad, Syed Rizwanuddin

    2003-01-01

    The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treati...

  15. [Evaluation of the safety of innovative drugs against viruses and infectious agents].

    Science.gov (United States)

    Kobayashi, Tetsu; Yusa, Keisuke; Kawasaki, Nana

    2013-01-01

    Recently, several novel cellular therapy products and biological drugs are being developed to treat various previously untreatable diseases. One of the most important issues regarding these innovations is how to ensure safety over infectious agents, including viruses and prions, in the earliest treatments with these products. The object of this study is a risk assessment of cases of human infectious with the agents and to present a sample risk management plan based on a collaboration among the National Institute of Health Sciences, universities, marketing authorization holders, and scientific societies. There are three subjects of study: (1) the viral safety of cellular therapy products, (2) the viral safety of biological drugs, and (3) the safety of prions. In this report, we describe the objects of the study, the project members, the study plan outline, and the ongoing plans. The results of the viral risk identification and the risk analysis of cellular therapy products will also be described, based on a review of the literature and case reports obtained during the first year of this project.

  16. Prospective drug safety monitoring using the UK primary-care General Practice Research Database: theoretical framework, feasibility analysis and extrapolation to future scenarios.

    Science.gov (United States)

    Johansson, Saga; Wallander, Mari-Ann; de Abajo, Francisco J; García Rodríguez, Luis Alberto

    2010-03-01

    Post-launch drug safety monitoring is essential for the detection of adverse drug signals that may be missed during preclinical trials. Traditional methods of postmarketing surveillance such as spontaneous reporting have intrinsic limitations, many of which can be overcome by the additional application of structured pharmacoepidemiological approaches. However, further improvement in drug safety monitoring requires a shift towards more proactive pharmacoepidemiological methods that can detect adverse drug signals as they occur in the population. To assess the feasibility of using proactive monitoring of an electronic medical record system, in combination with an independent endpoint adjudication committee, to detect adverse events among users of selected drugs. UK General Practice Research Database (GPRD) information was used to detect acute liver disorder associated with the use of amoxicillin/clavulanic acid (hepatotoxic) or low-dose aspirin (acetylsalicylic acid [non-hepatotoxic]). Individuals newly prescribed these drugs between 1 October 2005 and 31 March 2006 were identified. Acute liver disorder cases were assessed using GPRD computer records in combination with case validation by an independent endpoint adjudication committee. Signal generation thresholds were based on the background rate of acute liver disorder in the general population. Over a 6-month period, 8148 patients newly prescribed amoxicillin/clavulanic acid and 5577 patients newly prescribed low-dose aspirin were identified. Within this cohort, searches identified 11 potential liver disorder cases from computerized records: six for amoxicillin/clavulanic acid and five for low-dose aspirin. The independent endpoint adjudication committee refined this to four potential acute liver disorder cases for whom paper-based information was requested for final case assessment. Final case assessments confirmed no cases of acute liver disorder. The time taken for this study was 18 months (6 months for

  17. Medical Surveillance Monthly Report

    Science.gov (United States)

    2016-12-01

    Illness Prevention and Sun Safety. “Sun Safety.” https:// phc.amedd.army.mil/ topics /discond/hipss/Pages/ SunSafety.aspx. Accessed on 7 December 2016. 22...febrile illness; however, after its wide- spread introduction into immunologically MSMR Vol. 23 No. 12 December 2016 Page 8 naïve populations, a...October 2016 (data as of 22 November 2016) MSMR’s Invitation to Readers Medical Surveillance Monthly Report (MSMR) invites readers to submit topics for

  18. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Kejian, E-mail: kejian.wang.bio@gmail.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Weng, Zuquan [Japan National Institute of Occupational Safety and Health, Kawasaki (Japan); Sun, Liya [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Sun, Jiazhi; Zhou, Shu-Feng [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); He, Lin, E-mail: helin@Bio-X.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China)

    2015-02-13

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.

  19. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

    International Nuclear Information System (INIS)

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-01-01

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development

  20. Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy

    Directory of Open Access Journals (Sweden)

    Fegert Jörg M

    2009-04-01

    Full Text Available Abstract Most psychotropic drugs used in the treatment of children and adolescents are applied "off label" with a direct risk of under- or overdosing and a delayed risk of long-term side effects. The selection of doses in paediatric psychiatric patients requires a consideration of pharmacokinetic parameters and the development of central nervous system, and warrants specific studies in children and adolescents. Because these are lacking for most of the psychotropic drugs applied in the Child and Adolescent and Psychiatry, therapeutic drug monitoring (TDM is a valid tool to optimise pharmacotherapy and to enable to adjust the dosage of drugs according to the characteristics of the individual patient. Multi-centre TDM studies enable the identification of age- and development-dependent therapeutic ranges of blood concentrations and facilitate a highly qualified standardized documentation in the child and adolescent health care system. In addition, they will provide data for future research on psychopharmacological treatment in children and adolescents, as a baseline for example for clinically relevant interactions with various co-medications. Therefore, a German-Austrian-Swiss "Competence Network on Therapeutic Drug Monitoring in Child and Adolescent Psychiatry" was founded 1 introducing a comprehensive internet data base for the collection of demographic, safety and efficacy data as well as blood concentrations of psychotropic drugs in children and adolescents.

  1. Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

    Science.gov (United States)

    Castleden, C M; Pickles, H

    1988-10-01

    1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age.

  2. Characterization of adolescent prescription drug abuse and misuse using the Researched Abuse Diversion and Addiction-related Surveillance (RADARS(®)) System.

    Science.gov (United States)

    Zosel, Amy; Bartelson, Becki Bucher; Bailey, Elise; Lowenstein, Steven; Dart, Rick

    2013-02-01

    To describe the characteristics and health effects of adolescent (age 13-19 years) prescription drug abuse and misuse using the Researched Abuse Diversion and Addiction-Related Surveillance (RADARS(®)) System. Secondary analysis of data collected from RADARS System participating poison centers was performed. Data for all intentional exposures from 2007 through 2009 were used to describe adolescent prescription opioid (oxycodone, fentanyl, hydrocodone, hydromorphone, morphine, methadone, buprenorphine, and tramadol) and stimulant (methylphenidate and amphetamines) exposures. A total of 16,209 intentional adolescent exposures to prescription drugs were identified, 68% to opioids and 32% to stimulants. The mean age was 16.6 years (SD ± 1.7 years). Slightly more than half (52.4%) of drug mentions involved females. The five most frequently misused or abused drugs were hydrocodone (32%), amphetamines (18%), oxycodone (15%), methylphenidate (14%), and tramadol (11%). Of all exposures, 38% were classified as suspected suicidal. Of adolescents who intentionally exposed themselves to prescription drugs, 30% were treated in a health care facility, 2,792 of whom were admitted to the hospital, including 1,293 to the intensive care unit. A total of 17.2% of intentional exposures were associated with no effect, 38.9% minor effects, 23.3% moderate effects, 3.6% major effects, and 0.1% were associated with death. Oxycodone and methadone were associated with the most deaths. No deaths were associated with exposures to stimulants. Prescription drug misuse and abuse poses an important health problem and results in thousands of hospitalizations of adolescents per year. Further work is needed to develop focused interventions and educational programs to prevent prescription drug abuse and misuse by adolescents. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Ayurpharmacoepidemiology en Route to Safeguarding Safety and Efficacy of Ayurvedic Drugs in Global Outlook

    Science.gov (United States)

    Debnath, Parikshit; Banerjee, Subhadip; Adhikari, Anjan; Debnath, Pratip K.

    2016-01-01

    Ayurpharmacoepidemiology is a new field developed by synergy of the fields of clinical pharmacology, epidemiology, and ayurveda. It will use the effects of ayurvedic medicinal products on large populations to describe and analyze the practices, evaluate the safety and efficacy, and carry out medicoeconomic evaluations. Good pharmacoepidemiology practices in ayurveda is projected to assist with issues of ayurpharmacoepidemiologic research. The embraced good pharmacoepidemiology practices guideline in this viewpoint will be able to provide valuable evidence about the health effects of ayurvedic herbs/drugs and consider different fields like pharmacovigilance, pharmacoeconomics, and drug discovery with ayurvedic reverse pharmacology approach, also pass out significant data for further basic sciences study in ayurveda biology, ayurgenomics, ayurnutrigenomics, and systems biology. Several unanswered questions about ayurvedic drug use and informed interventions or policies that can be addressed by informatics database, which will eventually demonstrate the credibility and rationality of ayurceuticals in the future. PMID:26721554

  4. Anti-Obesity Drugs: A Review about Their Effects and Safety

    Directory of Open Access Journals (Sweden)

    Jun Goo Kang

    2012-02-01

    Full Text Available The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.

  5. Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

    Directory of Open Access Journals (Sweden)

    Surender Singh

    2017-01-01

    Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

  6. The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.

    Science.gov (United States)

    Heal, D J; Cheetham, S C; Smith, S L

    2009-12-01

    Results from in vivo techniques, especially intracerebral microdialysis in freely-moving rats, have provided insights into potential mechanisms responsible for the efficacy and safety of catecholaminergic drugs for ADHD treatment. The drugs reviewed come from distinct pharmacological classes: psychostimulant releasing agents, eg d-amphetamine; psychostimulant reuptake inhibitors, eg dl-threo-methylphenidate (dl-MPH), and non-stimulant reuptake inhibitors, eg atomoxetine. Psychostimulants, which currently deliver the best efficacy in treating ADHD, exhibit the following characteristics on extraneuronal catecholamine concentrations in rodent brain in vivo: 1) They enhance the efflux and function of both noradrenaline and dopamine in the central nervous system. 2) The increase of dopamine efflux that they produce is not limited to cortical regions. 3) They have a rapid onset of action with no ceiling on drug effect. d-Amphetamine has a mechanism independent of neuronal firing rate, displacing intraneuronal stores of catecholamines, delaying their reuptake and inhibiting catabolism by monoamine oxidase. dl-MPH has an enigmatic, extraneuronal action that is neuronal firing rate-dependent and reuptake transporter-mediated, yet paradoxically, almost as powerful as that of d-amphetamine. In safety terms, these powerful catecholaminergic effects also make the psychostimulants liable for abuse. Since efficacy and safety derive from the same pharmacological mechanisms, it has not yet been possible to separate these two components. However, the development of once-daily psychostimulant formulations and a prodrug, lisdexamfetamine, has improved patient compliance and markedly reduced scope for their diversion/abuse. This review will discuss the in vivo pharmacological profiles of approved catecholaminergic drugs for treatment of ADHD and implications for their clinical efficacy and abuse liability.

  7. Improvement of risk informed surveillance test interval for the safety related instrument and control system of Ulchin units 3 and 4

    International Nuclear Information System (INIS)

    Jang, Seung Cheol; Lee, Yun Hwan; Lee, Seung Joon; Han, Sang Hoon

    2012-05-01

    The purpose of this research is the development of various methodologies necessary for the licensing of the risk informed surveillance test interval(STI) improvement for the safety related I and C systems in UCN 3 and 4, for instance, reactor protection system (RPS), engineered safety features actuation system (ESFAS), ESF auxiliary relay cabinet (ARC), and core protection calculator (CPC). The technical adequacy of the methodology was sufficiently verified through the application to the following STI changes. o CPC channel functional test (change from 1 month to 3 months including safety channel and log power test) o RPS channel functional test (change from 1 month to 3 months) o RPS logic and trip channel test (change from 1 month to 3 months. 1 month for RPS manual actuation test) o ESFAS channel functional test (change from 1 month to 3 months) o ESFAS logic and trip channel test (change from 1 month to 3 months) o ESF auxiliary relay test (change from 1 month to 3 months with staggered test. Manual actuation at the ESF ARC is added as a backup of ESF actuation signals during emergency operation

  8. Improvement of risk informed surveillance test interval for the safety related instrumentation and control system of Yonggwang units 3 and 4

    International Nuclear Information System (INIS)

    Jang, Seung Cheol; Lee, Yun Hwan; Lee, Seung Joon; Han, Sang Hoon

    2012-05-01

    The purpose of this research is the development of various methodologies necessary for the licensing of the risk informed surveillance test interval(STI) improvement for the safety related I and C systems in YGN 3 and 4, for instance, reactor protection system (RPS), engineered safety features actuation system (ESFAS), ESF auxiliary relay cabinet (ARC), and core protection calculator (CPC). The technical adequacy of the methodology was sufficiently verified through the application to the following STI changes. o CPC channel functional test (change from 1 month to 3 months including safety channel and log power test) o RPS channel functional test (change from 1 month to 3 months) o RPS logic and trip channel test (change from 1 month to 3 months. 1 month for RPS manual actuation test) o ESFAS channel functional test (change from 1 month to 3 months) o ESFAS logic and trip channel test (change from 1 month to 3 months) o ESF auxiliary relay test (change from 1 month to 3 months with staggered test. Manual actuation at the ESF ARC is added as a backup of ESF actuation signals during emergency operation

  9. Development of methodologies for optimization of surveillance testing and maintenance of safety related equipment at NPPs. Report of a research coordination meeting. Working material

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    This report summarizes the results of the first meeting of the Coordinated Research Programme (CRP) on Development of Methodologies for Optimization of Surveillance Testing and Maintenance of Safety Related Equipment at NPPs, held at the Agency Headquarters in Vienna, from 16 to 20 December 1996. The purpose of this Research Coordination Meeting (RCM) was that all Chief Scientific Investigators of the groups participating in the CRP presented an outline of their proposed research projects. Additionally, the participants discussed the objective, scope, work plan and information channels of the CRP in detail. Based on these presentations and discussions, the entire project plan was updated, completed and included in this report. This report represents a common agreed project work plan for the CRP. Refs, figs, tabs.

  10. Injury Surveillance and Safety Considerations for Large-Format Lead-Acid Batteries Used in Mining Applications.

    Science.gov (United States)

    Reyes, Miguel Angel; Novak, Thomas

    2016-03-01

    Large lead-acid batteries are predominantly used throughout the mining industry to power haulage, utility, and personnel-carrier vehicles. Without proper operation and maintenance, the use of these batteries can introduce mechanical and electrical hazards, particularly in the confined, and potentially dangerous, environment of an underground coal mine. A review of the Mine Safety and Health Administration accident/illness/injury database reveals that a significant number of injuries occur during the maintenance and repair of lead-acid batteries. These injuries include burns from electrical arcing and acid exposure, as well as strained muscles and crushed hands. The National Institute for Occupational Safety and Health investigated the design and implementation of these batteries to identify safety interventions that can mitigate these inherent hazards. This paper promotes practical design modifications, such as reducing the size and weight of battery assembly lids in conjunction with lift assists, as well as using five-pole cable connectors to improve safety.

  11. Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

    Directory of Open Access Journals (Sweden)

    Rosângela Teixeira

    Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

  12. Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

    Directory of Open Access Journals (Sweden)

    Rosângela Teixeira

    2013-04-01

    Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

  13. Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

    International Nuclear Information System (INIS)

    Nabili, Marjan; Geist, Craig; Zderic, Vesna

    2015-01-01

    Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm 2 , and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm 2 (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety of this

  14. Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

    Energy Technology Data Exchange (ETDEWEB)

    Nabili, Marjan, E-mail: mnabili@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, 800 22nd Street NW, Room 5000, Washington, DC 20052 (United States); Geist, Craig, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu [Department of Ophthalmology, The George Washington University, 2150 Pennsylvania Avenue NW, Floor 2A, Washington, DC 20037 (United States); Zderic, Vesna, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu [Department of Biomedical Engineering, The George Washington University, 800 22nd Street NW, Room 6670, Washington, DC 20052 (United States)

    2015-10-15

    Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm{sup 2}, and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm{sup 2} (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety

  15. Best practices: an electronic drug alert program to improve safety in an accountable care environment.

    Science.gov (United States)

    Griesbach, Sara; Lustig, Adam; Malsin, Luanne; Carley, Blake; Westrich, Kimberly D; Dubois, Robert W

    2015-04-01

    The accountable care organization (ACO), one of the most promising and talked about new models of care, focuses on improving communication and care transitions by tying potential shared savings to specific clinical and financial benchmarks. An important factor in meeting these benchmarks is an ACO's ability to manage medications in an environment where medical and pharmacy care has been integrated. The program described in this article highlights the critical components of Marshfield Clinic's Drug Safety Alert Program (DSAP), which focuses on prioritizing and communicating safety issues related to medications with the goal of reducing potential adverse drug events. Once the medication safety concern is identified, it is reviewed to evaluate whether an alert warrants sending prescribers a communication that identifies individual patients or a general communication to all physicians describing the safety concern. Instead of basing its decisions regarding clinician notification about drug alerts on subjective criteria, the Marshfield Clinic's DSAP uses an internally developed scoring system. The scoring system includes criteria developed from previous drug alerts, such as level of evidence, size of population affected, severity of adverse event identified or targeted, litigation risk, available alternatives, and potential for duration of medication use. Each of the 6 criteria is assigned a weight and is scored based upon the content and severity of the alert received.  In its first 12 months, the program targeted 6 medication safety concerns involving the following medications: topiramate, glyburide, simvastatin, citalopram, pioglitazone, and lovastatin. Baseline and follow-up prescribing data were gathered on the targeted medications. Follow-up review of prescribing data demonstrated that the DSAP provided quality up-to-date safety information that led to changes in drug therapy and to decreases in potential adverse drug events. In aggregate, nearly 10,000 total

  16. Safety and effectiveness of drug therapy for the acutely agitated patient (Part 2

    Directory of Open Access Journals (Sweden)

    Gianluca Airoldi

    2013-04-01

    Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the second in a 2-part series is to review published data on the efficacy and safety of antipsychotic medications currently available for managing situations of this type. Arrhythmias caused by QT-prolonging drugs occur infrequently, and multiple factors are often involved, including concomitant use of other drugs affecting the same pathway (most antipsychotic drugs prolong the QT interval by blocking potassium IKr current in HERG channels of myocardial cells, electrolyte disorders and, possibly, genetic predisposition. Judicious use of typical antipsychotics (mainly haloperidol and benzodiazepines (mainly lorazepam, given intramuscularly alone or in combination, has proved to be safe and effective for controlling acute motor agitation related to psychiatric illness; cocaine, methamphetamine, and ethanol toxicity; ethanol withdrawal; and other factors. They are still widely used and are particularly useful when limited data are available on the patient’s history of cardiovascular disease, current use of medication, and/or the likelihood of illicit drug or alcohol intoxication; when the diagnosis involves medical comorbidity or intoxication; or when there is no specific treatment (e.g., personality disorders, learning disabilities, mental retardation, organic brain damage. If rapid tranquillization is necessary before a formal diagnosis can be made and there are uncertainties regarding the patient’s medical history, lorazepam is often considered the first-line drug of choice. In

  17. Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients.

    Science.gov (United States)

    Buckley, Lorrene A; Salunke, Smita; Thompson, Karen; Baer, Gerri; Fegley, Darren; Turner, Mark A

    2018-02-05

    A public workshop entitled "Challenges and strategies to facilitate formulation development of pediatric drug products" focused on current status and gaps as well as recommendations for risk-based strategies to support the development of pediatric age-appropriate drug products. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary, panel, and case-study breakout sessions. By enabling practical and meaningful discussion between scientists representing the diversity of involved disciplines (formulators, nonclinical scientists, clinicians, and regulators) and geographies (eg, US, EU), the Excipients Safety workshop session was successful in providing specific and key recommendations for defining paths forward. Leveraging orthogonal sources of data (eg. food industry, agro science), collaborative data sharing, and increased awareness of the existing sources such as the Safety and Toxicity of Excipients for Paediatrics (STEP) database will be important to address the gap in excipients knowledge needed for risk assessment. The importance of defining risk-based approaches to safety assessments for excipients vital to pediatric formulations was emphasized, as was the need for meaningful stakeholder (eg, patient, caregiver) engagement. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Zero-inflated Poisson model based likelihood ratio test for drug safety signal detection.

    Science.gov (United States)

    Huang, Lan; Zheng, Dan; Zalkikar, Jyoti; Tiwari, Ram

    2017-02-01

    In recent decades, numerous methods have been developed for data mining of large drug safety databases, such as Food and Drug Administration's (FDA's) Adverse Event Reporting System, where data matrices are formed by drugs such as columns and adverse events as rows. Often, a large number of cells in these data matrices have zero cell counts and some of them are "true zeros" indicating that the drug-adverse event pairs cannot occur, and these zero counts are distinguished from the other zero counts that are modeled zero counts and simply indicate that the drug-adverse event pairs have not occurred yet or have not been reported yet. In this paper, a zero-inflated Poisson model based likelihood ratio test method is proposed to identify drug-adverse event pairs that have disproportionately high reporting rates, which are also called signals. The maximum likelihood estimates of the model parameters of zero-inflated Poisson model based likelihood ratio test are obtained using the expectation and maximization algorithm. The zero-inflated Poisson model based likelihood ratio test is also modified to handle the stratified analyses for binary and categorical covariates (e.g. gender and age) in the data. The proposed zero-inflated Poisson model based likelihood ratio test method is shown to asymptotically control the type I error and false discovery rate, and its finite sample performance for signal detection is evaluated through a simulation study. The simulation results show that the zero-inflated Poisson model based likelihood ratio test method performs similar to Poisson model based likelihood ratio test method when the estimated percentage of true zeros in the database is small. Both the zero-inflated Poisson model based likelihood ratio test and likelihood ratio test methods are applied to six selected drugs, from the 2006 to 2011 Adverse Event Reporting System database, with varying percentages of observed zero-count cells.

  19. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    International Nuclear Information System (INIS)

    Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

    2006-01-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

  20. Increases in self-reported fentanyl use among a population entering drug treatment: The need for systematic surveillance of illicitly manufactured opioids.

    Science.gov (United States)

    Cicero, Theodore J; Ellis, Matthew S; Kasper, Zachary A

    2017-08-01

    Recent reports indicate a sharp increase in fentanyl-related overdose deaths across the United States, much of which is likely related to the introduction of cheap, illicitly manufactured fentanyl derivatives. In this study, we sought to estimate the magnitude of illicit fentanyl use from 2012 to 2016 using a national opioid abuse surveillance system. The study program surveyed 10,900 individuals entering substance abuse treatment for opioid use disorder, with participants asked to endorse past month 'use to get high' of fentanyl drugs, stratified by identifiable (i.e., branded) fentanyl formulations or a 'type unknown' drug alleged to contain fentanyl. Total past-month fentanyl-use rose modestly from 2012 to 2016. While use of known fentanyl products remained relatively stable (mean=10.9%; P=0.25), endorsements of 'unknown' fentanyl products nearly doubled from 9% in 2013 to 15.1% by 2016 (Pfentanyl use shows that recent increases in fentanyl use seem to be due almost entirely to 'unknown' fentanyl presumed to be illicitly manufactured. Given that it is difficult to assess the extent to which fentanyl may have been substituted for another drug (i.e., oxycodone, alprazolam, etc.) or was used as a heroin admixture, our data likely represent an underestimation of the full magnitude of illicit fentanyl abuse. As such, this growing public health problem requires immediate attention and more systematic efforts to identify and track its abuse. Copyright © 2017. Published by Elsevier B.V.

  1. Human rights vs. Public safety -- When can you test your workers for drugs?

    Energy Technology Data Exchange (ETDEWEB)

    Kossowan, B. L.

    2002-06-01

    Legislative and regulatory aspects of drug testing of employees vs. public safety are discussed. While in Canada federal and provincial laws concerning human rights take precedence over public safety issues, laws and regulations vary from province to province, therefore there is good reason for concern about uncertainty. To compound the uncertainty, certain relevant laws of the United States are different (generally more stringent than corresponding Canadian laws), consequently there is the possibility that certain American companies might feel justified in refusing to do business with Canadian firms that do not follow their rigid standards. The conclusion is that while the situation may be clear enough in a legal situation, it does not always work equally well in practice. Unfortunately, at the present time there is not a whole lot of guidance available for companies to manage the workplace in a practical sense.

  2. Long-Term Safety of Drug-Eluting and Bare-Metal Stents

    DEFF Research Database (Denmark)

    Palmerini, Tullio; Benedetto, Umberto; Biondi-Zoccai, Giuseppe

    2015-01-01

    BACKGROUND: Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety....... RESULTS: Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial...... infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target...

  3. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.

    Science.gov (United States)

    Trelle, Sven; Reichenbach, Stephan; Wandel, Simon; Hildebrand, Pius; Tschannen, Beatrice; Villiger, Peter M; Egger, Matthias; Jüni, Peter

    2011-01-11

    To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Network meta-analysis. Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

  4. Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis.

    Science.gov (United States)

    Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

    2013-12-01

    Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar(®)), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups "41-65" (39.07%) and "over 65" (27.9%) were the most affected. Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

  5. Pharmacovigilance and drug safety 2011 in Calabria (Italy: Adverse events analysis

    Directory of Open Access Journals (Sweden)

    Francesca Scicchitano

    2012-01-01

    Full Text Available Background : Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs. The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. Materials and Methods: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Results : Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100 in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %. Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%. There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it, and there is a strong interest in participating to training courses in the field (95% are interested. Conclusions : Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

  6. Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis.

    Science.gov (United States)

    Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

    2012-09-01

    Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

  7. “For Your Safety” Effects of Camera Surveillance on Safety Impressions, Situation Construal and Attributed Intent

    NARCIS (Netherlands)

    van Rompay, Thomas Johannes Lucas; de Vries, Pieter Walter; Damink, Manon T.; MacTavish, Thomas; Basapur, Santosh

    2015-01-01

    Based on the assumption that monitoring technology in environmental settings impacts people’s state of mind and subsequent perceptions, the current study examines the influence of security camera’s on safety perceptions and citizen wellbeing. Participants watched a video of city streets that

  8. A Sensitivity Study of Human Errors in Optimizing Surveillance Test Interval (STI) and Allowed Outage Time (AOT) of Standby Safety System

    International Nuclear Information System (INIS)

    Chung, Dae Wook; Shin, Won Ky; You, Young Woo; Yang, Hui Chang

    1998-01-01

    In most cases, the surveillance test intervals (STIs), allowed outage times (AOTS) and testing strategies of safety components in nuclear power plant are prescribed in plant technical specifications. And, in general, it is required that standby safety system shall be redundant (i.e., composed of multiple components) and these components are tested by either staggered test strategy or sequential test strategy. In this study, a linear model is presented to incorporate the effects of human errors associated with test into the evaluation of unavailability. The average unavailabilities of 1/4, 2/4 redundant systems are computed considering human error and testing strategy. The adverse effects of test on system unavailability, such as component wear and test-induced transient have been modelled. The final outcome of this study would be the optimized human error domain from 3-D human error sensitivity analysis by selecting finely classified segment. The results of sensitivity analysis show that the STI and AOT can be optimized provided human error probability is maintained within allowable range. (authors)

  9. Pharmacokinetics in Drug Discovery: An Exposure-Centred Approach to Optimising and Predicting Drug Efficacy and Safety.

    Science.gov (United States)

    Reichel, Andreas; Lienau, Philip

    2016-01-01

    The role of pharmacokinetics (PK) in drug discovery is to support the optimisation of the absorption, distribution, metabolism and excretion (ADME) properties of lead compounds with the ultimate goal to attain a clinical candidate which achieves a concentration-time profile in the body that is adequate for the desired efficacy and safety profile. A thorough characterisation of the lead compounds aiming at the identification of the inherent PK liabilities also includes an early generation of PK/PD relationships linking in vitro potency and target exposure/engagement with expression of pharmacological activity (mode-of-action) and efficacy in animal studies. The chapter describes an exposure-centred approach to lead generation, lead optimisation and candidate selection and profiling that focuses on a stepwise generation of an understanding between PK/exposure and PD/efficacy relationships by capturing target exposure or surrogates thereof and cellular mode-of-action readouts in vivo. Once robust PK/PD relationship in animal PD models has been constructed, it is translated to anticipate the pharmacologically active plasma concentrations in patients and the human therapeutic dose and dosing schedule which is also based on the prediction of the PK behaviour in human as described herein. The chapter outlines how the level of confidence in the predictions increases with the level of understanding of both the PK and the PK/PD of the new chemical entities (NCE) in relation to the disease hypothesis and the ability to propose safe and efficacious doses and dosing schedules in responsive patient populations. A sound identification of potential drug metabolism and pharmacokinetics (DMPK)-related development risks allows proposing of an effective de-risking strategy for the progression of the project that is able to reduce uncertainties and to increase the probability of success during preclinical and clinical development.

  10. The sirolimus-eluting Cypher Select coronary stent for the treatment of bare-metal and drug-eluting stent restenosis: insights from the e-SELECT (Multicenter Post-Market Surveillance) registry.

    Science.gov (United States)

    Abizaid, Alexandre; Costa, J Ribamar; Banning, Adrian; Bartorelli, Antonio L; Dzavik, Vladimir; Ellis, Stephen; Gao, Runlin; Holmes, David R; Jeong, Muyng Ho; Legrand, Victor; Neumann, Franz-Josef; Nyakern, Maria; Orlick, Amy; Spaulding, Christian; Worthley, Stephen; Urban, Philip M

    2012-01-01

    This study sought to compare the 1-year safety and efficacy of Cypher Select or Cypher Select Plus (Cordis Corporation, Bridgewater, New Jersey) sirolimus-eluting stents (SES) with the treatment of bare-metal stents (BMS) and drug-eluting stent (DES) in-stent restenosis (ISR) in nonselected, real-world patients. There is paucity of consistent data on DES for the treatment of ISR, especially, DES ISR. The e-SELECT (Multicenter Post-Market Surveillance) registry is a Web-based, multicenter and international registry encompassing virtually all subsets of patients and lesions treated with at least 1 SES during the period from 2006 to 2008. We enrolled in this pre-specified subanalysis all patients with at least 1 clinically relevant BMS or DES ISR treated with SES. Primary endpoint was major adverse cardiac events and stent thrombosis rate at 1 year. Of 15,147 patients enrolled, 1,590 (10.5%) presented at least 1 ISR (BMS group, n = 1,235, DES group, n = 355). Patients with DES ISR had higher incidence of diabetes (39.4% vs. 26.9%, p target lesion revascularization and definite/probable late stent thrombosis were higher in patients with DES ISR (6.9% vs. 3.1%, p = 0.003, and 1.8% vs. 0.5%, p = 0.04, respectively). Use of SES for either BMS or DES ISR treatment is safe and associated with low target lesion revascularization recurrence and no apparent safety concern. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Quali-quantitative analysis of best selling drugs from pharmacy, street market and traditional herbal medicine: a pilot study of market surveillance in Senegal.

    Science.gov (United States)

    Pichini, Simona; Rotolo, Maria Concetta; Bellotti, Pasquale; Minutillo, Adele; Mastrobattista, Luisa; Pacifici, Roberta

    2015-02-01

    A pilot study of market surveillance in Senegal has been performed analyzing best selling drugs from an official pharmacy and a street market in two principal cities of Senegal and some traditional preparations from herbal medicine from the same market. A simple and rapid gas chromatography method with mass spectrometry detection has been applied after a liquid-liquid extraction of pharmaceutical products and traditional preparations at acidic, neutral and basic pH with chloroform-isopropanol (9:1, v/v). The assay was validated in the range from 10mg to 250 mg/g powder preparations with good determination coefficients (r(2)≥ 0.99) for the calibration curves. At three concentrations spanning the linear dynamic ranges of the calibration curves, mean recoveries of substances under investigation were always higher than 90% and intra-assay and inter-assay precision and accuracy were always better than 15%. The four best selling drugs purchased from a Dakar local pharmacy exactly contained the amount of active principles reported in the respective labels while the best selling drugs freely purchased from Kaolack market contained an amount of active ingredients lower than that declared on the label. No pharmacological active compound, but salicylic acid was found in one of the traditional herbal preparations. This pilot study showed that whereas official drugs sold in pharmacies at prices accessible for a very few portion of the population contained the amount of active principles as reported in the labels, those from street market bought by the majority of population contained an amount of active ingredients lower than that declared on the label and finally traditional herbal preparations seldom contain pharmacological active principles. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. A mortality index for postmarketing surveillance of new medications.

    Science.gov (United States)

    Rose, J C; Unis, A S

    2000-03-01

    The rate of introduction of new pharmaceuticals is growing as a result of advances in molecular pharmacology and targeted drug development. The Fatal Toxicity Index (FTI) has been proposed as a means for monitoring drug toxicity through post-marketing surveillance. The FTI requires data regarding the general availability of a particular agent in the community which, in the US, is proprietary. The authors propose a Mortality Index as an alternative method for calculating relative lethality that does not rely on proprietary information for postmarketing surveillance. Using data from the Toxic Exposure Surveillance System (TESS) a Mortality Index was calculated from the proportion of deaths occurring among all patients who present to a health care facility with an overdose on the same agent or class of agents. The average Mortality Index for various drugs or drug classes for the years 1989 to 1997 is reported. Because the Mortality Index for desipramine appeared much greater than that for the other tricyclics, a chi-squared analysis was performed. The authors conclude, based on this analysis, that desipramine is significantly more likely to lead to death after overdosage than any other tricyclic antidepressant in the study. Also, the Mortality Index appeared to identify the impact of pediatric formulations on overdose lethality. We conclude that the Mortality Index may be a useful tool for determining the safety of agents during the postmarketing surveillance phase.

  13. Safety of a clinical surveillance protocol with 3- and 6-week warfarin prophylaxis after total joint arthroplasty.

    Science.gov (United States)

    Goldstein, W M; Jimenez, M L; Bailie, D S; Wall, R; Branson, J

    2001-07-01

    The charts of 1869 patients were reviewed for the occurrence of deep venous thrombosis (DVT) and pulmonary embolism after total hip or knee arthroplasty. Prophylaxis consisted of 3 (group 1; n=1235) or 6 (group 2; n=634) weeks low-dose warfarin, pneumatic compression boots worn by patients in the hospital, mobilization on the first postoperative day, and a clinical surveillance protocol. Venous ultrasound or ventilation/perfusion lung scintigraphy (V/Q) was performed only if patients became symptomatic. patients. Twenty-three (1.8%) patients were positive for DVT. Ventilation/perfusion lung scintigraphy was performed on 25 patients, and 5 (0.4%) patients were positive for pulmonary embolism. In group 2, 117 patients were evaluated for DVT, and 19 (3%) patients had positive results determined by ultrasound. Twenty-five patients were evaluated with V/Q and only 1 (0.16%) patient was positive for pulmonary embolism. No patient developed a fatal pulmonary embolism or postphlebitic syndrome. This prophylaxis protocol is an efficient and cost-effective method for the prevention of significant events after surgery.

  14. Nonclinical safety biomarkers of drug-induced vascular injury: current status and blueprint for the future.

    Science.gov (United States)

    Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S

    2014-06-01

    Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).

  15. Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe

    DEFF Research Database (Denmark)

    Jelinek, Tomas; Peyerl-Hoffmann, Gabriele; Mühlberger, Nikolai

    2002-01-01

    and chloroquine. The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide. RESULTS: 337 isolates have been tested so far. Prevalence of mutations that are associated with resistance to chloroquine on the pfcrt and pfmdr genes...

  16. Locating Errors Through Networked Surveillance: A Multimethod Approach to Peer Assessment, Hazard Identification, and Prioritization of Patient Safety Efforts in Cardiac Surgery.

    Science.gov (United States)

    Thompson, David A; Marsteller, Jill A; Pronovost, Peter J; Gurses, Ayse; Lubomski, Lisa H; Goeschel, Christine A; Gosbee, John W; Wahr, Joyce; Martinez, Elizabeth A

    2015-09-01

    The objectives were to develop a scientifically sound and feasible peer-to-peer assessment model that allows health-care organizations to evaluate patient safety in cardiovascular operating rooms and to establish safety priorities for improvement. The locating errors through networked surveillance study was conducted to identify hazards in cardiac surgical care. A multidisciplinary team, composed of organizational sociology, organizational psychology, applied social psychology, clinical medicine, human factors engineering, and health services researchers, conducted the study. We used a transdisciplinary approach, which integrated the theories, concepts, and methods from each discipline, to develop comprehensive research methods. Multiple data collection was involved: focused literature review of cardiac surgery-related adverse events, retrospective analysis of cardiovascular events from a national database in the United Kingdom, and prospective peer assessment at 5 sites, involving survey assessments, structured interviews, direct observations, and contextual inquiries. A nominal group methodology, where one single group acts to problem solve and make decisions was used to review the data and develop a list of the top priority hazards. The top 6 priority hazard themes were as follows: safety culture, teamwork and communication, infection prevention, transitions of care, failure to adhere to practices or policies, and operating room layout and equipment. We integrated the theories and methods of a diverse group of researchers to identify a broad range of hazards and good clinical practices within the cardiovascular surgical operating room. Our findings were the basis for a plan to prioritize improvements in cardiac surgical care. These study methods allowed for the comprehensive assessment of a high-risk clinical setting that may translate to other clinical settings.

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

    Science.gov (United States)

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

    2017-12-01

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

  18. Impact of regulatory guidances and drug regulation on risk minimization interventions in drug safety: a systematic review.

    Science.gov (United States)

    Nkeng, Lenhangmbong; Cloutier, Anne-Marie; Craig, Camille; Lelorier, Jacques; Moride, Yola

    2012-07-01

    Therapeutic risk management has received growing interest in recent years, particularly since the publication of regulatory guidances in 2005 and 2006, paralleled with a change in drug regulation. The characteristics of risk minimization interventions (RMIs) that have been implemented or approved remain inadequately explored. The aim of this study was to review RMIs published in the literature or posted on regulatory agency websites over the past 10 years, and to assess whether publication of regulatory guidances on risk management is associated with changes in the number and types of interventions. Sources were searched for RMIs published/posted between 1 January 2000 and 31 December 2009. For the literature search, MEDLINE and EMBASE databases were used using key words related to drug safety (i.e. 'drug toxicity') and the individual RMI names. The website review involved searches of major regulatory authority websites such as the European Medicines Agency, US FDA, Health Canada, the UK's Medicines and Healthcare products Regulatory Agency, Japan's Pharmaceutical and Medical Devices Agency and Australia's Therapeutic Goods Administration. The following eligibility criteria were applied for inclusion in the review: published/posted between the years 2000 and 2009, inclusive; involving drug products; use in humans; and involving RMIs, or tools used to increase the reporting of adverse events (AEs). Natural healthcare products, devices, diagnostic chemicals, pregnancy registries without follow-up, medication errors and products not used as therapy for illness were not retained. For each source, the following characteristics were extracted: nature of the intervention, target population, therapeutic area, AE(s) of special interest, country/regulatory agency and year of publication. A total of 119 unique interventions were identified in the literature (54 published in 2000-4 and 65 published in 2005-9). Interventions included educational material (n = 37; 31%), black

  19. Surveillance of transmitted antiretroviral drug resistance among HIV-1 infected women attending antenatal clinics in Chitungwiza, Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Mqondisi Tshabalala

    Full Text Available The rapid scale-up of highly active antiretroviral therapy (HAART and use of single dose Nevirapine (SD NVP for prevention of mother-to-child transmission (pMTCT have raised fears about the emergence of resistance to the first line antiretroviral drug regimens. A cross-sectional study was conducted to determine the prevalence of primary drug resistance (PDR in a cohort of young (<25 yrs HAART-naïve HIV pregnant women attending antenatal clinics in Chitungwiza, Zimbabwe. Whole blood was collected in EDTA for CD4 counts, viral load, serological estimation of duration of infection using the BED Calypte assay and genotyping for drug resistance. Four hundred and seventy-one women, mean age 21 years; SD: 2.1 were enrolled into the study between 2006 and 2007. Their median CD4 count was 371cells/µL; IQR: 255-511 cells/µL. Two hundred and thirty-six samples were genotyped for drug resistance. Based on the BED assay, 27% were recently infected (RI whilst 73% had long-term infection (LTI. Median CD4 count was higher (p<0.05 in RI than in women with LTI. Only 2 women had drug resistance mutations; protease I85V and reverse transcriptase Y181C. Prevalence of PDR in Chitungwiza, 4 years after commencement of the national ART program remained below WHO threshold limit (5%. Frequency of recent infection BED testing is consistent with high HIV acquisition during pregnancy. With the scale-up of long-term ART programs, maintenance of proper prescribing practices, continuous monitoring of patients and reinforcement of adherence may prevent the acquisition and transmission of PDR.

  20. [A review on the advancement of internet-based public health surveillance program].

    Science.gov (United States)

    Zhao, Y Q; Ma, W J

    2017-02-10

    Internet data is introduced into public health arena under the features of fast updating and tremendous volume. Mining and analyzing internet data, researchers can model the internet-based surveillance system to assess the distribution of health-related events. There are two main types of internet-based surveillance systems, i.e. active and passive, which are distinguished by the sources of information. Through passive surveillance system, information is collected from search engine and social media while the active system gathers information through provision of the volunteers. Except for serving as a real-time and convenient complementary approach to traditional disease, food safety and adverse drug reaction surveillance program, Internet-based surveillance system can also play a role in health-related behavior surveillance and policy evaluation. Although several techniques have been applied to filter information, the accuracy of internet-based surveillance system is still bothered by the false positive information. In this article, we have summarized the development and application of internet-based surveillance system in public health to provide reference for a better surveillance program in China.

  1. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Kevin C., E-mail: ke@sc.edu [University of South Carolina, Department of Philosophy, USC NanoCenter (United States); Volz, David C. [University of South Carolina, Department of Environmental Health Sciences, Arnold School of Public Health (United States)

    2012-01-15

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

  2. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    International Nuclear Information System (INIS)

    Elliott, Kevin C.; Volz, David C.

    2012-01-01

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345–1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

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

    Science.gov (United States)

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

    2013-11-01

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

  4. Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology.

    Science.gov (United States)

    Roberts, Stanley A; Andrews, Paul A; Blanset, Diann; Flagella, Kelly M; Gorovits, Boris; Lynch, Carmel M; Martin, Pauline L; Kramer-Stickland, Kimberly; Thibault, Stephane; Warner, Garvin

    2013-12-01

    Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to cytotoxic small molecules. A number of these agents are currently being developed as anti-cancer agents designed to improve the therapeutic index of the cytotoxin (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it to tumor cells. This paper presents primary considerations for the nonclinical safety evaluation of ADCs and includes strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin). Considerations are presented on how to design a nonclinical safety assessment program to identify the on- and off-target toxicities to enable first-in-human (FIH) studies. Specific discussions are also included that provide details as to the need and how to conduct the studies for evaluating ADCs in genetic toxicology, tissue cross-reactivity, safety pharmacology, carcinogenicity, developmental and reproductive toxicology, biotransformation, toxicokinetic monitoring, bioanalytical assays, immunogenicity testing, test article stability and the selection of the FIH dose. Given the complexity of these molecules and our evolving understanding of their properties, there is no single all-encompassing nonclinical strategy. Instead, each ADC should be evaluated on a case-by-case scientifically-based approach that is consistent with ICH and animal research guidelines. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    Science.gov (United States)

    Elliott, Kevin C.; Volz, David C.

    2012-01-01

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

  6. A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

    Science.gov (United States)

    Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

    2018-06-01

    Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  7. Safety of Therapeutic Fever Induction in Cancer Patients Using Approved PAMP Drugs

    Directory of Open Access Journals (Sweden)

    Uwe Rudolf Max Reuter

    2018-04-01

    Full Text Available William Coley, between 1895 and 1936, treated hundreds of cancer patients using infusions of fever inducing bacerial extracts. Similar experiments were done by Klyuyeva and co-workers in the 1940ies in Russia using trypanosoma extracts. Many remissions and cures were reported. We have conjectured that pathogen associated molecular pattern substances (PAMP are the molecular explanation for the beneficial treatments in both groups. We could show that a combination of PAMP can eradicate solid tumours in cancer mice if applied several times. Accordingly, we suggested to combine PAMP containing approved drugs to treat cancer patients using a protocol similar to the old fever induction regimen. In this retrospective phase-1 study we report on the fever induction capacity and safety of applications of bacterial extracts, combinations of bacterial extracts with approved drugs, and combinations of approved drugs in 131 mainly cancer patients. Adverse reactions were those which can be expected during a feverish infection and mild. Over 523 fever inductions, no severe adverse reaction was observed.

  8. Safety profile of drugs used in the treatment of osteoporosis: a systematical review of the literature

    Directory of Open Access Journals (Sweden)

    M. Varenna

    2013-10-01

    Full Text Available The range of osteoporosis treatments is increasingly large and, like any disease, the pharmacological management of patients should involve a risk/benefit evaluation to attain the greatest reduction in risk of fracture with the lowest incidence of adverse events. The aim of this review is to critically appraise the literature about the safety issues of the main pharmacological treatments of osteoporosis. This document is the result of a consensus of experts based on a systematic review of regulatory documents, randomized controlled trials, metaanalyses, pharmacovigilance surveys and case series related to possible adverse drug reactions to osteoporosis treatment with calcium and vitamin D supplements, bisphosphonates, strontium ranelate, selective estrogen receptor modulators, denosumab, and teriparatide. As expected, randomized controlled trials showed only the most common adverse events due to the samples size and the short observation time. Case series and observational studies are able to provide data about uncommon side effects, but in some cases a sure cause-effect relationship needs still to be confirmed. Consistently with methodological limitations, the newer drugs have a tolerance profile that has not been fully explored yet. Osteoporosis treatments showed an overall good tolerance profile with rare serious adverse events that, however, must be well known by the clinician who prescribes these drugs. The concern about possible adverse events should be weighed against the reduction of morbidity and mortality associated with a significant fracture risk reduction.

  9. A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery

    International Nuclear Information System (INIS)

    Harush-Frenkel, Oshrat; Bivas-Benita, Maytal; Nassar, Taher; Springer, Chaim; Sherman, Yoav; Avital, Avraham; Altschuler, Yoram; Borlak, Jurgen; Benita, Simon

    2010-01-01

    Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

  10. Comparison of the safety information on drug labels in three developed countries: The USA, UK and Canada

    Directory of Open Access Journals (Sweden)

    Thamir M. Alshammari

    2017-12-01

    Full Text Available The safety information on drug labels of a company marketing the same drugs in different countries is sometimes different. The aim of the present study is to understand the differences in the volume and content of safety information on the drug labels from the same manufacturers in three developed countries: the United States of America (USA, the United Kingdom (UK and Canada. This study involved the calculation of the proportion of total safety information (PSI and of contraindications (PCI in comparison to all information on the label and the percentage of boxed warnings (PBW among the 100 labels studied from each country. The PSI on the labels of different countries is different with USA labels bearing lesser value PSI and UK labels bearing higher value PSI. The qualitative information provided on these drug labels from each country in ‘contraindications’ sections, ‘boxed/serious warnings’ and ‘overdosage’ sections presented differences in the information provided on most of the labels. We have found distinct differences between the safety information available on drug labels in terms of volume and content. We conclude that the safety information for the same products should be standardised across all countries.

  11. The impact of assay technology as applied to safety assessment in reducing compound attrition in drug discovery.

    Science.gov (United States)

    Thomas, Craig E; Will, Yvonne

    2012-02-01

    Attrition in the drug industry due to safety findings remains high and requires a shift in the current safety testing paradigm. Many companies are now positioning safety assessment at each stage of the drug development process, including discovery, where an early perspective on potential safety issues is sought, often at chemical scaffold level, using a variety of emerging technologies. Given the lengthy development time frames of drugs in the pharmaceutical industry, the authors believe that the impact of new technologies on attrition is best measured as a function of the quality and timeliness of candidate compounds entering development. The authors provide an overview of in silico and in vitro models, as well as more complex approaches such as 'omics,' and where they are best positioned within the drug discovery process. It is important to take away that not all technologies should be applied to all projects. Technologies vary widely in their validation state, throughput and cost. A thoughtful combination of validated and emerging technologies is crucial in identifying the most promising candidates to move to proof-of-concept testing in humans. In spite of the challenges inherent in applying new technologies to drug discovery, the successes and recognition that we cannot continue to rely on safety assessment practices used for decades have led to rather dramatic strategy shifts and fostered partnerships across government agencies and industry. We are optimistic that these efforts will ultimately benefit patients by delivering effective and safe medications in a timely fashion.

  12. Post-marketing safety surveillance for inactivated and live-attenuated Japanese encephalitis vaccines in China, 2008-2013.

    Science.gov (United States)

    Wu, Wendi; Liu, Dawei; Li, Keli; Nuorti, J Pekka; Nohynek, Hanna M; Xu, Disha; Ye, Jiakai; Zheng, Jingshan; Wang, Huaqing

    2017-06-22

    Two types of Japanese encephalitis (JE) vaccines, inactivated JE vaccine (JE-I) and live-attenuated JE vaccine (JE-L), are available and used in China. In particular, one JE-L, produced by a domestic manufacturer in China, was prequalified by WHO in 2013. We assessed the safety of JE vaccines in China during 2008-2013 using the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) data. We retrieved AEFI reporting data about JE vaccines from CNAEFIS, 2008-2013, examined demographic characteristics of AEFI cases, and used administrative data on vaccine doses as denominator to calculate and compare crude reporting rates. We also used disproportionality reporting analysis between JE-I and JE-L to assess potential safety signals. A total of 34,879 AEFIs related with JE-I and JE-L were reported, with a ratio of male to female as 1.3:1; 361 (1.0%) cases were classified as serious. JE vaccines were administered concurrently with one or more other vaccines in 13,592 (39.0%) of cases. The overall AEFI reporting rates were 214.4 per million vaccination doses for JE-L and 176.9 for JE-I (rate ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3) in 2010-2013. Febrile convulsions (FC) following JE-I was found as a signal of disproportionate reporting (SDR). However, there was no significant difference between the reporting rates of FC of JE-I and JE-L (0.3 per million vaccination doses for JE-L, 0.4 for JE-I, p=0.05). While our analysis did not find apparent safety concern of JE vaccines in China, further study should consider JE-I vaccines and febrile convulsion, and taking more sensitive methods to detect signals. Copyright © 2017. Published by Elsevier Ltd.

  13. The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science?

    Science.gov (United States)

    Horii, Ikuo

    2016-01-01

    Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as "biological responses to foreign substances." This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of "on-target" or "off-target", and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of "how can multidisciplinary toxicology contribute to innovative drug discovery and development?" And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision

  14. Heroin and fentanyl overdoses in Kentucky: Epidemiology and surveillance.

    Science.gov (United States)

    Slavova, Svetla; Costich, Julia F; Bunn, Terry L; Luu, Huong; Singleton, Michael; Hargrove, Sarah L; Triplett, Jeremy S; Quesinberry, Dana; Ralston, William; Ingram, Van

    2017-08-01

    The study aims to describe recent changes in Kentucky's drug overdose trends related to increased heroin and fentanyl involvement, and to discuss future directions for improved drug overdose surveillance. The study used multiple data sources (death certificates, postmortem toxicology results, emergency department [ED] records, law enforcement drug submissions, and prescription drug monitoring records) to describe temporal, geographic, and demographic changes in drug overdoses in Kentucky. Fentanyl- and heroin-related overdose death rates increased across all age groups from years 2011 to 2015 with the highest rates consistently among 25-34-year-olds. The majority of the heroin and fentanyl overdose decedents had histories of substantial exposures to legally acquired prescription opioids. Law enforcement drug submission data were strongly correlated with drug overdose ED and mortality data. The 2016 crude rate of heroin-related overdose ED visits was 104/100,000, a 68% increase from 2015 (62/100,000). More fentanyl-related overdose deaths were reported between October, 2015, and September, 2016, than ED visits, in striking contrast with the observed ratio of >10 to 1 heroin-related overdose ED visits to deaths. Many fatal fentanyl overdoses were associated with heroin adulterated with fentanyl; fentanyl and other synthetic drugs. In order to inform coordinated public health and safety responses, drug overdose surveillance must move from a reactive to a proactive mode, utilizing the infrastructure for electronic health records. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. A population-based case-control study of the safety of oral anti-tuberculosis drug treatment during pregnancy

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Olsen, J.

    2001-01-01

    OUTCOME MEASURES: Congenital abnormalities in newborn infants and fetuses diagnosed prenatally during the second and third trimesters, and postnatally from birth to the age of one year. RESULTS: Of 38,151 controls, 29 (0.08%) were exposed to anti-tuberculosis drug treatment during pregnancy......OBJECTIVE: To study the human teratogenic potential of isoniazid and other anti-tuberculosis drug treatment during pregnancy. DESIGN AND SETTING: Cases from a large population-based dataset at the Hungarian Case-Control Surveillance of Congenital Abnormalities, and controls from the National Birth...... Registry, between 1980 and 1996. Information on all oral anti-tuberculosis drug treatments during pregnancy was medically recorded. STUDY PARTICIPANTS: Women who had newborns or fetuses with congenital abnormalities (case group), and women who had babies with no congenital abnormality (control group). MAIN...

  16. Efficacy and safety of leflunomide in patients with rheumatoid arthritis in real-life clinical practice (results of the Russian multicenter surveillance study

    Directory of Open Access Journals (Sweden)

    R.M. Balabanova

    2014-01-01

    Full Text Available Methotrexate or leflunomide is recommended to be used as the first synthetic disease-modifying anti-rheumatic drug to treat rheumatoid arthri- tis (RA. In 2011, ELAFRA (leflunomide, Haupt Pharma Munster GmbH, Germany; license LP-000804 registered October 3, 2011 was cer- tified and approved in Russia. This surveillance study was aimed at assessing the effectiveness and tolerability of ELAFRA in RA patients in real-life clinical practice. Material and Methods. The study involved patients corresponding to the 1987 RA classification criteria, with varying disease duration. The patients were monitored at 33 Russian medical institutions in March–December 2013. According to the drug label, ELAFRA was prescribed at a dose of 10 mg/day during the first 3 days and subsequently at a dose of 20 mg/day. In case of adverse effects (AEs, the daily dose was recommended to be reduced to 10 mg. The patients were examined before the drug was prescribed; as well as 1, 3, 6 months after therapy was started. The number of painful swollen joints and pain intensity according to the Visual Analog Scale (VAS were assessed. The patients were subjected to laboratory exam- ination (blood test; ESR test; C-reactive protein (CRP test. RA activity was determined using the DAS28 index. AEs were identified. The data on 99 patients (87 females and 12 males; mean age: 51.1±11.1 years; mean disease duration 74.9±65.7 months were used for sta- tistical analysis. Disease activity was moderate in 9 patients and high in 90 patients.Results. Six-month therapy with ELAFRA reduced the mean number of swollen joints from 13.7 to 5.1 and the number of painful joints, from 14.9 to 9.5. VAS pain intensity decreased from 62.7 to 29.6 mm; ESR decreased from 38.8 to 22.18 mm/h; SRP, from 24.9 to 13.0. Low and moderate RA activity according to DAS28 and CDAI indices after treatment was observed in 63 and 46 patients, respectively. No serious AEs have been revealed; non-serious AEs were

  17. Introduction to surveillance studies

    CERN Document Server

    Petersen, JK

    2012-01-01

    Introduction & OverviewIntroduction Brief History of Surveillance Technologies & TechniquesOptical SurveillanceAerial Surveillance Audio Surveillance Radio-Wave SurveillanceGlobal Positioning Systems Sensors Computers & the Internet Data Cards Biochemical Surveillance Animal Surveillance Biometrics Genetics Practical ConsiderationsPrevalence of Surveillance Effectiveness of Surveillance Freedom & Privacy IssuesConstitutional Freedoms Privacy Safeguards & Intrusions ResourcesReferences Glossary Index

  18. Drug research methodology. Volume 1, The alcohol-highway safety experience and its applicability to other drugs

    Science.gov (United States)

    1980-03-01

    This report presents the findings of a workshop concerning the alcohol and highway safety experience, which includes research efforts to define the drinking-driving problem and societal responses to reduce the increased highway safety risk attributab...

  19. Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a brief report.

    Science.gov (United States)

    Meyer, Roger E; Salzman, Carl; Youngstrom, Eric A; Clayton, Paula J; Goodwin, Frederick K; Mann, J John; Alphs, Larry D; Broich, Karl; Goodman, Wayne K; Greden, John F; Meltzer, Herbert Y; Normand, Sharon-Lise T; Posner, Kelly; Shaffer, David; Oquendo, Maria A; Stanley, Barbara; Trivedi, Madhukar H; Turecki, Gustavo; Beasley, Charles M; Beautrais, Annette L; Bridge, Jeffrey A; Brown, Gregory K; Revicki, Dennis A; Ryan, Neal D; Sheehan, David V

    2010-08-01

    disagreement at the conference have been noted in the text. The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's encouragement of standard definitions and definable expectations for investigators and industry sponsors. Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the requirement that all central nervous system clinical drug trials must include a Columbia Classification Algorithm of Suicide Assessment (C-CASA)-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed. Copyright 2010 Physicians Postgraduate Press, Inc.

  20. Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a consensus statement.

    Science.gov (United States)

    Meyer, Roger E; Salzman, Carl; Youngstrom, Eric A; Clayton, Paula J; Goodwin, Frederick K; Mann, J John; Alphs, Larry D; Broich, Karl; Goodman, Wayne K; Greden, John F; Meltzer, Herbert Y; Normand, Sharon-Lise T; Posner, Kelly; Shaffer, David; Oquendo, Maria A; Stanley, Barbara; Trivedi, Madhukar H; Turecki, Gustavo; Beasley, Charles M; Beautrais, Annette L; Bridge, Jeffrey A; Brown, Gregory K; Revicki, Dennis A; Ryan, Neal D; Sheehan, David V

    2010-08-01

    . Any areas of disagreement have been noted. The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's effort to promote standard definitions and definable expectations for investigators and industry sponsors by endorsing the terminology in the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to build upon its new authority to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk within informative large health care-related databases in the United States and abroad. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the current Agency requirement that all CNS clinical drug trials must include a C-CASA-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed, and they need to be included to enable premarket assessments of the risks and benefits of medications related to suicidal ideation, suicidal behavior, and suicide in such patients. Copyright 2010 Physicians Postgraduate Press, Inc.

  1. Safety and effectiveness of drug therapy for the acutely agitated patient (Part I

    Directory of Open Access Journals (Sweden)

    Gianluca Airoldi

    2013-04-01

    Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone. Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5 and Fridericia

  2. The Internet and drug safety: what are the implications for pharmacovigilance?

    Science.gov (United States)

    Cobert, B; Silvey, J

    1999-02-01

    Use of the Internet is becoming widespread throughout the world. Its use in the domain of drug safety and pharmacovigilance is spreading rapidly. Governments and industry have taken the lead in developing extensive web sites. The US Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA) and other agencies have developed sites containing enormous amounts of information both on pharmacovigilance in general and on specific drugs in particular. Under the US 'Freedom of Information Act' the FDA has put major parts of its adverse event database on line. Regulatory documents are also available from the FDA site or from hyperlinks described in the site. The US Center for Drug Evaluation and Research updates its site most days and maintains a free automated e-mail announcement service of these updates. Similarly, the EMEA updates its site frequently and publishes extensive material including regulatory documents, guidelines, European Public Assessment Reports on newly approved medications and other useful information. A free update service by e-mail is also available. Although English is the primary language used on the EMEA site, some of the information is available in other languages. Pharmaceutical companies are not using the Internet for pharmacovigilance yet. Rather, the Internet is being used for promotion of their products and for informing consumers on general information on diseases, for financial and investor data and for employment opportunities, etc. Other organisations such as lobbies, consumer groups and medical journals are also beginning to use the Internet. The electronic transmission of safety information, using the standards developed by the International Conference on Harmonization, is currently being tested for the transmission of individual patient adverse event information between companies and governments. In addition, the FDA has begun to accept adverse events from healthcare providers and consumers

  3. A randomised controlled trial to compare opt-in and opt-out parental consent for childhood vaccine safety surveillance using data linkage: study protocol

    Directory of Open Access Journals (Sweden)

    Duszynski Katherine M

    2011-01-01

    Full Text Available Abstract Background The Vaccine Assessment using Linked Data (VALiD trial compared opt-in and opt-out parental consent for a population-based childhood vaccine safety surveillance program using data linkage. A subsequent telephone interview of all households enrolled in the trial elicited parental intent regarding the return or non-return of reply forms for opt-in and opt-out consent. This paper describes the rationale for the trial and provides an overview of the design and methods. Methods/Design Single-centre, single-blind, randomised controlled trial (RCT stratified by firstborn status. Mothers who gave birth at one tertiary South Australian hospital were randomised at six weeks post-partum to receive an opt-in or opt-out reply form, along with information explaining data linkage. The primary outcome at 10 weeks post-partum was parental participation in each arm, as indicated by the respective return or non-return of a reply form (or via telephone or email response. A subsequent telephone interview at 10 weeks post-partum elicited parental intent regarding the return or non-return of the reply form, and attitudes and knowledge about data linkage, vaccine safety, consent preferences and vaccination practices. Enrolment began in July 2009 and 1,129 households were recruited in a three-month period. Analysis has not yet been undertaken. The participation rate and selection bias for each method of consent will be compared when the data are analysed. Discussion The VALiD RCT represents the first trial of opt-in versus opt-out consent for a data linkage study that assesses consent preferences and intent compared with actual opting in or opting out behaviour, and socioeconomic factors. The limitations to generalisability are discussed. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12610000332022

  4. A randomised controlled trial to compare opt-in and opt-out parental consent for childhood vaccine safety surveillance using data linkage: study protocol.

    Science.gov (United States)

    Berry, Jesia G; Ryan, Philip; Braunack-Mayer, Annette J; Duszynski, Katherine M; Xafis, Vicki; Gold, Michael S

    2011-01-04

    The Vaccine Assessment using Linked Data (VALiD) trial compared opt-in and opt-out parental consent for a population-based childhood vaccine safety surveillance program using data linkage. A subsequent telephone interview of all households enrolled in the trial elicited parental intent regarding the return or non-return of reply forms for opt-in and opt-out consent. This paper describes the rationale for the trial and provides an overview of the design and methods. Single-centre, single-blind, randomised controlled trial (RCT) stratified by firstborn status. Mothers who gave birth at one tertiary South Australian hospital were randomised at six weeks post-partum to receive an opt-in or opt-out reply form, along with information explaining data linkage. The primary outcome at 10 weeks post-partum was parental participation in each arm, as indicated by the respective return or non-return of a reply form (or via telephone or email response). A subsequent telephone interview at 10 weeks post-partum elicited parental intent regarding the return or non-return of the reply form, and attitudes and knowledge about data linkage, vaccine safety, consent preferences and vaccination practices. Enrolment began in July 2009 and 1,129 households were recruited in a three-month period. Analysis has not yet been undertaken. The participation rate and selection bias for each method of consent will be compared when the data are analysed. The VALiD RCT represents the first trial of opt-in versus opt-out consent for a data linkage study that assesses consent preferences and intent compared with actual opting in or opting out behaviour, and socioeconomic factors. The limitations to generalisability are discussed. Australian New Zealand Clinical Trials Registry ACTRN12610000332022.

  5. Surveillance Culture

    DEFF Research Database (Denmark)

    2017-01-01

    What does it mean to live in a world full of surveillance? In this documentary film, we take a look at everyday life in Denmark and how surveillance technologies and practices influence our norms and social behaviour. Researched and directed by Btihaj Ajana and Anders Albrechtslund....

  6. Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Kenji Ikemura

    2017-12-01

    Full Text Available Proton pump inhibitors (PPIs, H+/K+-ATPase inhibitors, are the most commonly prescribed drugs for the treatment of gastroesophageal reflux and peptic ulcer diseases; they are highly safe and tolerable. Since PPIs are frequently used in cancer patients, studies investigating interactions between PPIs and anticancer agents are of particular importance to achieving effective and safe cancer chemotherapy. Several studies have revealed that PPIs inhibit not only the H+/K+-ATPase in gastric parietal cells, but also the vacuolar H+-ATPase (V-ATPase overexpressed in tumor cells, as well as the renal basolateral organic cation transporter 2 (OCT2 associated with pharmacokinetics and/or renal accumulation of various drugs, including anticancer agents. In this mini-review, we summarize the current knowledge regarding the impact of PPIs on the efficacy and safety of cancer chemotherapeutics via inhibition of targets other than the H+/K+-ATPase. Co-administration of clinical doses of PPIs protected kidney function in patients receiving cisplatin and fluorouracil, presumably by decreasing accumulation of cisplatin in the kidney via OCT2 inhibition. In addition, co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles to enhance the sensitivity of the tumor cells to the anticancer agents. In the present mini-review, we suggest that PPIs enhance the efficacy and safety of anticancer agents via off-target inhibition (e.g., of OCT2 and V-ATPase, rather than on-target inhibition of the H+/K+-ATPase. The present findings should provide important information to establish novel supportive therapy with PPIs during cancer chemotherapy.

  7. Specialty pharmacies and other restricted drug distribution systems: financial and safety considerations for patients and health-system pharmacists.

    Science.gov (United States)

    Kirschenbaum, Bonnie E

    2009-12-15

    To discuss the role of restricted drug distribution systems in the implementation of risk evaluation and mitigation strategies (REMS), health-system pharmacists' concerns associated with the use of specialty pharmacies and other restricted drug distribution systems, reimbursement policies for high-cost specialty drugs, supply chain models for traditional and specialty drugs, and emerging trends in the management of and reimbursement for specialty pharmaceuticals. Restricted drug distribution systems established by pharmaceutical manufacturers, specialty pharmacies, or other specialty suppliers may be a component of REMS, which are required by the Food and Drug Administration for the management of known or potential serious risks from certain drugs. Concerns of health-system pharmacists using specialty suppliers include access to pharmaceuticals, operational challenges, product integrity, financial implications, continuity of care, and patient safety. An ambulatory care patient taking a specialty drug product from home to a hospital outpatient clinic or inpatient setting for administration, a practice known as "brown bagging," raises concerns about product integrity and institutional liability. An institution's finances, tolerance for liability, and ability to skillfully manage the processes involved often determine its choice between an approach that prohibits brown bagging but is costly and one that permits the practice under certain conditions and is less costly. The recent shift from a traditional supply chain model to a specialty pharmacy supply chain model for high-cost pharmaceuticals has the potential to increase pharmaceutical costs for health systems. A dialogue is needed between health-system pharmacists and group purchasing organizations to address the latter's role in mitigating the financial implications of this change and to help clarify the safety issues. Some health plans have shifted part of the cost of expensive drugs to patients by establishing a

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

    Science.gov (United States)

    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.

  9. [Extrapyramidal toxicity caused by metoclopramide and clebopride: study of voluntary notifications of adverse effects to the Spanish Drug Surveillance System].

    Science.gov (United States)

    Cuena Boy, R; Maciá Martínez, M A

    1998-03-31

    To clarify if there is any basis for the hypothesis that Clebopride leads to more extrapyramidal reactions than Metoclopramide. Observational, longitudinal, retrospective and comparative study of two series of cases. The entire Spanish healthcare system. Those notified to the Spanish Drug watch system as possibly having suffered an adverse reaction to Metoclopramide (n = 98) or Clebopride (n = 123) between 1/1/1990 and 10/6/1997. None. 84.3% of suspected adverse reactions to Clebopride and 51.6% of those to Metoclopramide had a non-hospital precedence (P Clebopride, there was extrapyramidal toxicity (P = 0.021). There is a basis for the hypothesis that Clebopride causes more extrapyramidal reactions than Metoclopramide. It was reasonable to realize a study based on this hypothesis.

  10. The role of veterinary services in animal health and food safety surveillance, and coordination with other services.

    Science.gov (United States)

    Bellemain, V

    2013-08-01

    The control of animal health and food safety has undergone profound changes and is now seen in terms of a global approach, 'from the stable to the table'. The risks themselves have also evolved, principally due to changing practices, and this, coupled with increased knowledge and changes in consumer demands, has led to a more global conception of production chains. In terms of official controls, targeted control of the final food product has gradually been replaced by control of the production processes and an integrated approach to hazards throughout the production chain. This, in turn, has resulted in a new division of responsibilities among the producers (farmers), the manufacturers and the administration; namely, Veterinary Services. The areas in which veterinarians are involved have gradually been extended from animal production to all levels of the food production chain. Animal health interventions on farms are comparable to interventions in agri-food companies. Both are, or should be, included in veterinary training and education. To meet new challenges, the current trend is for Veterinary Services to be responsible for, or coordinate, sanitary interventions from the stable to the table. Coordination between Veterinary Services and other relevant authorities is a key component of good public governance, especially for effective action and optimal management of the resources available.

  11. Predicting Drug Safety and Communicating Risk: Benefits of a Bayesian Approach.

    Science.gov (United States)

    Lazic, Stanley E; Edmunds, Nicholas; Pollard, Christopher E

    2018-03-01

    Drug toxicity is a major source of attrition in drug discovery and development. Pharmaceutical companies routinely use preclinical data to predict clinical outcomes and continue to invest in new assays to improve predictions. However, there are many open questions about how to make the best use of available data, combine diverse data, quantify risk, and communicate risk and uncertainty to enable good decisions. The costs of suboptimal decisions are clear: resources are wasted and patients may be put at risk. We argue that Bayesian methods provide answers to all of these problems and use hERG-mediated QT prolongation as a case study. Benefits of Bayesian machine learning models include intuitive probabilistic statements of risk that incorporate all sources of uncertainty, the option to include diverse data and external information, and visualizations that have a clear link between the output from a statistical model and what this means for risk. Furthermore, Bayesian methods are easy to use with modern software, making their adoption for safety screening straightforward. We include R and Python code to encourage the adoption of these methods.

  12. Toxicological study on the safety of DTPA as a drug, (1)

    International Nuclear Information System (INIS)

    Fukuda, Satoshi; Iida, Haruzo

    1983-01-01

    In order to clarify the safety of Ca-DTPA and Zn-DTPA recommended to use as drugs in the therapeutic removal of incorporated radionuclides from the human body, the teratological study on these two agents was carried out in rats as one of a series of the toxicological tests. The teratological effects of DTPA were observed because the fetus is highly susceptible to any drug. The pregnant females of Wistar rat were injected subcutaneously daily on days 9-13 of gestation with 1, 6, 12, 24 and 36 H.D. (H.D. = human dose, 1 H.D. = 30μmol/kg body weight) of Ca-DTPA or Zn-DTPA, respectively. In the dams, no toxic effects were observed. In the fetuses, the decrease of the survival rate was observed in only the group injected daily with 36 H.D. of Ca-DTPA. Some cases of gross defects of fetuses: the exencephaly, microphthalmia, anophthalmia and fusion of ribs were observed in the groups injected daily with 12, 24 and 36 H.D. of Ca-DTPA. The results obtained show that Ca-DTPA should not be given to a pregnant woman. However, no toxic effects of either Ca-DTPA or Zn-DTPA observed in the dams ana of Zn-DTPA even in the fetuses indicate that these agents can be used by a radiation worker who usually is an adult man. (author)

  13. Toxicological study on the safety of DTPA as a drug, (1). Teratological study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Satoshi; Iida, Haruzo (National Inst. of Radiological Sciences, Chiba (Japan))

    1983-03-01

    In order to clarify the safety of Ca-DTPA and Zn-DTPA recommended to use as drugs in the therapeutic removal of incorporated radionuclides from the human body, the teratological study on these two agents was carried out in rats as one of a series of the toxicological tests. The teratological effects of DTPA were observed because the fetus is highly susceptible to any drug. The pregnant females of Wistar rat were injected subcutaneously daily on days 9-13 of gestation with 1, 6, 12, 24 and 36 H.D. (H.D. = human dose, 1 H.D. = 30..mu..mol/kg body weight) of Ca-DTPA or Zn-DTPA, respectively. In the dams, no toxic effects were observed. In the fetuses, the decrease of the survival rate was observed in only the group injected daily with 36 H.D. of Ca-DTPA. Some cases of gross defects of fetuses: the exencephaly, microphthalmia, anophthalmia and fusion of ribs were observed in the groups injected daily with 12, 24 and 36 H.D. of Ca-DTPA. The results obtained show that Ca-DTPA should not be given to a pregnant woman. However, no toxic effects of either Ca-DTPA or Zn-DTPA observed in the dams or of Zn-DTPA even in the fetuses indicate that these agents can be used by a radiation worker who usually is an adult man.

  14. Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis

    Science.gov (United States)

    Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; de Morales, José M. García Ruiz; Herreras, Jose M.; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

    2017-01-01

    Abstract Background: To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Methods: Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). Results: We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Conclusions: Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients. PMID:29049193

  15. Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis: A systematic literature review.

    Science.gov (United States)

    Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; Morales, José M García Ruiz de; Herreras, Jose M; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

    2017-10-01

    To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.

  16. Pharmaceutical quality of "party pills" raises additional safety concerns in the use of illicit recreational drugs.

    Science.gov (United States)

    Young, Simon A; Thrimawithana, Thilini R; Antia, Ushtana; Fredatovich, John D; Na, Yonky; Neale, Peter T; Roberts, Amy F; Zhou, Huanyi; Russell, Bruce

    2013-06-14

    To determine the content and release kinetics of 1-benzylpiperazine (BZP) and 1-(3-trifluoromethyl-phenyl)piperazine (TFMPP) from "party pill" formulations. From these data, the possible impact of pharmaceutical quality upon the safety of such illicit formulations may be inferred. The amount of BZP and TFMPP in party pill formulations was determined using a validated HPLC method. The in-vitro release kinetics of selected party pill brands were determined using a USP dissolution apparatus (75 rpm, 37.5 degrees Celsius). The release data were then fitted to a first order release model using PLOT software and the time taken to achieve 90% release reported. Many of the tested party pill brands contained amounts of BZP and TFMPP that varied considerably from that stated on the packaging; including considerable TFMPP content in some brands not labelled to contain this drug. Dissolution studies revealed that there was considerable variability in the release kinetics between brands; in one case 90% release required >30 minutes. Lack of quality control in party pill manufacture may have led to the toxic effects reported by users unaware of the true content and release of drug from pills. More stringent regulation in the manufacture and quality control of "new generation party pills" is essential to the harm reduction campaign.

  17. Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs

    Directory of Open Access Journals (Sweden)

    Denilson C. Albuquerque

    2005-08-01

    Full Text Available OBJECTIVE: To evaluate the efficacy, safety and tolerability of sildenafil among Brazilian patients with hypertension treated with combinations of anti-hypertensive drugs. MATERIALS AND METHODS: One hundred twenty hypertensive men aged 30 to 81 years old under treatment with 2 or more anti-hypertensive drugs and with erectile dysfunction (ED lasting for at least 6 months were enrolled at 7 research centers in Brazil. Patients were randomized to receive treatment with either sildenafil or placebo taken 1 hour before sexual intercourse (initial dose of 50 mg, adjusted to 25 mg or 100 mg according to efficacy and toxicity. During the following 8 weeks, patients were evaluated regarding vital signs, adverse events, therapeutic efficacy, satisfaction with treatment and use of concurrent medications. RESULTS: The primary evaluation of efficacy, which was based on responses to questions 3 and 4 of the International Index of Erectile Function, showed significant differences regarding treatment with sildenafil (p = 0.0002 and p < 0.0001, respectively. In the assessment of global efficacy, 87% of the patients treated with sildenafil reported improved erections, as compared with 37% of patients given placebos (p < 0.0001. The other secondary evaluations supported the results favoring sildenafil. The most frequent adverse events among patients treated with sildenafil were headaches (11.4%, vasodilation (11.4% and dyspepsia (6.5%. There were no significant changes in blood pressure measurements in both groups. CONCLUSION: Sildenafil is efficacious and safe for the treatment of hypertensive patients with ED who receive concurrent combinations of anti-hypertensive drugs.

  18. Enhanced HIV-1 surveillance using molecular epidemiology to study and monitor HIV-1 outbreaks among intravenous drug users (IDUs) in Athens and Bucharest.

    Science.gov (United States)

    Paraskevis, Dimitrios; Paraschiv, Simona; Sypsa, Vana; Nikolopoulos, Georgios; Tsiara, Chryssa; Magiorkinis, Gkikas; Psichogiou, Mina; Flampouris, Andreas; Mardarescu, Mariana; Niculescu, Iulia; Batan, Ionelia; Malliori, Meni; Otelea, Dan; Hatzakis, Angelos

    2015-10-01

    A significant increase in HIV-1 diagnoses was reported among Injecting Drug Users (IDUs) in the Athens (17-fold) and Bucharest (9-fold) metropolitan areas starting 2011. Molecular analyses were conducted on HIV-1 sequences from IDUs comprising 51% and 20% of the diagnosed cases among IDUs during 2011-2013 for Greece and Romania, respectively. Phylodynamic analyses were performed using the newly developed birth-death serial skyline model which allows estimating of important epidemiological parameters, as implemented in BEAST programme. Most infections (>90%) occurred within four and three IDU local transmission networks in Athens and Bucharest, respectively. For all Romanian clusters, the viral strains originated from local circulating strains, whereas in Athens, the local strains seeded only two of the four sub-outbreaks. Birth-death skyline plots suggest a more explosive nature for sub-outbreaks in Bucharest than in Athens. In Athens, two sub-outbreaks had been controlled (Re1.0) and two had been controlled (Re<1.0). The lead times were shorter for the outbreak in Athens than in Bucharest. Enhanced molecular surveillance proved useful to gain information about the origin, causal pathways, dispersal patterns and transmission dynamics of the outbreaks that can be useful in a public health setting. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Evaluating the accuracy of sampling to estimate central line-days: simplification of the National Healthcare Safety Network surveillance methods.

    Science.gov (United States)

    Thompson, Nicola D; Edwards, Jonathan R; Bamberg, Wendy; Beldavs, Zintars G; Dumyati, Ghinwa; Godine, Deborah; Maloney, Meghan; Kainer, Marion; Ray, Susan; Thompson, Deborah; Wilson, Lucy; Magill, Shelley S

    2013-03-01

    To evaluate the accuracy of weekly sampling of central line-associated bloodstream infection (CLABSI) denominator data to estimate central line-days (CLDs). Obtained CLABSI denominator logs showing daily counts of patient-days and CLD for 6-12 consecutive months from participants and CLABSI numerators and facility and location characteristics from the National Healthcare Safety Network (NHSN). Convenience sample of 119 inpatient locations in 63 acute care facilities within 9 states participating in the Emerging Infections Program. Actual CLD and estimated CLD obtained from sampling denominator data on all single-day and 2-day (day-pair) samples were compared by assessing the distributions of the CLD percentage error. Facility and location characteristics associated with increased precision of estimated CLD were assessed. The impact of using estimated CLD to calculate CLABSI rates was evaluated by measuring the change in CLABSI decile ranking. The distribution of CLD percentage error varied by the day and number of days sampled. On average, day-pair samples provided more accurate estimates than did single-day samples. For several day-pair samples, approximately 90% of locations had CLD percentage error of less than or equal to ±5%. A lower number of CLD per month was most significantly associated with poor precision in estimated CLD. Most locations experienced no change in CLABSI decile ranking, and no location's CLABSI ranking changed by more than 2 deciles. Sampling to obtain estimated CLD is a valid alternative to daily data collection for a large proportion of locations. Development of a sampling guideline for NHSN users is underway.

  20. Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

    Science.gov (United States)

    Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

    2017-08-01

    To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

  1. Supporting surveillance capacity for antimicrobial resistance: Laboratory capacity strengthening for drug resistant infections in low and middle income countries [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Anna C. Seale

    2017-09-01

    Full Text Available Development of antimicrobial resistance (AMR threatens our ability to treat common and life threatening infections. Identifying the emergence of AMR requires strengthening of surveillance for AMR, particularly in low and middle-income countries (LMICs where the burden of infection is highest and health systems are least able to respond. This work aimed, through a combination of desk-based investigation, discussion with colleagues worldwide, and visits to three contrasting countries (Ethiopia, Malawi and Vietnam, to map and compare existing models and surveillance systems for AMR, to examine what worked and what did not work. Current capacity for AMR surveillance varies in LMICs, but and systems in development are focussed on laboratory surveillance. This approach limits understanding of AMR and the extent to which laboratory results can inform local, national and international public health policy. An integrated model, combining clinical, laboratory and demographic surveillance in sentinel sites is more informative and costs for clinical and demographic surveillance are proportionally much lower. The speed and extent to which AMR surveillance can be strengthened depends on the functioning of the health system, and the resources available. Where there is existing laboratory capacity, it may be possible to develop 5-20 sentinel sites with a long term view of establishing comprehensive surveillance; but where health systems are weaker and laboratory infrastructure less developed, available expertise and resources may limit this to 1-2 sentinel sites. Prioritising core functions, such as automated blood cultures, reduces investment at each site. Expertise to support AMR surveillance in LMICs may come from a variety of international, or national, institutions. It is important that these organisations collaborate to support the health systems on which AMR surveillance is built, as well as improving technical capacity specifically relating to AMR

  2. Safety

    International Nuclear Information System (INIS)

    1998-01-01

    A brief account of activities carried out by the Nuclear power plants Jaslovske Bohunice in 1997 is presented. These activities are reported under the headings: (1) Nuclear safety; (2) Industrial and health safety; (3) Radiation safety; and Fire protection

  3. A comprehensive review of assay methods to determine drugs in breast milk and the safety of breastfeeding when taking drugs.

    Science.gov (United States)

    Fríguls, Bibiana; Joya, Xavier; García-Algar, Oscar; Pallás, C R; Vall, Oriol; Pichini, Simona

    2010-06-01

    Most of the licit and illicit drugs consumed by the breastfeeding woman pass into the milk and can modify the production, volume and composition of the milk, as well as hypothetically have short- and long-term harmful effects on the infant. There is much confusion in the scientific community regarding this issue: should a woman breastfeed her baby while continuing to use prescription drugs and/or drugs of abuse? There are many case reports of clinically significant toxicity in breast-fed infants from some substances used by mothers (such as irritability, vomiting, sedation, respiratory depression, shock), but there are too few data on studies conducted in breastfeeding women and their infants to make a realistic risk assessment. The objective measurement of a drug and/or metabolites in maternal milk is the first step when investigating the amount of drug excreted in milk and subsequently calculating the daily dose administered to the breast-fed infant. The present review reports the analytical methods developed to detect different drugs in the breast milk, listing the principal characteristics and validation parameters, advantages and disadvantages. Furthermore, the mechanisms of drug transfer into breast milk are discussed, the correlation between the concentration of the drug in breast milk and potential adverse outcomes on the infant are described for each drug, and suggested harm minimization strategies and approved breastfeeding recommendations are indicated.

  4. Surface Environmental Surveillance Procedures Manual

    International Nuclear Information System (INIS)

    Hanf, Robert W.; Poston, Ted M.

    2000-01-01

    Shows and explains certain procedures needed for surface environmental surveillance. Hanford Site environmental surveillance is conducted by the Pacific Northwest National Laboratory (PNNL) for the U.S. Department of Energy (DOE) under the Surface Environmental Surveillance Project (SESP). The basic requirements for site surveillance are set fourth in DOE Order 5400.1, General Environmental Protection Program Requirements. Guidance for the SESP is provided in DOE Order 5484.1, Environmental Protection, Safety, and Health Protection Information Reporting Requirements and DOE Order 5400.5, Radiation Protection of the Public and Environment. Guidelines for environmental surveillance activities are provided in DOE/EH-0173T, Environmental Regulatory Guide for Radiological Effluent Monitoring and Environmental Surveillance. An environmental monitoring plan for the Hanford Site is outlined in DOE/RL 91-50 Rev. 2, Environmental Monitoring Plan, United States Department of Energy, Richland Operations Office. Environmental surveillance data are used in assessing the impact of current and past site operations on human health and the environment, demonstrating compliance with applicable local, state, and federal environmental regulations, and verifying the adequacy of containment and effluent controls. SESP sampling schedules are reviewed, revised, and published each calendar year in the Hanford Site Environmental Surveillance Master Sampling Schedule. Environmental samples are collected by SESP staff in accordance with the approved sample collection procedures documented in this manual. Personnel training requirements are documented in SESP-TP-01 Rev.2, Surface Environmental Surveillance Project Training Program.

  5. The algorithmic performance of J-Tpeak for drug safety clinical trial.

    Science.gov (United States)

    Chien, Simon C; Gregg, Richard E

    The interval from J-point to T-wave peak (JTp) in ECG is a new biomarker able to identify drugs that prolong the QT interval but have different ion channel effects. If JTp is not prolonged, the prolonged QT may be associated with multi ion channel block that may have low torsade de pointes risk. From the automatic ECG measurement perspective, accurate and repeatable measurement of JTp involves different challenges than QT. We evaluated algorithm performance and JTp challenges using the Philips DXL diagnostic 12/16/18-lead algorithm. Measurement of JTp represents a different use model. Standard use of corrected QT interval is clinical risk assessment on patients with cardiac disease or suspicion of heart disease. Drug safety trials involve a very different population - young healthy subjects - who commonly have J-waves, notches and slurs. Drug effects include difficult and unusual morphology such as flat T-waves, gentle notches, and multiple T-wave peaks. The JTp initiative study provided ECGs collected from 22 young subjects (11 males and females) in randomized testing of dofetilide, quinidine, ranolazine, verapamil and placebo. We compare the JTp intervals between DXL algorithm and the FDA published measurements. The lead wise, vector-magnitude (VM), root-mean-square (RMS) and principal-component-analysis (PCA) representative beats were used to measure JTp and QT intervals. We also implemented four different methods for T peak detection for comparison. We found that JTp measurements were closer to the reference for combined leads RMS and PCA than individual leads. Differences in J-point location led to part of the JTp measurement difference because of the high prevalence of J-waves, notches and slurs. Larger differences were noted for drug effect causing multiple distinct T-wave peaks (Tp). The automated algorithm chooses the later peak while the reference was the earlier peak. Choosing among different algorithmic strategies in T peak measurement results in the

  6. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Cros, C., E-mail: caroline.cros@hotmail.co.uk [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Skinner, M., E-mail: Matthew.Skinner@astrazeneca.com [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Moors, J. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Lainee, P. [Sanofi-Aventis R and D, 371, rue du Pr Joseph Blayac, 34184 Montpellier Cedex 04 (France); Valentin, J.P. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom)

    2012-12-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two

  7. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    International Nuclear Information System (INIS)

    Cros, C.; Skinner, M.; Moors, J.; Lainee, P.; Valentin, J.P.

    2012-01-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I Na ) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I Na , this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E max 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two out of three

  8. Potential Misclassification of Urinary Tract-Related Bacteremia Upon Applying the 2015 Catheter-Associated Urinary Tract Infection Surveillance Definition From the National Healthcare Safety Network.

    Science.gov (United States)

    Greene, M Todd; Ratz, David; Meddings, Jennifer; Fakih, Mohamad G; Saint, Sanjay

    2016-04-01

    The Centers for Disease Control and Prevention recently updated the surveillance definition of catheter-associated urinary tract infection to include only urine culture bacteria of at least 1 × 10(5) colony-forming units/mL. Our findings suggest that the new surveillance definition may fail to capture clinically meaningful catheter-associated urinary tract infections.

  9. 77 FR 44256 - Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510...

    Science.gov (United States)

    2012-07-27

    ...] Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510(k... serious and sometimes fatal consequences to patients. This guidance provides recommendations to 510(k... unintended connections between enteral and nonenteral devices. This draft guidance is not final nor is it in...

  10. Data-driven drug safety signal detection methods in pharmacovigilance using electronic primary care records: A population based study

    Directory of Open Access Journals (Sweden)

    Shang-Ming Zhou

    2017-04-01

    Data-driven analytic methods are a valuable aid to signal detection of ADEs from large electronic health records for drug safety monitoring. This study finds the methods can detect known ADE and so could potentially be used to detect unknown ADE.

  11. Characteristics of plasmids in multi-drug-resistant Enterobacteriaceae isolated during prospective surveillance of a newly opened hospital in Iraq.

    Directory of Open Access Journals (Sweden)

    Xiao-Zhe Huang

    Full Text Available BACKGROUND: Gram-negative multidrug-resistant (MDR bacteria are major causes of nosocomial infections, and antibiotic resistance in these organisms is often plasmid mediated. Data are scarce pertaining to molecular mechanisms of antibiotic resistance in resource constrained areas such as Iraq. METHODOLOGY/PRINCIPAL FINDINGS: In this study, all MDR Enterobacteriaceae (n = 38 and randomly selected non-MDR counterparts (n = 41 isolated from patients, healthcare workers and environmental surfaces in a newly opened hospital in Iraq were investigated to characterize plasmids found in these isolates and determine their contribution to antibiotic resistance. Our results demonstrated that MDR E. coli and K. pneumoniae isolates harbored significantly more (≥ 3 plasmids compared to their non-MDR counterparts, which carried ≤ 2 plasmids (p<0.01. Various large plasmids (~52 to 100 kb from representative isolates were confirmed to contain multiple resistance genes by DNA microarray analysis. Aminoglycoside (acc, aadA, aph, strA/B, and ksgA, β-lactam (bla(TEM1, bla(AMPC, bla(CTX-M-15, bla(OXA-1, bla(VIM-2 and bla(SHV, sulfamethoxazole/trimethoprim (sul/dfr, tetracycline (tet and chloramphenicol (cat resistance genes were detected on these plasmids. Additionally, multiple plasmids carrying multiple antibiotic resistance genes were found in the same host strain. Genetic transfer-associated genes were identified on the plasmids from both MDR and non-MDR isolates. Seven plasmid replicon types (FII, FIA, FIB, B/O, K, I1 and N were detected in the isolates, while globally disseminated IncA/C and IncHI1 plasmids were not detected in these isolates. CONCLUSIONS/SIGNIFICANCE: This is the first report of the characteristics of the plasmids found in Enterobacteriaceae isolated following the opening of a new hospital in Iraq. The information provided here furthers our understanding of the mechanisms of drug resistance in this specific region and their evolutionary

  12. Surveillance Pleasures

    DEFF Research Database (Denmark)

    Albrechtslund, Anders

    The notorious intensification and digitalization of surveillance technologies and practices in today’s society has brought about numerous changes. These changes have been widely noticed, described and discussed across many academic disciplines. However, the contexts of entertainment, play...

  13. Assessment of the accuracy and consistency in the application of standardized surveillance definitions: A summary of the American Journal of Infection Control and National Healthcare Safety Network case studies, 2010-2016.

    Science.gov (United States)

    Wright, Marc-Oliver; Allen-Bridson, Katherine; Hebden, Joan N

    2017-06-01

    The Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) surveillance definitions are the most widely used criteria for health care-associated infection (HAI) surveillance. NHSN participants agree to conduct surveillance in accordance with the NHSN protocol and criteria. To assess the application of these standardized surveillance specifications and offer infection preventionists (IPs) opportunities for ongoing education, a series of case studies, with questions related to NHSN definitions and criteria were published. Beginning in 2010, case studies with multiple-choice questions based on standard surveillance criteria and protocols were written and published in the American Journal of Infection Control with a link to an online survey. Participants anonymously submitted their responses before receiving the correct answers. The 22 case studies had 7,950 respondents who provided 27,790 responses to 75 questions during the first 6 years. Correct responses were selected 62.5% of the time (17,376 out of 27,290), but ranged widely (16%-87%). In a subset analysis, 93% of participants self-identified as IPs (3,387 out of 3,640), 4.5% were public health professionals (163 out of 3,640), and 2.5% were physicians (90 out of 3,640). IPs responded correctly (62%) more often than physicians (55%) (P = .006). Among a cohort of voluntary participants, accurate application of surveillance criteria to case studies was suboptimal, highlighting the need for continuing education, competency development, and auditing. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

  14. Impact of revising the National Nosocomial Infection Surveillance System definition for catheter-related bloodstream infection in ICU: reproducibility of the National Healthcare Safety Network case definition in an Australian cohort of infection control professionals.

    Science.gov (United States)

    Worth, Leon J; Brett, Judy; Bull, Ann L; McBryde, Emma S; Russo, Philip L; Richards, Michael J

    2009-10-01

    Effective and comparable surveillance for central venous catheter-related bloodstream infections (CLABSIs) in the intensive care unit requires a reproducible case definition that can be readily applied by infection control professionals. Using a questionnaire containing clinical cases, reproducibility of the National Nosocomial Infection Surveillance System (NNIS) surveillance definition for CLABSI was assessed in an Australian cohort of infection control professionals participating in the Victorian Hospital Acquired Infection Surveillance System (VICNISS). The same questionnaire was then used to evaluate the reproducibility of the National Healthcare Safety Network (NHSN) surveillance definition for CLABSI. Target hospitals were defined as large metropolitan (1A) or other large hospitals (non-1A), according to the Victorian Department of Human Services. Questionnaire responses of Centers for Disease Control and Prevention NHSN surveillance experts were used as gold standard comparator. Eighteen of 21 eligible VICNISS centers participated in the survey. Overall concordance with the gold standard was 57.1%, and agreement was highest for 1A hospitals (60.6%). The proportion of congruently classified cases varied according to NNIS criteria: criterion 1 (recognized pathogen), 52.8%; criterion 2a (skin contaminant in 2 or more blood cultures), 83.3%; criterion 2b (skin contaminant in 1 blood culture and appropriate antimicrobial therapy instituted), 58.3%; non-CLABSI cases, 51.4%. When survey questions regarding identification of cases of CLABSI criterion 2b were removed (consistent with the current NHSN definition), overall percentage concordance increased to 62.5% (72.2% for 1A centers). Further educational interventions are required to improve the discrimination of primary and secondary causes of bloodstream infection in Victorian intensive care units. Although reproducibility of the CLABSI case definition is relatively poor, adoption of the revised NHSN definition

  15. The Prevalence of Transmitted Drug Resistance in Newly Diagnosed HIV-Infected Individuals in Croatia: The Role of Transmission Clusters of Men Who Have Sex with Men Carrying the T215S Surveillance Drug Resistance Mutation

    Science.gov (United States)

    Grgic, Ivana; Lunar, Maja M.; Poljak, Mario; Vince, Adriana; Vrakela, Ivana Baca; Planinic, Ana; Seme, Katja; Begovac, Josip

    2013-01-01

    Abstract The aim of this study was to determine the prevalence of transmitted drug resistance (TDR) in newly diagnosed and treatment-naive HIV-infected patients from Croatia and evaluate a possible contribution of transmission clusters to the spread of resistant virus. The study enrolled treatment-naive HIV-infected patients that entered clinical care at the Croatian Reference Center for HIV/AIDS between 2006 and 2008. The protease gene and a part of the reverse transcriptase gene of the HIV-1 genome were sequenced by using the Trugene HIV-1 Genotyping System. The prevalence of transmitted drug resistance was analyzed by using the surveillance drug resistance mutations (SDRM) list recommended by the WHO in 2009. We report findings for 118 of 180 eligible patients (65.6% coverage). SDRM were detected in 26 of 118 patients (22.0%) who were infected with subtype B and belonged mostly to the men having sex with men (MSM). The majority of patients with primary resistance carried SDRM associated with resistance to nucleoside analogues reverse transcriptase inhibitors (NRTIs, 23 of 118 patients, 19.5%). The most frequently found NRTI SDRM was T215S (17 of 118 patients, 14.4%). SDRM associated with resistance to nonnucleoside reverse transcriptase inhibitors were detected in three (2.5%) patients and primary resistance to protease inhibitors was not detected. Non-B subtypes were detected in 13/118 patients (11%). A total of 12 transmission pairs and eight distinct transmission clusters were identified with the largest cluster harboring sequences from 19 patients; among them all but two were carrying the T215S mutation. This study showed a high prevalence of TDR in newly diagnosed MSM from Croatia and is an important contribution concerning the relationship between local transmission clusters and the spread of resistant virus. PMID:22906365

  16. The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs

    Directory of Open Access Journals (Sweden)

    Russell Barrett Van Dyke

    2016-05-01

    Full Text Available The Surveillance Monitoring for ART Toxicities (SMARTT cohort of the Pediatric HIV/AIDS Cohort Study (PHACS includes over 3500 HIV-exposed but uninfected (HEU infants and children at 22 sites in the U.S. including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARV and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental, behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain with exposure to combination ARVs (cARV, any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a neurodevelopmental case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With neurodevelopmental testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir were associated with lower performance, although all groups were within the normal range. No ARVs or classes were

  17. Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

    Science.gov (United States)

    Stegemann, Sven

    2018-06-01

    The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

  18. How do pharmaceutical companies handle consumer adverse drug reaction reports? An overview based on a survey of French drug safety managers and officers.

    Science.gov (United States)

    Fleuranceau-Morel, P

    2002-01-01

    It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side-effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e-mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated

  19. Cardiovascular safety of non-steroidal anti-inflammatory drugs among healthy individuals

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Køber, Lars; Torp-Pedersen, Christian

    2010-01-01

    Studies have raised concern on the cardiovascular safety of NSAIDs. We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.......Studies have raised concern on the cardiovascular safety of NSAIDs. We studied safety of NSAID therapy in a nationwide cohort of healthy individuals....

  20. Sponsors’ and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials

    Science.gov (United States)

    Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

    2017-01-01

    Background/aims: The Food and Drug Administration’s final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. Methods: In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative–nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. Results: The investigative site’s responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors’“filtering” of

  1. Sponsors' and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials.

    Science.gov (United States)

    Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

    2017-06-01

    The Food and Drug Administration's final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative-nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. The investigative site's responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors'"filtering" of reports and increased sponsor communication. Sponsors

  2. Use of toxicogenomics in drug safety evaluation: Current status and an industry perspective.

    Science.gov (United States)

    Vahle, John L; Anderson, Ulf; Blomme, Eric A G; Hoflack, Jean-Christophe; Stiehl, Daniel P

    2018-04-18

    Toxicogenomics held great promise as an approach to enable early detection of toxicities induced by xenobiotics; however, there remain questions regarding the impact of the discipline on pharmaceutical nonclinical safety assessment. To understand the current state of toxicogenomics in the sector, an industry group surveyed companies to determine the frequency of toxicogenomics use in in vivo studies at various stages of drug discovery and development and to assess how toxicogenomics use has evolved over time. Survey data were compiled during 2016 from thirteen pharmaceutical companies. Toxicogenomic analyses were infrequently conducted in the development phase and when performed were done to address specific mechanistic questions. Prior to development, toxicogenomics use was more frequent; however, there were significant differences in approaches among companies. Across all phases, gaining mechanistic insight was the most frequent reason cited for pursing toxicogenomics with few companies using toxicogenomics to predict toxicities. These data were consistent with the commentary submitted in response to survey questions asking companies to describe the evolution of their toxicogenomics strategy. Overall, these survey data indicate that toxicogenomics is not widely used as a predictive tool in the pharmaceutical industry but is used regularly by some companies and serves a broader role in mechanistic investigations and as a complement to other technologies. Copyright © 2018. Published by Elsevier Inc.

  3. Residues of carcinogenic animal drugs in food: difficulties in evaluation of human safety.

    Science.gov (United States)

    Somogyi, A

    1979-01-01

    The indisputable need to intensify animal production in order to provide an adequate food supply for the world population involves the use of substances that are highly potent pharmacologically and toxicologically. The history of regulatory action with regard to such additives is similar to that for other substances: first, no regulation; next, an over-reaction; and now decisions based on judicious evaluation of scientific facts. One factor that differentiates the chemicals used in animal production from other food additives is that both the parent compounds and their metabolites appear in edible products, posing problems both for the analytical detection and safety evaluation of such residues. It would be unrealistic to propose 'zero' tolerances for these additives, even if they are carcinogenic. The benefits gained from drugs that cure and prevent infections and parasitic diseases in food-producing animals, and the fact that analytical methods can now detect very small quantities make the presence of low levels of these substances in food unobjectionable.

  4. 78 FR 22270 - Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety...

    Science.gov (United States)

    2013-04-15

    ..., indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes... Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, for new drug...

  5. Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

    Science.gov (United States)

    Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

    2016-02-01

    Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

  6. The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

    Science.gov (United States)

    van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

    2015-07-15

    Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Evaluation of ADS-B Surveillance Data to Identify Flight Operations with Reduced Safety Margin in the National Airspace System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — As part of the FAA's plans for modernization of the Air Traffic Control (ATC) system, Automatic Dependent Surveillance - Broadcast (ADS-B) will be the basis of the...

  8. Situation of the environmental surveillance and situation of the water table and rivers labelling around nuclear sites and old radioactive waste storages. Report for the high committee for the transparency and information on nuclear safety

    International Nuclear Information System (INIS)

    2008-01-01

    The High Committee for the openness and information on nuclear safety (H.C.T.I.S.N.) requested a study at I.R.S.N. concerning the situation of the surveillance of media and their quality and the diffusion of this information near the public, the identification of ground water or rivers that would present a radiological or chemical labelling, the link of these elements with the future national network of the radioactivity measurement in environment. This assessment must also allow to take stock of the situation relative to the surveillance of the quality of ground water that flow out of the level of old radioactive waste storages, especially registered in the ANDRA inventory. I.R.S.N. chose to limit its contribution: to the sites housing nuclear base installations and nuclear base installations that have been classified secret that come under the Minister in charge of energy; to old radioactive wastes storages located in these installations. (N.C.)

  9. Trends in Drug Resistance of Acinetobacter baumannii over a 10-year Period: Nationwide Data from the China Surveillance of Antimicrobial Resistance Program

    Directory of Open Access Journals (Sweden)

    Lei Gao

    2017-01-01

    Conclusions: This longitudinal multicenter surveillance program revealed the nationwide emergence of A. baumannii in China and showed a significant increase in prevalence from 2004 to 2014. High levels of bacterial resistance were detected among samples collected from clinical settings in China, with IRAB and XDRAB being especially prevalent. This study will help to guide empirical therapy and identify at-risk groups requiring more intense interventional infection control measures, while also helping to focus surveillance efforts.

  10. 75 FR 2926 - Pipeline Safety: Reporting Drug and Alcohol Test Results for Contractors and Multiple Operator...

    Science.gov (United States)

    2010-01-19

    ... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket No... Operator Identification Numbers AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT... liquid, and carbon dioxide pipelines and liquefied natural gas facilities that the Pipeline and Hazardous...

  11. SAFETY

    CERN Multimedia

    Niels Dupont

    2013-01-01

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

  12. Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs

    Science.gov (United States)

    Schoellhammer, Carl M.; Srinivasan, Sharanya; Barman, Ross; Mo, Stacy H.; Polat, Baris E.; Langer, Robert; Blankschtein, Daniel

    2016-01-01

    Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet nonspecific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treatment times, however, have partially limited the attractiveness of this method. Building on recent advances made in this area, the simultaneous use of low- and high-frequency ultrasound is explored in a physiologically relevant experimental setup to enable the translation of this treatment to testing in vivo. Dual-frequency ultrasound, utilizing 20 kHz and 1 MHz wavelengths simultaneously, was found to significantly enhance the size of localized transport regions (LTRs) in both in vitro and in vivo models while decreasing the necessary treatment time compared to 20 kHz alone. Additionally, LTRs generated by treatment with 20 kHz + 1 MHz were found to be more permeable than those generated with 20 kHz alone. This was further corroborated with pore-size estimates utilizing hindered-transport theory, in which the pores in skin treated with 20 kHz + 1 MHz were calculated to be significantly larger than the pores in skin treated with 20 kHz alone. This demonstrates for the first time that LTRs generated with 20 kHz + 1 MHz are also more permeable than those generated with 20 kHz alone, which could broaden the range of therapeutics and doses administered transdermally. With regard to safety, treatment with 20 kHz + 1 MHz both in vitro and in vivo appeared to result in no greater skin disruption than that observed in skin treated with 20 kHz alone, an FDA-approved modality. This study demonstrates that dual-frequency ultrasound is more efficient and effective than single-frequency ultrasound and is well-tolerated in vivo. PMID:25662228

  13. Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

    Science.gov (United States)

    Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

    2016-12-15

    Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

  14. Influenza surveillance

    Directory of Open Access Journals (Sweden)

    Karolina Bednarska

    2016-04-01

    Full Text Available Influenza surveillance was established in 1947. From this moment WHO (World Health Organization has been coordinating international cooperation, with a goal of monitoring influenza virus activity, effective diagnostic of the circulating viruses and informing society about epidemics or pandemics, as well as about emergence of new subtypes of influenza virus type A. Influenza surveillance is an important task, because it enables people to prepare themselves for battle with the virus that is constantly mutating, what leads to circulation of new and often more virulent strains of influenza in human population. As vaccination is the most effective method of fighting the virus, one of the major tasks of GISRS is developing an optimal antigenic composition of the vaccine for the current epidemic season. European Influenza Surveillance Network (EISN has also developed over the years. EISN is running integrated epidemiological and virological influenza surveillance, to provide appropriate data to public health experts in member countries, to enable them undertaking relevant activities based on the current information about influenza activity. In close cooperation with GISRS and EISN are National Influenza Centres - national institutions designated by the Ministry of Health in each country.

  15. Surveillance Angels

    NARCIS (Netherlands)

    Rothkrantz, L.J.M.

    2014-01-01

    The use of sensor networks has been proposed for military surveillance and environmental monitoring applications. Those systems are composed of a heterogeneous set of sensors to observe the environment. In centralised systems the observed data will be conveyed to the control room to process the

  16. The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

    Science.gov (United States)

    Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

    2016-01-01

    With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug-induced ulcer in Japan.

    Science.gov (United States)

    Mizokami, Yuji

    2009-10-28

    To investigate the efficacy and safety of rabeprazole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal endoscopy revealed an ulcerous lesion (open ulcer) with diameter > or = 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classification. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events. Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64). The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID administration was confirmed.

  18. 78 FR 10107 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Science.gov (United States)

    2013-02-13

    ... AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA) is providing public meeting registration information for two FSMA related... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110...

  19. The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds

    Energy Technology Data Exchange (ETDEWEB)

    Marks, Louise, E-mail: louise.marks@astrazeneca.com [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Borland, Samantha; Philp, Karen; Ewart, Lorna; Lainée, Pierre; Skinner, Matthew [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Kirk, Sarah [Innovative Medicines, Discovery Sciences, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Valentin, Jean-Pierre [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom)

    2012-09-01

    Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil or vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt{sub max} and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability.

  20. The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds

    International Nuclear Information System (INIS)

    Marks, Louise; Borland, Samantha; Philp, Karen; Ewart, Lorna; Lainée, Pierre; Skinner, Matthew; Kirk, Sarah; Valentin, Jean-Pierre

    2012-01-01

    Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil or vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt max and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability. ► Haemodynamic

  1. Safety

    International Nuclear Information System (INIS)

    2001-01-01

    This annual report of the Senior Inspector for the Nuclear Safety, analyses the nuclear safety at EDF for the year 1999 and proposes twelve subjects of consideration to progress. Five technical documents are also provided and discussed concerning the nuclear power plants maintenance and safety (thermal fatigue, vibration fatigue, assisted control and instrumentation of the N4 bearing, 1300 MW reactors containment and time of life of power plants). (A.L.B.)

  2. Strategies for the early detection of drug-induced hepatic steatosis in preclinical drug safety evaluation studies

    International Nuclear Information System (INIS)

    Amacher, David E.

    2011-01-01

    Hepatic steatosis is characterized by the accumulation of lipid droplets in the liver. Although relatively benign, simple steatosis can eventually lead to the development of steatohepatitis, a more serious condition characterized by fibrosis, cirrhosis, and eventual liver failure if the underlying cause is not eliminated. According to the 'two hit' theory of steatohepatitis, the initial hit involves fat accumulation in the liver, and a second hit leads to inflammation and subsequent tissue injury. Because some xenobiotics target liver fatty acid metabolism, especially mitochondrial β-oxidation, it is important to avoid potential drug candidates that can contribute to either the initiation of liver steatosis or progression to the more injurious steatohepatitis. The gold standard for the detection of these types of hepatic effects is histopathological examination of liver tissue. In animal studies, these examinations are slow, restricted to a single sampling time, and limited tissue sections. Recent literature suggests that rapid in vitro screening methods can be used early in the drug R and D process to identify compounds with steatotic potential. Further, progress in the identification of potential serum or plasma protein biomarkers for these liver changes may provide additional in vivo tools to the preclinical study toxicologist. This review summarizes recent developments for in vitro screening and in vivo biomarker detection for steatotic drug candidates.

  3. Technical-evaluation report on the proposed technical-specification changes for the inservice surveillance of safety-related hydraulic and mechanical snubbers at the Millstone Nuclear Power Station, Unit 2 (Docket No. 50-336)

    International Nuclear Information System (INIS)

    Selan, J.C.

    1983-01-01

    This report documents the technical evaluation of the proposed Technical Specification changes to Limiting Conditions for Operation, Surveillance Requirements and Bases for safety-related hydraulic and mechanical snubbers at the Millstone Nuclear Power Station, Unit 2. The evaluation is to determine whether the proposed Technical Specifications are in conformance with the model Standard Technical Specification set forth by the NRC. A check list, Appendix A of this report, compares the licensee's submittal with the NRC requirements and includes Proposed Resolution of the Deviations

  4. Technical-evaluation report on the proposed technical-specification changes for the inservice surveillance of safety-related hydraulic and mechanical snubbers at the Indian Point Nuclear Power Plant, Unit 3 (Docket No. 50-286)

    International Nuclear Information System (INIS)

    Selan, J.C.

    1983-01-01

    This report documents the technical evaluation of the proposed Technical Specification changes to Limiting Conditions for Operation, Surveillance Requirements and Bases for safety-related hydraulic and mechanical snubbers at the Indian Point Nuclear Power Plant, Unit 3. The evaluation is to determine whether the proposed Technical Specifications are in conformance with the model Standard Technical Specification set forth by the NRC. A check list, Appendix A of this report, compares the licensee's submittal with the NRC requirements and includes Proposed Resolution of the Deviations

  5. Technical-evaluation report on the proposed technical-specification changes for the inservice surveillance of safety-related hydraulic and mechanical snubbers at the James A. Fitzpatrick Nuclear Power Plant (Docket No. 50-333)

    International Nuclear Information System (INIS)

    Selan, J.C.

    1983-01-01

    This report documents the technical evaluation of the proposed Technical Specification changes to Limiting Conditions for Operation, Surveillance Requirements and Bases for safety-related hydraulic and mechanical snubbers at the James A. FitzPatrick Nuclear Power Plant. The evaluation is to determine whether the proposed Technical Specifications are in conformance with the model Standard Technical Specification set forth by the NRC. A check list, Appendix A of this report, compares the licensee's submittal with the NRC requirements and includes Proposed Resolution of the Deviations

  6. Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

    Science.gov (United States)

    Ocana, Alberto; Ethier, Josee-Lyne; Díez-González, Laura; Corrales-Sánchez, Verónica; Srikanthan, Amirrtha; Gascón-Escribano, María J; Templeton, Arnoud J; Vera-Badillo, Francisco; Seruga, Bostjan; Niraula, Saroj; Pandiella, Atanasio; Amir, Eitan

    2015-11-24

    Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.

  7. Development of novel, 384-well high-throughput assay panels for human drug transporters: drug interaction and safety assessment in support of discovery research.

    Science.gov (United States)

    Tang, Huaping; Shen, Ding Ren; Han, Yong-Hae; Kong, Yan; Balimane, Praveen; Marino, Anthony; Gao, Mian; Wu, Sophie; Xie, Dianlin; Soars, Matthew G; O'Connell, Jonathan C; Rodrigues, A David; Zhang, Litao; Cvijic, Mary Ellen

    2013-10-01

    Transporter proteins are known to play a critical role in affecting the overall absorption, distribution, metabolism, and excretion characteristics of drug candidates. In addition to efflux transporters (P-gp, BCRP, MRP2, etc.) that limit absorption, there has been a renewed interest in influx transporters at the renal (OATs, OCTs) and hepatic (OATPs, BSEP, NTCP, etc.) organ level that can cause significant clinical drug-drug interactions (DDIs). Several of these transporters are also critical for hepatobiliary disposition of bilirubin and bile acid/salts, and their inhibition is directly implicated in hepatic toxicities. Regulatory agencies took action to address transporter-mediated DDI with the goal of ensuring drug safety in the clinic and on the market. To meet regulatory requirements, advanced bioassay technology and automation solutions were implemented for high-throughput transporter screening to provide structure-activity relationship within lead optimization. To enhance capacity, several functional assay formats were miniaturized to 384-well throughput including novel fluorescence-based uptake and efflux inhibition assays using high-content image analysis as well as cell-based radioactive uptake and vesicle-based efflux inhibition assays. This high-throughput capability enabled a paradigm shift from studying transporter-related issues in the development space to identifying and dialing out these concerns early on in discovery for enhanced mechanism-based efficacy while circumventing DDIs and transporter toxicities.

  8. Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Chaparro, M; Verreth, A; Lobaton, T

    2018-01-01

    OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs...... in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non......-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox...

  9. El Sistema Cubano de Farmacovigilancia: seis años de experiencia en la detección de efectos adversos The Cuban system of drug surveillance: six years of experience in detecting adverse effects

    Directory of Open Access Journals (Sweden)

    Giset Jiménez López

    2006-04-01

    , teaching, drug information, therapeutic consultation, program for the rational utilization of drugs (PURMED and drug surveillance with the National Coordinating Unit. The objective of this paper was to present the main working results achieved in 6 years after the creation of this drug surveillance system. A retrospective descriptive study was performed to characterize the reports of suspected adverse reactions from the National Coordinating Unit of Drug Surveillance. In the period, 89 540 notifications of adverse drug reactions were received for an average of 17 908 notifications per year, and a report rate of more than 1000 notifications per 1 million inhabitants. These results reflected a regular behaviour in some of these indicators like the predominance of adverse effects in females, affected skin and digestive system as the most reported reactions and the prevalence of antimicrobials, non-steroidal antinflammatory drugs and antihypertensive drugs as the pharmacological groups with more reactions. Similarly, the number of less frequent adverse drug reactions has increased and serious adverse effects have been followed-up. Drug surveillance continue to be a very dynamic scientific and clinical discipline worldwide, being indispensable to face the possible problems of an armory of drugs that does not cease to grow in potency and variety. Therefore, it is necessary that, as soon as adverse effects or toxicity signs occur - mainly if they have not been yet classified - they must be notified and analyzed, and then the importance of the episode should be adequately reported to corresponding health professionals

  10. The Spanish national health care-associated infection surveillance network (INCLIMECC): data summary January 1997 through December 2006 adapted to the new National Healthcare Safety Network Procedure-associated module codes.

    Science.gov (United States)

    Pérez, Cristina Díaz-Agero; Rodela, Ana Robustillo; Monge Jodrá, Vincente

    2009-12-01

    In 1997, a national standardized surveillance system (designated INCLIMECC [Indicadores Clínicos de Mejora Continua de la Calidad]) was established in Spain for health care-associated infection (HAI) in surgery patients, based on the National Nosocomial Infection Surveillance (NNIS) system. In 2005, in its procedure-associated module, the National Healthcare Safety Network (NHSN) inherited the NNIS program for surveillance of HAI in surgery patients and reorganized all surgical procedures. INCLIMECC actively monitors all patients referred to the surgical ward of each participating hospital. We present a summary of the data collected from January 1997 to December 2006 adapted to the new NHSN procedures. Surgical site infection (SSI) rates are provided by operative procedure and NNIS risk index category. Further quality indicators reported are surgical complications, length of stay, antimicrobial prophylaxis, mortality, readmission because of infection or other complication, and revision surgery. Because the ICD-9-CM surgery procedure code is included in each patient's record, we were able to reorganize our database avoiding the loss of extensive information, as has occurred with other systems.

  11. Video Surveillance: Privacy Issues and Legal Compliance

    DEFF Research Database (Denmark)

    Mahmood Rajpoot, Qasim; Jensen, Christian D.

    2015-01-01

    Pervasive usage of video surveillance is rapidly increasing in developed countries. Continuous security threats to public safety demand use of such systems. Contemporary video surveillance systems offer advanced functionalities which threaten the privacy of those recorded in the video. There is a...

  12. Hysteroscopic Sterilization With Essure: Summary of the U.S. Food and Drug Administration Actions and Policy Implications for Postmarketing Surveillance.

    Science.gov (United States)

    Walter, Jessica R; Ghobadi, Comeron W; Hayman, Emily; Xu, Shuai

    2017-01-01

    In September 2015, the U.S. Food and Drug Administration (FDA) convened a meeting of the Obstetrics and Gynecology Advisory Board Committee to address the sudden increase of patient-reported adverse events surrounding Essure, a Class III device offering a less invasive method for permanent female sterilization. After a review of the premarketing and postmarketing data and existing scientific literature, the FDA concluded there was insufficient evidence to remove the device from the market. However, the FDA did release a new guidance document requiring a black box warning for the device and ordered a new postmarketing study comparing Essure's safety and efficacy with laparoscopic tubal sterilization. The device was first approved in 2002 based on nonrandomized, single-arm prospective clinical studies. Since its approval, the device has grown in popularity, particularly in the United States. The driving forces for the sudden increase in adverse event reporting starting in 2013 related to the device remain unclear. Until completion of the new postmarketing study, there will continue to be significant uncertainty of the technology's risk-benefit profile. The controversy with Essure underscores the need for obstetricians and gynecologists to be actively involved in the lifecycle of medical devices. This includes actively reporting adverse events associated with devices to the FDA, supporting the implementation of unique device identifiers enriched with clinical records and paired with insurance claims, and stewarding robust device-specific registries.

  13. Air surveillance

    International Nuclear Information System (INIS)

    Patton, G.W.

    1995-01-01

    This section of the 1994 Hanford Site Environmental Report summarizes the air surveillance and monitoring programs currently in operation at that Hanford Site. Atmospheric releases of pollutants from Hanford to the surrounding region are a potential source of human exposure. For that reason, both radioactive and nonradioactive materials in air are monitored at a number of locations. The influence of Hanford emissions on local radionuclide concentrations was evaluated by comparing concentrations measured at distant locations within the region to concentrations measured at the Site perimeter. This section discusses sample collection, analytical methods, and the results of the Hanford air surveillance program. A complete listing of all analytical results summarized in this section is reported separately by Bisping (1995)

  14. Air surveillance

    Energy Technology Data Exchange (ETDEWEB)

    Patton, G.W.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the air surveillance and monitoring programs currently in operation at that Hanford Site. Atmospheric releases of pollutants from Hanford to the surrounding region are a potential source of human exposure. For that reason, both radioactive and nonradioactive materials in air are monitored at a number of locations. The influence of Hanford emissions on local radionuclide concentrations was evaluated by comparing concentrations measured at distant locations within the region to concentrations measured at the Site perimeter. This section discusses sample collection, analytical methods, and the results of the Hanford air surveillance program. A complete listing of all analytical results summarized in this section is reported separately by Bisping (1995).

  15. Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study.

    Science.gov (United States)

    Tyczynski, Jerzy E; Oleske, Denise M; Klingman, David; Ferrufino, Cheryl P; Lee, Won Chan

    2012-08-01

    the UK [Germany: HR 0.47 (95% CI 0.17, 1.26), 0.43 (0.23, 0.81) and 0.44 (0.26, 0.75), respectively; UK: HR 0.44 (0.15, 1.31), 0.63 (0.25, 1.60) and 0.54 (0.27, 1.10), respectively]. Regardless of whether or not the model controlled for prior CV disease (CVD), the direction and statistical significance of the differences did not change. In the sensitivity analyses including only those without a history of CVD in the 365 days prior to the index date there was no increased risk of CV events in either Germany or the UK. This study offers a framework for the safety assessment of anti-obesity drugs using an observational epidemiological study design. Large electronic health databases were used to construct retrospective cohorts to examine the risk in a population using one specific anti-obesity drug. Use of sibutramine in general practice settings was not found to increase the risk of acute CV events.

  16. Rinderpest surveillance

    International Nuclear Information System (INIS)

    2003-01-01

    Rinderpest is probably the most lethal virus disease of cattle and buffalo and can destroy whole populations; damaging economies; undermining food security and ruining the livelihood of farmers and pastoralists. The disease can be eradicated by vaccination and control of livestock movement. The Department of Technical Co-operation is sponsoring a programme, with technical support from the Joint FAO/IAEA Division to provide advice, training and materials to thirteen states through the 'Support for Rinderpest Surveillance in West Asia' project. (IAEA)

  17. Health surveillance

    International Nuclear Information System (INIS)

    1981-01-01

    The Code includes a number of requirements for the health surveillance of employees associated with the mining and milling of radioactive ores. This guideline is particularly directed at determining the level of fitness of employees and prospective employees, detecting any symptom which might contraindicate exposure to the environment encountered in mine/mill situations, examination of any employee who may have been exposed to radiation in excess of defined limits and the accumulation and provision of data on the health of employees

  18. 78 FR 49988 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules on Foreign Supplier...

    Science.gov (United States)

    2013-08-16

    ... help manage the safety of their global food supply chains. The purpose of the public meeting is to... electronic or written comments to FDA's Division of Dockets Management. ADDRESSES: See section II, ``How to... protect public health by helping to ensure the safety and security of the food supply. FSMA amends the...

  19. 78 FR 57320 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules on Foreign Supplier...

    Science.gov (United States)

    2013-09-18

    ... help manage the safety of their global food supply chains. The purpose of these public meetings is to... submitting either electronic or written comments to FDA's Division of Dockets Management. ADDRESSES: See..., to better protect public health by helping to ensure the safety and security of the food supply. FSMA...

  20. Home closure as a weapon in the Dutch war on drugs: Does judicial review function as a safety net?

    Science.gov (United States)

    Bruijn, L Michelle; Vols, Michel; Brouwer, Jan G

    2018-01-01

    A widespread sense of a failing criminal justice system and increased feelings of insecurity changed the response to crime into a culture of control, which is characterized by policies that punish and exclude. In the Netherlands, these influences can be witnessed in the war on drugs where local authorities use their administrative power to close homes involved in drug-related crime. Citizens can invoke judicial review over these administrative interferences by claiming that such closure results in an unfair balance between purposes, means and consequences. This paper assesses whether judicial review functions as a safety net against losing one's home due to drug-related crime. We used doctrinal legal research methods to examine the "law in the books" and empirical legal research methods to analyse the "law in action". We used a survey to investigate how often the drug-related closure power was used in 2015, and we statistically analysed all published case law of Dutch lower courts between 2007 and 2016. The scope of the closure power broadened over the years and our data show that local authorities fiercely make use of this instrument. In 41.4% of the cases, citizens are successful in fighting the closure. While scholarly literature indicates that judicial courts function as safeguards by questioning the proportionality of administrative action, raising a proportionality defence does not necessarily result in a more favourable outcome for citizens. In fact, raising a proportionality defence makes it more likely to result in dismissal of the appeal. The stretched scope of the drug-related closure power together with the relatively low success rate of citizens who fight the loss of their home and a seemingly meaningless proportionality check show no sign of a safety net against the loss of one's home at the suit of a local authority. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Documentation of pediatric drug safety in manufacturers' product monographs: a cross-sectional evaluation of the canadian compendium of pharmaceuticals and specialities.

    Science.gov (United States)

    Uppal, Navjeet K; Dupuis, Lee L; Parshuram, Christopher S

    2008-01-01

    To describe the provision of pediatric drug safety information in a national formulary of manufacturers' drug product monographs. We performed a cross-sectional evaluation of comprehensive product monographs contained in the 2005 Canadian Compendium of Pharmaceuticals and Specialities (CPS). We abstracted data describing indications for prescription, statements about pediatric safety, available preparations, and provision of dosing guidelines. For each monograph we classified pediatric safety data as either present, present but limited or absent. We then described the pediatric safety data in CPS monographs for drugs listed in the published formulary of the Hospital for Sick Children, Toronto, Ontario, Canada. A total of 2232 product monographs were screened; 684 were excluded and 1548 (66%) were further analyzed. 1462 (94%) had indications that did not exclude children. Pediatric safety information was present in 592 (38%), present but limited in 148 (10%), and absent in 808 (52%) drug monographs. Safety statements were absent in 224 (14%) drug monographs that provided both dosing guidelines and formulations suitable for administration to children, and in 214 (52%) of 411 drugs in the pediatric hospital formulary. We evaluated a widely available national source of pediatric prescribing information. Safety data for children was not mentioned in more than half of the product monographs. Moreover, the provision of safety data was discordant with indications for prescription, the availability of pediatric formulations, and dosing guidelines within the monographs, and with inclusion in a pediatric hospital formulary. Our study suggests that the presentation of pediatric safety data in drug product monographs can be improved to better inform prescribing and to optimize pharmacotherapy in children.

  2. Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques.

    Science.gov (United States)

    Kirtane, Ameya R; Rothenberger, Meghan K; Frieberg, Abby; Nephew, Karla; Schultz-Darken, Nancy; Schmidt, Thomas; Reimann, Thomas; Haase, Ashley T; Panyam, Jayanth

    2017-07-01

    The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of ∼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. 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 : an analysis of European public assessment reports

    NARCIS (Netherlands)

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

    2011-01-01

    Background: 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. Objective:

  4. Illicit Internet availability of drugs subject to recall and patient safety consequences.

    Science.gov (United States)

    Mackey, Tim K; Aung, Phyo; Liang, Bryan A

    2015-12-01

    Permanently recalled drugs are a public health concern if they remain accessible in violation of applicable regulation. Illicit online pharmacies act as an alternative form of access and have been associated with the sale to patients of counterfeit/falsified/fraudulent/substandard drugs. We wished to determine if permanently recalled and significantly restricted drugs were illegally marketed for sale online. The study was conducted in two phases with two objectives. The first phase attempted to identify drugs subject to permanent recall in certain major pharmaceutical markets as well as those listed as recalled or significantly restricted by the United Nations. We also examined the market authorization status of identified drugs in China and India. The second phase used structured searches on the Internet to determine if identified drugs were marketed for sale online. The World Wide Web. After identification of permanently recalled and restricted drugs we conducted Internet searches for illegal "no prescription" marketing events. We assessed the form of marketing, whether a site offered direct-to-patient sale, use of social media marketing, and the site's compliance status with external monitoring bodies. Number of recalled drugs marketed as available for purchase on the Internet. We identified 16 class I equivalent permanently recalled or restricted drugs, 56.3 % (n = 9) of which maintained market authorization in either China or India. Half (n = 8) were marketed for sale online without a prescription direct-to-patient. Use of social media marketing was mixed, with only 18.8 % (n = 3) of recalled drugs having a presence on Facebook, though 50.0 % (n = 8) had content on Twitter. We also found the majority (68.8 %, n = 11) were available and marketed for sale by vendors on the wholesale/business-to-business website alibaba.com primarily as active pharmaceutical ingredient. Despite efforts in several countries to restrict access to these drugs or permanently remove

  5. Leachables and extractables handbook: safety evaluation, qualification, and best practices applied to inhalation drug products

    National Research Council Canada - National Science Library

    Ball, Douglas J

    2012-01-01

    ...). It discusses best practices for evaluation and management of leachables and extractables throughout the pharma product lifecycle by providing practical knowledge about how and why safety thresholds were developed...

  6. Nutritional surveillance.

    Science.gov (United States)

    Mason, J B; Mitchell, J T

    1983-01-01

    The concept of nutritional surveillance is derived from disease surveillance, and means "to watch over nutrition, in order to make decisions that lead to improvements in nutrition in populations". Three distinct objectives have been defined for surveillance systems, primarily in relation to problems of malnutrition in developing countries: to aid long-term planning in health and development; to provide input for programme management and evaluation; and to give timely warning of the need for intervention to prevent critical deteriorations in food consumption. Decisions affecting nutrition are made at various administrative levels, and the uses of different types of nutritional surveillance information can be related to national policies, development programmes, public health and nutrition programmes, and timely warning and intervention programmes. The information should answer specific questions, for example concerning the nutritional status and trends of particular population groups.Defining the uses and users of the information is the first essential step in designing a system; this is illustrated with reference to agricultural and rural development planning, the health sector, and nutrition and social welfare programmes. The most usual data outputs are nutritional outcome indicators (e.g., prevalence of malnutrition among preschool children), disaggregated by descriptive or classifying variables, of which the commonest is simply administrative area. Often, additional "status" indicators, such as quality of housing or water supply, are presented at the same time. On the other hand, timely warning requires earlier indicators of the possibility of nutritional deterioration, and agricultural indicators are often the most appropriate.DATA COME FROM TWO MAIN TYPES OF SOURCE: administrative (e.g., clinics and schools) and household sample surveys. Each source has its own advantages and disadvantages: for example, administrative data often already exist, and can be

  7. Product Failures in Respirators and Consumables: Analysis of Field Safety Notices of 2005-2013 Publicized by the Federal Institute for Drugs and Medical Devices in Germany.

    Science.gov (United States)

    Hannig, Jürgen; Siekmeier, Rüdiger

    2015-01-01

    The current European system governed by the three EC directives 93/42/EEC (Medical Device Directive), 98/79/EC (In-Vitro Diagnostic Directive) and 90/385/EEC (Active Implantable Medical Device Directive) regulates marketing and post-market surveillance of medical devices in the European Economic Area (EEA). In cases of incidents raising the field safety corrective actions (FSCA), manufacturers have to inform the responsible Competent Authority (CA; in Germany this is the Federal Institute for Drugs and Medical Devices, BfArM) and the public by field safety notices (FSN). In this study we analyzed FSN of respirators and consumables directly required for their function, whereas devices for anesthesia and gas delivery were excluded. FSCA and FSN of 2005-2013 publicized by BfArM for the included products were analyzed with respect to the MEDDEV 2.12-1 rev. 8. In total, 60 FSCA were publicized. German and English FSN were found in 59/53 cases, respectively. FSN were clearly characterized as FSN in 44/38 cases and declaration of the type of action in 45/44 cases, respectively. Product names were provided in all cases. Lot numbers or other information for product characterization were available in 7/7 and 43/40 cases, respectively. Detailed information regarding FSCA and product malfunction was found in all cases. Information on product related risks with previous use of affected devices was provided in 42/38 cases. In 53/53 cases manufacturers provided information to mitigate product related risks. Requests to pass FSN to persons needing awareness in the organization were found in 27/24 cases. Contact data were provided in 53/48 cases, respectively. Confirmation that a CA was informed was found in 28/26 cases and in 19/15 cases a customer confirmation was included. The identified risks were: total loss of function (19/16), short circuit (1/1) and burn (3/3), and inhalation of foreign particles (1/1) which might cause severe risk to patients and users. The most frequent

  8. EFFICACY AND SAFETY OF LIPID-LOWERING DRUGS IN PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASES IN THE ELDERLY

    Directory of Open Access Journals (Sweden)

    E. A. Ushkalova

    2016-01-01

    Full Text Available Effect of hyperlipidemia on morbidity and mortality in elderly patients is considered. Authors also cover issues of efficacy and safety of lipid-lowering therapy in primary and secondary prevention of cardiovascular diseases in patients ≥80 years of age who are the most quickly growing group of population and have the highest cardiovascular risk. They stress the need to take into account polymorbidity and polypharmacy that increase the risk of adverse reactions due to the use of both statins and their drug-drug interactions, which requires an assessment of risk/benefit ratio. In addition, there is a need for development of reliable prognostic tools to predict relevant outcomes (e.g., stroke, decrease in functionality/independence, quality of life reduction and rationales for lipid-lowering therapy in the elderly and also their adherence to treatment.

  9. Biocompatible Polymer Nanoformulation To Improve the Release and Safety of a Drug Mimic Molecule Detectable via ICP-MS.

    Science.gov (United States)

    Ferrari, Raffaele; Talamini, Laura; Violatto, Martina Bruna; Giangregorio, Paola; Sponchioni, Mattia; Morbidelli, Massimo; Salmona, Mario; Bigini, Paolo; Moscatelli, Davide

    2017-01-03

    Fluorescent poly(ε-caprolactone)-based nanoparticles (NPs) have been synthesized and successfully loaded with a titanium organometallic compound as a mimic of a water-insoluble drug. The nature of this nanovector enabled us to combine the quantification of the metal in tissues after systemic administration in healthy immunocompetent mice by inductively coupled plasma mass spectroscopy (ICP-MS) followed by the visualization of NPs in organ sections by confocal microscopy. This innovative method of nanodrug screening has enabled us to elucidate the crucial parameters of their kinetics. The organometallic compound is a good mimic of most anticancer drugs, and this approach is an interesting starting point to design the relevance of a broad range of nanoformulations in terms of safety and targeted delivery of the cargoes.

  10. Efficacy and Safety of Drug-Eluting Stents in the Real World: 8-Year Follow-Up

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrini, Denise Oliveira, E-mail: dennizmo@yahoo.com.br; Gomes, Vitor Osório; Lasevitch, Ricardo; Smidt, Luis; Azeredo, Marco Aurélio; Ledur, Priscila; Bodanese, Rodrigo; Sinnott, Leonardo; Moriguchi, Emílio; Caramori, Paulo [Hospital São Lucas PUC, Porto Alegre, RS (Brazil)

    2014-09-15

    Drug-eluting stents have been used in daily practice since 2002, with the clear advantages of reducing the risk of target vessel revascularization and an impressive reduction in restenosis rate by 50%-70%. However, the occurrence of a late thrombosis can compromise long-term results, particularly if the risks of this event were sustained. In this context, a registry of clinical cases gains special value. To evaluate the efficacy and safety of drug-eluting stents in the real world. We report on the clinical findings and 8-year follow-up parameters of all patients that underwent percutaneous coronary intervention with a drug-eluting stent from January 2002 to April 2007. Drug-eluting stents were used in accordance with the clinical and interventional cardiologist decision and availability of the stent. A total of 611 patients were included, and clinical follow-up of up to 8 years was obtained for 96.2% of the patients. Total mortality was 8.7% and nonfatal infarctions occurred in 4.3% of the cases. Target vessel revascularization occurred in 12.4% of the cases, and target lesion revascularization occurred in 8% of the cases. The rate of stent thrombosis was 2.1%. There were no new episodes of stent thrombosis after the fifth year of follow-up. Comparative subanalysis showed no outcome differences between the different types of stents used, including Cypher®, Taxus®, and Endeavor®. These findings indicate that drug-eluting stents remain safe and effective at very long-term follow-up. Patients in the 'real world' may benefit from drug-eluting stenting with excellent, long-term results.

  11. Patient safety: numerical skills and drug calculation abilities of nursing students and registered nurses.

    Science.gov (United States)

    McMullan, Miriam; Jones, Ray; Lea, Susan

    2010-04-01

    This paper is a report of a correlational study of the relations of age, status, experience and drug calculation ability to numerical ability of nursing students and Registered Nurses. Competent numerical and drug calculation skills are essential for nurses as mistakes can put patients' lives at risk. A cross-sectional study was carried out in 2006 in one United Kingdom university. Validated numerical and drug calculation tests were given to 229 second year nursing students and 44 Registered Nurses attending a non-medical prescribing programme. The numeracy test was failed by 55% of students and 45% of Registered Nurses, while 92% of students and 89% of nurses failed the drug calculation test. Independent of status or experience, older participants (> or = 35 years) were statistically significantly more able to perform numerical calculations. There was no statistically significant difference between nursing students and Registered Nurses in their overall drug calculation ability, but nurses were statistically significantly more able than students to perform basic numerical calculations and calculations for solids, oral liquids and injections. Both nursing students and Registered Nurses were statistically significantly more able to perform calculations for solids, liquid oral and injections than calculations for drug percentages, drip and infusion rates. To prevent deskilling, Registered Nurses should continue to practise and refresh all the different types of drug calculations as often as possible with regular (self)-testing of their ability. Time should be set aside in curricula for nursing students to learn how to perform basic numerical and drug calculations. This learning should be reinforced through regular practice and assessment.

  12. A comparative analysis of drug safety withdrawals in the UK and the US (1971-1992): implications for current regulatory thinking and policy.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2005-09-01

    By going beyond individual case studies and solely quantitative surveys, this paper systematically examines why there were over twice as many new prescription drugs withdrawn from the market on grounds of safety in the UK as there were in the US between 1971 and 1992. Drawing on interviews with regulators, industry scientists and others involved, and on regulatory data never before accessed outside governments and companies, five key hypotheses which might explain this difference in drug safety withdrawals are analysed. These are: (1) simply because the UK approved more new drugs than the US; (2) because of an industrial corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3) because British regulators were more vigilant at spotting post-marketing safety problems than their US counterparts; (4) because the slowness of the US in approving new drugs enabled regulators there to learn from, and avoid, safety problems that had already emerged in the UK or European market; and (5) because more stringent regulation in the US meant that they approved fewer unsafe drugs on to the market in the first place. It is concluded that the main explanation for fewer drug safety withdrawals in the US is that the regulatory agency there applied more stringent pre-market review and/or standards, which took longer than UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering the US market. Contrary to the claims frequently made by the pharmaceutical industry and regulatory agencies on both sides of the Atlantic, these results imply that it is likely that acceleration of regulatory review times in the US and the UK since the early 1990s is compromising drug safety.

  13. Drug safety in pregnancy: utopia or achievable prospect? Risk information, risk research and advocacy in Teratology Information Services.

    Science.gov (United States)

    Schaefer, Christof

    2011-03-01

    Even though from preclinical testing to drug risk labeling, the situation with drugs in pregnancy has improved substantially since the thalidomide scandal, there is still an increasing need to provide healthcare professionals and patients with updated individualized risk information for clinical decision making. For the majority of drugs, clinical experience is still insufficient with respect to their safety in pregnancy. There is often uncertainty in how to interpret the available scientific data. Based on 20 years of experience with Teratology Information Services (TIS) cooperating in the European Network of Teratology Information Services (ENTIS) methods of risk interpretation, follow-up of exposed pregnancies through the consultation process and their evaluation is discussed. Vitamin K antagonists, isotretinoin and angiotensin (AT) II-receptor-antagonists are presented as examples of misinterpretation of drug risks and subjects of research based on observational clinical data recorded in TIS. As many TIS are poorly funded, advocacy is necessary by establishing contacts with decision makers in health politics and administration, informing them of the high return in terms of health outcomes and cost savings provided by TIS as reference institutions in clinical teratology. © 2011 The Author. Congenital Anomalies © 2011 Japanese Teratology Society.

  14. A Cost Analysis of Hospitalizations for Infections Related to Injection Drug Use at a County Safety-Net Hospital in Miami, Florida

    OpenAIRE

    Tookes, Hansel; Diaz, Chanelle; Li, Hua; Khalid, Rafi; Doblecki-Lewis, Susanne

    2015-01-01

    Background Infections related to injection drug use are common. Harm reduction strategies such as syringe exchange programs and skin care clinics aim to prevent these infections in injection drug users (IDUs). Syringe exchange programs are currently prohibited by law in Florida. The goal of this study was to estimate the mortality and cost of injection drug use-related bacterial infections over a 12-month period to the county safety-net hospital in Miami, Florida. Additionally, the prevalence...

  15. A New Concept of a Drug Delivery System with Improved Precision and Patient Safety Features

    Directory of Open Access Journals (Sweden)

    Florian Thoma

    2014-12-01

    Full Text Available This paper presents a novel dosing concept for drug delivery based on a peristaltic piezo-electrically actuated micro membrane pump. The design of the silicon micropump itself is straight-forward, using two piezoelectrically actuated membrane valves as inlet and outlet, and a pump chamber with a piezoelectrically actuated pump membrane in-between. To achieve a precise dosing, this micropump is used to fill a metering unit placed at its outlet. In the final design this metering unit will be made from a piezoelectrically actuated inlet valve, a storage chamber with an elastic cover membrane and a piezoelectrically actuated outlet valve, which are connected in series. During a dosing cycle the metering unit is used to adjust the drug volume to be dispensed before delivery and to control the actually dispensed volume. To simulate the new drug delivery concept, a lumped parameter model has been developed to find the decisive design parameters. With the knowledge taken from the model a drug delivery system is designed that includes a silicon micro pump and, in a first step, a silicon chip with the storage chamber and two commercial microvalves as a metering unit. The lumped parameter model is capable to simulate the maximum flow, the frequency response created by the micropump, and also the delivered volume of the drug delivery system.

  16. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

    Science.gov (United States)

    Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

    2016-12-12

    The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

  17. Extension of Surveillance Test Interval of Safety Injection Pump for APR-1400 Reactors to Improve Reliability and Availability of the Pump

    Energy Technology Data Exchange (ETDEWEB)

    Osama, A. Rezk; Jung, J. C.; Lee, Yong-Kwan [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

    2015-10-15

    The safety features function to localize, control, mitigate, and terminate such incidents and to hold exposure levels below applicable limits. The safety injection system is comprised of four independent mechanical trains without any tie line among the injection paths and two electrical divisions. Each train has one active Safety Injection Pump (SIP) and one passive Safety Injection Tank (SIT) equipped with a Fluidic Device (FD), each train provides 50% of the minimum injection flow rate for breaks larger than the size of a direct vessel injection line. For breaks equal to or smaller than the size of a direct vessel injection line, each train has 100% of the required capacity. The low pressure injection pumps with common header installed in the conventional design are eliminated, and the functions for safety injection and shutdown cooling are separated. The arrangement of safety injection system for APR-1400 as shown in figure (1). The results obtained in this work show that STI extensions for the SIS feasible without any unacceptable increase in the plant total risk, STI extensions are acceptable for safety injection system to provide plant operational flexibility in the performance of both corrective and preventive maintenance for the safety injection system.

  18. Suspected Lonely Mouse Syndrome as a Cage Effect in a Drug Safety Study.

    Science.gov (United States)

    Ye, Xiaobu; Itzoe, MariaLisa; Sarabia-Estrada, Rachel; DeTolla, Louis; Tyler, Betty M; Guarnieri, Michael

    2018-01-01

    Studies have demonstrated that buprenorphine, a front line drug for veterinary analgesia, may alleviate symptoms of chronic pain. A cage side observation protocol was used to record behavioral signs in a mouse clinical trial of extended release buprenorphine. A retrospective review of the observations for signs of pain and stress revealed that mice given a fivefold overdose of buprenorphine (16.25 mg/kg) showed lethargy and facial signs associated with stress. However, similar signs were observed in the drug-free control mice as early as Day 3 of single-cage housing. This appears to be the first report of cage effects in a clinical trial for a veterinary drug.

  19. Suspected Lonely Mouse Syndrome as a Cage Effect in a Drug Safety Study

    Directory of Open Access Journals (Sweden)

    Xiaobu Ye

    2018-01-01

    Full Text Available Studies have demonstrated that buprenorphine, a front line drug for veterinary analgesia, may alleviate symptoms of chronic pain. A cage side observation protocol was used to record behavioral signs in a mouse clinical trial of extended release buprenorphine. A retrospective review of the observations for signs of pain and stress revealed that mice given a fivefold overdose of buprenorphine (16.25 mg/kg showed lethargy and facial signs associated with stress. However, similar signs were observed in the drug-free control mice as early as Day 3 of single-cage housing. This appears to be the first report of cage effects in a clinical trial for a veterinary drug.

  20. Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing

    Directory of Open Access Journals (Sweden)

    Francis A. Ortega

    2018-01-01

    Full Text Available Dynamic clamp, a hybrid-computational-experimental technique that has been used to elucidate ionic mechanisms underlying cardiac electrophysiology, is emerging as a promising tool in the discovery of potential anti-arrhythmic targets and in pharmacological safety testing. Through the injection of computationally simulated conductances into isolated cardiomyocytes in a real-time continuous loop, dynamic clamp has greatly expanded the capabilities of patch clamp outside traditional static voltage and current protocols. Recent applications include fine manipulation of injected artificial conductances to identify promising drug targets in the prevention of arrhythmia and the direct testing of model-based hypotheses. Furthermore, dynamic clamp has been used to enhance existing experimental models by addressing their intrinsic limitations, which increased predictive power in identifying pro-arrhythmic pharmacological compounds. Here, we review the recent advances of the dynamic clamp technique in cardiac electrophysiology with a focus on its future role in the development of safety testing and discovery of anti-arrhythmic drugs.

  1. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    International Nuclear Information System (INIS)

    Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y.

    2014-01-01

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

  2. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y., E-mail: frank.hsieh@nextcea.com

    2014-09-15

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

  3. Safety of antiretroviral drugs in pregnancy and breastfeeding for mother and child

    NARCIS (Netherlands)

    Newell, Marie-Louise; Bunders, Madeleine J.

    2013-01-01

    Purpose of reviewThe introduction of combination ART to prevent mother-to-child-transmission (MTCT) has substantially decreased MTCT rates. However, there are concerns regarding safety of ART exposure for the mother, pregnancy outcome and infant. Changing MTCT prevention guidelines, with expanded

  4. Double pharmacological challenge on repolarization opens new avenues for drug safety research

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard

    2007-01-01

    pointes (TdP) arrhythmia. Both the pharmaceutical industry and the regulatory bodies are neglecting the available proarrhythmia models. In vitro studies have suggested that combined pharmacological hits on repolarization will produce a superior substrate for in vivo proarrhythmia, compared to the single......-drug assessment. By using consecutive pharmacological challenges, a simple model is proposed, in which combinatorial pharmacology is employed to provoke TdP in the conscious dog. The pharmaceutical industry interested in evaluating the proarrhythmic potential of their present and future drugs now has a simple...

  5. Surveillance and Critical Theory

    Directory of Open Access Journals (Sweden)

    Christian Fuchs

    2015-09-01

    Full Text Available In this comment, the author reflects on surveillance from a critical theory approach, his involvement in surveillance research and projects, and the status of the study of surveillance. The comment ascertains a lack of critical thinking about surveillance, questions the existence of something called “surveillance studies” as opposed to a critical theory of society, and reflects on issues such as Edward Snowden’s revelations, and Foucault and Marx in the context of surveillance.

  6. The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity

    International Nuclear Information System (INIS)

    Amacher, David E.

    2010-01-01

    Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in

  7. A geographical information system for the management of the aquaculture data in the Adriatic Sea – the Strengthening of Centres for Aquaculture Production and Safety surveillance in the Adriatic countries experience: Present capabilities, tools and functions

    Directory of Open Access Journals (Sweden)

    Susanna Tora

    2017-11-01

    Full Text Available The European Commission (EC regulation no. 854/2004 requires a systematic monitoring of chemical and microbiological contaminants in live bivalve molluscs, live echinoderms, live tunicates and live marine gastropods for human consumption through surveillance plans to be implemented in all European Union (EU countries.A consortium of five Adriatic countries was set up in the framework of the Instrument of Pre-accession Assistance Adriatic Cross-border Cooperation Programme (IPA Adriatic CBC 2007- 2013 with the aim of collecting data and distribute information on harvesting and production in mollusc areas. A web-based geographical information system (GIS application was developed to support the partners to manage data and to make these data available to final users, policy makers and to risk assessors. The GIS for the Strengthening of Centres for Aquaculture Production and Safety surveillance in the Adriatic countries (CAPS2 is divided into two levels, the national and the supranational one, and it distributes spatial and epidemiological information coming from various data acquisition and management sites. The great innovation is the possibility for each country to use online drawing, modifying and change of the geographic areas according to national surveillance needs. Currently it hosts data coming from about 230 production and relay areas with more than 29,478 laboratory tests performed on collected samples since August 2014. Data collected are used by each national competent authority to classify production or relay areas according to the EC regulation mentioned and to conduct risk assessment studies to evaluate the level of consumers’ exposure to contaminants in the consumption of bivalve mollusc products.

  8. Changes in drug use patterns reported on the web after the introduction of ADF OxyContin: findings from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Web Monitoring Program.

    Science.gov (United States)

    Vosburg, Suzanne K; Haynes, Colleen; Besharat, Andrea; Green, Jody L

    2017-09-01

    This qualitative study summarizes information that individuals shared online about use of OxyContin following the August 2010 introduction of the abuse deterrent formulation (ADF). The primary objective was to study online posts that endorsed continued use of OxyContin or a switch from OxyContin to another formulation of oxycodone or another substance altogether following the introduction of the ADF. A secondary objective was to determine whether posts revealed that the ADF led to cessation of OxyContin use. Data were collected with the Researched Abuse, Diversion, and Addiction-Related Surveillance System Web Monitoring Program, an online surveillance system that collects and organizes posts about prescription drugs from social media websites, blogs, and forums from 3Q2009 to 4Q2014 using a commercially available web platform. Posts were categorized by whether they conveyed a switch to drugs other than reformulated OxyContin or a continuation of reformulated OxyContin abuse. "Switch posts" primarily discussed switching to immediate-release opioids. "Continue abusing" posts identified tampering strategies for alternate routes of administration, oral use, and continued use although post authors were generally unhappy with the experience. No reference to OxyContin cessation as a function of the introduction of the ADF was found; however, discontinued use was discussed. Web Monitoring data are useful for capturing cross sections of Internet conversation reflecting reactions to new drug formulations. These data support the notion that users will gravitate to non-ADFs generally, and to immediate-release non-ADF opioid formulations, specifically, as long as these options remain on the market. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Essential Aspects in Assessing the Safety Impact of Interactions between a Drug Product and Its Associated Manufacturing System.

    Science.gov (United States)

    Jenke, Dennis

    2012-01-01

    An emerging trend in the biotechnology industry is the utilization of plastic components in manufacturing systems for the production of an active pharmaceutical ingredient (API) or a finished drug product (FDP). If the API, the FDP, or any solution u