WorldWideScience

Sample records for drug safety concerns

  1. Nonbioequivalent prescription drug interchangeability, concerns on patient safety and drug market dynamics in Brazil.

    Science.gov (United States)

    Paumgartten, Francisco José Roma; Oliveira, Ana Cecilia Amado Xavier de

    2017-08-01

    Since the enforcement of Generics Act (1999), three types of pharmaceutically equivalent products are marketed in Brazil: innovative reference (REF), "similar" (S) and generic (G) drugs. The S (brand name) and G (generic name) borrow from REF (brand name) clinical data on safety and efficacy and dosage regimen. G (but not S) is bioequivalent to and interchangeable with REF. Starting in 2003, Brazilian Sanitary Surveillance Agency (Anvisa) has required data on relative bioavailability tests (with REF) to approve (or renew registration of) S drugs. In 2014, Anvisa extended interchangeability notion to similar drugs with a "comparable" bioavailability, i.e., an "equivalent" similar drug (EQ). Drugs for chronic diseases and "critical dose medicines" are listed among the EQ drugs approved. Interchangeability of nonbioequivalent medicines raises deep concerns regarding therapeutic failures and adverse events. Concerns are even more worrisome if patients switch from one drug to another during an ongoing treatment for illnesses such as epilepsy, congestive heart failure, hypertension, diabetes and/or substitutable drugs have a narrow therapeutic index.

  2. Nonbioequivalent prescription drug interchangeability, concerns on patient safety and drug market dynamics in Brazil

    Directory of Open Access Journals (Sweden)

    Francisco José Roma Paumgartten

    Full Text Available Abstract Since the enforcement of Generics Act (1999, three types of pharmaceutically equivalent products are marketed in Brazil: innovative reference (REF, “similar” (S and generic (G drugs. The S (brand name and G (generic name borrow from REF (brand name clinical data on safety and efficacy and dosage regimen. G (but not S is bioequivalent to and interchangeable with REF. Starting in 2003, Brazilian Sanitary Surveillance Agency (Anvisa has required data on relative bioavailability tests (with REF to approve (or renew registration of S drugs. In 2014, Anvisa extended interchangeability notion to similar drugs with a “comparable” bioavailability, i.e., an “equivalent” similar drug (EQ. Drugs for chronic diseases and “critical dose medicines” are listed among the EQ drugs approved. Interchangeability of nonbioequivalent medicines raises deep concerns regarding therapeutic failures and adverse events. Concerns are even more worrisome if patients switch from one drug to another during an ongoing treatment for illnesses such as epilepsy, congestive heart failure, hypertension, diabetes and/or substitutable drugs have a narrow therapeutic index.

  3. 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 ...

  4. Free Drug Samples in the United States: Characteristics of Pediatric Recipients and Safety Concerns

    Science.gov (United States)

    Cutrona, Sarah L.; Woolhandler, Steffie; Lasser, Karen E.; Bor, David H.; Himmelstein, David U.; Shrank, William H.; LeLeiko, Neal S.

    2009-01-01

    OBJECTIVES Free drug samples frequently are given to children. We sought to describe characteristics of free sample recipients, to determine whether samples are given primarily to poor and uninsured children, and to examine potential safety issues. METHODS We analyzed data on 10 295 US residents Adderall (amphetamine/dextroamphetamine), and 4 medications that received new or revised black box warnings between 2004 and 2007, Elidel (pimecrolimus), Advair (fluticasone/salmeterol), Strattera (atomoxetine), and Adderall (amphetamine/dextroamphetamine). CONCLUSIONS Poor and uninsured children are not the main recipients of free drug samples. Free samples do not target the neediest children selectively, and they have significant safety considerations. PMID:18829796

  5. Nanotechnology safety concerns revisited.

    Science.gov (United States)

    Stern, Stephan T; McNeil, Scott E

    2008-01-01

    Nanotechnology is an emerging science involving manipulation of matter at the nanometer scale. Due to concerns over nanomaterial risks, there has been a dramatic increase in focused safety research. The present review provides a summary of these published findings, identifying areas of agreement and discordance with regard to: (1) the potential for nanomaterial exposure, (2) the relative hazard nanomaterials pose to humans and the environment, and (3) the present deficits in our understanding of risk. Special attention is paid to study design and methodologies, offering valuable insight into the complexities encountered with nanomaterial safety assessment. Recent data highlight the impact of surface characteristics on nanomaterial biocompatibility and point to the inadequacy of the current size-dependent mechanistic paradigms, with nanoscale materials lacking unique or characteristic toxicity profiles. The available data support the ability of the lung, gastrointestinal tract, and skin to act as a significant barrier to the systemic exposure of many nanomaterials. Furthermore, the acute systemic toxicity of many nanomaterials appear to be low. By contrast, the potential pulmonary toxicity of certain nanomaterials, such as carbon nanotubes, is significant, requiring a better understanding of exposure to further evaluate their risk. While these findings arrive at an overall picture of material-specific rather than nanogeneralized risk, any conclusions should clearly be tempered by the fact that nanomaterial safety data are limited. Until such time as the exposures, hazards, and environmental life cycle of nanomaterials have been more clearly defined, cautious development and implementation of nanotechnology is the most prudent course.

  6. 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

    To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies of major depression, bipolar disorder, schizophrenia, substance abuse/dependence, and other psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this scholarly article, which has been developed by the authors with feedback from all participants at the meeting and represents a consensus view

  7. Safety concerns us all

    CERN Document Server

    SC/GS/S

    2004-01-01

    In spite of periodic safety inspections, risks can never be entirely excluded. The Safety Commission invites you to inform your supervisor or Territorial Safety Officer (TSO) of any hazardous situations you may be aware of. Actions to be taken following the fall of two windowpanes A few weeks ago, a windowpane fell from the third floor of an office building, causing minor damage to a car parked outside. No one was hurt in the incident. The putty holding the window in place had gradually deteriorated over time, and strong winds undoubtedly triggered the incident. A few weeks later, a sudden draft caused a window on the fifth floor of the same building to shatter and fall to the ground below. No one was hurt and there was no material damage. The incident was caused by a fan set into the opening window: as the window slammed shut, the weight of the fan caused the glass to break. What can we do to improve safety? examine the windows of our offices and workshops and report any problems or faults, such as dam...

  8. Other Safety Concerns and Self-Neglect

    Science.gov (United States)

    ... Asked Questions DONATE Other Safety Concerns and Self-Neglect Other safety concerns focus on instances of seniors ... When To Report Other Safety Concerns and Self-Neglect? If you witness a life-threatening situation involving ...

  9. Nordic projects concerning nuclear safety

    International Nuclear Information System (INIS)

    Soerensen, H.C.

    1988-11-01

    The report describes the nature of the work done in the first half of 1988 within the field of nuclear safety (1985-89) under the Nordic program for 1985-89. Five programmes and their documentation, are described and complete lists of addresses and of persons involved is given. (AB)

  10. 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.

  11. Safety studies concerning nuclear power reactors

    International Nuclear Information System (INIS)

    Bailly, Jean; Pelce, Jacques

    1980-01-01

    The safety of nuclear installations poses different technical problems, whether concerning pressurized water reactors or fast reactors. But investigating methods are closely related and concern, on the one hand, the behavior of shields placed between fuel and outside and, on the other, analysis of accidents. The article is therefore in two parts based on the same plan. Concerning light water reactors, the programme of studies undertaken in France accounts for the research carried out in countries where collaboration agreements exist. Concerning fast reactors, France has the initiative of their studies owing to her technical advance, which explains the great importance of the programmes under way [fr

  12. Parental vaccine safety concerns in 2009.

    Science.gov (United States)

    Freed, Gary L; Clark, Sarah J; Butchart, Amy T; Singer, Dianne C; Davis, Matthew M

    2010-04-01

    Vaccine safety concerns can diminish parents' willingness to vaccinate their children. The objective of this study was to characterize the current prevalence of parental vaccine refusal and specific vaccine safety concerns and to determine whether such concerns were more common in specific population groups. In January 2009, as part of a larger study of parents and nonparents, 2521 online surveys were sent to a nationally representative sample of parents of children who were aged vaccine safety and whether the parent had ever refused a vaccine that a doctor recommended for his or her child. The response rate was 62%. Most parents agreed that vaccines protect their child(ren) from diseases; however, more than half of the respondents also expressed concerns regarding serious adverse effects. Overall, 11.5% of the parents had refused at least 1 recommended vaccine. Women were more likely to be concerned about serious adverse effects, to believe that some vaccines cause autism, and to have ever refused a vaccine for their child(ren). Hispanic parents were more likely than white or black parents to report that they generally follow their doctor's recommendations about vaccines for their children and less likely to have ever refused a vaccine. Hispanic parents were also more likely to be concerned about serious adverse effects of vaccines and to believe that some vaccines cause autism. Although parents overwhelmingly share the belief that vaccines are a good way to protect their children from disease, these same parents express concerns regarding the potential adverse effects and especially seem to question the safety of newer vaccines. Although information is available to address many vaccine safety concerns, such information is not reaching many parents in an effective or convincing manner.

  13. Pet food safety: a shared concern.

    Science.gov (United States)

    Buchanan, Robert L; Baker, Robert C; Charlton, Adrian J; Riviere, Jim E; Standaert, Robert

    2011-10-01

    The safety of the food supply is a subject of intense interest to consumers, particularly as a result of large-scale outbreaks that involve hundreds and sometimes thousands of consumers. During the last decade, this concern about food safety has expanded to include the diets of companion animals as a result of several incidences of chemical toxicities and infectious disease transmission. This has led to increased research into the causes and controls for these hazards for both companion animals and their owners. The following summary provides an introduction to the issues, challenges and new tools being developed to ensure that commercial pet foods are both nutritious and safe.

  14. Pet Food Safety A Shared Concern

    Energy Technology Data Exchange (ETDEWEB)

    Buchanan, Robert L [University of Maryland; Baker, Robert C [Mars, Inc.; Charlton, Adrian J [UK Food and Environmental Research Agency, Sand Hutton, York, UK; Riviere, Jim E [North Carolina State University; Standaert, Robert F [ORNL

    2011-01-01

    The safety of the food supply is a subject of intense interest to consumers, particularly as a result of large scale outbreaks that involve hundreds and sometimes thousands of consumers. During the last decade this concern about food safety has expanded to include the diets of companion animals as a result of several incidences of chemical toxicities and infectious disease transmission. This has led to increased research into the causes and controls for these hazards for both companion animals and their owners. The following summary provides an introduction to the issues, challenges, and new tools being developed to ensure that commercial pet foods are both nutritious and safe.

  15. Drug use and highway safety : a review of the literature

    Science.gov (United States)

    1971-07-01

    This report reviews the research literature concerning several aspects of drug use as it relates to traffic safety. Some of the topics covered include the effects of drugs, types of drug users; research problems in assessing risk; laboratory findings...

  16. Aviation Safety Concerns for the Future

    Science.gov (United States)

    Smith, Brian E.; Roelen, Alfred L. C.; den Hertog, Rudi

    2016-01-01

    The Future Aviation Safety Team (FAST) is a multidisciplinary international group of aviation professionals that was established to identify possible future aviation safety hazards. The principle was adopted that future hazards are undesirable consequences of changes, and a primary activity of FAST became identification and prioritization of possible future changes affecting aviation. Since 2004, FAST has been maintaining a catalogue of "Areas of Change" (AoC) that could potentially influence aviation safety. The horizon for such changes is between 5 to 20 years. In this context, changes must be understood as broadly as possible. An AoC is a description of the change, not an identification of the hazards that result from the change. An ex-post analysis of the AoCs identified in 2004 demonstrates that changes catalogued many years previous were directly implicated in the majority of fatal aviation accidents over the past ten years. This paper presents an overview of the current content of the AoC catalogue and a subsequent discussion of aviation safety concerns related to these possible changes. Interactions among these future changes may weaken critical functions that must be maintained to ensure safe operations. Safety assessments that do not appreciate or reflect the consequences of significant interaction complexity will not be fully informative and can lead to inappropriate trade-offs and increases in other risks. The FAST strongly encourages a system-wide approach to safety risk assessment across the global aviation system, not just within the domain for which future technologies or operational concepts are being considered. The FAST advocates the use of the "Areas of Change" concept, considering that several possible future phenomena may interact with a technology or operational concept under study producing unanticipated hazards.

  17. Safety and health concerns in forestry operations

    Science.gov (United States)

    Robert B. Rummer

    1997-01-01

    The author discusses several safety models, including the "Three E?s": engineering, education, and enforcement; the Heinrich-Lateiner model; the organizational model; and the behavioral safety model. Rummer encourages approaching safety from a broader perspective, enabling the industry to track changes in all aspects and to keep leading the safety target....

  18. Effectively managing public concerns about immunization safety

    Directory of Open Access Journals (Sweden)

    2002-01-01

    Full Text Available Los beneficios de la vacunación frente a las enfermedades prevenibles de este modo son muy superiores a sus mínimos riesgos. Con el fin de mantener o fortalecer los programas nacionales de vacunación, los trabajadores de todos los niveles de la salud pública deberían recibir formación sobre los temas relacionados con la vacunación y estar preparados para responder a las dudas planteadas por el público. Una respuesta rápida y franca a los temores del público acerca de las vacunas podría garantizar la integridad de los programas de vacunación en todo el continente americano, según el documento "Directrices para enfrentarse a los temores sobre la seguridad de las vacunaciones" (Guidelines for Managing Immunization Safety Concerns, elaborado por la División de Vacunas e Inmunización de la Organización Panamericana de la Salud (OPS y resumido aquí. Todo acontecimiento médico que se considere posiblemente relacionado con una vacuna debe ser investigado en el ámbito local. Si su distribución temporal y los síntomas respaldan la sospecha de que pueda estar relacionado con una vacuna, se debe iniciar una investigación más formal y, una vez finalizada, el acontecimiento debe ser clasificado en una de las cuatro categorías siguientes: 1 relacionado con el programa, 2 relacionado con la vacuna, 3 no relacionado, o 4 desconocido (investigación no concluyente. Dependiendo de la categoría a la que haya sido asignado el acontecimiento, las acciones posteriores pueden consistir en tranquilizar a los padres, a los cuidadores y a otros adultos; comunicarse con el público y con otros trabajadores de la salud; instaurar tratamiento; corregir los errores del programa, como pueden ser la manipulación de la vacuna, su almacenamiento, su administration o los problemas relacionados con la jeringuilla; comentar con los fabricantes problemas relacionados con la calidad y eficacia de la vacuna; retirar la vacuna del mercado, o iniciar nuevas

  19. HTGR safety research concerns at NRC

    International Nuclear Information System (INIS)

    Minogue, R.B.

    1982-01-01

    A general discussion of HTGR technical and safety-related problems is given. The broad areas of current research programs specific to the Fort St. Vrain reactor and applicable to HTGR technology are summarized

  20. Physician attitudes towards pharmacological cognitive enhancement: safety concerns are paramount.

    Directory of Open Access Journals (Sweden)

    Opeyemi C Banjo

    2010-12-01

    Full Text Available The ethical dimensions of pharmacological cognitive enhancement have been widely discussed in academic circles and the popular media, but missing from the conversation have been the perspectives of physicians - key decision makers in the adoption of new technologies into medical practice. We queried primary care physicians in major urban centers in Canada and the United States with the aim of understanding their attitudes towards cognitive enhancement. Our primary hypothesis was that physicians would be more comfortable prescribing cognitive enhancers to older patients than to young adults. Physicians were presented with a hypothetical pharmaceutical cognitive enhancer that had been approved by the regulatory authorities for use in healthy adults, and was characterized as being safe, effective, and without significant adverse side effects. Respondents overwhelmingly reported increasing comfort with prescribing cognitive enhancers as the patient age increased from 25 to 65. When asked about their comfort with prescribing extant drugs that might be considered enhancements (sildenafil, modafinil, and methylphenidate or our hypothetical cognitive enhancer to a normal, healthy 40 year old, physicians were more comfortable prescribing sildenafil than any of the other three agents. When queried as to the reasons they answered as they did, the most prominent concerns physicians expressed were issues of safety that were not offset by the benefit afforded the individual, even in the face of explicit safety claims. Moreover, many physicians indicated that they viewed safety claims with considerable skepticism. It has become routine for safety to be raised and summarily dismissed as an issue in the debate over pharmacological cognitive enhancement; the observation that physicians were so skeptical in the face of explicit safety claims suggests that such a conclusion may be premature. Thus, physician attitudes suggest that greater weight be placed upon the

  1. Fire safety concerns in space operations

    Science.gov (United States)

    Friedman, Robert

    1987-01-01

    This paper reviews the state-of-the-art in fire control techniques and identifies important issues for continuing research, technology, and standards. For the future permanent orbiting facility, the space station, fire prevention and control calls for not only more stringent fire safety due to the long-term and complex missions, but also for simplified and flexible safety rules to accommodate the variety of users. Future research must address a better understanding of the microgravity space environment as it influences fire propagation and extinction and the application of the technology of fire detection, extinguishment, and material assessment. Spacecraft fire safety should also consider the adaptation of methods and concepts derived from aircraft and undersea experience.

  2. Safety Concerns in Today’s Thailand

    Directory of Open Access Journals (Sweden)

    Lareta R. Etumyan

    2012-05-01

    Full Text Available The article discloses the wonderful features of Thailand as the country, attracting tourists from different world regions. But at the same time the country faces many problems in regard to safety, such as political instability, crime situation and natural hazards. The article recommends the safest tourist destinations.

  3. College Rampage Renews School Safety Concerns

    Science.gov (United States)

    Maxwell, Lesli A.

    2007-01-01

    Coming just four days before the anniversary of the Columbine school shootings, the mass slayings by a student gunman at Virginia Polytechnic Institute last week revived vexing questions and raised familiar fears for educators across the country who grapple daily with ensuring the safety of their students and staffs. The April 16 killings provoked…

  4. Chinese consumers concerns about food safety: Case of Tianjin

    NARCIS (Netherlands)

    Zhang XiaoYong, Xiaoyong

    2005-01-01

    The objective of this study is to gain an insight to Chinese consumers' knowledge and concerns over food safety from a case study in Tianjin city. The results indicate that Chinese consumers are very much concerned about food safety, particularly with regard to vegetables and dairy products. Chinese

  5. New safety valve addresses environmental concerns

    International Nuclear Information System (INIS)

    Taylor, J.; Austin, R.

    1992-01-01

    This paper reports that Conoco Pipeline is using a unique relief valve to reduce costs while improving environmental protection at its facilities. Conoco Pipeline Co. Inc. began testing new relief valves in 1987 to present over-pressuring its pipelines while enhancing the safety, environmental integrity and profitability of its pipelines. Conoco worked jointly with Rupture Pin Technology Inc., Oklahoma City, to seek a solution to a series of safety, environmental, and operational risks in the transportation of crude oil and refined products through pipelines. Several of the identified problems were traced to a single equipment source: the reliability of rupture discs used at pipeline stations to relieve pressure by diverting flow to tanks during over-pressure conditions. Conoco's corporate safety and environmental policies requires solving problems that deal with exposure to hydrocarbon vapors, chemical spills or the atmospheric release of fugitive emissions, such as during rupture disc maintenance. The company had used rupture pin valves as vent relief devices in conjunction with development by Rick Austin of inert gas methods to protect the inner casing wall and outer carrier pipeline wall in pipeline road crossings. The design relies on rupture pin valves set at 5 psi to isolate vent openings from the atmosphere prior to purging the annular space between the pipeline and casing with inert gas to prevent corrosion. Speciality Pipeline Inspection and Engineering Inc., Houston, is licensed to distribute the equipment for the new cased-crossing procedure

  6. Regulatory considerations concerning IND radiopharmaceutical drug products

    International Nuclear Information System (INIS)

    Nissel, M.

    1985-01-01

    The Food and Drug Administration is charged by the Food, Drug, and Cosmetic Act, as presently amended, to assure that any drug introduced into interstate commerce is safe and effective for the purposes for which it is labeled. A radiopharmaceutical is, by definition, a new drug unless there is in effect an approved New Drug Application (NDA) for it. Before the data for the NDA are compiled, investigative studies have to be done. Before such studies can be performed in humans, an exemption from the Act is necessary. This exemption, technically the Claimed Exemption for an Investigational New Drug, is termed the IND. Both the scientific and the administrative requirements for an IND are discussed. For radiopharmaceutical drug products (RDP's), the radiation hazards, as well as the pharmacological ones, must be documented. Should the early studies demonstrate a potential for efficacy in a certain condition or disease state, an investigative protocol for an extended clinical trial is presented. The necessary requirements for Institutional Review Board (IRB) approval and consent forms are discussed. For certain research purposes, uniquely for radioactive drugs, an IND is not required for certain specific studies; the requirements for such a research study, conducted under the auspices of an approved radioactive drug research committee, are outlined

  7. Industrial radiography in the Philippines: safety concerns

    International Nuclear Information System (INIS)

    David, Jocelyn L.; Artificio, Thelma P.; Cerbolles, Justina S.; Caseria, Estrella S.; Agron, Inocencio A.

    2005-01-01

    Industrial radiography utilizes the highest activity (5.55 tera becquerel (TBq) to 7.4 TBq) among the various mobile application of radioisotopes. It is highly possible that radiographers exceed the annual dose limits for workers occupationally exposed to radiation (as prescribed in the Code of PNRI Regulations part 3) if they do not give cautious consideration to the factors that determine the radiation dose, namely: the gamma source dose rates, time distance and shielding. To enhance the safety culture among radiographers, various strategies are recommended to be undertaken by the Philippine Nuclear Research Institute as well as the licensed companies undertaking activities in industrial radiography. (Authors)

  8. Radiation safety concerns during interventional radiology

    International Nuclear Information System (INIS)

    Victor Raj, D.; Livingstone, Roshan Samuel

    2001-01-01

    Interventional radiological procedures are on the increase by virtue of the fact that these procedures replace highly invasive surgical and other procedures. Radiation dose to patients and hospital workers are of significance since these procedures tend to impart large dose to them. Moreover, long term risk from radiation absorbed by patients is of concern since the life expectancy of major fraction of patients is long after undergoing the procedure. This study intends to measure radiation dose imparted to patients as well as personnel- radiologists, technologists, nurses, etc. and estimate the risk factor involved

  9. Losing nuclear expertise - A safety concern

    International Nuclear Information System (INIS)

    Ziakova, M.

    2002-01-01

    Full text: Since the mid of eighties several important changes in human beings behaviour, which influence nuclear field, can be observed - the loss of interest in studying technical disciplines (namely nuclear), strong pressure of environmental movements, stagnation of electricity consumption and deregulation of electric markets. All these factors create conditions which are leading to the decrease of job positions related to the nuclear field connected particularly with research, design and engineering. Loss of interest in studying nuclear disciplines together with the decrease of number of job positions has led to the declining of university enrolments, closing of university departments and research reactors. In this manner just a very small number of appropriately educated new experts are brought In the same moment the additional internal factor - the relative ageing of the human workforce on both sites operators of nuclear facilities and research and engineering organisations can be observed. All these factors, if not addressed properly, could lead to the loss of nuclear expertise and the loss of nuclear expertise represents the direct thread to the nuclear safety. The latest studies have shown that at present NPPs cannot be replaced by other kinds of electric sources and in no case by renewable ones in an efficient manner. Therefore it is necessary to carefully manage knowledge gathered in the nuclear field during the years and to keep on the nuclear safety research, education and training to ensure and upgrade safe and reliable operation of existing and future nuclear facilities. This is responsibility of both the governments of the states using nuclear applications and owners of nuclear facilities. (author)

  10. Do Online Bicycle Routing Portals Adequately Address Prevalent Safety Concerns?

    Directory of Open Access Journals (Sweden)

    Martin Loidl

    2018-03-01

    Full Text Available Safety concerns are among the most prevalent deterrents for bicycling. The provision of adequate bicycling infrastructure is considered as one of the most efficient means to increase cycling safety. However, limited public funding does not always allow agencies to implement cycling infrastructure improvements at the desirable level. Thus, bicycle trip planners can at least partly alleviate the lack of adequate infrastructure by recommending optimal routes in terms of safety. The presented study provides a systematic review of 35 bicycle routing applications and analyses to which degree they promote safe bicycling. The results show that most trip planners lack corresponding routing options and therefore do not sufficiently address safety concerns of bicyclists. Based on these findings, we developed recommendations on how to better address bicycling safety in routing portals. We suggest employing current communication technology and analysis to consider safety concerns more explicitly.

  11. Aviation Safety: FAA and DOD Response to Similar Safety Concerns

    National Research Council Canada - National Science Library

    2002-01-01

    .... The Federal Aviation Administration (FAA) and the military services often face common safety issues as they oversee the operation of similar aircraft or even dissimilar aircraft that use common parts and materials...

  12. in OECD countries concerning biological drugs

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... system, the trading system conditions, R and D co-operations, human resources, financial matters, entrepreneurship, the market, R and ... In 2003, there were 334 biotechnology companies in. Japan. In recent years, the ..... biological drugs market is its attractiveness for the commercial sector which means ...

  13. Ayurveda formulations: A roadmap to address the safety concerns

    Directory of Open Access Journals (Sweden)

    Kishor Patwardhan

    2017-10-01

    Full Text Available It is a matter of serious concern that the number of case reports pointing at a possible association between the clinical toxicity and the use of Ayurveda formulations is increasing significantly over the years in scientific medical literature. Though most of these cases are connected with the presence of heavy metals such as lead, mercury and arsenic in these formulations, there are also reports suggesting toxicity due to the presence of toxic chemicals of herbal origin. In the year 2008, the Government of India took an initiative of establishing the National Pharmacovigilance Programme for Ayurveda, Siddha and Unani drugs in a structured way. However, due to lack of sustained support, this program has now become defunct. This issue is of vital importance and needs to be addressed effectively on a priority basis. In this communication, we propose the following crucial policy interventions to be introduced at different levels: a. Amendments to Drug and Cosmetic Act, b. Issuing consumer guidelines, c. Issuing prescription guidelines, d. Issuing clinical monitoring guidelines, e. Implementation of good manufacturing guidelines, f. Promoting documentation of clinical safety, g. Identifying the sources of contamination, and, h. Provision for stringent punishment. If these policy interventions are taken up and implemented, a significant positive change in the scenario can be expected in the near future.

  14. Social Capital, Safety Concerns, Parenting, and Early Adolescents' Antisocial Behavior

    Science.gov (United States)

    Vieno, Alessio; Nation, Maury; Perkins, Douglas D.; Pastore, Massimiliano; Santinello, Massimo

    2010-01-01

    This study explores the relations between neighborhood social capital (neighbor support and social climate), safety concerns (fear of crime and concern for one's child), parenting (solicitation and support), and adolescent antisocial behavior in a sample of 952 parents (742 mothers) and 588 boys and 559 girls from five middle schools (sixth…

  15. International antiterrorist conventions concerning the safety of air transport

    Directory of Open Access Journals (Sweden)

    Jacek BARCIK

    2008-01-01

    Full Text Available In this article the international law regulations are presented concerning the civilian safety of the air transport. The history concerning air terrorism and international antiterrorist conventions was described in detail, involving The Chicago Convention, The Tokyo Convention, The Hague Convention and Montreal Convention.

  16. 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

  17. Key factors influencing management decisions concerning safety equipment selection.

    Science.gov (United States)

    Chinda, Thanwadee; Ammarapala, Veeris; Suanmali, Suthathip

    2017-08-31

    The construction industry involves many hazardous activities that may expose workers to a wide variety of health hazards. Selection of construction safety equipment is crucial in ensuring workers' safety. This article aims to examine key factors influencing management decisions concerning safety equipment selection, utilizing exploratory factor analysis (EFA) and the analytic hierarchy process (AHP). A questionnaire survey is conducted in the construction companies in Bangkok, Thailand. The factor analysis extracts 103 sets of data into six key factors - namely supplier agreements, supplier support, personal, equipment design, safety-related policies and cost value factors - with a total of 20 associated items. The AHP results conclude that the safety-related policies, equipment design and personal factors are the most important factors when selecting construction safety equipment. A construction company can use the study results as a checklist to help assess different safety equipment, and to select the best equipment.

  18. Safety considerations concerning light water reactors in Sweden

    International Nuclear Information System (INIS)

    Nilsson, T.

    1977-01-01

    In 1975 the Swedish Nuclear Power Inspectorate was commissioned by the Government to perform a Reactor Safety Study concerning commercial light water reactors. The study will contain an account of: - rules and regulations for reactor designs; - operation experience of the Swedish nuclear power plants with international comparisons; - the development of reactor designs during the last 10 years; - demands and conditions for inspection and inspection methods; - nuclear power plant operation organization; - training of operators; and - the results of research into nuclear safety. The study is scheduled for completion by July 1st, 1977, however, this paper gives a summary of the results of the Reactor Safety Study already available. The paper contains detailed statistics concerning safety related occurrences and reactor scrams in Sweden from July 1st, 1974 until the beginning of 1977

  19. Post-Approval Safety Issues with Innovative Drugs : A European Cohort Study

    NARCIS (Netherlands)

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

    2013-01-01

    Background At time of approval, knowledge of the full benefit risk of any drug is limited, in particular with regards to safety. Post-approval surveillance of potential drug safety concerns is recognized as an important task of regulatory agencies. For innovative, often first-in-class drugs, safety

  20. Food safety concerns of fast food consumers in urban Ghana.

    Science.gov (United States)

    Omari, Rose; Frempong, Godfred

    2016-03-01

    In Ghana, out-of-home ready-to-eat foods including fast food generally have been associated with food safety problems. Notwithstanding, fast food production and consumption are increasing in Ghana and therefore this study sought to determine the food safety issues of importance to consumers and the extent to which they worry about them. First, through three focus group discussions on consumers' personal opinions about food safety issues, some emergent themes were obtained, which were used to construct an open-ended questionnaire administered face-to-face to 425 respondents systematically sampled from 20 fast food restaurants in Accra. Findings showed that most fast food consumers were concerned about food hazards such as pesticide residue in vegetables, excessive use of artificial flavour enhancers and colouring substances, bacterial contamination, migrated harmful substances from plastic packages, and general unhygienic conditions under which food is prepared and sold. Consumers also raised concerns about foodborne diseases such as cholera, typhoid, food poisoning, diarrhoea, bird flu and swine flu. The logistic regression model showed that being male increased the likelihood of worrying about general food safety issues and excessive use of flavour enhancers than in females while being youthful increased the likelihood of being worried about typhoid fever than in older consumers. These findings imply that consumers in urban Ghana are aware and concerned about current trends of food safety and foodborne disease challenges in the country. Therefore, efforts targeted at improving food safety and reducing incidences of foodborne diseases should not only focus on public awareness creation but should also design more comprehensive programmes to ensure the making of food safety rules and guidelines and enforcing compliance to facilitate availability and consumers' choice of safe foods. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. FDA Drug Safety Podcasts: resources for drug information.

    Science.gov (United States)

    Wu, Kimberly; Shepherd, Jennifer; Jackson, Steven; Chew, Catherine

    2013-01-01

    To describe a Web-based drug information service provided by the Food and Drug Administration (FDA) to increase the reach of Drug Safety Communications to pharmacists and other health professionals. The Division of Drug Information (DDI) within the FDA Center for Drug Evaluation and Research (CDER), Office of Communications, Silver Spring, MD, between January 2010 and April 2012. DDI provides drug information services regarding human drug products and expert advice and guidance on all aspects of CDER activities. Customers include consumers, health professionals, regulated industry, insurance companies, academia, law enforcement, and other government agencies (national and international). Use of audio podcasts to disseminate timely drug safety information targeted toward pharmacists and other health professionals. RESULTS Since 2010, DDI has recorded and published 119 FDA Drug Safety Podcasts that have reached more than 620,000 individuals. FDA Drug Safety Podcasts serve as portable and convenient options for pharmacists to stay current on the latest drug safety information. Pharmacists are encouraged to explore incorporating Web-based technologies, such as audio podcasts, into their practices.

  2. Food colors: Existing and emerging food safety concerns.

    Science.gov (United States)

    Oplatowska-Stachowiak, Michalina; Elliott, Christopher T

    2017-02-11

    Food colors are added to different types of commodities to increase their visual attractiveness or to compensate for natural color variations. The use of these additives is strictly regulated in the European Union, the United States, and many other countries worldwide. There is a growing concern about the safety of some commonly used legal food colorants and there is a trend to replace the synthetic forms with natural products. Additionally, a number of dyes with known or suspected genotoxic or carcinogenic properties have been shown to be added illegally to foods. Robust monitoring programs based on reliable detection methods are required to assure the food is free from harmful colors. The aim of this review is to present an up to date status of the various concerns arising from use of color additives in food. The most important food safety concerns in the field of food colors are lack of uniform regulation concerning legal food colors worldwide, possible link of artificial colors to hyperactive behavior, replacement of synthetic colors with natural ones, and the presence of harmful illegal dyes-both known but also new, emerging ones in food. The legal status of food color additives in the EU, United States, and worldwide is summarized. The reported negative health effects of both legal and illegal colors are presented. The European Rapid Alert System for Food and Feed notifications and US import alerts concerning food colors are analyzed and trends in fraudulent use of color additives identified. The detection methods for synthetic colors are also reviewed.

  3. Cyber-pharmacies and emerging concerns on marketing drugs online

    Directory of Open Access Journals (Sweden)

    Vinod Scaria

    2003-08-01

    Full Text Available The booming e-commerce and a regulation-less environment online have led to the rise of a new generation of websites that market drugs and other products over the Internet. Some of these drugs are often herbal products or of dubious quality, often marketed with a mix of professional design and unverified/fraudulent claims. Several concerns have arisen from different corners and evidence of malpractice has emerged. But there is a lack of sufficient evidence confirming the concerns.

  4. Shoe concerns and foot problems of wearers of safety footwear.

    Science.gov (United States)

    Marr, S J; Quine, S

    1993-05-01

    In Australia workers in many industries are required to wear safety footwear (footwear incorporating a steel toe cap). An investigation of the problems reported by 321 workers (70 per cent male) employed in a broad range of work activities and required to wear safety footwear was conducted in 1990 and 1991. Respondents were interviewed by a professionally trained podiatrist using a structured questionnaire followed by a foot examination. An extremely high percentage (91 per cent) of subjects reported one or more foot problems (which were verified by the podiatrist), and most considered that the safety footwear either caused the problem or adversely affected an existing foot condition. The main shoe concerns reported were excessive heat (65 per cent of all respondents), inflexible soles (52 per cent), weight (48 per cent) and pressure from steel toe cap (47 per cent). Certain gender differences were identified. General recommendations are made.

  5. 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...

  6. The safety concept of the Federal Government concerning waste management

    International Nuclear Information System (INIS)

    Pfaffelhuber, J.K.

    1976-01-01

    The safety concept of the FRG concerning waste management is based on the ultimate aim of having in operation until 1985 nuclear power plants with a capacity of approx. 45,000 MWe, i.e. 50 nuclear power plants with an annual fuel consumption of 1,500 tons. A critical survey shows that there is still a great number of questions to be solved, concerning the fuel cycle in particular in terms of industrial standards, and that various problems ought to be the subject of R and D activities. Activities in the field of waste management so far are concerned only with project studies and details of project definition studies. On the one hand, the principles of the safety concept for waste management are to make possible and to guarantee the operation of nuclear facilities, and on the other hand, they are to subject those facilities which serve the purpose of waste disposal to similar safety regulations as the nuclear power plants are subjected to. The integrated waste disposal system of the Federal government for CWRs until the mid eighties is described. R+D activities are still necessary, in particular concerning reprocessing techniques, techniques in the reprocessing of Pu, the conditioning of highly active wastes, testing final storage techniques, and in the field of retention of gaseous radioactive nuclides (iodine, krypton, tritium) and of safeguarding waste disposal parks against terrorists and sabotage. The legal basis for the protection of the citizen is the Atomic Energy Act and its ordinances, EURATOM basic standards, and ICRP recommendations, some of which were tightened up for the FRG. Some recommendations of the Strahlenschutzkommision - radiation exposure, storage and separation of 85 Kr, 129 J, 131 J, and 133 Xe - are dealt with in detail. (HPH/LN) [de

  7. Predictive toxicology in drug safety

    National Research Council Canada - National Science Library

    Xu, Jinghai J; Urban, Laszlo

    2011-01-01

    .... Each specific area of toxicology relevant for drug discovery is discussed in detail, including theory, experimental approaches, and data interpretation supported by comprehensive up-to-date references...

  8. Questionnaire responses concerning safety issues in MR examination

    International Nuclear Information System (INIS)

    Yamaguchi-Sekino, Sachiko; Nakai, Toshiharu; Muranaka, Hiroyuki

    2011-01-01

    Recently, the rising numbers of medical implants and scanners with higher static magnetic field have increased safety concerns for magnetic resonance (MR) examination. To determine future safety focus, we distributed anonymous questionnaires to 3250 members of the Japanese Society for Magnetic Resonance in Medicine (JSMRM) and received 978 responses. Safety issues on the questionnaire concentrated on the handling of patients with implants (Q7-18, appendix), acoustic trauma due to scanning (Q19-21, appendix), and MR compatibility within the scanner room (Q22-25, appendix). Ninety-three percent of respondents indicated they had encountered cases with implants or medical materials of unknown MR compatibility; 21.7% reported heating problems and 15.0%, nerve stimulation problems, in patients with implants during MR examination. Although 88.7% of respondents recognized the term ''MR compatibility'', 68.2% indicated limited detailed understanding of the term. Eleven percent had had cases with suspected acoustic injury from MR scanner noise. Scanner noise levels were not clarified in any way in 37.4% cases, but 69.5% applied ear protection to patients. Labeling of ''MR compatibility'' of equipment brought into the MR scanner room was reported by 71.9%. More than 50% experienced MR compatibility issues related to equipment brought into the MR scanner room. With regard to safety issues on metallic objects which are implanted in MR workers, 88.1% indicated they would continue current operations even the implant is inside the body. Respondents identified lectures and seminars by professional societies, safety training by manufacturers, and information from the Internet and literature as the 3 main sources for up-dating safety information for MR examination. (author)

  9. [Pediatric caudal anesthesia: importance and aspects of safety concerns].

    Science.gov (United States)

    Mauch, J; Weiss, M

    2012-08-01

    Caudal block is a safe procedure commonly used for pediatric perioperative analgesia. Complications are extremely rare but nevertheless local and systemic contraindications must be excluded. Optimal safety and quality result when strict attention is paid to technical details. A local anesthetic (LA) containing epinephrine allows early detection of inadvertent intravascular LA administration; therefore an epinephrine/LA mixture is recommended at least for the test dose. In terms of safety the choice of LA itself is probably of secondary importance. Clonidine as an adjuvant has an excellent risk/benefit profile with minimal side effects. Inadvertent systemic LA intoxication is a rare but potentially fatal complication of regional anesthesia and measures for prevention and early detection are essential. Should circulatory arrest occur, immediate resuscitation following standard guidelines is to be initiated including the use of epinephrine as the first line drug. Intravenous administration of lipid solutions may be beneficial as a secondary adjunct to stabilize hemodynamics but is not an alternative to epinephrine.

  10. Development of safety analysis technology for integral reactor; evaluation on safety concerns of integral reactor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Chul; Kim, Woong Sik; Lee, J. H. [Korea Institute of Nuclear Safety, Taejeon (Korea)

    2002-03-01

    The Nuclear Desalination Plant (NDP) is being developed to produce electricity and fresh water, and is expected to locate near population zone. In the aspect of safety, it is required to protect the public and environment from the possible releases of fission products and to prevent the fresh water from the contamination of radioactivity. Thus, in this study, the safety characteristics of the integral reactor adopting passive and inherent safety features significantly different from existing nuclear power plants were investigated. Also, safety requirements applicable to the NDP were analyzed based on the regulatory requirements for current light water reactor and advanced reactor designs, and user requirements for small-medium size reactors. Based on these analyses, some safety concerns to be considered in the design stage have been identified and discussed. They include the use of proven technology for new safety features, systematic event classification and selection, strengthening containment function, and the safety impacts on desalination-related systems. The study presents the general safety requirements applicable to licensing of an integral reactor and suggests additional regulatory requirements, which need to be developed, based on the direction to resolution of the safety concerns. The efforts to identify and technically resolve the safety concerns in the design stage will provide the early confidence of SMART safety and the technical basis to evaluate the safety to designers and reviewers in the future. Suggestion on the development of additional regulatory requirements will contribute for the regulator to taking actions for licensing of an integral reactor. 66 refs., 5 figs., 24 tabs. (Author)

  11. [Legislation concerning alcohol and drug intake in the workplace].

    Science.gov (United States)

    Goszczyńiska, Eliza

    2013-01-01

    It is likely that the complex law concerning alcohol and drugs in the workplace is one of the reasons for unwillingness to resolve the problem of intake of such psychoactive substances by employees. 'Iherefore, the author made an attempt to depict Polish legislation in this field based on the review of legal acts and regulations, as well as on their extensive judiciary interpretation. Such an information can be used by employers in developing their workplace policy of diminishing the intake of psychoactive substances by employees. This information can also be helpful for the bodies supporting workplaces in solving problems derived from alcohol and drugs consumption, such as occupational medicine specialists and local governments.

  12. [IV drug perfusions: safety principles].

    Science.gov (United States)

    Lelieur, Florence; Cabelguenne, Delphine; Marcel, Marie; Favier, Claudine; Piriou, Vincent

    2017-05-01

    An intravenous perfusion is a procedure which comprises infection and medication risks. To manage these risks, caregivers must respect, in addition to the usual hygiene rules, a series of best practices, ensuring the proper use and management of the medical devices and administered drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. 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...... and Denmark were analysed using interrupted time series analysis, with EMA drug warnings for thiazolidinediones (TZDs) in 2007 and 2011 as the intervention. Monthly drug utilisation data per substance in defined daily dosages (DDD) consumed per 1000 insurees were retrieved from the Danish national drug...... prescriptions register and one large statutory sickness fund in Germany. Results TZDs were generally reimbursed in Germany but restricted to individual reimbursement in Denmark. Consequently, utilisation of TZDs was much higher in Germany in 2007 compared with Denmark. For rosiglitazone, the drug warning had...

  14. Legislation concerning alcohol and drug intake in the workplace

    Directory of Open Access Journals (Sweden)

    Eliza Goszczyńska

    2013-08-01

    Full Text Available It is likely that the complex law concerning alcohol and drugs in the workplace is one of the reasons for unwillingness to resolve the problem of intake of such psychoactive substances by employees. Therefore, the author made an attempt to depict Polish legislation in this field based on the review of legal acts and regulations, as well as on their extensive judiciary interpretation. Such an information can be used by employers in developing their workplace policy of diminishing the intake of psychoactive substances by employees. This information can also be helpful for the bodies supporting workplaces in solving problems derived from alcohol and drugs consumption, such as occupational medicine specialists and local governments. Med Pr 2013;64(4:593–608

  15. Social media in health--what are the safety concerns for health consumers?

    Science.gov (United States)

    Lau, Annie Y S; Gabarron, Elia; Fernandez-Luque, Luis; Armayones, Manuel

    Recent literature has discussed the unintended consequences of clinical information technologies (IT) on patient safety, yet there has been little discussion about the safety concerns in the area of consumer health IT. This paper presents a range of safety concerns for consumers in social media, with a case study on YouTube. We conducted a scan of abstracts on 'quality criteria' related to YouTube. Five areas regarding the safety of YouTube for consumers were identified: (a) harmful health material targeted at consumers (such as inappropriate marketing of tobacco or direct-to-consumer drug advertising); (b) public display of unhealthy behaviour (such as people displaying self-injury behaviours or hurting others); (c) tainted public health messages (i.e. the rise of negative voices against public health messages); (d) psychological impact from accessing inappropriate, offensive or biased social media content; and (e) using social media to distort policy and research funding agendas. The examples presented should contribute to a better understanding about how to promote a safe consumption and production of social media for consumers, and an evidence-based approach to designing social media interventions for health. The potential harm associated with the use of unsafe social media content on the Internet is a major concern. More empirical and theoretical studies are needed to examine how social media influences consumer health decisions, behaviours and outcomes, and devise ways to deter the dissemination of harmful influences in social media.

  16. The root cause of patient safety concerns in an Internet pharmacy.

    Science.gov (United States)

    Montoya, Isaac D

    2008-07-01

    The Internet has become a revolutionary technology that affords worldwide opportunities never seen before. One such opportunity is the purchase of drugs over the Internet and the business of Internet pharmacies which has become prolific. Associated with this proliferation is the concern for patient safety. Numerous studies have shown that drugs purchased over the Internet come from pharmacies in a country other than the one where the patient resides and these pharmacies are not licensed, sometimes provide drugs without a prescription and that are not of the same composition as they should be, and do not provide adequate directions to the patient. In addition, the packaging of the drugs may be compromised resulting in altered medication. This paper examines the root cause of patient safety issues in Internet pharmacies. A review of the literature including the marketing literature was conducted. Healthcare marketing concepts guide business owners to identify patients' wants and distinguish them from their needs. Marketing principles detail aggressive marketing strategies within an organization's mission and in an ethical manner. Some Internet pharmacies misinterpret proven marketing principles and become overly aggressive in the market place focusing only on sales and profit rather than focusing on patient safety and long-term success of the Internet pharmacy.

  17. Monitoring drug safety in Astrakhan, Russia.

    Science.gov (United States)

    Kirilochev, O O; Dorfman, I P; Umerova, A R

    2015-01-01

    The problem of drug safety will never disappear as new drugs are delivered in increasing numbers. They have high biological activity and adverse drug reactions (ADR) [1]. Currently, adverse drug reactions are the fourth leading cause of death for patients.There are databases of ADRs (Vigibase, Eudravigilance), but we know that ADR manifestations may vary in different countries and regions, due to the demographic, genetic characteristics of the population and the quality of manufactured drugs [2]. In this regard, the study of the ADR at the regional level is very relevant. We aimed to optimize the work on monitoring drug safety in Astrakhan region through pharmacoepidemiological research and development of computer database for analysis of information coming to the center for drug safety monitoring (CDSM). 1. To study the rates of ADR reporting and the structure in the Astrakhan region at the regional center for drug safety monitoring.2. To analyze the outcomes of registered adverse drug reactions.3. To determine the causality of adverse drug reactions.4. To identify reports on the ineffectiveness of drugs.5. To analyze the rates and structure of ADR reporting for drugs prescribed off-label. We studied spontaneous adverse event reporting. The adverse event reports received by the regional CDSM for the period of 2010 to 2014 was analyzed. The groups of drugs were categorized according by Anatomical Therapeutic Chemical classification system. The data were analyzed using Microsoft Office Excel. The likelihood of whether an ADR was actually due to the drugs was assessed with the Naranjo algorithm. The analysis of the results showed that the establishment of the CDSM in September 2010, contributed to improvement of drug safety monitoring in health facilities of the region. Noteworthy was the increasing the number of adverse event reports in 2011 and 2012, compared with the beginning of the year 2010, when the CDSM was not yet functioning.The decrease of adverse event

  18. Nanoparticles and the blood coagulation system. Part II: safety concerns

    Science.gov (United States)

    Ilinskaya, Anna N; Dobrovolskaia, Marina A

    2014-01-01

    Nanoparticle interactions with the blood coagulation system can be beneficial or adverse depending on the intended use of a nanomaterial. Nanoparticles can be engineered to be procoagulant or to carry coagulation-initiating factors to treat certain disorders. Likewise, they can be designed to be anticoagulant or to carry anticoagulant drugs to intervene in other pathological conditions in which coagulation is a concern. An overview of the coagulation system was given and a discussion of a desirable interface between this system and engineered nanomaterials was assessed in part I, which was published in the May 2013 issue of Nanomedicine. Unwanted pro- and anti-coagulant properties of nanoparticles represent significant concerns in the field of nanomedicine, and often hamper the development and transition into the clinic of many promising engineered nanocarriers. This part will focus on the undesirable effects of engineered nanomaterials on the blood coagulation system. We will discuss the relationship between the physicochemical properties of nanoparticles (e.g., size, charge and hydrophobicity) that determine their negative effects on the blood coagulation system in order to understand how manipulation of these properties can help to overcome unwanted side effects. PMID:23730696

  19. Production of neutrons in particle accelerators: a PNRI safety concern

    International Nuclear Information System (INIS)

    Garcia, Corazon M.; Cayabo, Lynette B.; Artificio, Thelma P.; Melendez, Johnylen V.; Piquero, Myrna E.; Parami, Vangeline K.

    2002-09-01

    In the safety assessment made for the first cyclotron facility in the Philippines, that is the cyclotron in the P.E.T. (Positron Emission Tomography) center of the St. Luke's Medical Center, the concern on the production of neutrons associated with the operation of particle accelerators has been identified. This takes into consideration the principles in the operation of particle accelerators and the associated production of neutrons resulting from their operation, the hazards and risks in their operation. The Bureau of Health Devices and Technology (BHDT) of the Department of Health in the Philippines regulates and controls the presently existing six (6) linear accelerators distributed in different hospitals in the country, being classified as x-ray producing devices. From the results of this study, it is evident that the production of neutrons from the operation of accelerators, produces neutrons and that activation due to neutrons can form radioactive materials. The PNRI (Philippine Nuclear Research Institute) being mandated by law to regulate and control any equipment or devices producing or utilizing radioactive materials should take the proper steps to subject all accelerator facilities and devices in the Philippines such as linear accelerators under its regulatory control in the same manner as it did with the first cyclotron in the country. (Author)

  20. Nuclear safety. Concerns about the nuclear power reactors in Cuba

    International Nuclear Information System (INIS)

    Wells, Jim; Aloise, Gene; Flaherty, Thomas J.; Fitzgerald, Duane; Zavala, Mario; Hayward, Mary Alice

    1992-09-01

    the atmosphere, contains defective welds. Another said that reactor operator trainees have received training on inadequate reactor simulators. In contrast, a representative of the Cuban government told us that Cuba wants to build its reactor in accordance with safety standards. Also, according to information provided to us by a representative of the Russian government, Cuba's reactor has been constructed according to safety rules that take into account, among other things, the possible impacts of an earthquake. State Department, NRC, and DOE officials have expressed a number of concerns about the construction and operation of Cuba's nuclear power reactors. According to State Department officials, the United States maintains a comprehensive embargo on any U.S. transactions with Cuba and discourages other countries from providing assistance, except for safety purposes, to Cuba's nuclear power program. The United States would prefer that the construction of the reactors never be completed and wants Cuba to sign the Non-Proliferation Treaty or the Treaty of Tlatelolco, both of which bind signatories to blanket nonproliferation commitments for their entire nuclear program, before the United States considers reversing its policy of discouraging other countries from assisting Cuba with the construction of the reactors. The United States has asked Russia to cease providing any nuclear assistance until Cuba has signed either treaty. NRC officials are aware of, but could not verify, the Cuban emigres' allegations of safety deficiencies because available information was limited. They said, however, that if the allegations were true, the cited deficiencies could affect the safety of the reactors operation. In addition, they expressed concern about the ability of Cuba's industrial infrastructure to support the nuclear power reactors, the lack of a regulatory structure, the adequacy of training for reactor operators, the quality of the civil construction, and the design of the

  1. Safety Implications Concerning Usage of Tools in Complex System

    OpenAIRE

    Augusto, Rafael; Silva, Nuno

    2016-01-01

    International audience; Integration of tools and configuration data is nowadays present in all railway systems and plays a central role in functionality, flexibility and the safety of railway systems. This paper aims to present the challenges and the importance of tools, the configuration data integrity and the toolchain definition in the design of railway systems safety. We focus on the relevant implications on the safety analysis and safety assurance of such systems. Two examples of the usa...

  2. 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

  3. Safety Issues Concerning the Medical Use of Cannabis and Cannabinoids

    OpenAIRE

    Mark A Ware; Vivianne L Tawfik

    2005-01-01

    Safety issues are a major barrier to the use of cannabis and cannabinoid medications for clinical purposes. Information on the safety of herbal cannabis may be derived from studies of recreational cannabis use, but cannabis exposure and effects may differ widely between medical and recreational cannabis users. Standardized, quality-controlled cannabinoid products are available in Canada, and safety profiles of approved medications are available through the Canadian formulary. In the present a...

  4. Safety regulations concerning instrumentation and control systems for research reactors

    International Nuclear Information System (INIS)

    El-Shanshoury, A.I.

    2009-01-01

    A brief study on the safety and reliability issues related to instrumentation and control systems in nuclear reactor plants is performed. In response, technical and strategic issues are used to accomplish instrumentation and control systems safety. For technical issues there are ; systems aspects of digital I and C technology, software quality assurance, common-mode software, failure potential, safety and reliability assessment methods, and human factors and human machine interfaces. The strategic issues are the case-by-case licensing process and the adequacy of the technical infrastructure. The purpose of this work was to review the reliability of the safety systems related to these technical issues for research reactors

  5. New Automated System Available for Reporting Safety Concerns | Poster

    Science.gov (United States)

    A new system has been developed for reporting safety issues in the workplace. The Environment, Health, and Safety’s (EHS’) Safety Inspection and Issue Management System (SIIMS) is an online resource where any employee can report a problem or issue, said Siobhan Tierney, program manager at EHS.

  6. Safety Issues Concerning the Medical Use of Cannabis and Cannabinoids

    Directory of Open Access Journals (Sweden)

    Mark A Ware

    2005-01-01

    Full Text Available Safety issues are a major barrier to the use of cannabis and cannabinoid medications for clinical purposes. Information on the safety of herbal cannabis may be derived from studies of recreational cannabis use, but cannabis exposure and effects may differ widely between medical and recreational cannabis users. Standardized, quality-controlled cannabinoid products are available in Canada, and safety profiles of approved medications are available through the Canadian formulary. In the present article, the evidence behind major safety issues related to cannabis use is summarized, with the aim of promoting informed dialogue between physicians and patients in whom cannabinoid therapy is being considered. Caution is advised in interpreting these data, because clinical experience with cannabinoid use is in the early stages. There is a need for long-term safety monitoring of patients using cannabinoids for a wide variety of conditions, to further guide therapeutic decisions and public policy.

  7. India's power program and its concern over environmental safety

    International Nuclear Information System (INIS)

    Prasad, G.E.; Mittra, J.

    2001-01-01

    India's need of electrical power is enormous and per capita consumption of power is to be increased at least by ten times to reach the level of world average. Thermal Power generation faces two fold problems. First, there is scarcity of good quality fuel and second, increasing environmental pollution. India's self reliant, three stage, 'closed-fuel-cycle' nuclear power program is promising better solution to the above problems. To ensure Radiation Protection and Safety of Radiation Sources, Indian Nuclear Power program emphasizes upon design and engineering safety by incorporating necessary safety features in the design, operational safety through structured training program and typically through software packages to handle rare unsafe events and regulation by complying safety directives. A health survey among the radiation workers indicates that there is no extra threat to the public from nuclear power program. Based on latest technology, as available in case of nuclear power option, it is quite possible to meet high energy requirement with least impact on the environment.. (authors)

  8. India's power programs and its concern over environmental safety

    International Nuclear Information System (INIS)

    Prasad, G.E.; Mittra, J.; Sarma, M.S.R.

    2000-01-01

    India's need for electrical power is enormous and per capita consumption of power is to be increased at least by 10 times to reach the level of the world average. Thermal power generation faces two-fold problems. First, there is scarcity of good quality fuel and second, increasing environmental pollution. India 's self reliant, . three stage, 'closed-fuel-cycle' nuclear power program is promising a better solution to the above problems. To ensure Radiation Protection and Safety of Radiation Sources, the Indian Nuclear Power program emphasizes upon design and engineering safety by incorporating' necessary safety features in the design, operational safety through a structured training program and typically through software packages to handle rare unsafe events and regulation by complying safety directives. A health survey among the radiation workers indicates that there is no extra threat to the public from the nuclear power program. Based on the latest technology, as available in case of the nuclear power option, it is quite possible to meet high energy requirements with least impact on the environment. (authors)

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

    Science.gov (United States)

    Schwappach, D L B; Gehring, K

    2015-05-01

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

  10. 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

  11. A narrative review of the safety concerns of deprescribing in older adults and strategies to mitigate potential harms.

    Science.gov (United States)

    Reeve, Emily; Moriarty, Frank; Nahas, Rayan; Turner, Justin P; Kouladjian O'Donnell, Lisa; Hilmer, Sarah N

    2018-01-01

    As with prescribing or continuing medications, deprescribing brings with it the potential for harm as well as benefit. Uncertainty and avoidance of harm has been reported as a barrier to deprescribing in practice and may contribute to continuation of inappropriate medications. Areas covered: This narrative review covers four main safety concerns/potential harms of deprescribing in older adults: adverse drug withdrawal events, return of medical condition(s), reversal of drug-drug interactions and damage to the doctor-patient relationship. These are discussed in relation to medications in general, with some examples of medication classes used to illustrate the potential safety concerns. The majority of these harms can be minimized or even prevented by using a patient-centered, structured deprescribing process with planning, tapering and close monitoring during, and after medication withdrawal. Expert opinion: More research is needed into the safety concerns of deprescribing, however, avenues exist during drug development and post-marketing surveillance to gain knowledge on this topic. Questions remain about when it is suitable to discontinue certain medications/medication classes and there is uncertainty about the harms and benefits of both medication continuation and discontinuation in complex older adults.

  12. Identifying Food Safety Concerns when Communication Barriers Exist

    Science.gov (United States)

    Neal, Jack A.; Dawson, Mary; Madera, Juan M.

    2011-01-01

    Abstract: Students must be prepared to lead a diverse workforce. The objective of this study was to establish a teaching method that helps students identify barriers to food safety while working in a simulated environment with communication barriers. This study employed a perspective taking exercise based upon the principles of social learning…

  13. Who wants safer streets? Explaining concern for public safety in Brazil

    NARCIS (Netherlands)

    Pradhan, M.P.; Ravallion, M.

    2003-01-01

    Public action to prevent crime is often driven by concerns about public safety. But what generates those concerns? Is it crime, or something else? Using survey data for Brazil, we find that the desire for greater public safety has a positive own-income effect, but a negative neighborhood-income

  14. Clinical alarm hazards: a "top ten" health technology safety concern.

    Science.gov (United States)

    Keller, James P

    2012-01-01

    For the past several years ECRI Institute has published a list of Top Ten Health Technology Hazards. This list is based on ECRI's extensive research in health technology safety and on data provided to its problemreporting systems. For every year that the Top Ten list has been published, Alarm Hazards have been at or near the top of the list. Improving alarm safety requires a systematic review of a hospital's alarm-based technologies and analysis of alarm management policies like alarm escalation strategies and staffing patterns. It also requires careful selection of alarm setting criteria for each clinical care area. This article will overview the clinical alarm problems that have been identified through ECRI Institute's research and analysis of various problem reporting databases, including those operated by ECRI Institute. It will also highlight suggestions for improvement, particularly from a technology design and technology management perspective. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures.

    Science.gov (United States)

    Mash, D C; Kovera, C A; Pablo, J; Tyndale, R F; Ervin, F D; Williams, I C; Singleton, E G; Mayor, M

    2000-09-01

    Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyibogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.

  16. Intravenous drugs infusion safety through smart pumps

    Directory of Open Access Journals (Sweden)

    C. Gómez-Baraza

    2014-07-01

    Full Text Available Objective: To analyze the role of smart infusion pumps in reducing errors related with the administration of intravenous medications. Method: Retrospective, observational study analyzing the implementation of a system with smart intravenous infusion pumps (Hospira MedNetTM and the role of the safety system for the detection of errors during the administration of drugs, sera, and blood. We included infusions administered at the day-care hospitals of hematology, oncology, rheumatology, and oncopediatrics. We analyzed adherence to the safety system, the number of programming errors detected, the commonly implicated drugs in these errors, and improvement actions. Results: During the study period, 120 smart pumps were implemented and data on 70,028 infusions were gathered. The rate of adherence to the safety program was 62.30% in hematology (6,887 infusions, 60,30% in oncology (28,127 infusions, 46,50% in rheumatology (1,950 infusions and 1.8% in oncopediatrics (139 infusions. 3,481 out of the established limits programming alerts were generated by the pumps: 2,716 of relative limit and 765 of absolute limit. En 807 infusions (2.17%, errors that could have had consequences for the patients could be prevented. These findings allowed implementing a series of strategies aimed at minimizing these errors in the future. Conclusions: The Hospira MedNetTM system detects deviations from the established protocols of intravenous infusion, preventing in this way potential adverse events for the patients. It also allows establishing correction measures and implementing the improvement strategies.

  17. 75 FR 59935 - Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and...

    Science.gov (United States)

    2010-09-29

    .... SUMMARY: The Food and Drug Administration (FDA) is amending its regulations governing safety reporting... safety reporting for human drug products: Janet Norden, Center for Drug Evaluation and Research, Food and.... Costs of the Regulation (to Prepare and Submit Safety Reports) C. Benefits of the Regulation D. Final...

  18. A new crop of concerns: Congress investigates pesticide safety.

    Science.gov (United States)

    Taylor, D A

    2000-09-01

    A March 2000 report by the General Accounting Office, Pesticides: Improvements Needed to Ensure the Safety of Farmworkers and Their Children, states that much remains unknown about the risks faced by children in agriculture, and that enforcement of pesticide protection standards for farmworkers is patchy and unsystematic. Many cases of farmworkers' pesticide-related illnesses go unreported, leaving health workers with an inadequate basis for tracking patterns and fine-tuning pesticide standards, says the report. In addition, children are known to be more vulnerable to the effects of pesticides, but there is a lack of data regarding children's exposures and the precise effects of pesticides on children's health.

  19. Software Reliability Issues Concerning Large and Safety Critical Software Systems

    Science.gov (United States)

    Kamel, Khaled; Brown, Barbara

    1996-01-01

    This research was undertaken to provide NASA with a survey of state-of-the-art techniques using in industrial and academia to provide safe, reliable, and maintainable software to drive large systems. Such systems must match the complexity and strict safety requirements of NASA's shuttle system. In particular, the Launch Processing System (LPS) is being considered for replacement. The LPS is responsible for monitoring and commanding the shuttle during test, repair, and launch phases. NASA built this system in the 1970's using mostly hardware techniques to provide for increased reliability, but it did so often using custom-built equipment, which has not been able to keep up with current technologies. This report surveys the major techniques used in industry and academia to ensure reliability in large and critical computer systems.

  20. Women with Epilepsy: Drug Risks and Safety During Pregnancy

    Science.gov (United States)

    ... Guideline for PATIENTS and their FAMILIES WOMEN WITH EPILEPSY: DRUG RISKS AND SAFETY DURING PREGNANCY This fact ... you understand which drugs are safest for treating epilepsy during pregnancy. It also gives information on how ...

  1. Safety concerns for first entry operations of orbiting spacecraft

    Science.gov (United States)

    Wilson, Steven H.; Limero, Thomas F.; James, John T.

    1994-01-01

    The Space Station Freedom crew will face operational problems unique to the spacecraft environment due to the absence of convection currents and the confined atmosphere within the habitable modules. Airborne contaminants from the materials offgassing or contingency incidents like thermodegradation may accumulate until they reach hazardous concentrations. Flow modeling and experiences from previous space flight missions confirm that caution must be exercised during first-entry operations. A review of the first-entry procedures performed during the Skylab Program will be presented to highlight the necessity for carefully planned operations. Many of the environmental conditions that can be expected on the Space Station are analogous to those which exist in confined storage or work spaces in the industrial setting. Experience with closed-loop environmental operations (e.g., atmospheric control of submarines) have also demonstrated that the buildup of trace contaminant gases could result in conditions that lead to mission termination or loss of crew. Consequently, some first-entry issues for the Station can be addressed by comparing them to familiar techniques developed on Earth. The instruments of the Environmental Health System (EHS) will provide the necessary monitoring capability to protect crew health and safety during the planned first-entry procedures of the MTC phase of the SSF Program. The authors of this paper will describe those procedures and will cite an example of the consequences when proper first-entry procedures are not followed.

  2. University Deals with Drug Companies Raise Concerns over Autonomy, Secrecy.

    Science.gov (United States)

    Nicklin, Julie L.

    1993-01-01

    The large, exclusive research deal the Scripps Research Institute (California) made with one drug company has drawn criticism for conflict of interest. Critics fear researchers will focus more on marketing than on pure science and will protect corporate interests. Much of the deal-making is with foreign companies, sending profits overseas. (MSE)

  3. An analysis of electronic health record-related patient safety concerns

    Science.gov (United States)

    Meeks, Derek W; Smith, Michael W; Taylor, Lesley; Sittig, Dean F; Scott, Jean M; Singh, Hardeep

    2014-01-01

    Objective A recent Institute of Medicine report called for attention to safety issues related to electronic health records (EHRs). We analyzed EHR-related safety concerns reported within a large, integrated healthcare system. Methods The Informatics Patient Safety Office of the Veterans Health Administration (VA) maintains a non-punitive, voluntary reporting system to collect and investigate EHR-related safety concerns (ie, adverse events, potential events, and near misses). We analyzed completed investigations using an eight-dimension sociotechnical conceptual model that accounted for both technical and non-technical dimensions of safety. Using the framework analysis approach to qualitative data, we identified emergent and recurring safety concerns common to multiple reports. Results We extracted 100 consecutive, unique, closed investigations between August 2009 and May 2013 from 344 reported incidents. Seventy-four involved unsafe technology and 25 involved unsafe use of technology. A majority (70%) involved two or more model dimensions. Most often, non-technical dimensions such as workflow, policies, and personnel interacted in a complex fashion with technical dimensions such as software/hardware, content, and user interface to produce safety concerns. Most (94%) safety concerns related to either unmet data-display needs in the EHR (ie, displayed information available to the end user failed to reduce uncertainty or led to increased potential for patient harm), software upgrades or modifications, data transmission between components of the EHR, or ‘hidden dependencies’ within the EHR. Discussion EHR-related safety concerns involving both unsafe technology and unsafe use of technology persist long after ‘go-live’ and despite the sophisticated EHR infrastructure represented in our data source. Currently, few healthcare institutions have reporting and analysis capabilities similar to the VA. Conclusions Because EHR-related safety concerns have complex

  4. 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

  5. Facts about Magnesium Sulfate: Time to Revise the Safety Concern in Obstetric Use

    Directory of Open Access Journals (Sweden)

    Zaida Rahman

    2014-09-01

    effects”. Similarly, the manufacturers of other MgSO4 injection products have made similar changes to their drug labels. In this review, the currently available knowledge of the pharmacokinetics of MgSO4 and its clinical usage for women with pre-eclampsia and eclampsia, its off-label use and safety concern regarding the warning announced by the FDA will be outlined.

  6. 47 CFR 101.203 - Communications concerning safety of life and property.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Communications concerning safety of life and property. 101.203 Section 101.203 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Operational Requirements § 101.203 Communications...

  7. Safety concerns and suggested design approaches to the HTGR Reformer process concept

    International Nuclear Information System (INIS)

    Green, R.C.

    1981-09-01

    This report is a safety review of the High Temperature Gas-Cooled Reactor Reformer Application Study prepared by Gas-Cooled Reactor Associates (GCRA) of La Jolla, California. The objective of this review was to identify safety concerns and suggests design approaches to minimize risk in the High Temperature Gas-Cooled Reactor Reformer (HTGR-R) process concept

  8. Clinical pharmacology: special safety considerations in drug development and pharmacovigilance.

    Science.gov (United States)

    Atuah, Kwame N; Hughes, Dyfrig; Pirmohamed, Munir

    2004-01-01

    The dose of a drug is a major determinant of its safety, and establishing a safe dose of a novel drug is a prime objective during clinical development. The design of pre-marketing clinical trials precludes the representation of important subpopulations such as children, the elderly and people with co-morbidities. Therefore, postmarketing surveillance (PMS) activities are required to monitor the safety profile of drugs in real clinical practice. Furthermore, individual variations in pharmacogenetic profiles, the immune system, drug metabolic pathways and drug-drug interactions are also important factors in the occurrence of adverse drug reactions. Thus, the safety of a drug is a major clinical consideration before and after it is marketed. A multidisciplinary approach is required to enhance the safety profile of drugs at all stages of development, including PMS activities. Clinical pharmacology encompasses a range of disciplines and forms the backbone of drug safety consideration during clinical drug development. In this review we give an overview of the clinical drug development process and consider its limitations. We present a discussion of several aspects of clinical pharmacology and their application to enhancing drug safety. Pharmacokinetic-pharmacodynamic modelling provides a method of predicting a clinically safe dose; consideration of drug pharmacokinetics in special populations may enhance safe therapeutics in a wider spectrum of patients, while pharmacogenetics provides the possibility of genotype-specific therapeutics. Pharmacovigilance activities are also discussed. Given the complex nature and unpredictability of type B reactions, PMS activities are crucial in managing the risks drugs pose to the general population. The various aspects of clinical pharmacology discussed make a strong case for this field as the backbone of optimising and promoting safe development and use of drugs.

  9. 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

  10. College Student Drug Use: Patterns, Concerns, Consequences, and Interest in Intervention

    Science.gov (United States)

    Palmer, Rebekka S.; McMahon, Thomas J.; Moreggi, Danielle I.; Rounsaville, Bruce J.; Ball, Samuel A.

    2012-01-01

    Although previous surveys have indicated high rates of illicit and prescription drug misuse among college students, few have assessed negative consequences, personal concerns, or interest in interventions for drug use. In a survey of 262 college students who self-reported lifetime use of an illicit drug, 69% reported at least one negative…

  11. Frequent food insecurity among injection drug users: correlates and concerns.

    Science.gov (United States)

    Strike, Carol; Rudzinski, Katherine; Patterson, Jessica; Millson, Margaret

    2012-12-08

    Food insecurity and nutrition are two topics that are under-researched among injection drug users (IDUs). Our study examined the extent and correlates of food insecurity among a sample of IDUs and explored whether there is an association between food insecurity and injection-related HIV risk. A cross-sectional survey was conducted using interviewer-administered questionnaires. Data were collected at a needle exchange program in London, Ontario, Canada between September 2006 and January 2007. Participants included 144 English-speaking IDUs who had injected drugs in the past 30 days. Participants were asked about their socio-demographic characteristics, HIV risk behaviours, food insecurity, and health/social service use. In the past 6 months, 54.5% of participants reported that on a daily/weekly basis they did not have enough to eat because of a lack of money, while 22.1% reported this type of food insecurity on a monthly basis. Moreover, 60.4% and 24.3% reported that they did not eat the quality or quantity of food they wanted on a daily/weekly or a monthly basis, respectively. Participants reported re-using someone else's injection equipment: 21% re-used a needle, 19% re-used water, and 37.3% re-used a cooker. The odds of sharing injection equipment were increased for food insecure individuals. Findings show that IDUs have frequent and variable experiences of food insecurity and these experiences are strongly correlated with sharing of injection-related equipment. Such behaviours may increase the likelihood of HIV and HCV transmission in this population. Addressing food-related needs among IDUs is urgently needed.

  12. Making the "Child Safe" Environment "Adult Safe": Occupational Health and Safety Concerns for Child Care Programs.

    Science.gov (United States)

    Whitebook, Marcy; Ginsburg, Gerri

    Results of a nonrandom nationwide survey of 89 child care workers in 20 states concerning work-related health and safety conditions confirm that similar hazardous conditions exist in child care programs throughout the nation. Results also confirm that concern and anger about such conditions and their potential consequences are widespread among…

  13. Summary of Tiger Team Assessment and Technical Safety Appraisal recurring concerns in the Maintenance Area

    International Nuclear Information System (INIS)

    1993-01-01

    Tiger Team Assessments and Technical Safety Appraisals (TSA) were reviewed and evaluated for concerns in the Maintenance Area (MA). Two hundred and thirty one (231) maintenance concerns were identified by the Tiger Team Assessments and TSA reports. These recurring concerns appear below. A summary of the Noteworthy Practices that were identified and a compilation of the maintenance concerns for each performance objective that were not considered as recurring are also included. Where the Tiger Team Assessment and TSA identified the operating contractor or facility by name, the concern has been modified to remove the name while retaining the intent of the comment

  14. 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.

  15. 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

  16. 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.

    Science.gov (United States)

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

    2011-11-01

    analysis (DHPCs related to contamination/medication error). Six 'index' drugs were paired, each with one to six 'follow-on' drugs. Three concerned drug-drug interactions (DDIs); the other three were intracranial haemorrhage, neuromuscular weakness and severe skin/hepatic reactions. All but one 'follow-on' drug had information in the EPAR on that specific ADR (i.e. attention was paid to the ADR). The DDIs were addressed in pre-marketing studies and/or the SmPC. Two of the other ADRs were addressed by postmarketing surveillance commitments; intracranial haemorrhage was not addressed. Three safety issues for two 'index' drugs could not be paired with a 'follow-on' drug as no drug in the same class was approved after the corresponding DHPCs were issued. Five of the nine safety issues were added to at least one of the current SmPCs for the 'older' drugs already on the market at the time of DHPC issue. Two safety issues were already in the SmPC of the 'older' drugs at time of market approval and two were not introduced into the SmPC of 'older' drugs. Population size to assess short-term safety complied with the guidelines for four 'index', seven 'follow-on' and three 'older' drugs; population size to assess long-term safety complied for one, three and two drugs, respectively. For five drugs, EPARs did not provide adequate information on population size. No statistically significant difference in development time between 'index' and 'follow-on' drugs was found. Generally, safety issues were taken into account in the approval process of other drugs in the class. The approaches were different and determined by the nature of the ADR. Taking safety issues into account in the approval process did not seem to impact on the time taken to perform the pre-approval clinical programme.

  17. Safety assessments and public concern for genetically modified food products: the American view.

    Science.gov (United States)

    Harlander, Susan K

    2002-01-01

    In the relatively short time since their commercial introduction in 1996, genetically modified (GM) crops have been rapidly adopted in the United States GM crops are regulated through a coordinated framework developed in 1992 and administered by three agencies-the US Department of Agriculture (USDA) that ensures the products are safe to grow, the Environmental Protection Agency (EPA) that ensures the products are safe for the environment, and the Food and Drug Administration (FDA) that ensures the products are safe to eat. Rigorous food and environmental safety assessments must be completed before GM crops can be commercialized. Fifty-one products have been reviewed by the FDA, including several varieties of corn, soybeans, canola, cotton, rice, sugar beets, potatoes, tomatoes, squash, papaya, and flax. Because FDA considers these crops "substantially equivalent" to their conventional counterparts, no special labeling is required for GM crops in the United States and they are managed as commodities with no segregation or identity preservation. GM crops have thus made their way through commodity distribution channels into thousands of ingredients used in processed foods. It has been estimated that 70% to 85% of processed foods on supermarket shelves in the United States today contain one or more ingredients potentially derived from GM crops. The food industry and retail industry have been monitoring the opinions of their consumers on the GM issue for the past several years. Numerous independent groups have also surveyed consumer concerns about GM foods. The results of these surveys are shared and discussed here.

  18. Drug-Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV

    Science.gov (United States)

    Scarsi, Kimberly K.; Darin, Kristin M.; Chappell, Catherine A.; Nitz, Stephanie M.; Lamorde, Mohammed

    2016-01-01

    Family planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17 million women living with human immunodeficiency virus (HIV) worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mortality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives, barriers to effective family planning methods exist for HIV-positive women. Specifically, drug-drug interactions can occur between some antiretroviral medications and some hormonal contraceptives, which may influence both contraceptive efficacy and tolerability. In addition, safety concerns have been raised about the impact of hormonal contraceptives on HIV disease progression, tolerability and the risk of female-to-male HIV transmission. This review article summarizes the potential for drug-drug interactions, tolerability, and contraceptive effectiveness when hormonal contraceptives are combined with ART. In addition, the evidence surrounding the influence of hormonal contraceptives on HIV transmission and HIV disease progression in women living with HIV are summarized. PMID:27562873

  19. An analysis of electronic health record-related patient safety concerns.

    Science.gov (United States)

    Meeks, Derek W; Smith, Michael W; Taylor, Lesley; Sittig, Dean F; Scott, Jean M; Singh, Hardeep

    2014-01-01

    A recent Institute of Medicine report called for attention to safety issues related to electronic health records (EHRs). We analyzed EHR-related safety concerns reported within a large, integrated healthcare system. The Informatics Patient Safety Office of the Veterans Health Administration (VA) maintains a non-punitive, voluntary reporting system to collect and investigate EHR-related safety concerns (ie, adverse events, potential events, and near misses). We analyzed completed investigations using an eight-dimension sociotechnical conceptual model that accounted for both technical and non-technical dimensions of safety. Using the framework analysis approach to qualitative data, we identified emergent and recurring safety concerns common to multiple reports. We extracted 100 consecutive, unique, closed investigations between August 2009 and May 2013 from 344 reported incidents. Seventy-four involved unsafe technology and 25 involved unsafe use of technology. A majority (70%) involved two or more model dimensions. Most often, non-technical dimensions such as workflow, policies, and personnel interacted in a complex fashion with technical dimensions such as software/hardware, content, and user interface to produce safety concerns. Most (94%) safety concerns related to either unmet data-display needs in the EHR (ie, displayed information available to the end user failed to reduce uncertainty or led to increased potential for patient harm), software upgrades or modifications, data transmission between components of the EHR, or 'hidden dependencies' within the EHR. EHR-related safety concerns involving both unsafe technology and unsafe use of technology persist long after 'go-live' and despite the sophisticated EHR infrastructure represented in our data source. Currently, few healthcare institutions have reporting and analysis capabilities similar to the VA. Because EHR-related safety concerns have complex sociotechnical origins, institutions with long-standing as well

  20. LMFBR conceptual design study: an overview of environmental and safety concerns

    International Nuclear Information System (INIS)

    Brenchley, D.L.

    1981-06-01

    The US Department of Energy (DOE) initiated the Liquid Metal Fast Breeder (LMFBR) Conceptual Design Study (CDS) with the objective of maintaining a viable breeder option. The project is scheduled to be completed in FY-1981 but decisions regarding plant construction will be delayed until at least 1985. This report provides a review of the potential environmental and safety engineering concerns for the CDS and recommends specific action for the Environmental and Safety Engineering Division of DOE

  1. Safety concerns to application of graphene compounds in pharmacy and medicine

    OpenAIRE

    Mogharabi, Mehdi; Abdollahi, Mohammad; Faramarzi, Mohammad Ali

    2014-01-01

    Graphene, the new allotrope of carbon is a single layer of monocrystalline graphite with sp2 hybridized carbon atoms. This compound has received worldwide attention due to its extraordinary physical and chemical properties. Duo to the widespread application of geraphenes, concerns are raising about its environmental safety or the safety protocols for handling and waste of graphene-based materials. The generation of reactive free radicals, adsorption of important biomolecules, and physical tox...

  2. LMFBR conceptual design study: an overview of environmental and safety concerns

    Energy Technology Data Exchange (ETDEWEB)

    Brenchley, D.L.

    1981-06-01

    The US Department of Energy (DOE) initiated the Liquid Metal Fast Breeder (LMFBR) Conceptual Design Study (CDS) with the objective of maintaining a viable breeder option. The project is scheduled to be completed in FY-1981 but decisions regarding plant construction will be delayed until at least 1985. This report provides a review of the potential environmental and safety engineering concerns for the CDS and recommends specific action for the Environmental and Safety Engineering Division of DOE.

  3. Ordinance of 14 March 1983 concerning the Federal Commission for the Safety of Nuclear Installations

    International Nuclear Information System (INIS)

    1983-01-01

    The Frederal Council issued a new Ordinance concerning the Federal Commission for the Safety of Nuclear Installations. This Ordinance replaces an Ordinance of 13 June 1960 and takes into account the distribution of tasks decided several years ago between the Commission, which operates on a part-time basis, and the principal Division for the Safety of Nuclear Installations attached to the Federal Office of Energy. (NEA) [fr

  4. Summary of Tiger Team Assessment and Technical Safety Appraisal recurring concerns in the Operations Area

    International Nuclear Information System (INIS)

    1993-01-01

    Fourteen Tiger Team Assessment and eight Technical Safety Appraisal (TSA) final reports have been received and reviewed by the DOE Training Coordination Program during Fiscal Year 1992. These assessments and appraisals included both reactor and non-reactor nuclear facilities in their reports. The Tiger Team Assessments and TSA reports both used TSA performance objectives, and list ''concerns'' as a result of their findings. However, the TSA reports categorized concerns into the following functional areas: (1) Organization and Administration, (2) Radiation Protection, (3) Nuclear Criticality Safety, (4) Occupational Safety, (5) Engineering/Technical Support, (6) Emergency Preparedness, (7) Safety Assessments, (8) Quality Verification, (9) Fire Protection, (10) Environmental Protection, and (11) Energetic Materials Safety. Although these functional areas match most of the TSA performance objectives, not all of the TSA performance objectives are addressed. For example, the TSA reports did not include Training, Maintenance, and Operations as functional areas. Rather, they included concerns that related to these topics throughout the 11 functional areas identified above. For consistency, the Operations concerns that were identified in each of the TSA report functional areas have been included in this summary with the corresponding TSA performance objective

  5. Can current electronic systems meet drug safety and effectiveness requirements?

    Science.gov (United States)

    Holbrook, Anne; Grootendorst, Paul; Willison, Don; Goldsmith, Charles; Sebaldt, Rolf; Keshavjee, Karim

    2005-01-01

    Every health policy jurisdiction is endeavoring to enhance its ability to evaluate drug effectiveness, safety and cost in the real world (pharmacosurveillance). A nominal group consensus conference of stakeholders finalized data items deemed necessary for pharmacosurveillance. Large administrative datasets (LADs), electronic health records (EHRs) and electronic patient registries (PRs), were investigated as sources of this information and for their vulnerability to methodologic bias. Health data privacy legislation and research guidelines were systematically reviewed for their constraint to linked data resource analyses. More than 129 data items were strongly recommended for routine pharmacosurveillance. LADs had very complete information, but restricted to a small number of required data items. EHRs, especially with e-pharmacy links, offer by far the most complete set of health information domains but data entry completeness is highly variable. Adjustment methods for channeling bias are inadequate to mimic randomized trials. Anonymized, linked data held within a secure academic research environment, poses the least privacy concerns. Notwithstanding major technical, methodologic and privacy challenges, individual-level linkage of health data resources poses the best option for pharmacosurveillance today. In future, drug regulators and reimbursement agencies should consider mandatory post-marketing randomized trials.

  6. Safety of available and emerging drug therapies for hyperhidrosis.

    Science.gov (United States)

    Hosp, Christine; Hamm, Henning

    2017-09-01

    Hyperhidrosis affects 4.8% of the U.S. population and has been underestimated by physicians for long time despite considerable interference with quality of life. Many patients suffer from primary (idiopathic) hyperhidrosis which results from over-activity of sympathetic nerves and is restricted to specific body areas, mostly the axillae, palms, soles, or head. Secondary hyperhidrosis is caused by an underlying disease or the intake of medications and often involves large parts of the body. Numerous effective therapies with topical or systemic drugs and surgical options are available. Areas covered: Efficacy and safety data on aluminum salts, anticholinergic drugs for topical or systemic application, and on intradermal botulinum toxin injections used to treat hyperhidrosis are critically evaluated, including data from clinical trials with focus on possible side effects and long-term complications in dispute. Expert opinion: Hyperhidrosis often responds well to available therapies. Depending on the type of hyperhidrosis treatment should be topical/local or systemic. Most of the side effects are mild, transient and easily manageable. In case of systemic treatment with anticholinergics low dosing and up-titration of medication is necessary to avoid severe adverse effects. Concerns about the promotion of breast cancer and Alzheimer disease by topical aluminum salts are unsolved.

  7. Safety concerns to application of graphene compounds in pharmacy and medicine.

    Science.gov (United States)

    Mogharabi, Mehdi; Abdollahi, Mohammad; Faramarzi, Mohammad Ali

    2014-01-22

    Graphene, the new allotrope of carbon is a single layer of monocrystalline graphite with sp2 hybridized carbon atoms. This compound has received worldwide attention due to its extraordinary physical and chemical properties. Duo to the widespread application of geraphenes, concerns are raising about its environmental safety or the safety protocols for handling and waste of graphene-based materials. The generation of reactive free radicals, adsorption of important biomolecules, and physical toxicity of graphene also matter. Hereby we criticize the concerns on the toxicity of graphenes to provide some perspective on the potential hazards of future development in graphene-based biomaterials.

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

    Science.gov (United States)

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

    2013-11-01

    At time of approval, knowledge of the full benefit risk of any drug is limited, in particular with regards to safety. Post-approval surveillance of potential drug safety concerns is recognized as an important task of regulatory agencies. For innovative, often first-in-class drugs, safety knowledge at time of approval is often even less extensive and these may require tighter scrutiny post approval. We evaluated whether more post-approval serious safety issues were identified for drugs with a higher level of innovation. A cohort study was performed that included all new active substances approved under the European Centralized Procedure and for which serious safety issues were identified post-approval from 1 January 1999 to 1 January 2012. Serious safety issues were defined as issues requiring a Direct Healthcare Professional Communication to alert individual healthcare professionals of a new serious safety issue, or a safety-related drug withdrawal. Data were retrieved from publicly available websites of the Dutch Medicines Evaluation Board and the European Medicines Agency. The level of innovation was scored using a validated algorithm, grading drugs as important (A), moderate (B) or modest (C) innovations or as pharmacological or technological (pharm/tech) innovations. The data were analyzed using appropriate descriptive statistics and Kaplan-Meier analysis, with a Mantel-Cox log-rank test, and Cox-regression models correcting for follow-up duration, to identify a possible trend in serious safety issues with an increasing level of innovation. In Europe, 279 new drugs were approved between 1999 and 2011. Fifty-nine (21 %) were graded as important, 63 (23 %) moderate, or 34 (12 %) modest innovations and 123 (44 %) as non-innovative (pharm/tech), while 15 (25 %), 13 (21 %), 8 (24 %) and 17 (14 %) had post-approval safety issues, respectively (p = 0.06, linear-by-linear test). Five drugs were withdrawn from the market. The Kaplan-Meier-derived probability for having

  9. Report of Subcommittee on Investigation of Empirical Formulas Concerning Reactor Safety Analysis

    International Nuclear Information System (INIS)

    1981-01-01

    For the safety evaluation when nuclear power stations are going to be installed, the transient state following the various abnormal events occurring in reactor facilities is analyzed. In the case of light water reactors, the most important safety analysis is related to the loss of coolant accident caused by the break of primary cooling pipes. At the time of the analysis, the safety analysis codes based on various models are used, and many empirical formulas and correlation formulas concerning heat transfer are included in them. In Japan Society of Mechanical Engineers, for the purpose of investigating and collecting the empirical and correlation formulas on heat transferring flow related to reactor safety analysis and contributing to the perfection of the basic data for reactor safety evaluation, the ''Subcommittee on investigation of empirical formulas concerning reactor safety analysis'' was established in February, 1978. This is the report on the results of investigation by the subcommittee, intended for general use. The correlation formulas on heat transfer in the analysis of LOCA in light water reactors are taken up, and classified into eight subjects. This report is significant for those who are going to develop the analysis codes or who engage in the safety analysis. (Kako, I.)

  10. Factors to Consider When Balancing Campus Safety Concerns with Students' Civil Rights

    Science.gov (United States)

    Ingersoll, Julia S.

    2017-01-01

    On April 16, 2007, a student at Virginia Tech University, known to be mentally ill, went on a rampage shooting 49 people on campus before taking his own life. When it was over, 32 people were dead, and the concept of a safe campus was forever changed. The incident revealed the inherent conflicts between campus safety concerns and students' civil…

  11. Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients

    NARCIS (Netherlands)

    Kroes, R.; Renwick, A.G.; Feron, V.; Galli, C.L.; Gibney, M.; Greim, H.; Guy, R.H.; Lhuguenot, J.C.; Sandt, J.J.M. van de

    2007-01-01

    The threshold of toxicological concern (TTC) has been used for the safety assessment of packaging migrants and flavouring agents that occur in food. The approach compares the estimated oral intake with a TTC value derived from chronic oral toxicity data for structurally-related compounds.

  12. Automated discovery of safety and efficacy concerns for joint & muscle pain relief treatments from online reviews.

    Science.gov (United States)

    Adams, David Z; Gruss, Richard; Abrahams, Alan S

    2017-04-01

    Product issues can cost companies millions in lawsuits and have devastating effects on a firm's sales, image and goodwill, especially in the era of social media. The ability for a system to detect the presence of safety and efficacy (S&E) concerns early on could not only protect consumers from injuries due to safety hazards, but could also mitigate financial damage to the manufacturer. Prior studies in the field of automated defect discovery have found industry-specific techniques appropriate to the automotive, consumer electronics, home appliance, and toy industries, but have not investigated pain relief medicines and medical devices. In this study, we focus specifically on automated discovery of S&E concerns in over-the-counter (OTC) joint and muscle pain relief remedies and devices. We select a dataset of over 32,000 records for three categories of Joint & Muscle Pain Relief treatments from Amazon's online product reviews, and train "smoke word" dictionaries which we use to score holdout reviews, for the presence of safety and efficacy issues. We also score using conventional sentiment analysis techniques. Compared to traditional sentiment analysis techniques, we found that smoke term dictionaries were better suited to detect product concerns from online consumer reviews, and significantly outperformed the sentiment analysis techniques in uncovering both efficacy and safety concerns, across all product subcategories. Our research can be applied to the healthcare and pharmaceutical industry in order to detect safety and efficacy concerns, reducing risks that consumers face using these products. These findings can be highly beneficial to improving quality assurance and management in joint and muscle pain relief. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. 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

  14. Radiation safety concerns and diagnostic reference levels for computed tomography scanners in Tamil Nadu

    OpenAIRE

    Livingstone Roshan; Dinakaran Paul

    2011-01-01

    Radiation safety in computed tomography (CT) scanners is of concern due its widespread use in the field of radiological imaging. This study intends to evaluate radiation doses imparted to patients undergoing thorax, abdomen and pelvic CT examinations and formulate regional diagnostic reference levels (DRL) in Tamil Nadu, South India. In-site CT dose measurement was performed in 127 CT scanners in Tamil Nadu for a period of 2 years as a part of the Atomic Energy Regulatory Board (AERB)-funded ...

  15. Training Needs of Rehabilitation Counselors concerning Alcohol and Other Drugs Abuse Assessment and Treatment

    Science.gov (United States)

    Ong, Lee Za; Cardoso, Elizabeth; Chan, Fong; Chronister, Julie; Chou, Chih Chin

    2007-01-01

    Forty-two rehabilitation counselors participated in a study regarding perceived training needs concerning alcohol and other drug abuse (AODA) treatment and assessment. Participants reported that 85% of consumers with whom they worked had AODA issues, yet over half rated their graduate training in AODA treatment and assessment as poor, and their…

  16. 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...

  17. Correlates of local safety-related concerns in a Swedish Community: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Timpka Toomas

    2009-07-01

    Full Text Available Abstract Background Crime in a neighbourhood has been recognized as a key stressor in the residential environment. Fear of crime is related to risk assessment, which depends on the concentration of objective risk in time and space, and on the presence of subjective perceived early signs of imminent hazard. The aim of the study was to examine environmental, socio-demographic, and personal correlates of safety-related concerns at the local level in urban communities. The specific aim was to investigate such correlates in contiguous neighbourhoods in a Swedish urban municipality. Methods A cross-sectional study design was used to investigate three neighbourhood settings with two pair-wise conterminous but socially contrasting areas within each setting. Crime data were retrieved from police records. Study data were collected through a postal questionnaire distributed to adult residents (n = 2476 (response rate 56%. Composite dimensions of perceived residential safety were derived through a factor analysis. Logistic regression analysis was used to examine associations between high-level scores of the three safety-related dimensions and area-level crime rate, being a victim of crime, area reputation, gender, age, education, country of birth, household civil status and type of housing. Results Three composite dimensions of perceived residential safety were identified: (I structural indicators of social disorder; (II contact with disorderly behavior; and (III existential insecurity. We found that area-level crime rates and individual-level variables were associated with the dimensions structural indicators of social disorder and existential insecurity, but only individual-level variables were associated with the dimension contact with disorderly behavior. Self-assessed less favorable area reputation was found to be strongly associated with all three factors. Being female accorded existential insecurity more than being a victim of crime. Conclusion We

  18. The Inverse Benefit Law: How Drug Marketing Undermines Patient Safety and Public Health

    Science.gov (United States)

    Light, Donald W.

    2011-01-01

    Recent highly publicized withdrawals of drugs from the market because of safety concerns raise the question of whether these events are random failures or part of a recurring pattern. The inverse benefit law, inspired by Hart's inverse care law, states that the ratio of benefits to harms among patients taking new drugs tends to vary inversely with how extensively the drugs are marketed. The law is manifested through 6 basic marketing strategies: reducing thresholds for diagnosing disease, relying on surrogate endpoints, exaggerating safety claims, exaggerating efficacy claims, creating new diseases, and encouraging unapproved uses. The inverse benefit law highlights the need for comparative effectiveness research and other reforms to improve evidence-based prescribing. PMID:21233426

  19. The inverse benefit law: how drug marketing undermines patient safety and public health.

    Science.gov (United States)

    Brody, Howard; Light, Donald W

    2011-03-01

    Recent highly publicized withdrawals of drugs from the market because of safety concerns raise the question of whether these events are random failures or part of a recurring pattern. The inverse benefit law, inspired by Hart's inverse care law, states that the ratio of benefits to harms among patients taking new drugs tends to vary inversely with how extensively the drugs are marketed. The law is manifested through 6 basic marketing strategies: reducing thresholds for diagnosing disease, relying on surrogate endpoints, exaggerating safety claims, exaggerating efficacy claims, creating new diseases, and encouraging unapproved uses. The inverse benefit law highlights the need for comparative effectiveness research and other reforms to improve evidence-based prescribing.

  20. Occupational Safety and Health Concerns in Logging: A Cross-Sectional Assessment in Virginia

    Directory of Open Access Journals (Sweden)

    Sunwook Kim

    2017-11-01

    Full Text Available Increased logging mechanization has helped improve logging safety and health, yet related safety risks and concerns are not well understood. A cross-sectional study was completed among Virginia loggers. Participants (n = 122 completed a self-administered questionnaire focusing on aspects of safety and health related to logging equipment. Respondents were at a high risk of workplace injuries, with reported career and 12-month injury prevalences of 51% and 14%, respectively. Further, nearly all (98% respondents reported experiencing musculoskeletal symptoms. Over half (57.4% of respondents reported symptoms related to diesel exhaust exposure in their career. Few (15.6%, however, perceived their jobs to be dangerous. Based on the opinions and suggestions of respondents, three priority areas were identified for interventions: struck-by/against hazards, situational awareness (SA during logging operations, and visibility hazards. To address these hazards, and to have a broader and more substantial positive impact on safety and health, we discuss the need for proactive approaches such as incorporating proximity technologies in a logging machine or personal equipment, and enhancing logging machine design to enhance safety, ergonomics, and SA.

  1. Spillover Effects of Drug Safety Warnings on Health Behavior

    NARCIS (Netherlands)

    Meltem Daysal, N.; Orsini, C.

    2012-01-01

    Abstract: We examine the impact of new medical information on drug safety on preventive health behavior. 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 that long-term Hormone

  2. [Comprehensive drug safety plan in a health department].

    Science.gov (United States)

    Bujaldón-Querejeta, N; Aznar-Saliente, T; Esplá-González, S; Ruíz-Darbonnéns, S; Pons-Martínez, L; Talens-Bolos, A; Martínez-Ramírez, M; Camacho-Romera, D; Aranaz-Andrés, J M

    2014-01-01

    To develop and implement a comprehensive drug safety plan in a hospital for the years 2009-2011. Applying the Strengths Weaknesses/Limitations Opportunities Threats (SWOT) methodology, the baseline situation was analyzed and a broad strategy or plan was subsequently developed, defining the scope, responsibilities, objectives and strategic actions and indicators in order to measure the achievement of the results. A comprehensive drug safety plan with the main objective of identifying and reducing the medication-related problems in patients treated in the Hospital de San Juan in Alicante has been developed. The plan contains five strategic objectives, twenty strategic actions and the indicators to assess its outcomes. It also contains a timetable for its establishment and evaluation. Developing a comprehensive strategic plan allows the current situation relating to drug safety to be determined. The results obtained after its introduction will define its applicability. Due to the lack of publications of similar plans and results, the evaluation of this plan will be useful whether it is favorable or not. As a side benefit of the development, the multidisciplinary team continues to work on improving patient safety in the care process, and the safety culture continues to grow among the professionals. Copyright © 2013 SECA. Published by Elsevier Espana. All rights reserved.

  3. 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

  4. 49 CFR Appendix A to Part 209 - Statement of Agency Policy Concerning Enforcement of the Federal Railroad Safety Laws

    Science.gov (United States)

    2010-10-01

    ..., information concerning any defenses or mitigating factors. The railroad safety statutes, in conjunction with... reasonable expectation that the safety of any member of the public'except a business guest, a licensee of the... case of highway-rail grade crossings, to the motoring public. The safety of highway users of highway...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. Perception vs. reality: an investigation of the misperceptions concerning the extent of peer novel drug use.

    Science.gov (United States)

    Sanders, Amber; Stogner, John M; Miller, Bryan Lee

    2013-01-01

    Misperceptions of peer substance use have previously been implicated as significant influences on individual use of both alcohol and illicit drugs. However, research on perceived social norms and related interventions are typically limited to binge drinking and marijuana and no empirical studies have explored misperceptions related to "novel drugs." The present study explored the extent of use and perceptions of use among a college sample (N = 2,349) for three categories of novel drugs: synthetic cannabinoids (Spice, K2, Mr. Miyagi, Pot-Pourri, etc.), synthetic cathinones (commonly known as "bath salts"), and Salvia divinorum. Results indicate that overall perceived use was significantly higher than actual reported use. The frequency of overestimation of peer use was particularly large for the emerging drugs when compared to alcohol and marijuana. This finding is concerning as these misperceptions have the potential to influence students toward experimentation with these substances and suggests that a possible target for intervention is misperceptions of emerging novel substances.

  11. Safety concerns in ultrahigh pressure capillary liquid chromatography using air-driven pumps.

    Science.gov (United States)

    Xiang, Yanqiao; Maynes, Daniel R; Lee, Milton L

    2003-04-04

    Ultrahigh pressure liquid chromatography (UHPLC) is an emerging technique which utilizes pressures higher than 10,000 p.s.i. to overcome the flow resistance imposed when using very small particles as packing materials in fused-silica capillary columns (1 p.s.i.=6894.76 Pa). This technique has demonstrated exceptionally high separation speeds and chromatographic efficiencies. However, safety is a concern when extremely high pressures are used. In this study, the safety aspects of capillary column rupture during operation were identified and carefully evaluated. First, liquid jets may be formed as a result of blow-out of the on-column frits or from rupture of the capillary at or near the column inlet. Second, incorrect installation of the capillary at the injector, failure of the ferrule used in the capillary connection, or rupture of the capillary can produce high speed projectiles of silica particles or column fragments. Experiments were carried out in the laboratory to produce liquid (water) jets and capillary projectiles using a UHPLC system, and the power density, an important parameter describing water jets in industrial practice, was calculated. Experimental results were in accordance with theoretical calculations. Both indicated that water jets and capillary projectiles under ultrahigh pressures might lead to skin penetration under limited conditions. The use of a plexiglass shroud to cover an initial length of the installed capillary column can eliminate any safety-related concerns about liquid jets or capillary projectiles.

  12. 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…

  13. 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...

  14. 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...

  15. 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.

  16. Health and safety concerns os migrant workers: the experience of tunisian workers in modena, Italy

    Directory of Open Access Journals (Sweden)

    Faïçal Daly

    2004-06-01

    Full Text Available This paper examines the relatively under-researched field of healthand safety of migrant workers, with special reference to Tunisian construction workers in the city of Modena in the Italian region of Emilia-Romagna. The empirical material comes from questionnaires and interviews with Tunisian migrants, plus smaller numbers of interviews with employers and trade union representatives in Modena. The paper starts by critically reviewing the scattered literature onthe health and safety of minority workers, most of which refers to the United States and the United Kingdom. The discussion then moves to a consideration of migrant health and safety questions in the contexts of racism, discrimination, social class, working conditions, labour market segmentation and (non- regulation. Specialattention is given to the failed role of trade unions in defending the rights of minority workers, in advanced countries generally and in Italy in particular. A case study is then made of the construction sector in Italy, enriched by personal accounts of the experiences of Tunisian migrant workers in Modena. Employer and tradeunion interviews reveal a lack of concern and ability to tackle the relevant issues. Barriers to health and safety awareness training are outlined. In the conclusion, recommendations are made for policy initiatives in this area.

  17. Drug safety in pregnancy--monitoring congenital anomalies.

    Science.gov (United States)

    Morgan, Margery; De Jong-van den Berg, Lolkje T W; Jordan, Sue

    2011-04-01

    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. Since the thalidomide disaster, use of drugs in pregnancy has been carefully monitored to prevent anything similar happening again. However, monitoring is incomplete and questions remain unanswered. Many medicines are essential for the health of pregnant women. However, drug use in pregnancy requires surveillance. Methods include spontaneous reporting of adverse events, cohort studies and case control studies. It is hoped that a Europe-wide study, combining data from several congenital anomaly registers, will provide a sufficiently large population to assess the impact of selected drugs on congenital anomalies. However, this work depends on the consistency of reporting by nurses and midwives. Drug safety in pregnancy remains undetermined. Collaboration across Europe has the potential to provide a framework for safety evaluation. Prescribers should consider the possibility of pregnancy in women of child-bearing age. Careful review of maternal drug use in early pregnancy is essential. Midwives and nurses should be aware of adverse event drug reporting systems, including congenital anomaly registers. © 2011 The Authors. Journal compilation © 2011 Blackwell Publishing Ltd.

  18. Report on the handling of safety information concerning flammable gases and ferrocyanide at the Hanford waste tanks

    International Nuclear Information System (INIS)

    1990-07-01

    This report discusses concerns safety issues, and management at Hanford Tank Farm. Concerns center on the issue of flammable gas generation which could ignite, and on possible exothermic reactions of ferrocyanide compounds which were added to single shell tanks in the 1950's. It is believed that information concerning these issues has been mis-handled and the problems poorly managed

  19. 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.

  20. Socializing Young People to Ethics via Play Experience: Browser Games and Parental Concerns for Safety Online

    Directory of Open Access Journals (Sweden)

    Divina Meigs

    2009-01-01

    Full Text Available This paper considers an online game and its relation to safety and privacy, in order to examine social and ethical issues raised by parental concern over harmful content. To gain real insights on the responsibility of adults, it develops a hands-on approach that takes into account the major stakeholders, especially young people and the related circle of people around them. Therefore the research question that is raised is: how do browser games provide reassurance to parents about their children’s safety and privacy? The issue of safety online is explored in three parts, using an ethnographic research framework: it explores a specific online game, it provides a profile of participants, it analyses their types of actions in relation to safety and privacy, and discusses the results in terms of incidence of risk, peer-monitoring and community control. The findings show that there is a rather strong tendency to self-regulation, but that tendency is partly due to a strong presence of mediating adults and peers. The results are discussed in terms of incidence of risk, peer-monitoring and networked means of control on the one hand, and in terms of scientific contribution to socialization theory on the other hand. They lead to final considerations on the repertoire of ethical strategies set up online and its meaning for the concerns of adults towards online risk as well as the need for policies on regulation and self-regulation. They also lead to extensions on the socialization to norms and the appropriation of ethics by young people.

  1. Notes on the nuclear safety regulations concerning research reactors and use of nuclear fuel material

    International Nuclear Information System (INIS)

    Tanzawa, Tomio

    2014-01-01

    Nuclear regulation system of Japan has drastically reconsidered after the nuclear disaster caused by the reactor accident of Fukushima Daiichi Nuclear Power Plant. As a result a law was enacted to establish a nuclear regulation authority in June 27, 2012, and the laws relating the atomic power were largely revised. In this article, we show major revisions in the laws concerning research reactor facilities and those facilities which treat nuclear fuel materials. It should be noted that the law is only a formality and that the application of the law by persons enables to produces effectiveness. Persons hold the key to the safety. (J.P.N.)

  2. Sports injuries, drowning and exposure to radiation concern Canada Safety Council meeting

    International Nuclear Information System (INIS)

    Oliver, Caroline.

    1979-01-01

    Hazards associated with surface sports, aquatic sports and exposure to radiation were considered at a meeting of the Canada Safety Council in late 1979. The session on radiation noted that 6 of 20000 radiation workers wearing dosimeters were exposed to a dose in excess of 5 rem, the annual limit set by the Atomic Energy Control Board. Radiographers were in the job classification receiving the highest doses of ionizing radiation. Concern was expressed for the emission of damaging radiation from broken mercury vapour lamps. Increased regulation rather than training was seen as the most effective solution. (T.I.)

  3. List of reports from the BMFT, CEA, EPRI, JSTA and USNRC concerning reactor safety research

    International Nuclear Information System (INIS)

    1981-09-01

    This list reviews reports from the Federal Republic of Germany, from France, from Japan and from the United States of America concerning special Problems in the field of Reactor Safety Research. According to the cooperation of the Bundesminister fuer Forschung und Technologie (BMFT) with the Commissariat a l'Energie Atomique (CEA) the Japan Science and Technology Agency (JSTA) the Electric Power Research Institute (EPRI) and the United States Nuclear Regulatory Commission these reports are available in the Gesellschaft fuer Reaktorsicherheit (GRS). The list pursues the following order: Country of origin, problem area concerned, according to the Reactor Saftety Research Program of the BMFT, reporting organization. The list of reports appears quarterly. (orig./HP) [de

  4. [The utilization and safety of medicinal plants and crude drugs].

    Science.gov (United States)

    Satake, M

    1998-01-01

    Recently, herbal remedy and health caring food are widely used throughout the generation. These main plant materials have been characterized and classified into 5 categories, by the Ministry of Health and Welfare (MHW), Japanese Government, in 1971, which include 3 medicine divisions and 2 food divisions. These categories, having only limited number of plants, were quite difficult to classify the newly imported plant materials. In order to solve this problem, each category was updated to include new herbal materials in March 1998. Kampo medicines are Japanese traditional medicines, which has been used for the patients mostly by doctors of western medicine and 3 kinds of Kampo prescription had been reevaluated by the drug reevaluation system of Japan. But, along with the expanding consumption of the Kampo medicines in the clinical treatments, several side effects of the Kampo medicines has recently been reported by the collection of adverse reaction data of MHW, these side effects are important signals for believing the safety of natural drugs. The chapter I is definition of medicinal plant and crude drugs, and chapter II is reported of WHO guidelines for the traditional medicines. Chapter III is 4 section; 1. safety of the medicinal plants and crude drugs is included the poisonous plant and the side effect of Kampo medicines, 2. the pesticide for the crude drugs in Japanese Pharmacopoeia, 3. limited test of contamination of microorganisms, 4. Identification of medicinal plant names. Chapter IV is the definition of drugs and food. The chapter V is the drugs type materials used in young generation for hallucinogenic or sexual purpose. Chapter VI is the stance to research work for the new drugs from plant gene resources in the world.

  5. 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

  6. 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.

  7. Cardiovascular Safety Profile of Currently Available Diabetic Drugs

    Science.gov (United States)

    Azimova, Komola; Juan, Zinnia San; Mukherjee, Debabrata

    2014-01-01

    Background Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, underscoring the importance of choosing drugs that do not increase cardiovascular risk and reduce the risk of cardiovascular events. Since 2008, the US Food and Drug Administration has recommended that new drugs for type 2 diabetes undergo clinical trials to demonstrate cardiovascular safety in addition to glycemic benefit. In 2012, the European Medicines Agency issued a similar recommendation. Methods We searched the PubMed, Cochrane CENTRAL, EMBASE, and CINAHL databases from inception through August 2013 and compiled and reviewed the existing data on the cardiovascular safety profiles of currently available diabetic drugs. Results While intensive glycemic control in diabetics has been consistently shown to reduce the risk of microvascular complications, the data on macrovascular risk reduction have not been as clear, and questions have been raised about possible increases in cardiovascular morbidity and mortality. Conclusion Careful selection of drug therapy—paying particular attention to cardiovascular safety—is important in optimizing diabetic therapy. PMID:25598727

  8. Safety Communication Tools and Healthcare Professionals' Awareness of Specific Drug Safety Issues in Europe: A Survey Study.

    Science.gov (United States)

    de Vries, Sieta T; van der Sar, Maartje J M; Coleman, Anna Marie; Escudero, Yvette; Rodríguez Pascual, Alfonso; Maciá Martínez, Miguel-Ángel; Cupelli, Amelia; Baldelli, Ilaria; Šipić, Ivana; Andrić, Adriana; Michan, Line; Denig, Petra; Mol, Peter G M

    2018-03-02

    % aware of the diclofenac issue to 66% of the ivabradine issue). Cardiologists' awareness ranged from 91% for the ivabradine issue to 34% for the valproate issue. Overall, DHPCs were a common source through which GPs (range: 45% of those aware of the contraceptives issue to 60% of those aware of the valproate issue), cardiologists (range: 33% for the contraceptives issue to 61% for the valproate issue), and pharmacists (range: 41% for the contraceptives issue to 51% for the ivabradine issue) had become aware of the specific safety issues, followed by information on websites or in newsletters. GPs, cardiologists, and pharmacists were to a similar extent (highly) familiar with DHPCs, but they differed in awareness levels of specific safety issues. Cardiologists were less aware of safety issues associated with non-cardiology drugs even if these had cardiovascular safety concerns. This implies that additional strategies may be needed to reach specialists when communicating safety issues regarding drugs outside their therapeutic area but with risks related to their field of specialisation. DHPCs were an important source for the different professions to become aware of specific safety issues, but other sources were also often used. NCAs should consider the use of a range of sources when communicating important safety issues to HCPs.

  9. Weight-related concerns related to drug use for women in substance abuse treatment: prevalence and relationships with eating pathology.

    Science.gov (United States)

    Warren, Cortney S; Lindsay, Anne R; White, Emily K; Claudat, Kim; Velasquez, Sara C

    2013-01-01

    Women in substance abuse treatment increasingly report weight-related concerns as motivation for drug use. However, limited research has explored the nature of these concerns or examined whether women in substance abuse treatment with weight-related concerns related to drug use differ from those who do not on variables relevant to eating pathology. Using a sample of 297 women in substance abuse treatment, this study examined two intertwined issues: (1) the prevalence and nature of weight-related concerns related to drug use and (2) whether women who endorse weight-related concerns related to drug use differ from those without weight-related concerns on body dissatisfaction, eating pathology, perceived pressure and internalization of thin-ideal media, and appearance-related drug-use expectancies. Descriptive analyses indicated that the majority of participants were concerned about gaining weight during treatment and/or that weight gain could trigger drug relapse. Analyses of variance revealed that women who reported weight-based concerns (both with regards to weight gain during treatment and relapse potential) endorsed higher levels of body dissatisfaction, dieting, bulimic symptoms, and thin-ideal internalization than women who did not endorse weight-related concerns. Results suggest that substance abuse treatment programs should be aware of and address weight-related concerns around drug use for women. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Study concerning the power plant control and safety equipment by integrated distributed systems

    International Nuclear Information System (INIS)

    Optea, I.; Oprea, M.; Stanescu, P.

    1995-01-01

    The paper deals with the trends existing in the field of nuclear control and safety equipment and systems, proposing a high-efficiency integrated system. In order to enhance the safety of the plant and reliability of the structure system and components, we present a concept based on the latest computer technology with an open, distributed system, connected by a local area network with high redundancy. A modern conception for the control and safety system is to integrate all the information related to the reactor protection, active engineered safeguard and auxiliary systems parameters, offering a fast flow of information between all the agencies concerned so that situations can be quickly assessed. The integrated distributed control is based on a high performance operating system for realtime applications, flexible enough for transparent networking and modular for demanding configurations. The general design considerations for nuclear reactors instrumentation reliability and testing methods for real-time functions under dynamic regime are presented. Taking into account the fast progress in information technology, we consider the replacement of the old instrumentation of Cernavoda-1 NPP by a modern integrated system as an economical and efficient solution for the next units. (Author) 20 Refs

  11. Predictors of likelihood of speaking up about safety concerns in labour and delivery.

    Science.gov (United States)

    Lyndon, Audrey; Sexton, J Bryan; Simpson, Kathleen Rice; Rosenstein, Alan; Lee, Kathryn A; Wachter, Robert M

    2012-09-01

    Despite widespread emphasis on promoting 'assertive communication' by care givers as essential to patient-safety-improvement efforts, little is known about when and how clinicians speak up to address safety concerns. In this cross-sectional study, the authors use a new measure of speaking up to begin exploring this issue in maternity care. The authors developed a scenario-based measure of clinician's assessment of potential harm and likelihood of speaking up in response to perceived harm. The authors embedded this scale in a survey with measures of safety climate, teamwork climate, disruptive behaviour, work stress, and personality traits of bravery and assertiveness. The survey was distributed to all registered nurses and obstetricians practising in two US Labour & Delivery units. The response rate was 54% (125 of 230 potential respondents). Respondents were experienced clinicians (13.7±11 years in specialty). A higher perception of harm, respondent role, specialty experience and site predicted the likelihood of speaking up when controlling for bravery and assertiveness. Physicians rated potential harm in common clinical scenarios lower than nurses did (7.5 vs 8.4 on 2-10 scale; pclimate scores. Differing assessments of potential harms inherent in everyday practice may be a target for teamwork intervention in maternity care.

  12. Modulation of Brain Activity with Noninvasive Transcranial Direct Current Stimulation (tDCS: Clinical Applications and Safety Concerns

    Directory of Open Access Journals (Sweden)

    Haichao Zhao

    2017-05-01

    Full Text Available Transcranial direct current stimulation (tDCS is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children. This review covers the typical characteristics and the underlying neural mechanisms of tDCS treatment in such studies. This is followed by a discussion of safety, especially when the current intensity is increased or the stimulation duration is prolonged. Given such concerns, we provide detailed suggestions regarding safety procedures for tDCS operation. Lastly, future research directions are discussed. They include foci on the development of multi-tech combination with tDCS such as with TMS and fMRI; long-term behavioral and morphological changes; possible applications in other research domains, and more animal research to deepen the understanding of the biological and physiological mechanisms of tDCS stimulation.

  13. 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.

  14. Genetically modified foods: safety, risks and public concerns-a review.

    Science.gov (United States)

    Bawa, A S; Anilakumar, K R

    2013-12-01

    Genetic modification is a special set of gene technology that alters the genetic machinery of such living organisms as animals, plants or microorganisms. Combining genes from different organisms is known as recombinant DNA technology and the resulting organism is said to be 'Genetically modified (GM)', 'Genetically engineered' or 'Transgenic'. The principal transgenic crops grown commercially in field are herbicide and insecticide resistant soybeans, corn, cotton and canola. Other crops grown commercially and/or field-tested are sweet potato resistant to a virus that could destroy most of the African harvest, rice with increased iron and vitamins that may alleviate chronic malnutrition in Asian countries and a variety of plants that are able to survive weather extremes. There are bananas that produce human vaccines against infectious diseases such as hepatitis B, fish that mature more quickly, fruit and nut trees that yield years earlier and plants that produce new plastics with unique properties. Technologies for genetically modifying foods offer dramatic promise for meeting some areas of greatest challenge for the 21st century. Like all new technologies, they also pose some risks, both known and unknown. Controversies and public concern surrounding GM foods and crops commonly focus on human and environmental safety, labelling and consumer choice, intellectual property rights, ethics, food security, poverty reduction and environmental conservation. With this new technology on gene manipulation what are the risks of "tampering with Mother Nature"?, what effects will this have on the environment?, what are the health concerns that consumers should be aware of? and is recombinant technology really beneficial? This review will also address some major concerns about the safety, environmental and ecological risks and health hazards involved with GM foods and recombinant technology.

  15. Research Lasers and Air Traffic Safety: Issues, Concerns and Responsibilities of the Research Community

    Science.gov (United States)

    Nessler, Phillip J., Jr.

    1998-01-01

    The subject of outdoor use of lasers relative to air traffic has become a diverse and dynamic topic. During the past several decades, the use of lasers in outdoor research activities have increased significantly. Increases in the outdoor use of lasers and increases in air traffic densities have changed the levels of risk involved. To date there have been no documented incidents of air traffic interference from research lasers; however, incidents involving display lasers have shown a marked increase. As a result of the national response to these incidents, new concerns over lasers have arisen. Through the efforts of the SAE G-10T Laser Safety Hazards Subcommittee and the ANSI Z136.6 development committee, potential detrimental effects to air traffic beyond the traditional eye damage concerns have been identified. An increased emphasis from the Federal Aviation Administration (FAA), the Center for Devices and Radiological Hazards (CDRH), and the National Transportation Safety Board (NTSB) along with increased concern by the public have resulted in focused scrutiny of potential hazards presented by lasers. The research community needs to rethink the traditional methods of risk evaluation and application of protective measures. The best current approach to assure adequate protection of air traffic is the application of viable hazard and risk analysis and the use of validated protective measures. Standards making efforts and regulatory development must be supported by the research community to assure that reasonable measures are developed. Without input, standards and regulations can be developed that are not compatible with the needs of the research community. Finally, support is needed for the continued development and validation of protective measures.

  16. 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.

  17. Preclinical Data on Efficacy of 10 Drug-Radiation Combinations: Evaluations, Concerns, and Recommendations

    Directory of Open Access Journals (Sweden)

    Helen B. Stone

    2016-02-01

    Full Text Available BACKGROUND: Clinical testing of new therapeutic interventions requires comprehensive, high-quality preclinical data. Concerns regarding quality of preclinical data have been raised in recent reports. This report examines the data on the interaction of 10 drugs with radiation and provides recommendations for improving the quality, reproducibility, and utility of future studies. The drugs were AZD6244, bortezomib, 17-DMAG, erlotinib, gefitinib, lapatinib, oxaliplatin/Lipoxal, sunitinib (Pfizer, Corporate headquarters, New York, NY, thalidomide, and vorinostat. METHODS: In vitro and in vivo data were tabulated from 125 published papers, including methods, radiation and drug doses, schedules of administration, assays, measures of interaction, presentation and interpretation of data, dosimetry, and conclusions. RESULTS: In many instances, the studies contained inadequate or unclear information that would hamper efforts to replicate or intercompare the studies, and that weakened the evidence for designing and conducting clinical trials. The published reports on these drugs showed mixed results on enhancement of radiation response, except for sunitinib, which was ineffective. CONCLUSIONS: There is a need for improved experimental design, execution, and reporting of preclinical testing of agents that are candidates for clinical use in combination with radiation. A checklist is provided for authors and reviewers to ensure that preclinical studies of drug-radiation combinations meet standards of design, execution, and interpretation, and report necessary information to ensure high quality and reproducibility of studies. Improved design, execution, common measures of enhancement, and consistent interpretation of preclinical studies of drug-radiation interactions will provide rational guidance for prioritizing drugs for clinical radiotherapy trials and for the design of such trials.

  18. 75 FR 2926 - Pipeline Safety: Reporting Drug and Alcohol Test Results for Contractors and Multiple Operator...

    Science.gov (United States)

    2010-01-19

    .... PHMSA-2009-0408] Pipeline Safety: Reporting Drug and Alcohol Test Results for Contractors and Multiple... Materials Safety Administration (PHMSA), Office of Pipeline Safety (OPS), is modifying the Drug & Alcohol... begin collecting annual drug and alcohol testing data for contractor employees with Management...

  19. 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.

  20. 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

  1. 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....

  2. ‘Saying it without words’: a qualitative study of oncology staff's experiences with speaking up about safety concerns

    Science.gov (United States)

    Schwappach, D L B; Gehring, K

    2014-01-01

    Objectives To explore the experiences of oncology staff with communicating safety concerns and to examine situational factors and motivations surrounding the decision whether and how to speak up using semistructured interviews. Setting 7 oncology departments of six hospitals in Switzerland. Participants Diverse sample of 32 experienced oncology healthcare professionals. Results Nurses and doctors commonly experience situations which raise their concerns and require questioning, clarifying and correcting. Participants often used non-verbal communication to signal safety concerns. Speaking-up behaviour was strongly related to a clinical safety issue. Most episodes of ‘silence’ were connected to hygiene, isolation and invasive procedures. In contrast, there seemed to exist a strong culture to communicate questions, doubts and concerns relating to medication. Nearly all interviewees were concerned with ‘how’ to say it and in particular those of lower hierarchical status reflected on deliberate ‘voicing tactics’. Conclusions Our results indicate a widely accepted culture to discuss any concerns relating to medication safety while other issues are more difficult to voice. Clinicians devote considerable efforts to evaluate the situation and sensitively decide whether and how to speak up. Our results can serve as a starting point to develop a shared understanding of risks and appropriate communication of safety concerns among staff in oncology. PMID:24838725

  3. 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.

  4. Identifying Health and Safety Concerns in Southeast Asian Immigrant Nail Salon Workers.

    Science.gov (United States)

    White, Hannah; Khan, Khalid; Lau, Christine; Leung, Holden; Montgomery, Dede; Rohlman, Diane S

    2015-01-01

    Nail salon workers are exposed to a variety of toxic chemicals at levels that remain unreported and have undetermined health consequences. The objective of the study was to gather information about the hazards in nail salons along with safety practices and health concerns of nail salon workers. A survey was conducted on 65 nail salon workers who were immigrants from Southeast Asia in Oregon, USA. More than 20% of the participants reported nose irritation and allergies as the most common health problems. Rare and no use of gloves and mask were reported among 72% and 32% of the participants, respectively. A significantly higher number of participants with "fair" or "poor" self-reported general health condition was found among the workers who applied acrylic nails compared with those who were not involved in this application. Findings of the study emphasize the need for more research to determine the relationship between chemical exposures in nail salons and health outcomes.

  5. 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...

  6. 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...

  7. A decade of e-cigarettes: Limited research & unresolved safety concerns.

    Science.gov (United States)

    Kaisar, Mohammad Abul; Prasad, Shikha; Liles, Tylor; Cucullo, Luca

    2016-07-15

    It is well known that tobacco consumption is a leading cause of preventable deaths worldwide and has been linked to major diseases ranging from cancer to chronic obstructive pulmonary disease, atherosclerosis, stroke and a host of neurological/neurodegenerative disorders. In the past decade a number of alternative vaping products have hit the market, rapidly gaining consumers especially among the younger population. Electronic nicotine delivery systems or e-cigarettes have become the sought-after product due to the belief that they are much safer than traditional cigarettes. However, inadequate research and lack of regulatory guidelines for both the manufacturing process and the content of the vaping solution of the e-cigarette has become a major concern. Highly debated and unresolved questions such as whether e-cigarettes may help smokers quit and whether e-cigarettes will promote the use of nicotine among non-smokers add to the confusion of the safety of e-cigarettes. In this review article, we summarize the current understanding (and lack thereof) of the potential health impacts of e-cigarettes. We will also highlight the most recent studies (in vivo/in vitro) which seem to conflict with the broad safety claims put forward by the manufacturers. Finally, we provide potential solutions to overcome the research gap of the short and long-term health impact of e-cigarettes. Published by Elsevier Ireland Ltd.

  8. Predictors of Likelihood of Speaking Up about Safety Concerns in Labour and Delivery

    Science.gov (United States)

    Lyndon, Audrey; Sexton, J. Bryan; Simpson, Kathleen Rice; Rosenstein, Alan; Lee, Kathryn A.; Wachter, Robert M.

    2011-01-01

    Background Despite widespread emphasis on promoting “assertive communication” by caregivers as essential to patient safety improvement efforts, fairly little is known about when and how clinicians speak up to address safety concerns. In this cross-sectional study we use a new measure of speaking up to begin exploring this issue in maternity care. Methods We developed a scenario-based measure of clinician’s assessment of potential harm and likelihood of speaking up in response to perceived harm. We embedded this scale in a survey with measures of safety climate, teamwork climate, disruptive behaviour, work stress, and personality traits of bravery and assertiveness. The survey was distributed to all registered nurses and obstetricians practicing in two US Labour & Delivery units. Results The response rate was 54% (125 of 230 potential respondents). Respondents were experienced clinicians (13.7 ± 11 years in specialty). Higher perception of harm, respondent role, specialty experience, and site predicted likelihood of speaking up when controlling for bravery and assertiveness. Physicians rated potential harm in common clinical scenarios lower than nurses did (7.5 vs. 8.4 on 2–10 scale; p<0.001). Some participants (12%) indicated they were unlikely to speak up despite perceiving high potential for harm in certain situations. Discussion This exploratory study found nurses and physicians differed in their harm ratings, and harm rating was a predictor of speaking up. This may partially explain persistent discrepancies between physicians and nurses in teamwork climate scores. Differing assessments of potential harms inherent in everyday practice may be a target for teamwork intervention in maternity care. PMID:22927492

  9. Exposures Resulting in Safety and Health Concerns for Child Laborers in Less Developed Countries

    Directory of Open Access Journals (Sweden)

    Derek G. Shendell

    2016-01-01

    Full Text Available Objectives. Worldwide, over 200 million children are involved in child labor, with another 20 million children subjected to forced labor, leading to acute and chronic exposures resulting in safety and health (S&H risks, plus removal from formal education and play. This review summarized S&H issues in child labor, including forced or indentured domestic labor as other sectors of child labor. Specifically, we focused on exposures leading to S&H risks. Methods. We used PubMed, Scopus, Science Direct, and Google Scholar. References were in English, published in 1990–2015, and included data focused on exposures and S&H concerns of child labor. Results. Seventy-six journal articles were identified, 67 met criteria, 57 focused on individual countries, and 10 focused on data from multiple countries (comparing 3–83 countries. Major themes of concern were physical exposures including ergonomic hazards, chemical exposure hazards, and missed education. Childhood labor, especially forced, exploitative labor, created a significant burden on child development, welfare, and S&H. Conclusions. More field researche data emphasizing longitudinal quantitative effects of exposures and S&H risks are needed. Findings warranted developing policies and educational interventions with proper monitoring and evaluation data collection, plus multiple governmental, international organization and global economic reform efforts, particularly in lower-income, less developed countries.

  10. Therapeutic drug monitoring in pharmacovigilance and pharmacotherapy safety.

    Science.gov (United States)

    Haen, E

    2011-09-01

    Quantification of serum or plasma concentrations of medications is essential to find out if an adverse drug effect (ADE) is associated with an elevated drug concentration. In former years TDM was therefore often used in pharmacovigilance just to confirm that an ADE that had already occurred was due to an elevated drug plasma concentration without identifying the underlying cause for the surprising high concentration. This old approach of Therapeutic Drug Monitoring (TDM) in pharmacovigilance needs to be revised due to new developments in information technology, new analytical procedures and due to the inclusion of clinical pharmacological expert opinions in the presentation of laboratory medicine results. Today, TDM may be used to prevent ADE, rather than just confirming a suggested cause of an ADE that has happened in the past. This approach means that blood should be drawn for TDM analysis after the pharmacokinetic steady state has been reached (5 times of the elimination half life of the drug) with low to moderate dosages under the intended (poly)medication if the patient is clinically regarded as not belonging to the "normal" patient population. With the availability of reliable automated analytical methods this can be performed at a reasonable price. Funds may be saved to the health care system, because hospitalization will be thereby shortened and expensive diagnoses and treatment of ADE will be avoided. However, this has still to be proven in cross-system studies: Budget will be saved in 2 areas of the health system (hospital stay and drug costs), whereas a much smaller amount of money has to be invested for laboratory analyses in another area. TDM may thus change pharmacovigilance as a tool for monitoring and documentation of ADE to a safety tool in drug therapy for prevention of ADE. Georg Thieme Verlag KG Stuttgart · New York.

  11. 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.

  12. 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

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket Nos. FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and Innovation Act Title VII--Drug Supply Chain; Standards for Admission of Imported Drugs, Registration of...

  13. The role of quantitative safety evaluation in regulatory decision making of drugs.

    Science.gov (United States)

    Chakravarty, Aloka G; Izem, Rima; Keeton, Stephine; Kim, Clara Y; Levenson, Mark S; Soukup, Mat

    2016-01-01

    Evaluation of safety is a critical component of drug review at the US Food and Drug Administration (FDA). Statisticians are playing an increasingly visible role in quantitative safety evaluation and regulatory decision-making. This article reviews the history and the recent events relating to quantitative drug safety evaluation at the FDA. The article then focuses on five active areas of quantitative drug safety evaluation and the role Division of Biometrics VII (DBVII) plays in these areas, namely meta-analysis for safety evaluation, large safety outcome trials, post-marketing requirements (PMRs), the Sentinel Initiative, and the evaluation of risk from extended/long-acting opioids. This article will focus chiefly on developments related to quantitative drug safety evaluation and not on the many additional developments in drug safety in general.

  14. 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.

  15. The effect of globalization of drug manufacturing, production, and sourcing and challenges for American drug safety.

    Science.gov (United States)

    Woo, J; Wolfgang, S; Batista, H

    2008-03-01

    Americans benefit from one of the safest drug supplies and one of the highest standards of consumer protection in the world. Over the past decade, though, a general trend toward globalization of the supply chains for finished pharmaceutical products and active pharmaceutical ingredients has created new challenges for the Food and Drug Administration (FDA) in ensuring the safety and quality of the drug supply. Explosive growth in pharmaceutical manufacturing for the US market is particularly evident in the developing regions of Asia. Manufacturing sites in China and India now comprise approximately 40% of all FDA-registered foreign sites, having increased from 30% in 2002. (In 2001, when legislation first went into effect requiring registration of all foreign drug manufacturing sites, 140 registered sites in China listed 797 drug items for potential importation; as of 1 October 2007, that number had grown to 815 registered sites and well over 3,000 listed items.) In total in 2006, the United States received >145,000 line entries of imported drug products from >160 countries, up from only 1,300 line entries in 2000. FDA regulatory oversight resources (e.g., those allocated to inspection and testing of imports) are being challenged to keep up with the explosive growth of imported drugs. (In 2006, the FDA performed inspections at 212 foreign drug firms. This number has remained relatively consistent over the past 6 years, starting at 249 in 2001 and ranging from 190 to 260 on an annual basis.)

  16. 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.

  17. Reducing HIV Risks Among Active Injection Drug and Crack Users: The Safety Counts Program

    OpenAIRE

    Rotheram-Borus, Mary Jane; Rhodes, Fen; Desmond, Katherine; Weiss, Robert E.

    2009-01-01

    The efficacy of Safety Counts, a CDC-diffused intervention, was reanalyzed. In a quasi experimental, cross-over design, injection drug users (IDU) and crack users in two neighborhoods were assigned by neighborhood to receive individual Voluntary HIV Counseling and Testing or Safety Counts and 78% were reassessed at 5?9?months. Drug users in the Safety Counts program reported significantly greater reductions in risky sex, crack and hard drug use, and risky drug injection. The more sessions of ...

  18. Human biology-based drug safety evaluation: scientific rationale, current status and future challenges.

    Science.gov (United States)

    Kenna, J Gerry

    2017-05-01

    Animal toxicity studies used to assess the safety of new candidate pharmaceuticals prior to their progression into human clinical trials are unable to assess the risk of non-pharmacologically mediated idiosyncratic adverse drug reactions (ADRs), the most frequent of which are drug-induced liver injury and cardiotoxicity. Idiosyncratic ADRs occur only infrequently and in certain susceptible humans, but are caused by many hundreds of different drugs and may lead to serious illness. Areas covered: Idiosyncratic ADRs are initiated by drug-related chemical insults, which cause toxicity due to susceptibility factors that manifest only in certain patients. The chemical insults can be detected using in vitro assays. These enable useful discrimination between drugs that cause high versus low levels of idiosyncratic ADR concern. Especially promising assays, which have been described recently in peer-reviewed scientific literature, are highlighted. Expert opinion: Effective interpretation of in vitro toxicity data requires integration of endpoints from multiple assays, which each address different mechanisms, and must also take account of human systemic and tissue drug exposure in vivo. Widespread acceptance and use of such assays has been hampered by the lack of correlation between idiosyncratic human ADR risk and toxicities observed in vivo in animals.

  19. Safety report concerning Melusine (after power increase to 4 MW). Descriptive part. Volumes 1 and 2

    International Nuclear Information System (INIS)

    Baas, C.; Delcroix, V.; Jacquemain, M.; Marouby, R.; Meunier, C.; De Robien, E.; Rossillon, F.

    1967-03-01

    Construction of Melusine was started in January 1957, It first diverged on July 1, 1958. It operated at: 1 MW from March 1959; 1.4 MW from April 1960; 2 MW from September 1961; 4 MW from December 1965. Various modifications have been made since the reactor was built. They concern: - the addition of a hot cell. - the effluents: 2 reservoirs of 15 m 3 for liquid waste have been installed. The resin regeneration equipment has been completely modified. - the building: offices have been added - experimental zones have been set up in the hall - the electrical supply. - the cooling and purification circuits (installation of a second exchanger, replacement of the primary pumps, creation of a hot layer, etc... ). - the fuel elements (at the moment of the MTR type enriched to 90 per cent). - the swimming-pool (which has been partially equipped with a stainless steel coating). - the core (placing of 'stools', of a diving-board, etc...). - the ventilation: the hall has been de-pressurized during normal working in the event of an accident, the hall can be isolated and a safety circuit can be started up. A chimney has been installed. - the hall (which has been strengthened and sealed more effectively). - the control electronics (modification of the principle, and which are now entirely transistorized). So many changes have been made that the reactor now bears only a slight resemblance to the initial model. It has appeared necessary to make a brief review of these improvements in order to be able to judge more effectively the installations present safety characteristics; these latter are furthermore fairly well known as a result of the experiments carried out not only by the Thermal Transfer Service in Grenoble but also at Cadarache (Cabri) and Toulon (the work of Mr. PASCOUET). (authors) [fr

  20. Food safety concerns deriving from the use of silver based food packaging materials: a case study.

    Directory of Open Access Journals (Sweden)

    Alessandra ePezzuto

    2015-10-01

    Full Text Available The formulation of innovative packaging solutions, exerting a functional antimicrobial role in slowing down food spoilage, is expected to have a significant impact on the food industry, allowing both the maintenance of food safety criteria for longer periods and the reduction of food waste. Different materials are considered able to exert the required antimicrobial activity, among which are materials containing silver. However, challenges exist in the application of silver to food contact materials due to knowledge gaps in the production of ingredients, stability of delivery systems in food matrices and health risks caused by the same properties which also offer the benefits. Aims of the present study were to test the effectiveness and suitability of two packaging systems, one of which contained silver, for packaging and storing Stracchino cheese, a typical Italian fresh cheese, and to investigate if there was any potential for consumers to be exposed to silver, via migration from the packaging to the cheese. Results did not show any significant difference in the effectiveness of the packaging systems on packaged Stracchino cheese, excluding that the active packaging systems exerted an inhibitory effect on the growth of spoilage microorganisms. Moreover, silver migrated into the cheese matrix throughout the storage time (24 days. Silver levels in cheese finally exceeded the maximum established level for the migration of a non-authorised substance through a functional barrier (Commission Regulation (EC No. 450/2009. This result poses safety concerns and strongly suggests the need for more research aimed at better characterizing the new packaging materials in terms of their potential impacts on human health and the environment.

  1. Herbal products containing Hibiscus sabdariffa L., Crataegus spp., and Panax spp.: Labeling and safety concerns.

    Science.gov (United States)

    Nunes, Maria Antónia; Rodrigues, Francisca; Alves, Rita C; Oliveira, Maria Beatriz P P

    2017-10-01

    Herbs have been used from ancient times for infusion preparation based on their potential health effects. In particular, the consumption of Hibiscus sabdariffa L., Crataegus spp. and Panax spp. has been largely associated to cardiovascular benefits. In this work, the label information of 52 herbal products for infusion preparation containing the referred herbs was analyzed and discussed, taking into consideration the European Union regulation for herbal products, which intends to protect public health and harmonize the legal framework in Member States. Details about the cardiovascular-related statements and warning notifications about consumption were considered. Also, regulatory issues and possible herb-drug interactions were explored and discussed. A total of 14 of the 52 herbal products selected presented health claims/statements on the label. Hibiscus was present in the majority of the products and, in some cases, it was mentioned only in the ingredients list and not on the product front-of-pack. Despite the promising outcomes of these plants to modulate cardiovascular risk markers, consumers with some sort of cardiovascular dysfunction and/or under medication treatments should be aware to carefully analyze the labels and consult additional information related to these herbal products. Manufacturers have also a huge responsibility to inform consumers by presenting awareness statements. Lastly, health professionals must advise and alert their patients about possible interactions that could occur between the concomitant consumption of drugs and herbs. Overall, there is still a real need of additional studies and clinical trials to better understand herbs effects and establish a science-based guidance to assess their safety. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Radiation Safety in the Neonatal Intensive Care Unit: Too Little or Too Much Concern?

    Directory of Open Access Journals (Sweden)

    Cheng-Chung Yu

    2010-12-01

    Full Text Available With rising numbers of extremely premature infants in the neonatal intensive care unit (NICU who require multiple radiologic examinations for their complex medical conditions, concerns the risk of radiation exposure become a more prevalent issue. The biological effects from cumulative doses of both primary and secondary radiation can be particularly troubling for very premature babies due to their inherent sensitivity to both iatrogenic and environmental insults. Similarly, radiologic studies performed in the NICU pose potentially significant exposure risks to caretakers and to the families of patients often present in the NICU during these examinations. The purpose of this article is to critically review the available literature regarding current exposure rates in the NICU, address the validity of radiation exposure concerns, and suggest areas for improvement. With few exceptions, studies reveal that there were only low doses of radiation derived from any single radiographic examination in standard NICUs and that the radiation dosage used was in compliance with recommendations made by the Commission of European Communities (EC and International Commission on Radiological Protection (ICRP. However, there were wide variations in the radiation dose per single examination (mean entrance skin doses ranged from 15 to 73.6 μGy and in the frequency (mean ranged from 3.2 to 31 examinations per infant of those examinations. Studies also reported low secondary exposure rates from scatter radiation to others present in the NICU during radiographic examinations. Key to limiting unnecessary radiation exposure in the NICU is the employment of proper radiation techniques and safety measures. Thus, adhering to recommendations made by the EC and ICRP can help to reduce the anxiety of patients' families and medical staff regarding their risks from the effects of ionizing radiation in the NICU.

  3. Predicting the Drug Safety for Traditional Chinese Medicine through a Comparative Analysis of Withdrawn Drugs Using Pharmacological Network.

    Science.gov (United States)

    Xue, Mengzhu; Zhang, Shoude; Cai, Chaoqian; Yu, Xiaojuan; Shan, Lei; Liu, Xiaofeng; Zhang, Weidong; Li, Honglin

    2013-01-01

    As the major issue to limit the use of drugs, drug safety leads to the attrition or failure in clinical trials of drugs. Therefore, it would be more efficient to minimize therapeutic risks if it could be predicted before large-scale clinical trials. Here, we integrated a network topology analysis with cheminformatics measurements on drug information from the DrugBank database to detect the discrepancies between approved drugs and withdrawn drugs and give drug safety indications. Thus, 47 approved drugs were unfolded with higher similarity measurements to withdrawn ones by the same target and confirmed to be already withdrawn or discontinued in certain countries or regions in subsequent investigations. Accordingly, with the 2D chemical fingerprint similarity calculation as a medium, the method was applied to predict pharmacovigilance for natural products from an in-house traditional Chinese medicine (TCM) database. Among them, Silibinin was highlighted for the high similarity to the withdrawn drug Plicamycin although it was regarded as a promising drug candidate with a lower toxicity in existing reports. In summary, the network approach integrated with cheminformatics could provide drug safety indications effectively, especially for compounds with unknown targets or mechanisms like natural products. It would be helpful for drug safety surveillance in all phases of drug development.

  4. Predicting the Drug Safety for Traditional Chinese Medicine through a Comparative Analysis of Withdrawn Drugs Using Pharmacological Network

    Directory of Open Access Journals (Sweden)

    Mengzhu Xue

    2013-01-01

    Full Text Available As the major issue to limit the use of drugs, drug safety leads to the attrition or failure in clinical trials of drugs. Therefore, it would be more efficient to minimize therapeutic risks if it could be predicted before large-scale clinical trials. Here, we integrated a network topology analysis with cheminformatics measurements on drug information from the DrugBank database to detect the discrepancies between approved drugs and withdrawn drugs and give drug safety indications. Thus, 47 approved drugs were unfolded with higher similarity measurements to withdrawn ones by the same target and confirmed to be already withdrawn or discontinued in certain countries or regions in subsequent investigations. Accordingly, with the 2D chemical fingerprint similarity calculation as a medium, the method was applied to predict pharmacovigilance for natural products from an in-house traditional Chinese medicine (TCM database. Among them, Silibinin was highlighted for the high similarity to the withdrawn drug Plicamycin although it was regarded as a promising drug candidate with a lower toxicity in existing reports. In summary, the network approach integrated with cheminformatics could provide drug safety indications effectively, especially for compounds with unknown targets or mechanisms like natural products. It would be helpful for drug safety surveillance in all phases of drug development.

  5. 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

  6. Is formocresol obsolete? A fresh look at the evidence concerning safety issues.

    Science.gov (United States)

    Milnes, Alan R

    2008-01-01

    Concern has been expressed about the safety of formocresol use in pediatric dentistry Formaldehyde, a primary component in formocresol, is a hazardous substance and is considered a probable human carcinogen by the International Agency for Research on Cancer, Health Canada, the Agency for Toxic Substances and Disease Registry in the U.S. Department of Health and Human Services, and the U.S. Environmental Protection Agency Humans inhale and ingest formaldehyde daily however, and produce formaldehyde during cellular metabolism. The human body is physiologically equipped to handle formaldehyde through multiple conversion pathways. The resultant single carbon atom released during metabolism is deposited in the "1-carbon pool," which, in turn, is used for the biosynthesis of macromolecules including DNA and RNA. Reevaluation of earlier research that examined potential health risks associated with formaldehyde exposure has shown that this research was based on flawed assumptions, which resulted in erroneous conclusions. The purpose of this review was to examine more recent research about formaldehyde metabolism, phormacokinetics, and corcinogenicity. These results indicated that formaldehyde is probably not a potent human carcinogen under low exposure conditions. Extrapolation of these research results to pediatric dentistry suggests an inconsequential risk associated with formaldehyde use in pediatric pulp therapy/

  7. Radiation safety concerns and diagnostic reference levels for computed tomography scanners in Tamil Nadu.

    Science.gov (United States)

    Livingstone, Roshan S; Dinakaran, Paul M

    2011-01-01

    Radiation safety in computed tomography (CT) scanners is of concern due its widespread use in the field of radiological imaging. This study intends to evaluate radiation doses imparted to patients undergoing thorax, abdomen and pelvic CT examinations and formulate regional diagnostic reference levels (DRL) in Tamil Nadu, South India. In-site CT dose measurement was performed in 127 CT scanners in Tamil Nadu for a period of 2 years as a part of the Atomic Energy Regulatory Board (AERB)-funded project. Out of the 127 CT scanners,13 were conventional; 53 single-slice helical scanners (SSHS); 44 multislice CT (MSCT) scanners; and 17 refurbished scanners. CT dose index (CTDI) was measured using a 32-cm polymethyl methacrylate (PMMA)-body phantom in each CT scanner. Dose length product (DLP) for different anatomical regions was generated using CTDI values. The regional DRLs for thorax, abdomen and pelvis examinations were 557, 521 and 294 mGy cm, respectively. The mean effective dose was estimated using the DLP values and was found to be 8.04, 6.69 and 4.79 mSv for thorax, abdomen and pelvic CT examinations, respectively. The establishment of DRLs in this study is the first step towards optimization of CT doses in the Indian context.

  8. Radiation safety concerns and diagnostic reference levels for computed tomography scanners in Tamil Nadu

    Directory of Open Access Journals (Sweden)

    Livingstone Roshan

    2011-01-01

    Full Text Available Radiation safety in computed tomography (CT scanners is of concern due its widespread use in the field of radiological imaging. This study intends to evaluate radiation doses imparted to patients undergoing thorax, abdomen and pelvic CT examinations and formulate regional diagnostic reference levels (DRL in Tamil Nadu, South India. In-site CT dose measurement was performed in 127 CT scanners in Tamil Nadu for a period of 2 years as a part of the Atomic Energy Regulatory Board (AERB-funded project. Out of the 127 CT scanners,13 were conventional; 53 single-slice helical scanners (SSHS; 44 multislice CT (MSCT scanners; and 17 refurbished scanners. CT dose index (CTDI was measured using a 32-cm polymethyl methacrylate (PMMA-body phantom in each CT scanner. Dose length product (DLP for different anatomical regions was generated using CTDI values. The regional DRLs for thorax, abdomen and pelvis examinations were 557, 521 and 294 mGy cm, respectively. The mean effective dose was estimated using the DLP values and was found to be 8.04, 6.69 and 4.79 mSv for thorax, abdomen and pelvic CT examinations, respectively. The establishment of DRLs in this study is the first step towards optimization of CT doses in the Indian context.

  9. 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

  10. Immortal time bias in drug safety cohort studies: spontaneous abortion following nonsteroidal antiinflammatory drug exposure.

    Science.gov (United States)

    Daniel, Sharon; Koren, Gideon; Lunenfeld, Eitan; Levy, Amalia

    2015-03-01

    Experimental research of drug safety in pregnancy is generally not feasible because of ethical issues. Therefore, most of the information about drug safety in general and teratogenicity in particular is obtained through observational studies, which require careful methodologic design to obtain unbiased results. Immortal time bias occurs when some cases do not "survive" sufficient time in the study, and as such, they have reduced chances of being defined as "exposed" simply because the durations of their follow-ups were shorter. For example, studies that examine the risk for spontaneous abortions in women exposed to a drug during pregnancy are susceptible to immortal time bias because the chance of drug exposure increases the longer a pregnancy lasts. Therefore, the drug tested may falsely be found protective against the outcome tested. The objective of the current study was to illustrate the extent of immortal time bias using a cohort study of pregnancies assessing the risk for spontaneous abortions following nonsteroidal antiinflammatory drug exposure. We assembled 3 databases containing data on spontaneous abortions, births and drug dispensions to create the present study's cohort. The risk for spontaneous abortion was assessed using 2 statistical analysis methods that were compared for 2 definitions of exposure (dichotomous, exposed vs unexposed, regular Cox regression vs Cox regression with time-varying exposure). Significant differences were found in the risk for spontaneous abortions between the 2 statistical methods, both for groups and for most specific nonsteroidal antiinflammatory drugs (nonselective Cox inhibitors - hazard ratio, 0.70; 95% confidence interval, 0.61-0.94 vs hazard ratio, 1.10; 95% confidence interval, 0.99-1.22 for dichotomous vs time-varying exposure analyses, respectively). Furthermore, a significant correlation was found between the median misclassified immortal time for each drug and the extent of the bias. Immortal time bias can

  11. Enacting laws concerning radiation safety management for students using X-rays and electron beams under 1 MeV

    International Nuclear Information System (INIS)

    Nishizawa, Kunihide; Shibata, Michihiro; Saze, Takuya

    2004-01-01

    Laws concerning radiation safety management were analyzed from the point of view of defining precisely what is meant by radiation and what is meant by the subject. There are no laws to protect students from radiation hazards when using X-rays and electron beams under 1 MeV for research and/or education. The Law concerning Technical Standards for Preventing Radiation Hazards gives the authorities the power to enact new rules and regulations that will protect the students. The Radiation Council must take charge for enactment of all laws regarding radiation safety management. (author)

  12. Spontaneous ADR reporting and drug safety signal induction in perspective. To honour Professor Jens Schou.

    Science.gov (United States)

    Edwards, I R

    2000-01-01

    Drug safety signals will continue to come mainly from the reporting of alert clinicians and every effort should be made to enhance this and to ease the process. The use of multipurpose health databases for finding signals has much potential, if they are better planned so that the appropriate data is captured and examined routinely. Consumer reports give us information about their concerns and should not be ignored. Better information is needed on poisoning, drug misuse and on herbal remedies. The analysis of signals must be improved and speeded up, if we are even to maintain our current safety standards, given the global release of 'blockbuster products'. Benefit-risk analysis of medicines needs to be better understood in relationship to actual clinical use, both from an individual and public health perspective. Such analysis should become more logical rather than just listing the benefits and risks, and then expressing an essentially unsupported opinion. This is essential if therapies are to be compared, and their costs justified. The communication of medicines safety and benefit-risk information to clinicians, other health professionals and patients is an area where there needs to be considerable improvements. We need to be better informed about the consequences of guidance and warnings given, so that we may improve the service we offer to recipients. In the future, information technology, which provides exciting possibilities with what it offers now, will help us with all the above challenges.

  13. Turkish Final Year Medical Students' Exposure to and Attitudes Concerning Drug Company Interactions: A Perspective from a Minimally Regulated Environment for Medical Students.

    Directory of Open Access Journals (Sweden)

    Nazim Ercument Beyhun

    Full Text Available Interactions between drug companies and medical students may affect evidence-based medical practice and patient safety. The aim of this study was to assess drug company-medical student interactions in a medical faculty where limited specific national or institutional regulations apply between drug companies and medical students. The objectives of the study were to determine the exposure and attitudes of final year medical students in terms of drug company-medical student and physician interactions, to identify factors affecting those attitudes and to provide data for policymakers working on the regulation of interactions between drug companies and medical students. This anonymous questionnaire-based study of 154 medical final year medical students at the Karadeniz Technical University Medical Faculty, Trabzon, Turkey, in April and May 2015 attracted a response rate of 92.2% (n/N, 154/164. Exposure to interaction with a pharmaceutical representative was reported by 90.3% (139/154 of students, and 68.8% (106/154 reported experiencing such interaction alongside a resident. In addition, 83.7% (128/153 of students reported an interaction during internship. Furthermore, 69.9% (107/153 of students agreed that interactions influence physicians' prescription preferences, while 33.1% (51/154 thought that a medical student should never accept a gift from a drug company and 24.7% (38/154 agreed with the proposition that "drug companies should not hold activities in medical faculties". Students with rational prescription training expressed greater agreement with the statement "I am skeptical concerning the information provided by drug companies during interactions" than those who had not received such training, and this finding was supported by logistic regression [O.R.(C.I, p -3.7(1.2-11.5, p = 0.022]. Acceptance of advertisement brochures was found to significantly reduce the level of agreement with the proposition that "A physician should not accept any

  14. Caregivers' perception of drug administration safety for pediatric oncology patients.

    Science.gov (United States)

    Harris, Nariman; Badr, Lina Kurdahi; Saab, Raya; Khalidi, Aziza

    2014-01-01

    Medication errors (MEs) are reported to be between 1.5% and 90% depending on many factors, such as type of the institution where data were collected and the method to identify the errors. More significantly, the risk for errors with potential for harm is 3 times higher for children, especially those receiving chemotherapy. Few studies have been published on averting such errors with children and none on how caregivers perceive their role in preventing such errors. The purpose of this study was to evaluate pediatric oncology patient's caregivers' perception of drug administration safety and their willingness to be involved in averting such errors. A cross-sectional design was used to study a nonrandomized sample of 100 caregivers of pediatric oncology patients. Ninety-six of the caregivers surveyed were well informed about the medications their children receive and were ready to participate in error prevention strategies. However, an underestimation of potential errors uncovered a high level of "trust" for the staff. Caregivers echoed their apprehension for being responsible for potential errors. Caregivers are a valuable resource to intercept medication errors. However, caregivers may be hesitant to actively communicate their fears with health professionals. Interventions that aim at encouraging caregivers to engage in the safety of their children are recommended.

  15. Drug safety awareness in New Zealand: public knowledge and preferred sources for information.

    Science.gov (United States)

    Brounéus, Fredrik; Macleod, Greg; Maclennan, Karyn; Parkin, Lianne; Paul, Charlotte

    2012-12-01

    To make informed choices about medical treatment options, patients and consumers need knowledge about the benefits and the risks of drugs. Little is known about levels of drug safety knowledge or preferred sources of drug safety information in general population samples. To explore drug safety knowledge, experience of adverse drug reactions (ADRs), and preferred sources for drug safety information in the New Zealand public. We undertook a telephone survey of a random sample of adults (N=87) in the Dunedin area of New Zealand. Although 47% of those currently or recently using prescription or over-the-counter drugs (N=83) were unable to recall any safety information at all about the medicine they were taking, 84% felt confident they could use these medicines in a safe way. The experience of at least one ADR during the last five years was reported by 40%. The five most preferred sources for drug safety information among all participants were: doctor (92%), pharmacist (76%), information on/inside the medicine package (66%), nurse (57%), and the internet (41%). Our results add to findings from specific patient groups to show that there is a low level of drug safety knowledge in the general population. Primary health care practitioners have a recognised and vital part to play in promoting drug safety awareness.

  16. Addiction and Women Gender Differences Concerning Drug Abuse and its Treatment

    Directory of Open Access Journals (Sweden)

    Fatemeh Safari

    2003-05-01

    Full Text Available This article focuses on the quantitative grounds for the emergence and spread of addiction among women, its medical, social and psychological problems, impediments for the treatment of addiction among women as well as gender differences concerning drug abuse and its treatment. This article is a translation of a statistical research on addiction among women and a number of other researches. Based on conclusions drawn from the said researches, women become inclined to addiction mostly by their husbands due to their cordial relationships. Moreover, the negative attitudes of peer groups can overshadow girls and women more than boys and men. From the viewpoint of psychological disorders, the relationship between disorders resulting from psychological pressure after an incident and addiction is stronger among girls and women compared to boys and men. Addiction among women in addition to certain ailments such as malnutrition, hypertension and cancer, can expose them to dangerous diseases such as Hepatitis and AIDS. There is more possibility for addicted women to be infected with AIDS and other sexually transmitted diseases compared to men and they are more exposed to female ailments compared to other women. As far as treatment impediments are concerned, women face a greater social stigma due to their addiction compared to men. Social approach considering addicted women as an indecent person is a major impediment for their treatment. Taking care of the child is also another obstacle for their treatment. There is less possibility for women to receive support from their families for quitting their addiction compared to men. Treatment programs also unwantedly may create obstacles for the treatment of women such as financial constraints, administrative bureaucracy, concentration of treatment programs for men and lack of sensitivity towards women’s addiction. The psychological impediments to treatment include internalizing the notion that addiction is a

  17. 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

  18. How changes in drug-safety regulations affect the way drug and biotech companies invest in innovation.

    Science.gov (United States)

    Reed, Shelby D; Califf, Robert M; Schulman, Kevin A

    2006-01-01

    Changes in the economics of product development resulting from heightened safety regulations could have a sizable negative impact on drug and biotechnology companies' decisions about investing in innovation. We developed a model to compare the potential economic effects of pre- and postmarketing strategies to identify safety problems with new drugs. Although expanding Phase III clinical testing and postmarketing safety surveillance are not perfect substitutes, our findings suggest that even a large increase in funding for the latter will have a relatively small adverse impact on investment decisions by drug companies and venture capital firms, compared with the former.

  19. 75 FR 4305 - Regulatory Guidance Concerning the Applicability of the Federal Motor Carrier Safety Regulations...

    Science.gov (United States)

    2010-01-27

    ..., safety advocacy groups, senior law enforcement officials, the telecommunications industry, and the transportation industry suggest there is widespread support for a ban against texting while driving. However...

  20. 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

  1. 21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

    Science.gov (United States)

    2010-04-01

    ... convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug... are available on the Internet at http://www.fda.gov/medwatch/index.html. (e) Patient privacy...

  2. Trade-offs between voice and silence: a qualitative exploration of oncology staff's decisions to speak up about safety concerns.

    Science.gov (United States)

    Schwappach, David L B; Gehring, Katrin

    2014-07-14

    Research suggests that "silence", i.e., not voicing safety concerns, is common among health care professionals (HCPs). Speaking up about patient safety is vital to avoid errors reaching the patient and thus to prevent harm and also to improve a culture of teamwork and safety. The aim of our study was to explore factors that affect oncology staff's decision to voice safety concerns or to remain silent and to describe the trade-offs they make. In a qualitative interview study with 32 doctors and nurses from 7 oncology units we investigated motivations and barriers to speaking up towards co-workers and supervisors. An inductive thematic content analysis framework was applied to the transcripts. Based on the individual experiences of participants, we conceptualize the choice to voice concerns and the trade-offs involved. Preventing patients from serious harm constitutes a strong motivation to speaking up but competes with anticipated negative outcomes. Decisions whether and how to voice concerns involved complex considerations and trade-offs. Many respondents reflected on whether the level of risk for a patient "justifies" the costs of speaking up. Various barriers for voicing concerns were reported, e.g., damaging relationships. Contextual factors, such as the presence of patients and co-workers in the alarming situation, affect the likelihood of anticipated negative outcomes. Speaking up to well-known co-workers was described as considerably easier whereas "not knowing the actor well" increases risks and potential costs of speaking up. While doctors and nurses felt strong obligation to prevent errors reaching individual patients, they were not engaged in voicing concerns beyond this immediacy. Our results offer in-depth insight into fears and conditions conducive of silence and voicing and can be used for educational interventions and leader reinforcement.

  3. International Drug Trafficking--a Growing National Security Concern for Low Intensity Conflict

    Science.gov (United States)

    1990-03-01

    take drugs occasionally, but can and do stop, either voluntarily or under some compulsion . There may be a small number of people who use drugs...largely market function influenced by the variable "supply" of drug sellers and the variable "demand" of drug buyers . So far, so good. But it is just as

  4. We have to eat, right? : food safety concerns and shopping for daily vegetables in modernizing Vietnam

    NARCIS (Netherlands)

    Wertheim-Heck, S.C.O.

    2015-01-01

    This thesis analyses how people during everyday life confront real food safety risks that are difficult to influence and come to grips with and focuses on food safety risks in modernizing Vietnam. Over the past 40 years Vietnam has developed from war torn country with a highly centralized planned

  5. We have to eat, right? : food safety concerns and shopping for daily vegetables in modernizing Vietnam

    NARCIS (Netherlands)

    Wertheim-Heck, S.C.O.

    2015-01-01

    This thesis analyses how people during everyday life confront real food safety risks that are difficult to influence and come to grips with and focuses on food safety risks in modernizing Vietnam.

    Over the past 40 years Vietnam has developed from war torn country with a highly centralized

  6. Drug safety surveillance in China and other countries: a review and comparison.

    Science.gov (United States)

    Du, Wenmin; Guo, Jeff J; Jing, Yonghua; Li, Xing; Kelton, Christina M L

    2008-03-01

    Drug safety and postmarketing surveillance have become important public health issues in China. This study reviews the relatively new drug safety surveillance system in China and compares it with the systems in the United States and Europe. An extensive literature review was conducted in the following four areas: 1) the organizational structure of the State Food and Drug Administration (SFDA) in China; 2) the development of an adverse drug reaction (ADR) monitoring system in China; 3) regulatory issues related to drug safety in China; and 4) similarities and differences between drug safety surveillance in China and surveillance in the United States and Europe. The SFDA oversees an extensive network of drug safety "watchdogs," including the China National Center for ADR Monitoring and 32 regional centers throughout China. China's system has faced a number of recent challenges. It has had to respond quickly to the withdrawal of various high-profile drugs like Vioxx (rofecoxib) and Baycol (cerivastatin) from other markets. Together with China's Ministry of Health, the SFDA has faced several unique drug safety events. Three of those events, involving the injectable form of the heartleaf houttuyinia herb (Yu Xing Cao), Armillarisni A injections, and clindamycin glucose infusions (Xinfu), are discussed. The rapid development of drug safety surveillance in China is manifested in extensive organizational structure, development of large databases, and laws and regulations supporting drug safety. The two major laws are the China Drug Administration Law issued in February 2001 and the Regulation for the Administration of ADR Reporting and Monitoring issued in March 2004. The study also discusses and compares recent developments in drug safety surveillance in the United States and the European Union. These developments will most likely have implications for the Chinese system in the near future. While postmarketing surveillance guidelines are not yet available in China, we

  7. 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.

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

    Science.gov (United States)

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

    2010-03-01

    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.

  9. 78 FR 76443 - Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over...

    Science.gov (United States)

    2013-12-17

    ... and Drug Administration 21 CFR Parts 310 and 333 Safety and Effectiveness of Consumer Antiseptics... Docket No. 1975N-0183H) RIN 0910-AF69 Safety and Effectiveness of Consumer Antiseptics; Topical... monograph or proposed rule (the 1994 TFM) for over-the-counter (OTC) antiseptic drug products. In this...

  10. [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.

  11. Annual Report 1999 concerning the nuclear safety and radiological protection in the Swiss nuclear installations

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-08-15

    The report presents detailed information about the nuclear safety and radiological protection in the Swiss nuclear power plants, the central interim storage at Wuerenlingen, the Paul Scherrer Institute (PSI) and other nuclear installations in Switzerland.

  12. Annual Report 1998 concerning the nuclear safety and radiological protection in the Swiss nuclear installations

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-05-01

    The report presents detailed information about the nuclear safety and radiological protection in the Swiss nuclear power plants, the central interim storage at Wuerenlingen, the Paul Scherrer Institute (PSI) and other nuclear installations in Switzerland.

  13. Annual report 1996 concerning the nuclear safety and radiological protection in the Swiss nuclear installations

    International Nuclear Information System (INIS)

    1997-05-01

    The report presents detailed information about the nuclear safety and radiological protection in the Swiss nuclear power plants, the central interim storage at Wuerenlingen, the Paul Scherrer Institute (PSI) and other nuclear installations in Switzerland. figs., tabs., refs

  14. Annual Report 1999 concerning the nuclear safety and radiological protection in the Swiss nuclear installations

    International Nuclear Information System (INIS)

    2000-08-01

    The report presents detailed information about the nuclear safety and radiological protection in the Swiss nuclear power plants, the central interim storage at Wuerenlingen, the Paul Scherrer Institute (PSI) and other nuclear installations in Switzerland

  15. Annual report 1996 concerning the nuclear safety and radiological protection in the Swiss nuclear installations

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-05-01

    The report presents detailed information about the nuclear safety and radiological protection in the Swiss nuclear power plants, the central interim storage at Wuerenlingen, the Paul Scherrer Institute (PSI) and other nuclear installations in Switzerland. figs., tabs., refs.

  16. Annual Report 1998 concerning the nuclear safety and radiological protection in the Swiss nuclear installations

    International Nuclear Information System (INIS)

    1999-05-01

    The report presents detailed information about the nuclear safety and radiological protection in the Swiss nuclear power plants, the central interim storage at Wuerenlingen, the Paul Scherrer Institute (PSI) and other nuclear installations in Switzerland

  17. We have to eat, right? : food safety concerns and shopping for daily vegetables in modernizing Vietnam

    OpenAIRE

    Wertheim-Heck, S.C.O.

    2015-01-01

    This thesis analyses how people during everyday life confront real food safety risks that are difficult to influence and come to grips with and focuses on food safety risks in modernizing Vietnam. Over the past 40 years Vietnam has developed from war torn country with a highly centralized planned economy ranking among the world’s most impoverished nations to a socialist-oriented market economic power house, currently ranking highest among the world’s largest growth economies. Throughout this ...

  18. [The issue of harm reduction in Polish legislation concerning drug addiction. A comparative study].

    Science.gov (United States)

    Sobeyko, Justyna

    2008-01-01

    The aim of work is the assessment of legal permissibility for health and social harm reduction programmes resulting from drug use in the context of the polish legislation on narcotic drug use and drug addiction. The thesis outlines harm reduction programmes implemented worldwide, role of penal code in counteracting both narcotic drug supply and demand, attitude of United Nations and European Union to the drug problem including harm reduction programmes, solutions adopted in the selected European Union member states. The main part of the thesis presents the evolution of polish legislation regarding drug use and analysis of legal permissibility for harm reduction programmes in this context. The conclusion inferred is the statement that implementation of the harm reduction programmes requires a certain minimal depenalisation of the drug use by a legislator and the fact that restrictive legal system impedes programme realization. Thus the thesis postulates depenalisation of small drug quantities for personal use.

  19. Current regulatory developments concerning the implementation of probabilistic safety analyses for external hazards in Germany

    International Nuclear Information System (INIS)

    Krauss, Matias; Berg, Heinz-Peter

    2014-01-01

    The Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) initiated in September 2003 a comprehensive program for the revision of the national nuclear safety regulations which has been successfully completed in November 2012. These nuclear regulations take into account the current recommendations of the International Atomic Energy Agency (IAEA) and Western European Nuclear Regulators Association (WENRA). In this context, the recommendations and guidelines of the Nuclear Safety Standards Commission (KTA) and the technical documents elaborated by the respective expert group on Probabilistic Safety Analysis for Nuclear Power Plants (FAK PSA) are being updated or in the final process of completion. A main topic of the revision was the issue external hazards. As part of this process and in the light of the accident at Fukushima and the findings of the related actions resulting in safety reviews of nuclear power plants at national level in Germany and on European level, a revision of all relevant standards and documents has been made, especially the recommendations of KTA and FAK PSA. In that context, not only design issues with respect to events such as earthquakes and floods have been discussed, but also methodological issues regarding the implementation of improved probabilistic safety analyses on this topic. As a result of the revision of the KTA 2201 series 'Design of Nuclear Power Plants against Seismic Events' with their parts 1 to 6, part 1 'Principles' was published as the first standard in November 2011, followed by the revised versions of KTA 2201.2 (soil) and 2201.4 (systems and components) in 2012. The modified the standard KTA 2201.3 (structures) is expected to be issued before the end of 2013. In case of part 5 (seismic instrumentation) and part 6 (post>seismic actions) draft amendments are expected in 2013. The expert group 'Probabilistic Safety Assessments for Nuclear Power Plants' (FAK PSA) is an advisory body of the Federal

  20. Formal training in vaccine safety to address parental concerns not routinely conducted in U.S. pediatric residency programs.

    Science.gov (United States)

    Williams, S Elizabeth; Swan, Rebecca

    2014-05-30

    To determine if U.S. pediatric residency programs provide formal training in vaccine safety to address parental vaccine concerns. An electronic survey was mailed to all members of the Association of Pediatric Program Directors (APPD) to assess (1) if U.S. pediatric residency programs were providing formal vaccine safety training, (2) the content and format of the training if provided, and (3) interest in a training module for programs without training. Two follow-up surveys were mailed at 2 week intervals. Responses to the survey were collected at 4 weeks following the last mailing and analyzed. Logistic regression was used to assess the impact of program size on the likelihood of vaccine safety training. Pearson's chi square was used to compare programs with and without formal vaccine safety training in 5 U.S. regions. The survey was sent to 199 APPD members; 92 completed the survey (response rate 46.2%). Thirty-eight respondents (41%) had formal training in vaccine safety for pediatric residents at their programs; 54 (59%) did not. Of those that did not, the majority (81.5%) were interested in formal vaccine safety training for their residents. Of all respondents, 78% agreed that training in vaccine safety was a high priority for resident education. Thirty-five percent of all respondents agreed that local parental attitudes about vaccines influenced the likelihood of formal vaccine safety training. Most pediatric residency programs surveyed do not include formal training on vaccine safety; yet, such training is supported by pediatric residency program directors as a priority for pediatric residents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. 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.

  2. Evidence of secondary traumatic stress, safety concerns, and burnout among a homogeneous group of judges in a single jurisdiction.

    Science.gov (United States)

    Chamberlain, Jared; Miller, Monica K

    2009-01-01

    Active judges are likely to face numerous work-related experiences (e.g., traumatic cases) that affect performance of their occupational duties. Three occupational experiences (secondary traumatic stress [STS], safety concerns, and burnout) are outlined and applied to the judiciary. Results from nine case study interviews conducted in a single jurisdiction among a homogeneous cohort suggest that judges are at risk of having these experiences. Although no judge demonstrated extreme symptoms, all had low levels of symptoms associated with STS, safety concerns, and/or burnout. Several recommendations are proposed to prevent or minimize these occupational experiences. Recognizing and addressing the problem are essential for the protection of our nation's judges and the integrity of our judicial system.

  3. Food Safety as a contributor to Food Security: global policy concerns & challenges

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Chattu

    2015-12-01

    Full Text Available The theme for World Health Day campaign for this year 2015 is “Food safety: from farm to plate, make food safe”. The day focuses on demonstrating the importance of food safety along the whole length of the food chain in a globalized world, from production and transport, to preparation and consumption (1. Everyone needs food and needs it every day either plant sources or animal sources or both. The food we eat must be nutritious and safe but we often ignore or overlook the issue of food safety. Many cases of food borne diseases either acute poisoning or chronic exposure are largely under reported. In this globalized world, though the food chain extends over thousands of miles from different continents, an error or contamination in one country can affect the health of consumers on the other part of the world. To ensure full impact, these actions must build on principles of government stewardship, engagement of civil society, (2.According to UN, access to a safe and secure food supply is a basic human right. Food safety and food security are interrelated concepts which have an impact on the health outcomes and quality of human lives. As per Food and Agricultural Organization (FAO, Food security is a situation that exists when all people, at all times, have physical, social and economic access to sufficient, safe and nutritious food that meets their dietary needs and food preferences for an active and healthy life, (3. Based on the definition of Food security, four food security dimensions can be identified: food availability, economic and physical access to food, food utilization and stability over time. Apart from that food security is also affected by Poverty and Climate change.Food safety is an umbrella term that encompasses many aspects like food items handling, preparation and storage of food to prevent illness and injury. The other important issues are chemical, microphysical and microbiological aspects of food safety, (4. Control of

  4. A public-professional web-bridge for vaccines and vaccination: user concerns about vaccine safety.

    Science.gov (United States)

    García-Basteiro, Alberto L; Alvarez-Pasquín, María-José; Mena, Guillermo; Llupià, Anna; Aldea, Marta; Sequera, Victor-Guillermo; Sanz, Sergi; Tuells, Jose; Navarro-Alonso, José-Antonio; de Arísteguí, Javier; Bayas, José-María

    2012-05-28

    Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. The TSN bill concerning transparency and safety in the nuclear sector

    International Nuclear Information System (INIS)

    Leger, M.; Lahorgue, M.B.; Strohl, P.

    2009-01-01

    This document gathers together 3 articles whose common purpose is to shed light on the 13. June 2006 French law on transparency and safety in the nuclear sector. This law is fundamental because it gave, for the first time, the legal definitions of basic concepts like nuclear safety, public information or transparency. It also gave a series of principles on which the right in nuclear activities, has to rely: the principle of precaution, the principle of prevention, the principle of remedial action, the principle of who pollutes has to pay, and the principle of public information. The law gives also a clear scheme of the roles and responsibilities in the nuclear sector: the state, the government, the nuclear safety authority, the nuclear facility operator and the land (on which the nuclear facility stands) owner. (A.C.)

  6. Aflatoxins: A Global Concern for Food Safety, Human Health and Their Management.

    Science.gov (United States)

    Kumar, Pradeep; Mahato, Dipendra K; Kamle, Madhu; Mohanta, Tapan K; Kang, Sang G

    2016-01-01

    The aflatoxin producing fungi, Aspergillus spp. , are widely spread in nature and have severely contaminated food supplies of humans and animals, resulting in health hazards and even death. Therefore, there is great demand for aflatoxins research to develop suitable methods for their quantification, precise detection and control to ensure the safety of consumers' health. Here, the chemistry and biosynthesis process of the mycotoxins is discussed in brief along with their occurrence, and the health hazards to humans and livestock. This review focuses on resources, production, detection and control measures of aflatoxins to ensure food and feed safety. The review is informative for health-conscious consumers and research experts in the fields. Furthermore, providing knowledge on aflatoxins toxicity will help in ensure food safety and meet the future demands of the increasing population by decreasing the incidence of outbreaks due to aflatoxins.

  7. Anesthetic drug wastage in the operation room: A cause for concern

    Directory of Open Access Journals (Sweden)

    Kapil Chaudhary

    2012-01-01

    Full Text Available Context: The cost of anesthetic technique has three main components, i.e., disposable supplies, equipments, and anesthetic drugs. Drug budgets are an easily identifiable area for short-term savings. Aim: To assess and estimate the amount of anesthetic drug wastage in the general surgical operation room. Also, to analyze the financial implications to the hospital due to drug wastage and suggest appropriate steps to prevent or minimize this wastage. Settings and Design: A prospective observational study conducted in the general surgical operation room of a tertiary care hospital. Materials and Methods: Drug wastage was considered as the amount of drug left unutilized in the syringes/vials after completion of a case and any ampoule or vial broken while loading. An estimation of the cost of wasted drug was made. Results: Maximal wastage was associated with adrenaline and lignocaine (100% and 93.63%, respectively. The drugs which accounted for maximum wastage due to not being used after loading into a syringe were adrenaline (95.24%, succinylcholine (92.63%, lignocaine (92.51%, mephentermine (83.80%, and atropine (81.82%. The cost of wasted drugs for the study duration was 46.57% (Rs. 16,044.01 of the total cost of drugs issued/loaded (Rs. 34,449.44. Of this, the cost of wastage of propofol was maximum being 56.27% (Rs. 9028.16 of the total wastage cost, followed by rocuronium 17.80% (Rs. 2856, vecuronium 5.23% (Rs. 840, and neostigmine 4.12% (Rs. 661.50. Conclusions: Drug wastage and the ensuing financial loss can be significant during the anesthetic management of surgical cases. Propofol, rocuronium, vecuronium, and neostigmine are the drugs which contribute maximally to the total wastage cost. Judicious use of these and other drugs and appropriate prudent measures as suggested can effectively decrease this cost.

  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. Food Safety as a contributor to Food Security: global policy concerns & challenges

    OpenAIRE

    Vijay Kumar Chattu

    2015-01-01

    The theme for World Health Day campaign for this year 2015 is “Food safety: from farm to plate, make food safe”. The day focuses on demonstrating the importance of food safety along the whole length of the food chain in a globalized world, from production and transport, to preparation and consumption (1). Everyone needs food and needs it every day either plant sources or animal sources or both. The food we eat must be nutritious and safe but we often ignore or overlook the issue of food safet...

  10. Surveys of research projects concerning nuclear facility safety, financed by the Federal Ministry for the Environment, Nature Protection and Reactor Safety, 1987

    International Nuclear Information System (INIS)

    1988-06-01

    Each progress report is a collection of individual reports, categorized by subject matter. They are a documentation of the contractor's progress, rendered by themselves on standardized forms, published, for the sake of general information on progress made in investigations concerning reactor safety, by the project attendance department of the GRS. The individual reports have serial numbers. Each report includes particulars of the objective, work carried out, results obtained and plans for project continuation. (orig.) [de

  11. Geological disposal of nuclear waste: II. From laboratory data to the safety analysis – Addressing societal concerns

    International Nuclear Information System (INIS)

    Grambow, Bernd; Bretesché, Sophie

    2014-01-01

    Highlights: • Models for repository safety can only partly be validated. • Long term risks need to be translated in the context of societal temporalities. • Social sciences need to be more strongly involved into safety assessment. - Abstract: After more than 30 years of international research and development, there is a broad technical consensus that geologic disposal of highly-radioactive waste will provide for the safety of humankind and the environment, now, and far into the future. Safety analyses have demonstrated that the risk, as measured by exposure to radiation, will be of little consequence. Still, there is not yet an operating geologic repository for highly-radioactive waste, and there remains substantial public concern about the long-term safety of geologic disposal. In these two linked papers, we argue for a stronger connection between the scientific data (paper I, Grambow et al., 2014) and the safety analysis, particularly in the context of societal expectations (paper II). In this paper (II), we assess the meaning of the technical results and derived models (paper I) for the determination of the long-term safety of a repository. We consider issues of model validity and their credibility in the context of a much broader historical, epistemological and societal context. Safety analysis is treated in its social and temporal dimensions. This perspective provides new insights into the societal dimension of scenarios and risk analysis. Surprisingly, there is certainly no direct link between increased scientific understanding and a public position for or against different strategies of nuclear waste disposal. This is not due to the public being poorly informed, but rather due to cultural cognition of expertise and historical and cultural perception of hazards to regions selected to host a geologic repository. The societal and cultural dimension does not diminish the role of science, as scientific results become even more important in distinguishing

  12. Safety report concerning the reactor Pegase - volume 1 - Description of the installation - volume 2 - Safety of the installations

    International Nuclear Information System (INIS)

    Lacour, J.

    1964-01-01

    In the first volume: This report is a description of the reactor Pegase, given with a view to examine the safety of the installations. The Cadarache site at which they are situated is briefly described, in particular because of the consequences on the techniques employed for building Pegase. A description is also given of the original aspects of the reactor. The independent loops which are designed for full-scale testing of fuel elements used in natural uranium-gas-graphite reactor systems are described in this report, together with their operational and control equipment. In the second volume: In the present report are examined the accidents which could cause damage to the Pegase reactor installation. Among possible causes of accidents considered are the seismicity of the region, an excessive power excursion of the reactor and a fracture in the sealing of an independent loop. Although all possible precautions have been taken to offset the effects of such accidents, their ultimate consequences are considered here. The importance is stressed of the security action and regulations which, added to the precautions taken for the construction, ensure the safety of the installations. (authors) [fr

  13. 76 FR 30727 - Food and Drug Administration Food Safety Modernization Act: Focus on Inspections and Compliance

    Science.gov (United States)

    2011-05-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0366] Food and Drug Administration Food Safety Modernization Act: Focus on Inspections and Compliance AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting; request for comments. SUMMARY: The...

  14. 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...

  15. Reducing HIV risks among active injection drug and crack users: the safety counts program.

    Science.gov (United States)

    Rotheram-Borus, Mary Jane; Rhodes, Fen; Desmond, Katherine; Weiss, Robert E

    2010-06-01

    The efficacy of Safety Counts, a CDC-diffused intervention, was reanalyzed. In a quasi experimental, cross-over design, injection drug users (IDU) and crack users in two neighborhoods were assigned by neighborhood to receive individual Voluntary HIV Counseling and Testing or Safety Counts and 78% were reassessed at 5-9 months. Drug users in the Safety Counts program reported significantly greater reductions in risky sex, crack and hard drug use, and risky drug injection. The more sessions of Safety Counts attended, the greater were the reductions in risky acts. Different analytic decisions result in very different findings for the same intervention. Safety Counts is an effective intervention for IDU and crack users. Analytic decision of intervention outcomes is highly related to evaluations of an intervention's efficacy.

  16. Position Paper. Safety for K-12 students: United States policy concerning LGBT student safety must provide inclusion

    Directory of Open Access Journals (Sweden)

    April Sanders

    2013-07-01

    Full Text Available Students who identify as lesbian, gay, bisexual, or transgender (LGBT are at risk for harassment due to their sexual orientation or gender identification with over 85% of LGBT students in the United States (US reporting such harassment. These statistics demonstrate one aspect of the significance of this issue, but the cost of human life in some instances has revealed another layer of importance related to a need for safety policies for LGBT students. Even though a need exists for such policies, the practice of heteronormativity found in US policymaking regarding bullying does not protect victims or curb the violence. This essay highlights several recent developments in anti-bullying policy in US schools that shows the existence of heteronormativity, which is not helping to pro-tect LGBT students. By understanding the discrimination encouraged by current policy, future policy can be better shaped to protect LGBT students.

  17. Safety concerning the partial alteration of the fuel reprocessing facility in Power Reactor and Nuclear Fuel Development Corporation

    International Nuclear Information System (INIS)

    1978-01-01

    A report of the Committee on Examination of Nuclear Fuel Safety was presented to the Atomic Energy Commission of Japan, which is concerned with the safety in the partial alteration of the fuel reprocessing facility in the Power Reactor and Nuclear Fuel Development Corporation. Its safety was confirmed. The alteration is as follows. In order to raise the storage capacity of low-level radioactive solid wastes, the second storage is installed. The building for low-level solid waste storage is a ferro-concrete structure, total floor space is 1,260 m 2 , two-storied with one basement floor. The basement floor is for storage, the first floor for receiving, storage, etc., and the second floor for storage and machinery room. The capacity of the second storage is for about 9,500 200 l drums (equivalent to about four years waste discharge). The contents of the safety examination are safety of facilities such as aseismatic property and radiation protection, and effects on the surrounding environment. (Mori, K

  18. A pharmacoepidemiological network model for drug safety surveillance: statins and rhabdomyolysis.

    Science.gov (United States)

    Reis, Ben Y; Olson, Karen L; Tian, Lu; Bohn, Rhonda L; Brownstein, John S; Park, Peter J; Cziraky, Mark J; Wilson, Marcus D; Mandl, Kenneth D

    2012-05-01

    Recent withdrawals of major drugs have highlighted the critical importance of drug safety surveillance in the postmarketing phase. Limitations of spontaneous report data have led drug safety professionals to pursue alternative postmarketing surveillance approaches based on healthcare administrative claims data. These data are typically analysed by comparing the adverse event rates associated with a drug of interest to those of a single comparable reference drug. The aim of this study was to determine whether adverse event detection can be improved by incorporating information from multiple reference drugs. We developed a pharmacological network model that implemented this approach and evaluated its performance. We studied whether adverse event detection can be improved by incorporating information from multiple reference drugs, and describe two approaches for doing so. The first, reported previously, combines a set of related drugs into a single reference cohort. The second is a novel pharmacoepidemiological network model, which integrates multiple pair-wise comparisons across an entire set of related drugs into a unified consensus safety score for each drug. We also implemented a single reference drug approach for comparison with both multi-drug approaches. All approaches were applied within a sequential analysis framework, incorporating new information as it became available and addressing the issue of multiple testing over time. We evaluated all these approaches using statin (HMG-CoA reductase inhibitors) safety data from a large healthcare insurer in the US covering April 2000 through March 2005. We found that both multiple reference drug approaches offer earlier detection (6-13 months) than the single reference drug approach, without triggering additional false positives. Such combined approaches have the potential to be used with existing healthcare databases to improve the surveillance of therapeutics in the postmarketing phase over single-comparator methods

  19. Health and human rights concerns of drug users in detention in Guangxi Province, China.

    Directory of Open Access Journals (Sweden)

    J Elizabeth Cohen

    2008-12-01

    Full Text Available BACKGROUND: Although confinement in drug detoxification ("detox" and re-education through labor (RTL centers is the most common form of treatment for drug dependence in China, little has been published about the experience of drug users in such settings. We conducted an assessment of the impact of detention on drug users' access to HIV prevention and treatment services and consequent threats to fundamental human rights protections. METHODS AND FINDINGS: Chinese government HIV and anti-narcotics legislation and policy documents were reviewed, and in-depth and key informant interviews were conducted with 19 injection drug users (IDUs and 20 government and nongovernmental organization officials in Nanning and Baise, Guangxi Province. Significant contradictions were found in HIV and antinarcotics policies, exemplified by the simultaneous expansion of community-based methadone maintenance therapy and the increasing number of drug users detained in detox and RTL center facilities. IDU study participants reported, on average, having used drugs for 14 y (range 8-23 y and had been confined to detox four times (range one to eight times and to RTL centers once (range zero to three times. IDUs expressed an intense fear of being recognized by the police and being detained, regardless of current drug use. Key informants and IDUs reported that routine HIV testing, without consent and without disclosure of the result, was the standard policy of detox and RTL center facilities, and that HIV-infected detainees were not routinely provided medical or drug dependency treatment, including antiretroviral therapy. IDUs received little or no information or means of HIV prevention, but reported numerous risk behaviors for HIV transmission while detained. CONCLUSIONS: Legal and policy review, and interviews with recently detained IDUs and key informants in Guangxi Province, China, found evidence of anti-narcotics policies and practices that appear to violate human rights

  20. Risks of drowning and safety concerns at the beaches of Karachi--perspective from lifeguards.

    Science.gov (United States)

    Shaikh, Masood Ali

    2014-05-01

    Going to beaches is a popular pastime for many people in Karachi. Lifeguards have been deployed on many beaches for the safety and protection of beachgoers. This cross-sectional survey was conducted to study the opinions and experiences of lifeguards posted at eight beaches of Karachi. Ignorance among beachgoers about how dangerous it could be at seaside, was reported by 19 (61.3%) out of 31 lifeguards interviewed. Lifeguards had to put up with verbal and physical abuse while discharging their duties, with verbal abuse being the universal experience. Improved record keeping of drowning and near-drowning data would help make better evidence-informed beach-safety decisions in Karachi for reducing the morbidity and mortality burden owing to drowning.

  1. Safety basis for selected activities in single-shell tanks with flammable gas concerns. Revision 1

    International Nuclear Information System (INIS)

    Schlosser, R.L.

    1996-01-01

    This is full revision to Revision 0 of this report. The purpose of this report is to provide a summary of analyses done to support activities performed for single-shell tanks. These activities are encompassed by the flammable gas Unreviewed Safety Question (USQ). The basic controls required to perform these activities involve the identification, elimination and/or control of ignition sources and monitoring for flammable gases. Controls are implemented through the Interim Safety Basis (ISB), IOSRs, and OSDs. Since this report only provides a historical compendium of issues and activities, it is not to be used as a basis to perform USQ screenings and evaluations. Furthermore, these analyses and others in process will be used as the basis for developing the Flammable Gas Topical Report for the ISB Upgrade

  2. Results of safety analysis concerning level gauge of pressurizer and related measures for Ohi Nuclear Power Station

    International Nuclear Information System (INIS)

    1979-01-01

    The results of safety analysis concerning the level gauge of a pressurizer and the related measures for the Ohi Nuclear Power Station, which were reported by the Ministry of International Trade and Industry on May 1, 1979, and then investigated and presented by the Nuclear Reactor Safety Special Investigation Committee, are regarded as appropriate by the Atomic Energy Safety Commission (AESC) on May 19, 1979. This analysis and investigation were conducted in relation to the accident in the Three Mile Island (TMI) No. 2 nuclear power plant, occurred on March 28, 1979. In this investigation the influences of the problem concerning the level gauge for a pressurizer of the Ohi Nuclear Power Station on the function and the performance of emergency core cooling system (ECCS) for pressurized water reactors were analyzed, simulating the initial phenomena of the accident in TMI. As for the adequacy of the prior conditions of safety analysis and the analytical codes, the following three points were investigated; 1) the adequacy of accident conditions which were set as the subjects of safety analysis, 2) the adequacy of the assumption supposing that the auxiliary feed water pump is started by manual operation fifteen minutes after accident occurrence, and 3) the adequacy of the analytical Codes MARVEL and SATAN-6. The analytical results showed that the relief valve on a pressurizer does not operate at the similar accident to TMI in the Ohi Nuclear Power Station, because the difference of design exists between both plants, and also even if the relief valve on a pressurizer operates and does not close, the core is cooled sufficiently in the Ohi Nuclear Power Station. (Nakai, Y.)

  3. 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.

  4. 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.)

  5. 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

  6. 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...

  7. Concerns related to Safety Management of Engineered Nanomaterials in research environment

    International Nuclear Information System (INIS)

    Groso, A; Meyer, Th

    2013-01-01

    Since the rise of occupational safety and health research on nanomaterials a lot of progress has been made in generating health effects and exposure data. However, when detailed quantitative risk analysis is in question, more research is needed, especially quantitative measures of workers exposure and standards to categorize toxicity/hazardousness data. In the absence of dose-response relationships and quantitative exposure measurements, control banding (CB) has been widely adopted by OHS community as a pragmatic tool in implementing a risk management strategy based on a precautionary approach. Being in charge of health and safety in a Swiss university, where nanomaterials are largely used and produced, we are also faced with the challenge related to nanomaterials' occupational safety. In this work, we discuss the field application of an in-house risk management methodology similar to CB as well as some other methodologies. The challenges and issues related to the process will be discussed. Since exact data on nanomaterials hazardousness are missing for most of the situations, we deduce that the outcome of the analysis for a particular process is essentially the same with a simple methodology that determines only exposure potential and the one taking into account the hazardousness of ENPs. It is evident that when reliable data on hazardousness factors (as surface chemistry, solubility, carcinogenicity, toxicity etc.) will be available, more differentiation will be possible in determining the risk for different materials. On the protective measures side, all CB methodologies are inclined to overprotection side, only that some of them suggest comprehensive protective/preventive measures and others remain with basic advices. The implementation and control of protective measures in research environment will also be discussed.

  8. Concerns related to Safety Management of Engineered Nanomaterials in research environment

    Science.gov (United States)

    Groso, A.; Meyer, Th

    2013-04-01

    Since the rise of occupational safety and health research on nanomaterials a lot of progress has been made in generating health effects and exposure data. However, when detailed quantitative risk analysis is in question, more research is needed, especially quantitative measures of workers exposure and standards to categorize toxicity/hazardousness data. In the absence of dose-response relationships and quantitative exposure measurements, control banding (CB) has been widely adopted by OHS community as a pragmatic tool in implementing a risk management strategy based on a precautionary approach. Being in charge of health and safety in a Swiss university, where nanomaterials are largely used and produced, we are also faced with the challenge related to nanomaterials' occupational safety. In this work, we discuss the field application of an in-house risk management methodology similar to CB as well as some other methodologies. The challenges and issues related to the process will be discussed. Since exact data on nanomaterials hazardousness are missing for most of the situations, we deduce that the outcome of the analysis for a particular process is essentially the same with a simple methodology that determines only exposure potential and the one taking into account the hazardousness of ENPs. It is evident that when reliable data on hazardousness factors (as surface chemistry, solubility, carcinogenicity, toxicity etc.) will be available, more differentiation will be possible in determining the risk for different materials. On the protective measures side, all CB methodologies are inclined to overprotection side, only that some of them suggest comprehensive protective/preventive measures and others remain with basic advices. The implementation and control of protective measures in research environment will also be discussed.

  9. Problems and concerns in radiation safety management related with decommissioning of tritium facility

    International Nuclear Information System (INIS)

    Kawano, Takao

    2005-01-01

    The tritium facility at the National Institute for Fusion Science has been closed in 2002 after decommissioning procedure. A number of works have been completed including technical measures and administrative documentations to be reported to the Ministry of Education, Culture, Sport, Science and Technology. All the operations were carried out in three successive terms; 1) survey and preparations, 2) actual decommissioning works, and 3) report of all procedures to the Minister. A valuable experience we had during this project has been summarized, and some problems have also been pointed out from a viewpoint of radiation safety management. (author)

  10. 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.

  11. Safety concerns of herbal products and traditional Chinese herbal medicines: dehydropyrrolizidine alkaloids and aristolochic acid.

    Science.gov (United States)

    Stegelmeier, Bryan L; Brown, Ammon W; Welch, Kevin D

    2015-12-01

    In many countries, including the United States, herbal supplements, tisanes and vegetable products, including traditional Chinese medicines, are largely unregulated and their content is not registered, monitored or verified. Consequently, potent plant toxins including dehydropyrrolizidine alkaloids and other potential carcinogens can contaminate these products. As herbal and food supplement producers are left to their own means to determine the safety and purity of their products prior to marketing, disturbingly often good marketing practices currently in place are ignored and content is largely undocumented. Historical examples of poisoning and health issues relating to plant material containing dehydopyrrolizidine alkaloids and aristolochic acids were used as examples to demonstrate the risk and potential toxicity of herbal products, food supplements, or traditional medicines. More work is needed to educate consumers of the potential risk and require the industry to be more responsible to verify the content and insure the safety of their products. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  12. Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010.

    Science.gov (United States)

    Downing, Nicholas S; Shah, Nilay D; Aminawung, Jenerius A; Pease, Alison M; Zeitoun, Jean-David; Krumholz, Harlan M; Ross, Joseph S

    2017-05-09

    Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near-regulatory deadline approval, and regulatory review time. A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P safety

  13. Crash safety concerns for out-of-position occupant postures: A look towards safety in highly automated vehicles.

    Science.gov (United States)

    McMurry, Timothy L; Poplin, Gerald S; Shaw, Greg; Panzer, Matthew B

    2018-04-09

    Highly automated vehicle occupants will all be passengers, and may be free to ride while in postures for which existing occupant safety systems such as seat belts and air bags were not originally designed. These occupants could therefore face increased risk of injury when a crash occurs. Given that current vehicles are capable of supporting a variety of occupant postures outside of the normal design position, such as reclined or turned passengers, an evaluation of current field data was performed to better understand the risks of being out-of-position. We investigated the frequency, demographics, and injury outcomes for out-of-position occupants using the National Automotive Sampling System, Crashworthiness Data System (NASS-CDS). A matched analysis was performed to compare injury outcomes for out-of-position passengers with in-position drivers involved in similar crashes. Finally, case studies for out-of-position occupants were examined in the Crash Injury Research (CIREN) database. Only 0.5% of occupants in NASS-CDS with a coded posture were out-of-position at the time of crash. Of the out-of-position occupants, being turned or seated sideways was almost as likely as being reclined. Out-of-position occupants were younger and less likely to be belted than their in-position counterparts. Analysis of the injury data indicated a trend that being out-of-position was associated with an elevated risk for serious injury. However, the number of out-of-position occupants was too small to provide a definitive or statistically significant conclusions on injury outcome. While highly automated vehicles may eventually reduce the number of crashes and traffic fatalities in the future, there will be a transition period when these vehicles remain at risk from collisions with human driven vehicles. These crashes could cause higher than anticipated rates of injury if occupants are less likely to be belted, or tend to be in positions for which restraints are not optimized. This study

  14. Manganese--a public health concern: its relevance for occupational health and safety policy and regulation in South Africa.

    Science.gov (United States)

    Hermanus, M A

    2000-01-01

    Concerns about the effects of low-level manganese exposures on human health arise at a time when South Africa finds itself in competition with newcomers to the market economy, China and the CIS. This case study illustrates how decisions about occupational health and safety and the environment are influenced by incompleteness of scientific knowledge, competing interests, differences over what is fair or just, and the compartmentalization of public policy. In addition, an assessment is made of the ability of the occupational health and safety system in South Africa in its current form to address the challenges posed by manganese-related issues. The importance of tracking developments abroad, strengthening participatory processes, developing national policy, linking economic policy and OHS policy, and establishing appropriate trade agreements is stressed.

  15. SAFETY

    CERN Document Server

    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...

  16. Regulatory oversight report 2012 concerning nuclear safety in Swiss nuclear installations

    International Nuclear Information System (INIS)

    2013-04-01

    The Swiss Federal Nuclear Safety Inspectorate (ENSI) assesses and monitors nuclear facilities in Switzerland. These include the five nuclear power plants, the interim storage facilities based at each plant, the Central Interim Storage Facility (ZWILAG) and the nuclear facilities at the Paul Scherrer Institute (PSI), at the Federal Institute of Technology in Lausanne (EPFL) and at the University of Basel. Using a combination of inspections, regulatory meetings, examinations and analyses together with reports from the licensees of individual facilities, ENSI obtains the required overview of nuclear safety in the relevant facilities. It ensures that the facilities comply with the regulations and operate as required by law. Its regulatory responsibilities also include the transport of radioactive materials from and to nuclear facilities and the preparations for a deep geological repository for nuclear waste. ENSI maintains its own emergency organisation. It formulates and updates its own guidelines which stipulate the criteria for evaluating the current activities and future plans of the operators of nuclear facilities. ENSI produces regular reports on its regulatory activities and nuclear safety in Swiss nuclear facilities. It fulfils its statutory obligation to provide the public with information on particular events and findings in nuclear facilities. In 2012, the five nuclear power plants in Switzerland were all operated safely. 34 events were reported; on the international INES scale of 0 to 7, ENSI rated 33 events as Level 0 and 1 as Level 1. ENSI evaluates the safety of each nuclear power plant as part of a systematic safety evaluation taking account of both reportable events and other findings, in particular the results of more than 400 inspections conducted by ENSI during 2012. ZWILAG consists of several interim storage halls, a conditioning plant and an incineration/melting plant. At the end of 2012, the cask storage hall contained 40 transport/storage casks

  17. 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...

  18. Safety and Security Concerns of Nurses Working in the Intensive Care Unit: A Qualitative Study.

    Science.gov (United States)

    Keys, Yolanda; Stichler, Jaynelle F

    Intensive care units (ICUs) exist to serve as a safe place for critically ill patients to receive care from skilled practitioners. In this qualitative study, ICU nurses shared their perspectives on elements that promote safety and security on their units. After obtaining institutional review board approval, participants participated in telephone interviews with a nurse researcher who has experience as a bedside ICU nurse. Five categories and 14 themes were identified and then confirmed using member checking. Results indicate that participants prefer to provide care in ICUs with no more than 12 to 14 beds and provide the following: visibility of patients and coworkers; more than 1 way to exit; and can be locked in case of emergency or threat. Nearly all respondents mentioned adequate staffing as the most important attribute of a safe, secure care environment for patients and families. More research is needed to identify design features that make the most impact on providing a safe, secure ICU environment.

  19. Assessment of regulations set up under public law concerning questions of safety technology

    International Nuclear Information System (INIS)

    Steiff, A.; Althaus, W.; Dietz, B.; Gross, H.J.; Stasiczek, M.; Salzwedel, J.; Reinhardt, M.

    1992-02-01

    A goal of the preliminary study was to assess the need for a data-processing system, to analyze the goals of such a system, to conceptualize it and examine possibilities for implementing it and to do a cost-benefit analysis of it. It serves as a means of assistance for - licensing and supervisory authorities, - the manufacturers and operators of plants, - the control institutions, - the communes, the governments of the Laender and the federal government, - trade associations and professional associations, - employers' organizations and employees' organizations in their efforts to solve problems and carry out tasks regarding safety technology. Such problems arise during the planning, construction, operation, alteration, closure and removal of plants as well as during the transport and storing of materials and goods. (orig./DG) [de

  20. [The legislation of subjects of the Russian Federation concerning prevention of alcoholism, drug addiction and toxicomania].

    Science.gov (United States)

    2011-01-01

    The article deals with analysis of the laws "On prevention of alcoholism, drug addiction and toxicomania" introduced in some subjects of the Russian Federation (Permskaya, Tomskaya, Murmanskaya oblast, the Republics of Bashkortostan, Mordovia, Buryatia, Mari El, etc.). The laws stipulate the participation of the authorities of public and municipal administration, public health, social protection, home affairs and others in the prevention activities. The integral part of this activity is the approval of corresponding regional programs with adequate financing and coordination. The laws on prevention of alcoholism, drug addiction and toxicomania, adopted in the subjects of the Russian Federation are of advance character and testify the necessity of adoption of relevant Federal law.

  1. Joint medicine-information and pharmacovigilance services could improve detection and communication about drug-safety problems

    Directory of Open Access Journals (Sweden)

    Schjøtt J

    2014-07-01

    Full Text Available Jan Schjøtt,1–3 Jenny Bergman3 1Section of Clinical Pharmacology, Laboratory of Clinical Biochemistry, Haukeland University Hospital, 2Institute of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, 3Regional Medicines Information and Pharmacovigilance Centre (RELIS Vest, Haukeland University Hospital, Bergen, Norway Background: RELIS is a Norwegian network of four regional medicine-information and pharmacovigilance centers where pharmacists and clinical pharmacologists provide feedback to health care professionals in spontaneous drug-related questions and adverse drug-reaction (ADR reports published in a question–answer pair (QAP database (the RELIS database and the Norwegian ADR database, respectively. Objective: To describe the potential of RELIS's dual service to improve detection and communication of drug-safety problems. Materials and methods: We searched the RELIS database for QAPs about ADRs with use of the Norwegian ADR database as a reference. We also searched the Norwegian ADR database for reports that used the RELIS database as a reference. Both searches were limited to the years 2003–2012. We then selected the example of pregabalin and drug abuse after the marketing of Lyrica in Norway in September 2004 to illustrate RELIS's potential to detect new drug-safety information through a limited number of QAPs and ADR reports. Results: A total of 5,427 (26% of 21,071 QAPs in the RELIS database concerned ADRs. QAPs from this database were used as references in 791 (4% of a total of 22,090 reports in the Norwegian ADR database. The Norwegian ADR database was used as a reference in 363 (7% of 5,427 QAPs that concerned ADRs. Between September 2004 and September 2008, RELIS received eleven questions and 13 ADR reports about suspicion of Lyrica (pregabalin and different aspects of abuse. Conclusion: RELIS processes data through two databases that facilitate communication about ADRs. Our service also has the

  2. "Is it still safe to eat traditional food?" Addressing traditional food safety concerns in aboriginal communities.

    Science.gov (United States)

    Bordeleau, Serge; Asselin, Hugo; Mazerolle, Marc J; Imbeau, Louis

    2016-09-15

    Food insecurity is a growing concern for indigenous communities worldwide. While the risk of heavy metal contamination associated to wild food consumption has been extensively studied in the Arctic, data are scarce for the Boreal zone. This study addressed the concerns over possible heavy metal exposure through consumption of traditional food in four Anishnaabeg communities living in the Eastern North American boreal forest. Liver and meat samples were obtained from 196 snowshoe hares (Lepus americanus) trapped during winter 2012 across the traditional lands of the participating communities and within 56-156km of a copper smelter. Interviews were conducted with 78 household heads to assess traditional food habits, focusing on snowshoe hare consumption. Concentrations in most meat and liver samples were below the detection limit for As, Co, Cr, Ni and Pb. Very few meat samples had detectable Cd and Hg concentrations, but liver samples had mean dry weight concentrations of 3.79mg/kg and 0.15mg/kg respectively. Distance and orientation from the smelter did not explain the variability between samples, but percent deciduous and mixed forest cover had a marginal negative effect on liver Cd, Cu and Zn concentrations. The estimated exposition risk from snowshoe hare consumption was low, although heavy consumers could slightly exceed recommended Hg doses. In accordance with the holistic perspective commonly adopted by indigenous people, the nutritional and sociocultural importance of traditional food must be considered in risk assessment. Traditional food plays a significant role in reducing and preventing serious health issues disproportionately affecting First Nations, such as obesity, diabetes, and cardiovascular diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Recent developments concerning the application of the Mannich reaction for drug design.

    Science.gov (United States)

    Biersack, Bernhard; Ahmed, Khursheed; Padhye, Subhash; Schobert, Rainer

    2018-01-01

    The versatile multicomponent Mannich reaction occupies a salient position in organic chemistry and drug design. Sound knowledge of its scope and variations and of the biological activities of Mannich bases is crucial for the development and improvement of drugs for various diseases. Areas covered: The following article provides an overview of the latest developments in the field of drugs based on the Mannich reaction. Web-based literature searching tools such as PubMed and SciFinder were applied to obtain useful articles. In addition, pertinent literature that was recently published by the authors is discussed in this manuscript. The chemical structures of bioactive Mannich bases are also given. Expert opinion: The Mannich reaction represents a feasible and cost-effective procedure with great potential for drug development. Several newly discovered Mannich bases exhibit sound activities against various human diseases as well as favorable pharmacokinetics. Thus, scientific research about Mannich bases is prospering and appears very attractive both for chemists and for clinicians.

  4. 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 ...

  5. 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 we...

  6. 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 the...

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

    NARCIS (Netherlands)

    Sanz, Ferran; Pognan, François; Steger-Hartmann, Thomas; Díaz, Carlos; Cases, Montserrat; Pastor, Manuel; Marc, Philippe; Wichard, Joerg; Briggs, Katharine; Watson, David K; Kleinöder, Thomas; Yang, Chihae; Amberg, Alexander; Beaumont, Maria; Brookes, Anthony J; Brunak, Søren; Cronin, Mark T D; Ecker, Gerhard F; Escher, Sylvia; Greene, Nigel; Guzmán, Antonio; Hersey, Anne; Jacques, Pascale; Lammens, Lieve; Mestres, Jordi; Muster, Wolfgang; Northeved, Helle; Pinches, Marc; Saiz, Javier; Sajot, Nicolas; Valencia, Alfonso; van der Lei, Johan; Vermeulen, Nico P E; Vock, Esther; Wolber, Gerhard; Zamora, Ismael

    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 the

  8. 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

  9. 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

  10. ROCKET AF adds more concerns about Digoxin safety in patients with atrial fibrillation

    Science.gov (United States)

    ElMaghawry, Mohamed

    2015-01-01

    In a recent article in the Journal, we have reviewed the adverse cardiovascular outcomes observed with digoxin use in the PALLAS study.1 The PALLAS study was designed to determine if dronedarone would reduce major vascular events in patients with permanent atrial fibrillation (AF).2 However the study was stopped early because of safety reasons, as a significant number of patients on the dronedarone arm reached the co-primary end point composite of stroke, myocardial infarction, systemic embolism, or cardiovascular death. Data sub-analyses suggested that digoxin-dronedarone interaction was responsible for the higher arrhythmic death rate observed in the trial. These observations are consistent with several other studies that demonstrate the potential hazard of the use of digoxin in heart failure and/or atrial fibrillation. A more recent article published in the Lancet studied the use and outcomes of digoxin in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism in Atrial Fibrillation (ROCKET AF) trial.3 The investigators concluded that digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. PMID:26779514

  11. Implementation of a safety program for handling hazardous drugs in a community hospital.

    Science.gov (United States)

    Massoomi, Firouzan Fred; Neff, Bill; Pick, Amy; Danekas, Paula

    2008-05-01

    The implementation of a safety program for handling hazardous drugs in a community hospital is described. A committee of representatives of the departments of pharmacy, nursing, human resources, safety, radiology, performance improvement, employee health, and environmental services and members of the hospital administration was formed to formally address the management of hazardous drugs in a community, not-for-profit, adult hospital in Omaha, Nebraska. Published guidelines and regulations were reviewed to determine the hospital's compliance with the handling of hazardous drugs. A knowledge deficit regarding the risk and severity of occupational exposure to hazardous drugs was identified. A formal education plan was immediately implemented providing inservice education to all staff who may come into contact with hazardous drugs. Each drug was electronically tagged in the hospital computer system. The nitrile gloves used in the pharmacy were switched to a brand tested for resistance to chemotherapy drug permeation. The use of personal protective equipment for all health care workers who may come into contact with hazardous drugs was also instituted. Waste stream management was addressed, and a new waste stream was identifed and implemented to address chemicals regulated by the Resource Conservation Recovery Act. Nursing, pharmacy, and housekeeping personnel were extensively educated on the different waste streams and the importance of segregating waste at the point of use. All gloves for housekeeping and laundry service staff were replaced with hazardous-drug-rated nitrile gloves. A gap analysis allowed a multidisciplinary team to establish a safety program for managing hazardous drugs in a community hospital.

  12. Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure.

    Science.gov (United States)

    Armstead, Andrea L; Li, Bingyun

    As the number of commercial and consumer products containing engineered nanomaterials (ENMs) continually rises, the increased use and production of these ENMs presents an important toxicological concern. Although ENMs offer a number of advantages over traditional materials, their extremely small size and associated characteristics may also greatly enhance their toxic potentials. ENM exposure can occur in various consumer and industrial settings through inhalation, ingestion, or dermal routes. Although the importance of accurate ENM characterization, effective dosage metrics, and selection of appropriate cell or animal-based models are universally agreed upon as important factors in ENM research, at present, there is no "standardized" approach used to assess ENM toxicity in the research community. Of particular interest is occupational exposure to tungsten carbide cobalt (WC-Co) "dusts," composed of nano- and micro-sized particles, in hard metal manufacturing facilities and mining and drilling industries. Inhalation of WC-Co dust is known to cause "hard metal lung disease" and an increased risk of lung cancer; however, the mechanisms underlying WC-Co toxicity, the inflammatory disease state and progression to cancer are poorly understood. Herein, a discussion of ENM toxicity is followed by a review of the known literature regarding the effects of WC-Co particle exposure. The risk of WC-Co exposure in occupational settings and the updates of in vitro and in vivo studies of both micro- and nano-WC-Co particles are discussed.

  13. Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure

    Science.gov (United States)

    Armstead, Andrea L; Li, Bingyun

    2016-01-01

    As the number of commercial and consumer products containing engineered nanomaterials (ENMs) continually rises, the increased use and production of these ENMs presents an important toxicological concern. Although ENMs offer a number of advantages over traditional materials, their extremely small size and associated characteristics may also greatly enhance their toxic potentials. ENM exposure can occur in various consumer and industrial settings through inhalation, ingestion, or dermal routes. Although the importance of accurate ENM characterization, effective dosage metrics, and selection of appropriate cell or animal-based models are universally agreed upon as important factors in ENM research, at present, there is no “standardized” approach used to assess ENM toxicity in the research community. Of particular interest is occupational exposure to tungsten carbide cobalt (WC-Co) “dusts,” composed of nano- and micro-sized particles, in hard metal manufacturing facilities and mining and drilling industries. Inhalation of WC-Co dust is known to cause “hard metal lung disease” and an increased risk of lung cancer; however, the mechanisms underlying WC-Co toxicity, the inflammatory disease state and progression to cancer are poorly understood. Herein, a discussion of ENM toxicity is followed by a review of the known literature regarding the effects of WC-Co particle exposure. The risk of WC-Co exposure in occupational settings and the updates of in vitro and in vivo studies of both micro- and nano-WC-Co particles are discussed. PMID:27942214

  14. Chiral Analysis of Pesticides and Drugs of Environmental Concern: Biodegradation and Enantiomeric Fraction

    Directory of Open Access Journals (Sweden)

    Alexandra S. Maia

    2017-09-01

    Full Text Available The importance of stereochemistry for medicinal chemistry and pharmacology is well recognized and the dissimilar behavior of enantiomers is fully documented. Regarding the environment, the significance is equivalent since enantiomers of chiral organic pollutants can also differ in biodegradation processes and fate, as well as in ecotoxicity. This review comprises designed biodegradation studies of several chiral drugs and pesticides followed by enantioselective analytical methodologies to accurately measure the enantiomeric fraction (EF. The enantioselective monitoring of microcosms and laboratory-scale experiments with different environmental matrices is herein reported. Thus, this review focuses on the importance of evaluating the EF variation during biodegradation studies of chiral pharmaceuticals, drugs of abuse, and agrochemicals and has implications for the understanding of the environmental fate of chiral pollutants.

  15. 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

  16. 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...

  17. The effectiveness of telephone counselling in the treatment of illicit drug and alcohol use concerns.

    Science.gov (United States)

    Gates, Peter; Albertella, Lucy

    2016-03-01

    Technology-assisted substance use interventions such as 'high-tech' internet-based treatments are thought to be effective; however, the relatively 'low-tech' use of telephone counselling does not yet have an established evidence base. This paper reviews the literature including articles with information on the use of telephone counselling for the treatment of illicit drug or alcohol use. A systematic literature search using a set of telephone counselling and substance-related terms was conducted across four electronic databases. English studies prior to June 2014 that involved the use of telephone counselling with the treatment of illicit drug or alcohol use as a primary or secondary outcome were included. Review papers, opinion pieces, letters or editorials, case studies, published abstracts, and posters were excluded. In all, 94 publications were included in the review. The literature was supportive of telephone counselling for the treatment of alcohol use in the short term; however, literature regarding illicit drug use was particularly scarce. The generalisability of findings was limited by evident methodological issues in the included studies. © The Author(s) 2015.

  18. Drug safety: The concept, inception and its importance in patients' health.

    Science.gov (United States)

    Alshammari, Thamir M

    2016-07-01

    Drug safety is one of the hottest topics in daily medical practice, particularly with regard to approving new medication or questioning the possibility of withdrawing a drug from the market. The aim of this review is to highlight the importance of the drug safety concept and its impact on patients' health. A literature search was conducted using Pubmed®, EMBASE®, EBSCO and Medline in the period between 1980 and 2013. The terms used in the search included "Drug Safety", "Medication Safety", "Patient Safety", "Drug Interaction", "Drug Pharmacokinetic", and "Adverse Drug Reaction". All retrieved abstracts were evaluated within the context of the review objectives. The full texts of the selected articles were included in this review. Studies in non-English language were excluded in this review. Since the early days of the past century, many acts, laws, or amendments have been created to make sure that approved drugs are first safe and then effective. Furthermore, these regulations are continuing to change to make sure that these drugs have a positive benefit-risk balance. Personalized medicine should be considered when medications are given to patients because the pharmacokinetic process inside the body varies from patient to patient and from one specific disease state to another. However, adverse drug reactions can be minimized if more precautions are taken by healthcare professionals, especially including the patient as one pillar of the therapeutic plan and providing more patient counseling, which will improve drug safety. The drug safety concept has earned a lot of attention during the past decade due to the fact it plays a major role in patients' health. Recent laws stress this concept should be included in the process of new medications' approval and continued conduct of post-marketing drug evaluations. Benefit-risk assessment should be considered by all health care professionals when they need to give specific drugs to specific groups of patients. Therefore

  19. Pneumonia following antipsychotic prescriptions in electronic health records: a patient safety concern?

    Science.gov (United States)

    Star, Kristina; Bate, Andrew; Meyboom, Ronald HB; Edwards, I Ralph

    2010-01-01

    Background In screening the Intercontinental Medical Statistics (IMS) Health Disease Analyzer database of GP records from the UK, an increased registration of pneumonia subsequent to the prescription of some antipsychotic medicines was identified. Aim To investigate the temporal pattern between antipsychotic prescriptions and pneumonia with respect to age, type of pneumonia and other chest infections, and antipsychotic class. Design of study Self-controlled cohort analysis. Setting Electronic health records from the UK IMS Health Disease Analyzer database. Method Three groups of pneumonia-related International Classification of Diseases (ICD)-10 terms and prescriptions of atypical and conventional antipsychotic medicines were studied. Separate analyses were carried out for patients aged a65 years. The observed rate of pneumonia terms registered in different time periods in connection to antipsychotic prescriptions was contrasted to the overall rate of pneumonia terms relative to prescriptions of other drugs in the same dataset. Results In patients aged ≥65 years, an increased registration of a group of terms defined as ‘acute chest infections’, after atypical antipsychotic prescriptions, was identified. The corresponding increase after conventional antipsychotic prescriptions was much smaler. Bronchopneumonia had a striking increase after both atypical and conventional antipsychotic prescriptions, and was commonly recorded with fatal outcome. Few registrations of hypostatic pneumonia were noted. Patients aged atypical antipsychotic prescriptions in older people seen in this outpatient study, together with the higher risk shown in a previous study on hospitalised patients, suggests a causal relationship. This is of importance since bronchopneumonia seems highly linked to fatal outcome. In the absence of a mechanism, further investigation of the role of antipsychotics in older people is needed. PMID:20883613

  20. FDA gives final approval to Depo amid concerns over safety, cost and coercion.

    Science.gov (United States)

    1992-11-12

    In October 1992, the US Food and Drug Administration (FDA) approved Depo-Provera for contraceptive use thus increasing the number of available contraceptives to women. Yet USAID has distributed it through its family planning programs in developing countries for many years. It has been available in the US since 1969 for noncontraceptive purposes such as endometrial cancer treatment. More than 30 million women around the world have used it to prevent conception. Today about 9 million women in 90 countries use it. A reason FDA did not approve Depo-Provera is that some studies revealed a link between it and breast tumors and cervical cancer in animals. More recent research conducted by WHO shows no connection with cervical cancer or ovarian cancer. In fact, it demonstrates Depo-Provera may protect against endometrial cancer. Yet it does indicate an insignificant increased risk of breast cancer in younger women. Some research suggests Depo-Provera may decrease bone density leading to osteoporosis and may increase the risk of having a low birth weight infant if the child is conceived before an injection. Evidence exists that it may lead to longer delays in becoming pregnant than other forms of contraception. Still 70% do conceive within 12 months after the last injection. Each Depo-Provera injection delivers a progestin in a water-based solution over 12 weeks resulting in suppressed ovulation. Its failure rate is .5%/year, so Depo-Provera is one of the most effective reversible contraceptive available. The most common side effects are menstrual changes and weight gain (5-15 lbs.). Some contraindications include pregnancy, heart or liver disease, and breast cancer. As of November 1992, the FDA had not announced the cost or whether there would be a reduced price for family planning and public health clinics. Women's health and rights advocates plan on monitoring introduction of Depo-Provera to make sure that women have received comprehensive information and were not

  1. Manufacturing blood ex vivo: a futuristic approach to deal with the supply and safety concerns

    Directory of Open Access Journals (Sweden)

    Vimal kishor Singh

    2014-06-01

    Full Text Available Blood transfusions are routinely done in every medical regimen and a world wide established collection, processing/storage centers provide their services for the same. There have been extreme global demands for both raising the current collections and supply of safe/adequate blood due to increasingly demanding population. Since, various risks remain associated with the donor derived blood, and a number of post collection blood screening and processing methods put extreme constraints on supply system especially in the underdeveloped countries. A logistic approach to manufacture erythrocytes ex-vivo by using modern tissue culture techniques have surfaced in past few years. There are several reports showing possibilities of RBCs (and even platelets/ neutrophils expansion under tightly regulated conditions. In fact, ex vivo synthesis of few units of clinical grade RBCs from a single dose of starting material such as umbilical cord blood has been well established. Similarly, many different sources are also being explored for the same purpose such as embryonic stem cells, induced pluripotent stem cells. However, the major concerns remain elusive before the manufacture and clinical use of different blood components may be used to successfully replace the present system of donor derived blood transfusion. Most important factor shall include the large scale of RBCs production from each donation unit within a limited time period and cost of their production both of these issues need to be handled carefully since many of the recipients among developing countries are unable to pay even for the freely available donor derived blood. Anyways, keeping these issue in mind, present article shall be focused on the feasibilities of blood production and their use in near future.

  2. Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co nanoparticle exposure

    Directory of Open Access Journals (Sweden)

    Armstead AL

    2016-12-01

    Full Text Available Andrea L Armstead,1,2 Bingyun Li1–3 1Department of Orthopaedics, School of Medicine, 2School of Pharmacy, West Virginia University, 3Mary Babb Randolph Cancer Center, Morgantown, WV, USA Abstract: As the number of commercial and consumer products containing engineered nanomaterials (ENMs continually rises, the increased use and production of these ENMs presents an important toxicological concern. Although ENMs offer a number of advantages over traditional materials, their extremely small size and associated characteristics may also greatly enhance their toxic potentials. ENM exposure can occur in various consumer and industrial settings through inhalation, ingestion, or dermal routes. Although the importance of accurate ENM characterization, effective dosage metrics, and selection of appropriate cell or animal-based models are universally agreed upon as important factors in ENM research, at present, there is no “standardized” approach used to assess ENM toxicity in the research community. Of particular interest is occupational exposure to tungsten carbide cobalt (WC-Co “dusts,” composed of nano- and micro-sized particles, in hard metal manufacturing facilities and mining and drilling industries. Inhalation of WC-Co dust is known to cause “hard metal lung disease” and an increased risk of lung cancer; however, the mechanisms underlying WC-Co toxicity, the inflammatory disease state and progression to cancer are poorly understood. Herein, a discussion of ENM toxicity is followed by a review of the known literature regarding the effects of WC-Co particle exposure. The risk of WC-Co exposure in occupational settings and the updates of in vitro and in vivo studies of both micro- and nano-WC-Co particles are discussed. Keywords: engineered nanomaterial, occupational exposure, lung disease, cancer, toxicity, particle

  3. Who was concerned about radiation, food safety, and natural disasters after the great East Japan earthquake and Fukushima catastrophe? A nationwide cross-sectional survey in 2012.

    Science.gov (United States)

    Sugimoto, Takashi; Shinozaki, Tomohiro; Naruse, Takashi; Miyamoto, Yuki

    2014-01-01

    Disaster-related concerns by sub-populations have not been clarified after the great East Japan earthquake and the Fukushima nuclear power plant incidents. This paper assesses who was concerned about radiation, food safety, and natural disasters among the general population in order to buffer such concerns effectively. The hypothesis that women, parents, and family caregivers were most concerned about radiation, food safety, and natural disaster was tested using a varying-intercept multivariable logistic regression with 5809 responses from a nationwide cross-sectional survey random-sampled in March 2012. Many people were at least occasionally concerned about radiation (53.5%), food safety (47.3%), and about natural disaster (69.5%). Women were more concerned than men about radiation (OR = 1.67; 95% CI = 1.35-2.06), food safety (1.70; 1.38-2.10), and natural disasters (1.74; 1.39-2.19). Parents and family care needs were not significant. Married couples were more concerned about radiation (1.53; 1.33-1.77), food safety (1.38; 1.20-1.59), and natural disasters (1.30; 1.12-1.52). Age, child-cohabitation, college-completion, retirement status, homemaker status, and the house-damage certificate of the last disaster were also associated with at least one concern. Participants from the Kanto region were more concerned about radiation (2.08; 1.58-2.74) and food safety (1.30; 1.07-1.59), which demonstrate similar positive associations to participants from Tohoku where a disaster relief act was invoked (3.36; 2.25-5.01 about radiation, 1.49; 1.08-2.06 about food safety). Sectioning the populations by gender and other demographics will clarify prospective targets for interventions, allow for a better understanding of post-disaster concerns, and help communicate relevant information effectively.

  4. 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

    for all drugs except for adalimumab and secukinumab. Adverse events (predominantly infections) were most frequent for secukinumab and showed an increased (albeit low) incidence of cardiovascular events compared with the other agents. CONCLUSIONS: Ustekinumab was associated with the highest drug survival......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...

  5. 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.

  6. IMPACT OF HEALTH TECHNOLOGY ASSESSMENT IN LITIGATION CONCERNING ACCESS TO HIGH-COST DRUGS.

    Science.gov (United States)

    Aleman, Alicia; Perez Galan, Ana

    2017-01-01

    The impact of health technology assessment (HTA) in the judicialization of the right of health has not been deeply studied in Latin American countries. The purpose of this study is to review the process of judicialization of the access to high cost drugs in Uruguay and assess the impact HTAs have had on this process. The methodology used for this study included a comprehensive literature search in electronic databases, local journals, internal documents developed in the Ministry of Health, as well as conducting interviews with key informants. Judicialization of the access of high cost drugs has been increasing since 2010. The strategy of the Ministry of Health of Uruguay to decrease this problem included the organization of roundtables with judges and other stakeholders on the basis of HTA, the training of defense lawyers in the use and interpretation of HTA, and the participation of a professional who develops HTA in the preparation of the defense arguments. A year after the implementation of this strategy, 25 percent of writs of protection were won by the Ministry of Health. Even though the strategy implemented was effective in reducing the loss of litigations, it was not effective in reducing the growing number of writs of protection. It is essential to address this problem in a broad debate and to promote understanding between the parties.

  7. 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.

  8. [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).

  9. Posiva's application for a decision in principle concerning a disposal facility for spent nuclear fuel. STUK's statement and preliminary safety appraisal

    International Nuclear Information System (INIS)

    Ruokola, E.

    2000-03-01

    In May 1999, Posiva Ltd submitted to the Government an application, pursuant to the Nuclear Energy Act, for a Decision in Principle on a disposal facility for spent nuclear fuel from the Finnish nuclear power plants. The Ministry of Trade and Industry requested the Radiation and Nuclear Safety Authority (STUK) to draw up a preliminary safety appraisal concerning the proposed disposal facility. In the beginning of this report, STUK's statement to the Ministry and Industry concerning the proposed disposal facility is given. In that statement, STUK concludes that the Decision in Principle is currently justified from the standpoint of safety. The statement is followed by a safety appraisal, where STUK deems, how the proposed disposal concept, site and facility comply with the safety requirements included in the Government's Decision (478/1999). STUK's preliminary safety appraisal was supported by contributions from a number of outside experts. A collective opinion by an international group of ten distinguished experts is appended to this report. (orig.)

  10. Cause for Concern: A Mixed-Methods Study of Campus Safety and Security Practices in United States-Mexico Border Institutions of Higher Education

    Science.gov (United States)

    Holmes, Ryan Clevis

    2014-01-01

    Campus safety has been a source of concern since the 1990s. However, in 2007, the tragedy at the Virginia Polytechnic and State University sent a sense of alarm through many institutions of higher education. Immediately following this tragedy, institutions across the country began to evaluate and question their safety and security practices. While…

  11. [Effects of Xenobiotics on Drug Pharmacokinetics and Safety].

    Science.gov (United States)

    Katoh, Miki

    2015-01-01

    The use of nanotechnology has increased over the past 10 years, and various nanomaterials with a wide range of applications have been developed. Carbon nanotubes (CNTs), which are cylindrical molecules consisting of hexagonally arranged carbon atoms, are nanomaterials with high utility. Recently, applications of single-walled CNT (SWCNT) in the medical field for drug-delivery and as gene-delivery agents have been proposed. Due to its structural characteristics and physicochemical properties, the inhalation of SWCNT could be considered as one route for targeted drug delivery into the lungs. Therefore, it is necessary to investigate the effects of SWCNT on the physiological state and response of the cells upon delivery into the lung. We clarified the different response of two carcinoma cell lines to SWCNT exposure, and determined these differences may be due to different cell functions. Furthermore, SWCNT exposure resulted in a global downregulation of stress-responsive genes in normal human bronchial epithelial cells, thereby indicating that the factors involved in the stress responses were not activated by SWCNT. We then tried to ascertain the possible effect of SWCNT on the fate of drugs delivered with SWCNT. Exposure to SWCNT down-regulated the mRNA expression and enzymatic activity of CYP1A1 and CYP1B1 by preventing the binding of activated aryl hydrocarbon receptors to the enhancer region of these genes. This review provides basic information for the prediction of human responses to SWCNT exposure by inhalation, and in its use as a drug delivery carrier.

  12. Lumbar epidural catheter placement in the presence of low back tattoos: a review of the safety concerns.

    Science.gov (United States)

    Welliver, Dawn; Welliver, Mark; Carroll, Tammy; James, Peggy

    2010-06-01

    Current fashion in body art includes low back tattoos of varying designs and colors, a trend that presents unique concerns for anesthesia providers. Does the placement of epidural catheters risk the introduction of tattoo pigment dyes into the epidural space through the process of coring? Are there specific risks associated with tattoo dyes and epidural needle placement? We performed a comprehensive review of the literature using multiple search databases with the intent to form guidelines for practice using a level of evidence taxonomy. The available evidence does not identify any specific risks associated with epidural catheter placement through low back tattoos, although tissue coring with tissue transport to deeper sites has been confirmed. Continued investigation is necessary before comprehensive practice guidelines regarding the practice of placing epidural needles and catheters through lumbar tattoos can be developed. We suggest avoidance of piercing tattoos when performing epidural punctures until there is sound evidence of short-term and long-term safety.

  13. 75 FR 36427 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

    Science.gov (United States)

    2010-06-25

    ... Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee. ] General Function... and efficacy findings for sodium oxybate in the fibromyalgia population and the proposed Risk...

  14. Rowers' Self-Reported Behaviors, Attitudes, and Safety Concerns Related to Exercise, Training, and Competition During Pregnancy.

    Science.gov (United States)

    Franklin, Ashley; Mishtal, Joanna; Johnson, Teresa; Simms-Cendan, Judith

    2017-08-01

    Background The American College of Obstetrics and Gynecology notes that pregnant athletes require more supervision due to their involvement in strenuous training schedules throughout pregnancy. Currently, rowing is not mentioned in the guidelines despite its increasing popularity, high cardiovascular demands, and risk for abdominal trauma. Methods This study aimed to elicit information from competitive female rowers regarding exercise, training, and competition during pregnancy. We administered a survey consisting of 122 items to female Masters rowers in the United States, aged 21 to 49 years, from June to December 2013. Results A total of 224 recreational and elite rowers met the inclusion criteria. Pregnant rowers self-reported high levels of exercise engagement: 85.2% (n/N = 98/115) exercised during any past pregnancy; exercise adherence decreased throughout pregnancy with 51.3%, 42.4%, and 15.7% meeting and/or exceeding national guidelines during the first, second, and third trimesters, respectively. Rowers were significantly (p training, higher intensity exercise, competition, and increasing gestational age. Primary safety concerns were the risk of oar-induced abdominal trauma and physiological effects due to high intensities required by the sport. Novel barriers to exercise in pregnancy included guilt towards the team and a mental barrier due to decreased performance. Healthcare providers are the number one information source for rowers regarding exercise during pregnancy. Conclusion Pregnant rowers are a relevant obstetrics population and have barriers and sport-specific safety concerns not previously identified in the literature. Rowers consider exercising in pregnancy to be important and struggle to meet exercise guidelines like the general population, indicating the need for healthcare providers to provide prenatal and antenatal education and interventions to support exercise during pregnancy even amongst athletes.

  15. 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.

  16. Deep sequencing of plant and animal DNA contained within traditional Chinese medicines reveals legality issues and health safety concerns.

    Directory of Open Access Journals (Sweden)

    Megan L Coghlan

    Full Text Available Traditional Chinese medicine (TCM has been practiced for thousands of years, but only within the last few decades has its use become more widespread outside of Asia. Concerns continue to be raised about the efficacy, legality, and safety of many popular complementary alternative medicines, including TCMs. Ingredients of some TCMs are known to include derivatives of endangered, trade-restricted species of plants and animals, and therefore contravene the Convention on International Trade in Endangered Species (CITES legislation. Chromatographic studies have detected the presence of heavy metals and plant toxins within some TCMs, and there are numerous cases of adverse reactions. It is in the interests of both biodiversity conservation and public safety that techniques are developed to screen medicinals like TCMs. Targeting both the p-loop region of the plastid trnL gene and the mitochondrial 16S ribosomal RNA gene, over 49,000 amplicon sequence reads were generated from 15 TCM samples presented in the form of powders, tablets, capsules, bile flakes, and herbal teas. Here we show that second-generation, high-throughput sequencing (HTS of DNA represents an effective means to genetically audit organic ingredients within complex TCMs. Comparison of DNA sequence data to reference databases revealed the presence of 68 different plant families and included genera, such as Ephedra and Asarum, that are potentially toxic. Similarly, animal families were identified that include genera that are classified as vulnerable, endangered, or critically endangered, including Asiatic black bear (Ursus thibetanus and Saiga antelope (Saiga tatarica. Bovidae, Cervidae, and Bufonidae DNA were also detected in many of the TCM samples and were rarely declared on the product packaging. This study demonstrates that deep sequencing via HTS is an efficient and cost-effective way to audit highly processed TCM products and will assist in monitoring their legality and safety

  17. "Product on Stopper" in a Lyophilized Drug Product: Cosmetic Defect or a Product Quality Concern?

    Science.gov (United States)

    Mehta, Shyam B; Roy, Shouvik; Yang, Han-Chang Cathy

    2018-02-09

    During manufacturing of a lyophilized drug product, operator errors in product handling during loading of product filled vials onto the lyophilizer can lead to a seemingly cosmetic defect which can impact certain critical quality attributes of finished product. In this study, filling of a formulated monoclonal antibody in vials was performed using a peristaltic pump filling unit, and subsequently, the product was lyophilized. After lyophilization, upon visual inspection, around 40% of vials had cosmetic defect with residual product around stopper of the vial and were categorized as "product on stopper" vials, whereas remaining 60% vials with no cosmetic defect were called "acceptable vials." Both groups of vials from 1 single batch were tested for critical quality attributes including protein concentration (ultraviolet absorbance at 280), residual moisture (Karl Fischer), sterility (membrane filtration), and container closure integrity (CCI) (blue dye ingress). Analysis of protein quality attributes such as aggregation, protein concentration, residual moisture showed no significant difference between vials with "product on stopper" and "acceptable vials." However, CCI of the "product on stopper" vials was compromised due to the presence of product around stopper of the vial. The results from this case study demonstrate the following 2 important findings: (1) that a seemingly cosmetic defect may impact product quality, compromising the integrity of the product and (2) that CCI test method can be used as an orthogonal method to sterility testing to evaluate sterility assurance of the product. The corrective action proposed to mitigate this defect is use of a larger sized vial that can potentially minimize this defect that arises because of product handling errors. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Health Needs and Concerns of Male Adolescents.

    Science.gov (United States)

    Pinch, Winifred J.; And Others

    1986-01-01

    Examined male college students' (N=159) concerns in the areas of alcohol and other drug use, automobile safety, weight and dieting, smoking, sexuality, coping and stress, and selection and utilization of health care services. Identified major problems with alcohol use, automobile safety, weight control, stress, and sexuality. Also identified…

  19. [Reform Act on safety of drug and health products in France: announcement effect, strengthening or upheaval?].

    Science.gov (United States)

    Maillols-Perroy, Anne-Catherine; Tillet, Yves

    2012-01-01

    In France, the Médiator(®) scandal and the trauma it has created, are the source of Law n° 2011-2012 of 29 December 2011 on strengthening safety of drug and health products, intended by the Ministry of Labour, Employment and Health, adopted by the National Assembly and promulgated in order to restore confidence and enhance safety of drug and health products. This new law affects all stakeholders and health professionals impacts key points in the life cycle of the drug: MA, reimbursement, advertising, promotion, distribution, prescription, dispensing, and pharmacovigilance. It also provides for financial, administrative or criminal penalties, which are intended deterrent. Beyond strengthening constraints on safety of health products, this new law in France foreshadowed a revolution in behaviour, attitudes and overall scenery of the health system and no one today knows exactly the outline. © 2012 Société Française de Pharmacologie et de Thérapeutique.

  20. 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

    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...... 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...... 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...

  1. Nanotechnology in Drug Delivery: Safety and Toxicity Issues.

    Science.gov (United States)

    Jain, Keerti; Mehra, Neelesh Kumar; Jain, Narendra K

    2015-01-01

    Nanotoxicology deals with the new perception regarding nanotechnology i.e. risk and hazards associated with nanoscale materials. Although, nanotechnology is playing significant role in modern advancements from cell phones to medicines, yet it is necessary to consider their negative part as well that could be dangerous if not given proper attention. It is not certain that nanotechnology will essentially exert toxic effects since at present only few reports are available on their toxic effects and most of them are controversial. In this review we have summarized the advances in nanotechnology, their applications and, most importantly their safety issues that are often overlooked. However combined efforts are advocated to develop promising regulatory and ethical guidelines to control production, use and disposal of nanomaterials that will be safe to human health, environment and other living organisms.

  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. Effect of renal function on antihypertensive drug safety and efficacy in children.

    Science.gov (United States)

    Watt, Kevin M; Avant, Debbie; Sherwin, Jennifer; Benjamin, Daniel K; Hornik, Christoph; Benjamin, Daniel K; Li, Jennifer S; Smith, P Brian

    2018-01-01

    Hypertension and chronic kidney disease (CKD) are common comorbidities. Guidelines recommend treating hypertension in children with CKD because it is a modifiable risk factor for subsequent cardiovascular disease. Children with CKD are frequently excluded from antihypertensive drug trials. Consequently, safety and efficacy data for antihypertensive drugs are lacking in children with CKD. We determined the incidence of adverse events in 10 pediatric antihypertensive trials to determine the effect of renal function on antihypertensive safety and efficacy in children. These trials were submitted to the US Food and Drug Administration from 1998 to 2005. We determined the number and type of adverse events reported during the trials and compared these numbers in participants with normal renal function and those with decreased function (defined as an estimated glomerular filtration rate [eGFR] children in the 10 studies, 315 had decreased renal function. We observed no difference between the two cohorts in the incidence of adverse events or adverse drug reactions related to study drug. Only 5 participants, all with decreased renal function, experienced a serious adverse event; none was recorded by investigators to be study drug-related. Among treated participants, children with decreased renal function who received a high dose of study drug had a significantly larger drop in diastolic blood pressure compared with children with normal renal function. These data show that antihypertensive treatment in children with renal dysfunction can be safe and efficacious, and consideration should be given to their inclusion in selected drug development programs.

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

    Science.gov (United States)

    Price, John

    2018-03-28

    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.

  5. Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study

    OpenAIRE

    Mostaghim, Sana R; Gagne, Joshua J; Kesselheim, Aaron S

    2017-01-01

    Objective?To determine if drugs approved through the Food and Drug Administration?s expedited development and review pathways have different rates of safety related label changes after approval compared with drugs approved through standard non-expedited pathways. Design?Retrospective cohort study. Setting?FDA public records, January 1997 to April 2016. Participants?382 FDA approved drugs. Main outcome measures?The number of times a particular safety section of a label (boxed warning, contrain...

  6. Safety concerns associated with the use of serotonin reuptake inhibitors and other serotonergic/noradrenergic antidepressants during pregnancy: a review.

    Science.gov (United States)

    Tuccori, Marco; Testi, Arianna; Antonioli, Luca; Fornai, Matteo; Montagnani, Sabrina; Ghisu, Narcisa; Colucci, Rocchina; Corona, Tiberio; Blandizzi, Corrado; Del Tacca, Mario

    2009-06-01

    There is ongoing debate about the safety of selective serotonin reuptake inhibitors (SSRIs) and other serotonergic/noradrenergic antidepressants when used during pregnancy. This article reviews the available literature on the main safety concerns associated with the use of SSRIs and other serotonergic/noradrenergic antidepressants (serotonin-norepinephrine reuptake inhibitors, norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants) during pregnancy. English-language reports of analytical and descriptive studies, including case reports, case series, and meta-analyses, were identified through searches of MEDLINE, EMBASE, and PsycINFO (1966-April 2009). The search terms were fluoxetine, paroxetine, sertraline, Citalopram, escitalopram, fluvoxamine, venlafaxine, mirtazapine, reboxetine, duloxetine, SSRI, SNRI, NaSSA, and NRI in association with depression, pregnancy, prenatal exposure, miscarriage, spontaneous abortion, malformation, in utero exposure, and neonatal complications. Paroxetine has been associated with significant risks of major malformation, particularly cardiac defects, when used during pregnancy. Significant associations between maternal exposure to SSRIs and both persistent pulmonary hypertension of the newborn and a self-limiting neonatal behavioral syndrome have been reported in a number of recent original studies and meta-analyses. Some studies have suggested a relationship between the use of SSRIs or other serotonergic/noradrenergic antidepressants and the occurrence of miscarriage, although these studies had methodologic limitations that affected the strength of the data. Evidence for a possible association between in utero exposure to SSRIs or other serotonergic/noradrenergic antidepressants and alterations in neurobehavioral development, bleeding, and QTc-interval prolongation is currently weak. The available evidence suggests that SSRIs and other serotonergic/noradrenergic antidepressants should be used with

  7. Proactive Regional Pharmacovigilance System Versus National Spontaneous Reporting for Collecting Safety Data on Concerning Off-Label Prescribing Practices: An Example with Baclofen and Alcohol Dependence in France.

    Science.gov (United States)

    Auffret, Marine; Labreuche, Julien; Duhamel, Alain; Deheul, Sylvie; Cottencin, Olivier; Bordet, Régis; Gautier, Sophie; Rolland, Benjamin

    2017-03-01

    Off-label prescribing (OLP) may raise serious safety concerns that traditional spontaneous reporting of adverse drug reactions (ADRs) may not identify in a timely manner. In France, the 'Multidisciplinary Consultation Service for Off-Label Prescribing in Addiction Medicine' (CAMTEA) is a proactive regional system established to identify ADRs associated with the OLP of baclofen for alcohol dependence. The aim was to demonstrate, using the French pharmacovigilance database (FPVD), that CAMTEA allowed for the reporting of a substantial amount of ADRs, comparable in nature to those provided via spontaneous reporting. The 2012-2013 FPVD notifications associated with baclofen OLP were extracted. The ten most frequent types of ADRs among 'serious' and 'non-serious' reports were listed. The frequency of each type of ADR was compared between CAMTEA and spontaneous reporting, and the magnitudes of the differences were assessed using standardized differences. A total of 428 baclofen reports (1043 ADRs) were identified, among which 221 (51.64%) originated from CAMTEA. The ten most frequent ADRs in 'serious' reports were (1) confusion (17.3%), (2) seizures (11.5%), (3) drowsiness/sedation (11.5%), (4) agitation (10.9%), (5) coma (9.6%), (6) hallucinations (7.7%), (7) falls (7.1%), (8) behavioral disorders (5.8%), (9) withdrawal syndrome (5.1%), and (10) space-time disorientation (5.1%). A standardized difference of pharmacovigilance system could collect a substantial amount of safety data on a specific OLP practice. The profile of the ADRs collected was similar to that seen in the nationwide spontaneous reporting system.

  8. When Vacant Lots Become Urban Gardens: Characterizing the Perceived and Actual Food Safety Concerns of Urban Agriculture in Ohio.

    Science.gov (United States)

    Kaiser, Michelle L; Williams, Michele L; Basta, Nicholas; Hand, Michelle; Huber, Sarah

    2015-11-01

    This study was intended to characterize the perceived risks of urban agriculture by residents of four low-income neighborhoods in which the potential exists for further urban agriculture development and to provide data to support whether any chemical hazards and foodborne pathogens as potential food safety hazards were present. Sixty-seven residents participated in focus groups related to environmental health, food security, and urban gardening. In addition, soils from six locations were tested. Residents expressed interest in the development of urban gardens to improve access to healthy, fresh produce, but they had concerns about soil quality. Soils were contaminated with lead (Pb), zinc, cadmium (Cd), and copper, but not arsenic or chromium. Results from our study suggest paint was the main source of soil contamination. Detectable polyaromatic hydrocarbon (PAH) levels in urban soils were well below levels of concern. These urban soils will require further management to reduce Pb and possibly Cd bioavailability to decrease the potential for uptake into food crops. Although the number of locations in this study is limited, results suggest lower levels of soil contaminants at well-established gardens. Soil tillage associated with long-term gardening could have diluted the soil metal contaminants by mixing the contaminants with clean soil. Also, lower PAH levels in long-term gardening could be due to enhanced microbial activity and PAH degradation, dilution, or both due to mixing, similar to metals. No foodborne pathogen targets were detected by PCR from any of the soils. Residents expressed the need for clearness regarding soil quality and gardening practices in their neighborhoods to consume food grown in these urban areas. Results from this study suggest long-term gardening has the potential to reduce soil contaminants and their potential threat to food quality and human health and to improve access to fresh produce in low-income urban communities.

  9. Antiplatelet Drugs for Secondary Prevention of Cardiovascular Diseases : Drug Utilization, Effectiveness, and Safety

    NARCIS (Netherlands)

    Noorsyahdy, A.Y.

    2017-01-01

    Antiplatelet drugs are recommended for secondary prevention of recurrent cardiovascular events in patients who experience diseases in which the pathophysiology is associated with platelet aggregation and atherosclerosis, including acute coronary syndrome, transient ischemic attack, ischemic stroke,

  10. Safety and efficacy of drug eluting stents in patients with spontaneous coronary artery dissection

    NARCIS (Netherlands)

    Conrotto, Federico; D'Ascenzo, Fabrizio; Cerrato, Enrico; Fernández-Ortiz, Antonio; Gonzalo, Nieves; Macaya, Fernando; Tamburino, Corrado; Barbanti, Marco; van Lavieren, Martijn; Piek, Jan J.; Applegate, Robert J.; Latib, Azeem; Spinnler, Maria Teresa; Marzullo, Raffaella; Iannaccone, Mario; Pavani, Marco; Crimi, Gabriele; Fattori, Rossella; Chinaglia, Alessandra; Presbitero, Patrizia; Varbella, Ferdinando; Gaita, Fiorenzo; Escaned, Javier

    2017-01-01

    Aims: Given the different pathogenesis, use of drug eluting stent (DES) in patients with Spontaneous Coronary Artery Dissection SCAD may delay the healing of the dissected vessel. Aim of our studywas to compare the safety and the efficacy of DES vs. bare metal stent (BMS) in a cohort of patients who

  11. Drug safety alerting in computerized physician order entry: Unraveling and counteracting alert fatigue

    NARCIS (Netherlands)

    I.H. van der Sijs (Heleen)

    2009-01-01

    textabstractComputerized physician order entry systems (CPOEs) usually generate drug safety alerts to remind physicians to potentially unsafe situations. However, physicians may feel overwhelmed by high numbers of alerts that are not patient-tailored and they may consequently suffer from alert

  12. Who was concerned about radiation, food safety, and natural disasters after the great East Japan earthquake and Fukushima catastrophe? A nationwide cross-sectional survey in 2012.

    Directory of Open Access Journals (Sweden)

    Takashi Sugimoto

    Full Text Available BACKGROUND: Disaster-related concerns by sub-populations have not been clarified after the great East Japan earthquake and the Fukushima nuclear power plant incidents. This paper assesses who was concerned about radiation, food safety, and natural disasters among the general population in order to buffer such concerns effectively. METHODS: The hypothesis that women, parents, and family caregivers were most concerned about radiation, food safety, and natural disaster was tested using a varying-intercept multivariable logistic regression with 5809 responses from a nationwide cross-sectional survey random-sampled in March 2012. RESULTS: Many people were at least occasionally concerned about radiation (53.5%, food safety (47.3%, and about natural disaster (69.5%. Women were more concerned than men about radiation (OR = 1.67; 95% CI = 1.35-2.06, food safety (1.70; 1.38-2.10, and natural disasters (1.74; 1.39-2.19. Parents and family care needs were not significant. Married couples were more concerned about radiation (1.53; 1.33-1.77, food safety (1.38; 1.20-1.59, and natural disasters (1.30; 1.12-1.52. Age, child-cohabitation, college-completion, retirement status, homemaker status, and the house-damage certificate of the last disaster were also associated with at least one concern. Participants from the Kanto region were more concerned about radiation (2.08; 1.58-2.74 and food safety (1.30; 1.07-1.59, which demonstrate similar positive associations to participants from Tohoku where a disaster relief act was invoked (3.36; 2.25-5.01 about radiation, 1.49; 1.08-2.06 about food safety. CONCLUSIONS: Sectioning the populations by gender and other demographics will clarify prospective targets for interventions, allow for a better understanding of post-disaster concerns, and help communicate relevant information effectively.

  13. Geochemistry and mercury contamination in receiving environments of artisanal mining wastes and identified concerns for food safety.

    Science.gov (United States)

    Reichelt-Brushett, Amanda J; Stone, Jane; Howe, Pelli; Thomas, Bernard; Clark, Malcolm; Male, Yusthinus; Nanlohy, Albert; Butcher, Paul

    2017-01-01

    Artisanal small-scale gold mining (ASGM) using mercury (Hg) amalgamation has been occurring on Buru Island, Indonesia since early 2012, and has caused rapid accumulation of high Hg concentrations in river, estuary and marine sediments. In this study, sediment samples were collected from several sites downstream of the Mount Botak ASGM site, as well as in the vicinity of the more recently established site at Gogrea where no sampling had previously been completed. All sediment samples had total Hg (THg) concentrations exceeding Indonesian sediment quality guidelines and were up to 82 times this limit at one estuary site. The geochemistry of sediments in receiving environments indicates the potential for Hg-methylation to form highly bioavailable Hg species. To assess the current contamination threat from consumption of local seafood, samples of fish, molluscs and crustaceans were collected from the Namlea fish market and analysed for THg concentrations. The majority of edible tissue samples had elevated THg concentrations, which raises concerns for food safety. This study shows that river, estuary and marine ecosystems downstream of ASGM operations on Buru Island are exposed to dangerously high Hg concentrations, which are impacting aquatic food chains, and fisheries resources. Considering the high dietary dependence on marine protein in the associated community and across the Mollucas Province, and the short time period since ASGM operations commenced in this region, the results warrant urgent further investigation, risk mitigation, and community education. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 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.

  15. 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.

  16. The precautionary principle and the regulation of U.S. food and drug safety.

    Science.gov (United States)

    Soule, Ed

    2004-06-01

    This article probes the advisability of regulating U.S. food and drug safety according to the precautionary principle. To do so, a precautionary regulatory regime is formulated on the basis of the beliefs that motivate most proponents of this initiative. That hypothetical regime is critically analyzed on the basis of an actual instantiation of a similarly stylized initiative. It will be argued that the precautionary principle entails regulatory constraints that are apt to violate basis tenets of political legitimacy. The modifications that would change this finding would also change precautionary regulation to the point that it would be indistinguishable from orthodox safety protocols. It is concluded on the basis of its impoverished content that the precautionary principle should not be taken seriously as a formal approach to the regulation of U.S. food and drug safety.

  17. Potential conflict between TRIPS and GATT concerning parallel importation of drugs and possible solution to prevent undesirable market segmentation.

    Science.gov (United States)

    Lo, Chang-Fa

    2011-01-01

    From international perspective, parallel importation, especially with respect to drugs, has to do with the exhaustion principle in Article 6 of the TRIPS Agreement and the general exception in Article XX of the GATT 1994. Issues concerning the TRIPS Agreement have been constant topics of discussion. However, parallel importation in relation to the general rules of the GATT 1994 as well as to its exceptions provided in Article XX was not seriously discussed. In the view of the paper, there is a conflict between the provisions in these two agreements. The paper explains such conflict and tries to propose a method of interpretation to resolve the conflict between GATT Article XX and TRIPS Article 6 concerning parallel importation for the purpose of reducing the possible undesirable market segmentation in pharmaceutical sector. The method suggested in the paper is a proper application of good faith principle in the Vienna Convention to interpret GATT Article XX, so that there could be some flexibility for those prohibitions of parallel importation which have positive effect on international trade.

  18. Environmental benefits and concerns on safety: communicating latest results on nanotechnology safety research-the project DaNa2.0.

    Science.gov (United States)

    Kühnel, D; Marquardt, C; Nau, K; Krug, H F; Paul, F; Steinbach, C

    2017-04-01

    The use of nanotechnology and advanced materials promises to revolutionise many areas of technology and improve our daily life. In that respect, many positive effects on the environment are expected, either directly, by developing new technologies for remediation, filtering techniques or energy generation, or indirectly, by e.g. saving resources due to lower consumption of raw materials, or lower energy and fuel consumption due to reduced weight of vehicles. However, such beneficial effects of new technologies are often confronted by concerns regarding the safety of novel substances or materials. During the past 10 years, great effort has been put into research on potential hazards of nanomaterials towards environmental organisms. As the methodology for reliable assessment of nanomaterials was immature, many studies reporting contradictory results have been published, hindering both risk assessment for nanomaterials, as well as the knowledge communication to all involved stakeholders. Thus, DaNa 2.0 serves as a platform to implement trusted knowledge on nanomaterials for an objective discussion.

  19. A Drug Safety Rating System Based on Postmarketing Costs Associated with Adverse Events and Patient Outcomes.

    Science.gov (United States)

    Hoffman, Keith B; Dimbil, Mo; Kyle, Robert F; Tatonetti, Nicholas P; Erdman, Colin B; Demakas, Andrea; Chen, Dingguo; Overstreet, Brian M

    2015-12-01

    Given the multiple limitations associated with relatively homogeneous preapproval clinical trials, inadequate data disclosures, slow reaction times from regulatory bodies, and deep-rooted bias against disclosing and publishing negative results, there is an acute need for the development of analytics that reflect drug safety in heterogeneous, real-world populations. To develop a drug safety statistic that estimates downstream medical costs associated with serious adverse events (AEs) and unfavorable patient outcomes associated with the use of 706 FDA-approved drugs. All primary suspect case reports for each drug were collected from the FDA's Adverse Event Reporting System database (FAERS) from 2010-2014. The Medical Dictionary for Regulatory Activities (MedDRA) was used to code serious AEs and outcomes, which were tallied for each case report. Medical costs associated with AEs and poor patient outcomes were derived from Agency for Healthcare Research and Quality (AHRQ) survey data, and their corresponding ICD-9-CM codes were mapped to MedDRA terms. Nonserious AEs and outcomes were not included. For each case report, either the highest AE cost or, if no eligible AE was listed, the highest outcome cost was used. All costed cases were aggregated for each drug and divided by the number of patients exposed to obtain a downstream estimated direct medical cost burden per exposure. Each drug was assigned a corresponding 1-100 point total. The 706 drugs showed an exponential distribution of downstream costs, and the data were transformed using the natural log to approximate a normal distribution. The minimum score was 8.29, and the maximum score was 99.25, with a mean of 44.32. Drugs with the highest individual scores tended to be kinase inhibitors, thalidomide analogs, and endothelin receptor antagonists. When scores were analyzed across Established Pharmacologic Class (EPC), the kinase inhibitor and endothelin receptor antagonist classes had the highest total. However

  20. 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.

  1. 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...... exposure was assessed time dependently based on the prescription drug register from 2006-2009, adjusting for sociodemographics and comorbidities derived from national population-based registers. RESULTS: Exposure to etoricoxib, celecoxib, and nonselective NSAIDs was 7.6%, 3.9%, and 71.2%, respectively...

  2. 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...

  3. 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...... reduction is clearly desirable, the way SbD is currently communicated tends to treat safety as an inherent material property and that this is fundamentally problematic as it represents a recasting and reduction of societal issues into technical problems. SbD therefore faces a multitude of challenges, from...

  4. 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

  5. Laboratory markers in drug safety research: studies on drug-induced thrombocytopenia

    NARCIS (Netherlands)

    ten Berg, M.J.|info:eu-repo/dai/nl/304835986

    2009-01-01

    It regularly happens that medications are found to cause severe adverse effects that remained undetected during premarketing research. From the perspective of the patient, the public and drug manufacturers there is a need for better tools for earlier detection, quantification and mechanistic

  6. Geochemistry and mercury contamination in receiving environments of artisanal mining wastes and identified concerns for food safety

    International Nuclear Information System (INIS)

    Reichelt-Brushett, Amanda J.; Stone, Jane; Howe, Pelli; Thomas, Bernard; Clark, Malcolm; Male, Yusthinus; Nanlohy, Albert; Butcher, Paul

    2017-01-01

    Artisanal small-scale gold mining (ASGM) using mercury (Hg) amalgamation has been occurring on Buru Island, Indonesia since early 2012, and has caused rapid accumulation of high Hg concentrations in river, estuary and marine sediments. In this study, sediment samples were collected from several sites downstream of the Mount Botak ASGM site, as well as in the vicinity of the more recently established site at Gogrea where no sampling had previously been completed. All sediment samples had total Hg (THg) concentrations exceeding Indonesian sediment quality guidelines and were up to 82 times this limit at one estuary site. The geochemistry of sediments in receiving environments indicates the potential for Hg-methylation to form highly bioavailable Hg species. To assess the current contamination threat from consumption of local seafood, samples of fish, molluscs and crustaceans were collected from the Namlea fish market and analysed for THg concentrations. The majority of edible tissue samples had elevated THg concentrations, which raises concerns for food safety. This study shows that river, estuary and marine ecosystems downstream of ASGM operations on Buru Island are exposed to dangerously high Hg concentrations, which are impacting aquatic food chains, and fisheries resources. Considering the high dietary dependence on marine protein in the associated community and across the Mollucas Province, and the short time period since ASGM operations commenced in this region, the results warrant urgent further investigation, risk mitigation, and community education. - Highlights: • Mercury contamination of sediments and seafood due to artisanal gold mining. • Considerable risks to human and ecosystem health are identified. • Results emphasise the urgent need for risk mitigation and community education.

  7. 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

  8. 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

  9. Communication received from the Philippines concerning the Code of Conduct on the Safety and Security of Radioactive Sources: Guidance on the Import and Export of Radioactive Sources

    International Nuclear Information System (INIS)

    2006-01-01

    The Director General has received a letter dated 21 March 2006 from the Permanent Representative of the Philippines concerning the Code of Conduct on the Safety and Security of Radioactive Sources: Supplementary Guidance on the Import and Export of Radioactive Sources. As requested in that letter, it is attached herewith for the information of Member States

  10. Globalization of the pharmaceutical industry: the physician's role in evaluating drug safety.

    Science.gov (United States)

    Beg, M M

    1990-11-01

    The trend toward uniformity of drug registration procedures due to imminent European Economic Community globalization has encouraged pharmaceutical companies to conduct studies on a worldwide basis. This standardization of methods will facilitate the "poolability" of efficacy and safety data generated by these international studies into a common database. With the internationalization of the pharmaceutical marketplace, physicians in industry may be required to collect and interpret such reports from all over the globe. The globalization of the pharmaceutical industry will thus broaden the opportunities for physician involvement in safety detection.

  11. 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...

  12. Posiva's application for a decision in principle concerning a disposal facility for spent nuclear fuel. STUK's statement and preliminary safety appraisal

    Energy Technology Data Exchange (ETDEWEB)

    Ruokola, E. [ed.

    2000-03-01

    In May 1999, Posiva Ltd submitted to the Government an application, pursuant to the Nuclear Energy Act, for a Decision in Principle on a disposal facility for spent nuclear fuel from the Finnish nuclear power plants. The Ministry of Trade and Industry requested the Radiation and Nuclear Safety Authority (STUK) to draw up a preliminary safety appraisal concerning the proposed disposal facility. In the beginning of this report, STUK's statement to the Ministry and Industry concerning the proposed disposal facility is given. In that statement, STUK concludes that the Decision in Principle is currently justified from the standpoint of safety. The statement is followed by a safety appraisal, where STUK deems, how the proposed disposal concept, site and facility comply with the safety requirements included in the Government's Decision (478/1999). STUK's preliminary safety appraisal was supported by contributions from a number of outside experts. A collective opinion by an international group of ten distinguished experts is appended to this report. (orig.)

  13. Decree No 87-137 of 2 March 1987 concerning the High Council for nuclear safety and information

    International Nuclear Information System (INIS)

    1987-01-01

    This Decree amends the Decree of 13th March 1973 setting up a High Council for Nuclear Safety. Its purpose is to widen the terms of reference of the High Council for Nuclear Safety. In addition to its responsibilities as regards the safety of nuclear installations, it is now competent in the field of information. The Council is now charged with informing the media as well as the public not only on questions of safety proper but also on incidents and accidents occurring in nuclear installations. (NEA) [fr

  14. Cardiovascular safety and hemodynamic considerations in oncology drug development - webinar highlights October 10th 2012.

    Science.gov (United States)

    Braddock, Martin; Heilbraun, Jeff; Mendzelevski, Boaz

    2013-09-01

    Development of new drugs in oncology may have implications for cardiovascular risk. This report describes some aspects of our growing knowledge in the area of evaluating benefit-risk and may be of direct importance to scientists working in drug discovery and development. This report of webinar highlights entitled "Trends in CardiOncology: the evolution of blood pressure and electrocardiogram (ECG) Markers" covers the current state of pharmacology of selected drugs which induce blood pressure elevation and best practices in employing the measurement of blood pressure elevation and cardiac safety parameters for drug development in oncology. Oncology drug-induced cardiotoxicity has recently been recognised as an important drug development and clinical issue. The recognition of the risks and opportunities has prompted intensive research into mechanisms of chemotherapy-induced cardiotoxicity and potential prevention strategies. Drug-induced blood pressure elevation has emerged as a key area of interest, both as a marker of efficacy of vascular targeted chemotherapies as well as a target for early intervention strategies. While further research is ongoing, current data strongly suggest that early intervention strategies may provide significant short- and long-term clinical benefits to cancer patients undergoing chemotherapy.

  15. Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Folke, Fredrik; Jacobsen, Søren

    2010-01-01

    Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.......Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals....

  16. Trade-offs between voice and silence: a qualitative exploration of oncology staff’s decisions to speak up about safety concerns

    Science.gov (United States)

    2014-01-01

    Background Research suggests that “silence”, i.e., not voicing safety concerns, is common among health care professionals (HCPs). Speaking up about patient safety is vital to avoid errors reaching the patient and thus to prevent harm and also to improve a culture of teamwork and safety. The aim of our study was to explore factors that affect oncology staff’s decision to voice safety concerns or to remain silent and to describe the trade-offs they make. Methods In a qualitative interview study with 32 doctors and nurses from 7 oncology units we investigated motivations and barriers to speaking up towards co-workers and supervisors. An inductive thematic content analysis framework was applied to the transcripts. Based on the individual experiences of participants, we conceptualize the choice to voice concerns and the trade-offs involved. Results Preventing patients from serious harm constitutes a strong motivation to speaking up but competes with anticipated negative outcomes. Decisions whether and how to voice concerns involved complex considerations and trade-offs. Many respondents reflected on whether the level of risk for a patient “justifies” the costs of speaking up. Various barriers for voicing concerns were reported, e.g., damaging relationships. Contextual factors, such as the presence of patients and co-workers in the alarming situation, affect the likelihood of anticipated negative outcomes. Speaking up to well-known co-workers was described as considerably easier whereas “not knowing the actor well” increases risks and potential costs of speaking up. Conclusions While doctors and nurses felt strong obligation to prevent errors reaching individual patients, they were not engaged in voicing concerns beyond this immediacy. Our results offer in-depth insight into fears and conditions conducive of silence and voicing and can be used for educational interventions and leader reinforcement. PMID:25017121

  17. 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.

  18. A survey of paediatric CT radiation doses in two selected hospitals in Kampala, Uganda: a radiation safety concern

    Directory of Open Access Journals (Sweden)

    Harriet Kisembo

    2015-09-01

    Full Text Available Purpose: We describe radiation doses imparted to paediatric patients during Computerised (CT scan examinations by estimation Weighted CT dose index (CTDIw and Dose Length Product (DLP and compare these doses with the International dose reference values.Methods: Demographic data and acquisition parameters of 257paediatric CT scans done using Multi-Slice CT (MSCT and Dual Slice CT (DSCT were collected from request forms and CT scan consoles. The values of CTDIw, CTDIvol and DLP were calculated using ImPACT (Imaging Performance and Assessment of Computed Tomography dosimetry software for Philips MX-1800 scanner and GE Hispeed Dual scanner. Data was analysed using mean, range, 3rd quartile, as well as chi square.Results: The commonest indication was head injury with the majority patient aged 0-4 years and 10-14 years for MSCT and DSCT, respectively. There were significantly higher doses imparted by MSCT compared to DSCT on both the head CTDIw (mGy (40 vs 22, p = 0.000, CTDIvol (mGy (60 vs 7, p = 0.000, DLPmGy.cm (1022 vs 114, p = 0.000 and body CTDIw (mGy (41 vs 18, p =0.000, CTDIvol (mGy (27 vs 6 p-value=0.000 and DLP (782 vs 73 p-value=0.001 respectively. Paediatric 3rd quartile values for CTDIvol (mGy (57.7 vs 31 0-1 year, (74.5 vs 47 4-7 years and DLP mGy.cm (1068 vs 333 0-1 year and (1168 vs 374 4-6 years respectively for MSCT were higher than the recommended international values. The calculated CTDIvol for the head were significantly higher than the values displayed on the console (p-value=0.000, 95%CI for MSCT.Conclusion: The radiation dose values for CTDIw, CTDIvol and DLP for MSCT were significantly higher than those for DSCT and other countries which raise a radiation safety concern. Studies to establish the factors responsible for these high doses are recommended.

  19. [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.

  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. On the Issue of Regional Policy in the Sphere of Ecological Safety (Based on the Documents Concerning the Republic of Kalmykia

    Directory of Open Access Journals (Sweden)

    Elza I. Mantaeva

    2018-03-01

    Full Text Available The regional government should provide ecological safety in order to ensure stable social and economic development of the country. The article outlines theoretical approach and recommendations on practice concerning ecological issues, investigates state policy aiming to preserve nature and analyses sources of threat to ecological safety in the region. The modern paradigm of the country’s and region’s development is characterized by the combination of ecological and economic policy. The ecological policy providing measures for efficient use of natural resources, their protection and restoration is implemented in the economic strategy of highly developed countries and encourages stable social and economic development of the country and the region. Some researchers assert that Russia’s most regions do not possess sufficient resources necessary to implement structural shifts which can eliminate the main threats to ecological safety. The Republic of Kalmykia can be included into this list. It is rich in natural resources but they are not restored due to the lack of regulation for efficient consumption. The main concerns of the republic are water supply, desertification, and pollution of atmosphere, waste disposal, and protection of wildlife and environment, preservation of hunting ground, forest management. The republic generates no electricity so it is delivered by neighboring regions. The republic should use the renewable ways of producing energy which can contribute to the energy and ecological safety and can attract new investment funds. There is an urgent need for stricter state regulation to ensure socioeconomic development and ecological safety in Kalmykia.

  2. 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.

  3. Proposition of resolution tending to create an inquiry commission concerning the safety conditions of the radiotherapy practices

    International Nuclear Information System (INIS)

    2007-10-01

    Towards the number of radiotherapy acts made every year and the increase of the number of the revealed accidents, it is absolutely indispensable to have an feedback experience and an assessment of the existing means today to control the radioprotection. This work has to allow to give propositions to improve the radiotherapy quality and safety, and provide the patients safety before, during and after the ionizing radiation exposure. (N.C.)

  4. 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.

  5. 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

  6. Protocol between the Nuclear Protection and Safety Bureau of Portugal and the Nuclear Energy Commission of Spain on Technical Information concerning Nuclear Installations in Border Areas

    International Nuclear Information System (INIS)

    1980-01-01

    This Protocol was concluded under the Agreement of the same date on the safety of nuclear installations in border areas. Its purpose is to prescribe the type of information referred to in the Agreement. It lays down in detail all the documents to be supplied concerning the siting, construction, operation and decommissioning of nuclear installations, including the geological, seismological, meteorological, hydrological and ecological aspects of the sites concerned, for purposes of environmental protection; the characteristics of the projected installations and emergency plans must also be provided. Similarly to the Agreement, this Protocol will remain in force for a period of ten years. (NEA) [fr

  7. 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

    The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity. In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the

  8. Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study.

    Science.gov (United States)

    Mostaghim, Sana R; Gagne, Joshua J; Kesselheim, Aaron S

    2017-09-07

    Objective  To determine if drugs approved through the Food and Drug Administration's expedited development and review pathways have different rates of safety related label changes after approval compared with drugs approved through standard non-expedited pathways. Design  Retrospective cohort study. Setting  FDA public records, January 1997 to April 2016. Participants  382 FDA approved drugs. Main outcome measures  The number of times a particular safety section of a label (boxed warning, contraindication, warning, precaution, or adverse reaction) was changed during a drug's time on the market. The relative rate of safety related label changes per year for expedited pathway and non-expedited pathway drugs was compared by forming matched pairs of drugs in the same therapeutic class that were approved within three years of each other. Results  Among the 382 eligible new drugs, 135 (35%) were associated with an expedited development or review pathway, and matches were available for 96 (71%). The matched pairs were associated with a total of 1710 safety related label changes during the study period. Expedited pathway drugs were characterized by a rate of 0.94 safety related label changes for each drug per year, compared with 0.68 safety related label changes per year for non-expedited pathway drugs (rate ratio 1.38, 95% confidence interval 1.25 to 1.52). Compared with non-expedited pathway drugs, expedited pathway drugs had a 48% higher rate of changes to boxed warnings and contraindications, the two most clinically important categories of safety warnings (1.48, 95% confidence interval 1.07 to 2.06). A qualitative review of changes to the boxed warning sections revealed that less than 5% (3/67) were changed to describe reduced risks for patients. Conclusions  Expedited development and regulatory review pathways can accelerate the availability of new drugs, but drugs approved through these pathways are associated with increased safety related label changes after

  9. Brief report: Associations between in-person and electronic bullying victimization and missing school because of safety concerns among U.S. high school students.

    Science.gov (United States)

    Steiner, Riley J; Rasberry, Catherine N

    2015-08-01

    Although associations between bullying and health risk behaviors are well-documented, research on bullying and education-related outcomes, including school attendance, is limited. This study examines associations between bullying victimization (in-person and electronic) and missing school because of safety concerns among a nationally representative sample of U.S. high school students. We used logistic regression analyses to analyze data from the 2013 national Youth Risk Behavior Survey of students in grades 9-12. In-person and electronic victimization were each associated with increased odds of missing school due to safety concerns compared to no bullying victimization. Having been bullied both in-person and electronically was associated with greater odds of missing school compared to electronic bullying only for female students and in-person bullying only for male students. Collaborations between health professionals and educators to prevent bullying may improve school attendance. Published by Elsevier Ltd.

  10. Ethical considerations and proposed guidelines for the use of radio frequency identification: especially concerning its use for promoting public safety and national security.

    Science.gov (United States)

    Anderson, Amber McKee; Labay, Vladimir

    2006-04-01

    Radio Frequency Identification (RFID) is quickly growing in its applications. A variety of uses for the technology are beginning to be developed, including chips which can be used in identification cards, in individual items, and for human applications, allowing a chip to be embedded under the skin. Such chips could provide numerous benefits ranging from day-to-day convenience to the increased ability of the federal government to adequately ensure the safety of its citizens. However, there are also valid concerns about the potential of this technology to infringe on privacy, creating fears of a surveillance society. These are concerns that must be addressed quickly, with sensitivity to individual interests and societal welfare, allowing humanity to reap the benefits of convenience and safety without paying an unacceptable price in the loss of privacy.

  11. 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

  12. 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

  13. Assessment of the global trigger tool to measure, monitor and evaluate patient safety in cancer patients: reliability concerns are raised.

    Science.gov (United States)

    Mattsson, Thea Otto; Knudsen, Janne Lehmann; Lauritsen, Jens; Brixen, Kim; Herrstedt, Jørn

    2013-07-01

    Countries around the world are currently aiming to improve patient safety by means of the Institute for Healthcare Improvement global trigger tool (GTT), which is considered a valid tool for evaluating and measuring patient safety within organisations. So far, only few data on the measurement properties and utility of the GTT have been published. To determine and evaluate the effect of interrater variation between review teams on the standard outcome measures of the GTT and to assess and quantify measurement error of the GTT. Retrospective chart reviews were conducted on identical charts by two independent review teams in 2010 at a department of oncology in a university hospital. Standard GTT outcome measurements were obtained and compared between teams using statistical process control (SPC) charts. A Bland-Altman plot assessed measurement error and limits of agreement. Only 31% of adverse events (AE) were identified by both teams, and further differences in categorisation of identical events was found. Moderate interrater agreement (κ=0.45) between teams gave rise to different conclusions on the patient safety process when monitoring using SPC charts. The Bland-Altman plot suggests little systematic error but large random error. Review teams may identify different AE and reach different conclusions on the safety process when using the GTT on identical charts. Tracking true change in the safety level is difficult due to measurement error of the GTT. The results do not encourage further use of the GTT until additional evaluation studies on the measurement properties of the GTT have been conducted.

  14. The use of toxicokinetics for the safety assessment of drugs acting in the brain.

    Science.gov (United States)

    Campbell, D B

    1995-01-01

    Pharmacological and toxicological studies undertaken on drugs that affect the brain are frequently performed in disparate species under various experimental conditions, at doses often greatly in excess of those expected to be administered to humans, and the findings are extrapolated implicitly or explicitly with scant regard to differences in the biodisposition of the drugs. Such considerations are necessary since: 1. Species; 2. Strain; 3. Gender; 4. Route; 5. Dose; 6. Frequency and time of administration; 7. Temperature; 8. Coadministration of drugs; and 9. Surgical manipulation are but some of the factors that have been shown to influence the kinetics and metabolism of drugs. This article, using MDMA and other phenylethylamines as examples, provides evidence for the need to measure the exposure of the drugs and their active metabolites in blood and brain (toxicokinetics) in order that conclusions based only on dynamic, biochemical, or histological evidence are more pertinent. Further, the combined use of toxicokinetic-dynamic modeling can lead to a better appreciation of the mechanisms involved and a more useful approach to the calculation of safety margins.

  15. 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.

  16. Prospective associations of concerns about physique and the development of obesity, binge drinking, and drug use among adolescent boys and young adult men.

    Science.gov (United States)

    Field, Alison E; Sonneville, Kendrin R; Crosby, Ross D; Swanson, Sonja A; Eddy, Kamryn T; Camargo, Carlos A; Horton, Nicholas J; Micali, Nadia

    2014-01-01

    Relatively little is known about the prevalence of concerns with physique and eating disorders among males and their relation to subsequent adverse outcomes. A broader range of eating disorders needs to be defined to diagnose these illnesses appropriately in males. To investigate whether males with psychiatric symptoms related to disordered eating and concern about physique are more likely to become obese, to start using drugs, to consume alcohol frequently (binge drinking), or to develop high levels of depressive symptoms. The data come from questionnaires sent every 12 to 36 months from 1999 through 2010 to youth in a prospective cohort study, the Growing Up Today Study. The analysis included 5527 males aged 12 to 18 years in 1999 from across the United States who responded to the Growing Up Today Study questionnaires. Development of obesity and high levels of depressive symptoms and initiation of drug use and binge drinking at least monthly. From 1999 through 2011 in at least 1 study year, 9.2% of respondents reported high concerns with muscularity but no bulimic behaviors; 2.4%, high concerns with muscularity and use of supplements, growth hormone derivatives, or anabolic steroids to achieve their desired physique; 2.5%, high concerns with thinness but no bulimic behaviors; and 6.3%, high concerns with thinness and muscularity. For eating disorders, 0.8% had partial- or full-criteria bulimia nervosa or purging disorder and 2.9% had partial or full-criteria binge eating disorder but no association with the outcomes of interest. Infrequent binge eating or purging or overeating without a loss of control were reported by 31.0%. However, independent of age and body mass index, males with high concerns about thinness but not muscularity were more likely to develop high depressive symptoms (odds ratio, 2.72; 95% CI, 1.36-5.44). Males with high concerns about muscularity and thinness were more likely than their peers to use drugs (odds ratio, 2.13; 95% CI, 1

  17. 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

  18. Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening.

    Science.gov (United States)

    Mannhardt, Ingra; Saleem, Umber; Benzin, Anika; Schulze, Thomas; Klampe, Birgit; Eschenhagen, Thomas; Hansen, Arne

    2017-04-15

    Cardiac tissue engineering describes techniques to constitute three dimensional force-generating engineered tissues. For the implementation of these procedures in basic research and preclinical drug development, it is important to develop protocols for automated generation and analysis under standardized conditions. Here, we present a technique to generate engineered heart tissue (EHT) from cardiomyocytes of different species (rat, mouse, human). The technique relies on the assembly of a fibrin-gel containing dissociated cardiomyocytes between elastic polydimethylsiloxane (PDMS) posts in a 24-well format. Three-dimensional, force-generating EHTs constitute within two weeks after casting. This procedure allows for the generation of several hundred EHTs per week and is technically limited only by the availability of cardiomyocytes (0.4-1.0 x 10 6 /EHT). Evaluation of auxotonic muscle contractions is performed in a modified incubation chamber with a mechanical interlock for 24-well plates and a camera placed on top of this chamber. A software controls a camera moved on an XYZ axis system to each EHT. EHT contractions are detected by an automated figure recognition algorithm, and force is calculated based on shortening of the EHT and the elastic propensity and geometry of the PDMS posts. This procedure allows for automated analysis of high numbers of EHT under standardized and sterile conditions. The reliable detection of drug effects on cardiomyocyte contraction is crucial for cardiac drug development and safety pharmacology. We demonstrate, with the example of the hERG channel inhibitor E-4031, that the human EHT system replicates drug responses on contraction kinetics of the human heart, indicating it to be a promising tool for cardiac drug safety screening.

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

    Science.gov (United States)

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

    2006-12-01

    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.

  1. 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.

  2. 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.

  3. The programme of the Minister of the Interior for technical regulations concerning the safety of nuclear facilities

    International Nuclear Information System (INIS)

    Berg, K.H.

    1977-01-01

    The BMI is responsible for the Atomic Energy Act being implemented. A survey is presented of the BMI's programme for setting up technical safety regulations (bar the KTA) according to the following categories: the structure of objects (hardware); the functions of machinery and human behaviour (software); know-how, abilities, responsibility of humans (live-ware); environment. (HP) [de

  4. Serious adverse drug events related to non‐investigational drugs in academic clinical trials: another source of safety data for risk assessment?

    Science.gov (United States)

    Gimbert, Anne; Colin, Anne‐Laurène; Salvo, Francesco; Becker, Madlyne; Marty, Valérie; Montastruc, Jean‐Louis; Petitpain, Nadine

    2016-01-01

    Aims Sponsors of clinical trials have to analyze serious adverse events (SAEs). Both sponsors and investigators determine the relationship between the investigational medicinal product, the investigational device or procedure and SAEs. SAEs related to another cause, such as a non‐investigational medicinal product (NIMP), do not have clear pharmacovigilance reporting requirements. The aim of this study was to evaluate the amount and the nature of NIMP‐related SAEs recorded by three French academic sponsors and to propose pharmacovigilance requirements for these cases. Methods This was a retrospective descriptive study including all cases of NIMP‐related SAEs occurring in clinical trials and reported to three academic sponsors between January 2009 and October 2014. Results Among 5870 cases of SAEs, 300 (5%) were related to a NIMP in 50 clinical trials. Involved NIMPs were mainly antithrombotics, cytostatics and immunosuppressants. Some of these drugs were currently followed by a risk management plan (e.g. rivoxaban). The most frequent NIMP‐related SAEs were neurological, gastrointestinal and infectious disorders. Seven NIMP‐related SAEs were known as ‘rare’ or ‘very rare’ and two were ‘unlabelled’. Conclusions As far as we know, this is the first study to focus about NIMP‐related SAEs occurring in clinical trials. This work highlights the potential high quality source of safety data via NIMP‐related SAE collection. Globally, we propose that NIMP‐related SAEs occurring in clinical trials should systematically be notified to the pharmacovigilance system of the concerned country. Clearer procedures of interactions between safety units of academic sponsors and pharmacovigilance systems are needed to allow an effective recording of NIMP‐related SAEs. PMID:27276241

  5. Factors Influencing the Use of a Mobile App for Reporting Adverse Drug Reactions and Receiving Safety Information : A Qualitative Study

    NARCIS (Netherlands)

    de Vries, Sieta T.; Wong, Lisa; Sutcliffe, Alastair; Houyez, Francois; Ruiz, Carmen Lasheras; Mol, Peter G.M.

    Introduction A mobile app may increase the reporting of adverse drug reactions (ADRs) and improve the communication of new drug safety information. Factors that influence the use of an app for such two-way risk communication need to be considered at the development stage. Objective Our aim was to

  6. Mathematical calculation skills required for drug administration in undergraduate nursing students to ensure patient safety: A descriptive study: Drug calculation skills in nursing students.

    Science.gov (United States)

    Bagnasco, Annamaria; Galaverna, Lucia; Aleo, Giuseppe; Grugnetti, Anna Maria; Rosa, Francesca; Sasso, Loredana

    2016-01-01

    In the literature we found many studies that confirmed our concerns about nursing students' poor maths skills that directly impact on their ability to correctly calculate drug dosages with very serious consequences for patient safety. The aim of our study was to explore where students had most difficulty and identify appropriate educational interventions to bridge their mathematical knowledge gaps. This was a quali-quantitative descriptive study that included a sample of 726 undergraduate nursing students. We identified exactly where students had most difficulty and identified appropriate educational interventions to bridge their mathematical knowledge gaps. We found that the undergraduate nursing students mainly had difficulty with basic maths principles. Specific learning interventions are needed to improve their basic maths skills and their dosage calculation skills. For this purpose, we identified safeMedicate and eDose (Authentic World Ltd.), only that they are only available in English. In the near future we hope to set up a partnership to work together on the Italian version of these tools. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Evaluation of the Safety of Drugs and Biological Products Used During Lactation: Workshop Summary

    Science.gov (United States)

    Wang, J; Johnson, T; Sahin, L; Tassinari, MS; Anderson, PO; Baker, TE; Bucci-Rechtweg, C; Burckart, GJ; Chambers, CD; Hale, TW; Johnson-Lyles, D; Nelson, RM; Nguyen, C; Pica-Branco, D; Ren, Z; Sachs, H; Sauberan, J; Zajicek, A; Ito, S; Yao, LP

    2017-01-01

    This report serves as a summary of a 2-day public workshop sponsored by the US Food and Drug Administration (FDA) to discuss the safety of drugs and biological products used during lactation. The aim of the workshop was to provide a forum to discuss the collection of data to inform the potential risks to breastfed infants with maternal use of medications during lactation. Discussions included the review of current approaches to collect data on medications used during lactation, and the considerations for future approaches to design and guide clinical lactation studies. This workshop is part of continuing efforts to raise the awareness of the public for women who choose to breastfeed their infants. PMID:28510297

  8. Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy.

    Science.gov (United States)

    Cavero, Icilio; Guillon, Jean-Michel

    2014-01-01

    The rhythmic opening and tightly closing of cardiac valve leaflets are cardiac cyclic events imposing to blood a unidirectional course along the vascular tree. Drugs with 5-HT2B agonism properties can seriously compromise this biological function critical for hemodynamic efficiency as their intrinsic pro-fibrotic effects can, with time, make valvular coaptation blood regurgitant. Cardiac valve anatomy, physiology and pathology as well as 5-HT2B receptor properties (coupling, effects mediated, biased agonism) are briefly exposed. Approaches to unveil 5-HT2B receptor liability of drug candidates are detailed. In silico computational models can rapidly probe molecules for chemical signatures associated with 5-HT2B receptor affinity. In vitro radioligand competition assays allow quantifying receptor binding capacity (Ki, IC50), the pharmacological nature (agonism, antagonism) of which can be ascertained from cytosolic second messenger (inositol phosphates, Ca(++), MAPK2) changes. Potencies calculated from the latter data may exhibit variability as they are dependent upon the readout measured and the experimental conditions (e.g., receptor density level of cell material expressing human 5-HT2B receptors). The in vivo valvulopathy effects of 5-HT2B receptor agonists can be assessed by echocardiographic measurements and valve histology in rats chronically treated with the candidate drug. Finally, safety margins derived from from nonclinical and clinical data are evaluated in terms of the readout, usefulness and scientific reliability. The Safety Pharmacology toolbox for detecting possible 5-HT2B receptor agonism liabilities of candidate drugs requires meticulous optimization and validation of all its (in silico, in vitro and in vivo) components to perfect its human predictability power. In particular, since 5-HT2B receptor agonism is biased in nature, the most predictive readout(s) of valvular liability should be identified and prioritized in keeping with best scientific

  9. 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.

  10. 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.

  11. Safety analysis on CANDU-6 nuclear power plant: changes in thermal hydraulic operational conditions concerning regional over power trip setpoints

    International Nuclear Information System (INIS)

    Lee, Jae Yong; Kim, Yong Bae; Kim, Jong Hyun; Son, Hyung Min

    2009-01-01

    A CANDU-6 nuclear power plant has the variable of regional overpower trip (ROPT) to prevent regional overpower within the reactor core. ROPT setpoints are calculated on the basis of channel power where dryout starts to take place in each nuclear fuel channel (i.e. critical channel power; CCP), which is determined based on various core-physical configurations and thermal hydraulic boundary conditions that may be generated throughout the entire life of a nuclear reactor. Variables included in the thermal hydraulic boundary condition (i.e. temperature of the inlet header, pressure on the outlet header, and differential pressure between inlet and outlet headers) change gradually as the number of operational years increases. As for these three operational variables, their operational constraints in consideration of reactor safety are suggested in the operational technical specifications for nuclear power plants. This paper first uses NUCIRC, a code for analyzing thermal hydraulic power at the core of heavy water nuclear reactor, to examine the impacts of changes in these thermal hydraulic boundary condition variables on CCP. To analyze the impacts of changes in the variables for thermal hydraulic boundary conditions on the safety of nuclear reactors, safety analysis is then performed on three representative types of design basis accidents in heavy water reactors-small break loss of coolant accident (SBLOCA), loss of regulations (LOR), and loss of forced circulation-using CATHENA, a thermal hydraulic safety analysis code. By performing two types of thermal hydraulic analysis, the following additional operational margins are ensured against the current operating limits: +2.1 .deg. C for the temperature of the reactor inlet header; -60kPa for differential pressure between inlet and outlet headers; and -40kPa for pressure on the reactor outlet header. By revising the operating limits on this basis, it will be possible to prevent possible reactor power cutbacks caused by

  12. Early safety outcome following transcatheter aortic valve implantation: is the amount of contrast media used a matter of concern?

    Science.gov (United States)

    Vontobel, Jan; Possner, Mathias; Schütz, Philipp; Müller, Beat; Taramasso, Maurizio; Binder, Roland K; Haueis, Sabine; Attinger-Toller, Adrian; Maisano, Francesco; Nietlispach, Fabian

    2015-01-01

    The study objective was to evaluate the impact of the amount of contrast medium used for transcatheter aortic valve implantation (TAVI) on short-term outcome. Patients undergoing TAVI are exposed to repeat contrast medium application both for preprocedural screening and during the TAVI procedure itself. Whether the amount of contrast media is associated with worse outcome is unclear. A total of 257 patients were included (median age 82.7 years) and divided into two groups with preserved and reduced kidney function (glomerular filtration rate contrast media administered during and within 5 days prior to TAVI was analysed. A combined early safety endpoint at 30 days was evaluated. The early safety endpoint was reached by 31 patients and acute kidney injury occurred in 22 patients. The median total volume of contrast media administered was 144 ml (interquartile range 81-225 ml). The amount of contrast did not independently predict the early safety endpoint in the overall population (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.56 to 1.53, p = 0.774) and in subgroups with preserved and reduced kidney function. Change in creatinine was an independent strong predictor of the early safety endpoint in the overall population (OR 18.13, 95% CI 4.70 to 69.99, p contrast did not predict a change in creatinine within 72 hours following TAVI (r = 0.02, 95% CI -0.02 to 0.07, p = 0.368). Decreased kidney function after TAVI influences outcome. When rather small amounts of contrast media are used for screening and the TAVI procedure itself, the amount of contrast media seems not to be an independent predictor of outcome, further suggesting that decreased kidney function after TAVI is multifactorial.

  13. 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.

  14. Nuclear criticality safety: general. 4. The CASTOR X/32S Method of Covering mis-loading Concerns

    International Nuclear Information System (INIS)

    Lancaster, Dale B.; Rombough, Charles T.; Diersch, Rudolf; Spilker, Harry

    2001-01-01

    In the United States, most cask licenses do not directly consider mis-loading. If the enrichment limit for a shipping cask is high and the reactivity control is inherent in the cask, the reactivity effect of a mis-load is small. However, in large-capacity casks, such as the CASTOR X/32S, the effect can be much larger. The U.S. Department of Energy Topical Report on Actinide- Only Burnup Credit takes the position that a fuel assembly mis-load does need to be analyzed since there are multiple independent checks, and thus, the double-contingency principle is met. Unfortunately, 11 assemblies were mis-loaded at Palisades. This event has caused the U.S. Nuclear Regulatory Commission (NRC) to ask for more detail on prevention of mis-loading. In the summer of 1999, Palisades loaded 11 assemblies, which did not comply with the loading requirements for their VSC-24 cask. The cask requires 5 yr of cooling, and these 11 assemblies had just a little more than 4 yr of cooling. The mis-loading did not result in an unsafe condition but in an un-reviewed condition. This mis-loading was not identified until November 2000 during a review related to an NRC information notice. The loading plan for the cask was incorrect. The engineering review of the loading plan missed the error. The operators had loaded the cask consistent with the loading plan. The cask loading was then confirmed by comparing to the loading plan. The loading plan was in error since the engineer assumed that the entire region of fuel was discharged at the same time. The 11 assemblies of concern were reinserted in the reactor, and the engineer and the reviewer did not check for this. The reactor records for all the assemblies were correct but apparently were not checked by the engineer who created the loading plan. To prevent a mis-load criticality event, the following steps will be required for the CASTOR X/32S storage and transport cask: 1. A loading plan will be prepared for each cask loaded. This plan will be

  15. Postmarketing Safety Events Relating to New Drugs Approved in Brazil Between 2003 and 2013: A Retrospective Cohort Study.

    Science.gov (United States)

    Botelho, Stephanie Ferreira; Martins, Maria Auxiliadora Parreiras; Vieira, Liliana Batista; Reis, Adriano Max Moreira

    2017-04-01

    This study investigated postmarketing safety events (PMSEs) for new drugs approved in Brazil and evaluated whether a range of drug characteristics influenced the time between approval and the first PMSE. This retrospective study included new drugs registered between 2003 and 2013 by the National Health Surveillance Agency (ANVISA), which is responsible for medicines approval in Brazil. PMSEs were defined as any drug safety alert or drug withdrawal from the market. The existence of risk evaluation and mitigation strategies (REMS) by the US Food and Drug Administration (FDA) and Brazil were recorded. A Kaplan-Meier survival curve of the period between the date of ANVISA registration and the PMSE was calculated. We found a statistically significant difference between the time to PMSE for drugs with an FDA REMS compared with those without a REMS, with a log rank value (Mantel Cox) of 0.002. There was no association between the time to PMSE and the other drug characteristics investigated. This study demonstrated that the frequency of PMSEs for new drugs approved by ANVISA was statistically associated with the existence of an FDA REMS. The time between approval and first PMSE was shorter for drugs with an FDA REMS, and this finding may contribute to improved awareness of the risk/benefit balance required to ensure continued safe and effective use of new drugs. © 2016, The American College of Clinical Pharmacology.

  16. 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.

  17. Interpreting adverse drug reaction (ADR) reports as hospital patient safety incidents.

    Science.gov (United States)

    Davies, Emma C; Green, Christopher F; Mottram, David R; Pirmohamed, Munir

    2010-07-01

    Adverse drug reactions (ADRs) are a reporting category in the National Patient Safety Agency (NPSA) incident reporting system, though the Medicines and Healthcare Products Regulatory Agency (MHRA) pharmacovigilance system is the more established method for collecting ADR data. The majority of ADRs were shown to be of moderate risk to the patient, though some have a severe or catastrophic impact. Classification and reporting of ADRs according to NPSA guidance is possible but offers limited additional value to efforts to improve patient safety over and above the Yellow Card Scheme. In the UK, the National Patient Safety Agency (NPSA) includes adverse drug reactions as a reporting category, while the MHRA Yellow Card Scheme also collects data regarding adverse drug reactions (ADRs). In this study, we aimed to assess ADRs using NPSA criteria and discuss the resulting implications. ADRs identified in a 6-month prospective study of 3695 inpatient episodes were assessed according to their impact on the patient and on the organization, using tools developed by the NPSA. Seven hundred and thirty-three (100%) ADRs were assessed. In terms of impact on the patient, 537 (73.3%) were categorized as 'low' (minor treatment), 181 (24.7%) as 'moderate' (moderate increase in treatment, no permanent harm), 14 (1.91%) as 'severe' (permanent harm) and 1 (0.14%) was categorized as 'catastrophic' (direct cause of death). In terms of impact on the organization, none was categorized as 'no harm/no risk', 508 (69.3%) as 'insignificant', 188 (25.6%) as 'minor', 25 (3.4%) as 'moderate', 12 (1.6%) as 'major' and none was classed as 'catastrophic'. Less than 2% of ADRs would be eligible for detailed analysis according to the NPSA guidance. The ADRs that cause incidents of greater significance relate to bleeding, renal impairment and Clostridium difficile infection. Classification of ADRs according to NPSA guidance offers limited additional value over and above that offered by the Yellow Card

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

    Directory of Open Access Journals (Sweden)

    A. Anil Sinaci

    2015-01-01

    Full Text Available Postmarketing drug surveillance is a crucial aspect of the clinical research activities in pharmacovigilance and pharmacoepidemiology. Successful utilization of available Electronic Health Record (EHR data can complement and strengthen postmarketing safety studies. In terms of the secondary use of EHRs, access and analysis of patient data across different domains are a critical factor; we address this data interoperability problem between EHR systems and clinical research systems in this paper. We demonstrate that this problem can be solved in an upper level with the use of common data elements in a standardized fashion so that clinical researchers can work with different EHR systems independently of the underlying information model. Postmarketing Safety Study Tool lets the clinical researchers extract data from different EHR systems by designing data collection set schemas through common data elements. The tool interacts with a semantic metadata registry through IHE data element exchange profile. Postmarketing Safety Study Tool and its supporting components have been implemented and deployed on the central data warehouse of the Lombardy region, Italy, which contains anonymized records of about 16 million patients with over 10-year longitudinal data on average. Clinical researchers in Roche validate the tool with real life use cases.

  19. 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.

  20. 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.

  1. 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.

  2. RESPONSIBILITIES OF FOOD BUSINESS OPERATORS RELATED TO FOOD SAFETY: CONCERNS RELATED TO HACCP IN MICRO-BUSINESSES FOOD COMPANIES

    Directory of Open Access Journals (Sweden)

    T. Civera

    2012-08-01

    Full Text Available The research was aimed at collecting information on food safety knowledge by operators of small and less developed food businesses. This will allow to reveal what are the real drawbacks in HACCP application in these realities. Fifty meat producing plants located in Piedmont region were involved. In all the plants a questionnaire with questions on HACCP system was submitted. The analysis of the collected answers, evidenced that 42% of the operators needed to perform structural modifications in order to address the HACCP measures, whereas 40% applied modifications in working procedures. The most frequent shortcoming (44% of the answers of the HACCP system was represented by the applicability of Good Manufacturing Practices, and the most difficult control measure to be applied was the prevention of the cross-contaminations (40% of the answers. The information gathered within this project allowed to evidence the real needs of the micro businesses in the application of HACCP plan. These results can be useful for the institutions, which could elaborate HACCP alternative systems, able to better fulfil food safety requirements and Food Business Operator needs.

  3. Study on safety of a nuclear ship having an integral marine water reactor. Intelligent information database program concerned with thermal-hydraulic characteristics

    International Nuclear Information System (INIS)

    Inasaka, Fujio; Nariai, Hideki; Kobayashi, Michiyuki; Murata, Hiroyuki; Aya, Izuo

    2001-01-01

    As a high economical marine reactor with sufficient safety functions, an integrated type marine water reactor has been considered most promising. At the National Maritime Research Institute, a series of the experimental studies on the thermal-hydraulic characteristics of an integrated/passive-safety type marine water reactor such as the flow boiling of a helical-coil type steam generator, natural circulation of primary water under a ship rolling motion and flashing-condensation oscillation phenomena in pool water has been conducted. This current study aims at making use of the safety analysis or evaluation of a future marine water reactor by developing an intelligent information database program concerned with the thermal-hydraulic characteristics of an integral/passive-safety reactor on the basis of the above-mentioned valuable experimental knowledge. Since the program was created as a Windows application using the Visual Basic, it is available to the public and can be easily installed in the operating system. Main functions of the program are as follows: (1) steady state flow boiling analysis and determination of stability limit for any helical-coil type once-through steam generator design. (2) analysis and comparison with the flow boiling data, (3) reference and graphic display of the experimental data, (4) indication of the knowledge information such as analysis method and results of the study. The program will be useful for the design of not only the future integrated type marine water reactor but also the small sized water reactor. (author)

  4. 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

  5. Regulatory oversight report 2012 concerning nuclear safety in Swiss nuclear installations; Aufsichtsbericht 2012 zur nuklearen Sicherheit in den schweizerischen Kernanlagen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-04-15

    The Swiss Federal Nuclear Safety Inspectorate (ENSI) assesses and monitors nuclear facilities in Switzerland. These include the five nuclear power plants, the interim storage facilities based at each plant, the Central Interim Storage Facility (ZWILAG) and the nuclear facilities at the Paul Scherrer Institute (PSI), at the Federal Institute of Technology in Lausanne (EPFL) and at the University of Basel. Using a combination of inspections, regulatory meetings, examinations and analyses together with reports from the licensees of individual facilities, ENSI obtains the required overview of nuclear safety in the relevant facilities. It ensures that the facilities comply with the regulations and operate as required by law. Its regulatory responsibilities also include the transport of radioactive materials from and to nuclear facilities and the preparations for a deep geological repository for nuclear waste. ENSI maintains its own emergency organisation. It formulates and updates its own guidelines which stipulate the criteria for evaluating the current activities and future plans of the operators of nuclear facilities. ENSI produces regular reports on its regulatory activities and nuclear safety in Swiss nuclear facilities. It fulfils its statutory obligation to provide the public with information on particular events and findings in nuclear facilities. In 2012, the five nuclear power plants in Switzerland were all operated safely. 34 events were reported; on the international INES scale of 0 to 7, ENSI rated 33 events as Level 0 and 1 as Level 1. ENSI evaluates the safety of each nuclear power plant as part of a systematic safety evaluation taking account of both reportable events and other findings, in particular the results of more than 400 inspections conducted by ENSI during 2012. ZWILAG consists of several interim storage halls, a conditioning plant and an incineration/melting plant. At the end of 2012, the cask storage hall contained 40 transport/storage casks

  6. New initiatives for pharmacovigilance in South Korea: introducing the Korea Institute of Drug Safety and Risk Management (KIDS).

    Science.gov (United States)

    Shin, Ju-Young; Jung, Sun-Young; Ahn, So-Hyeon; Lee, Shin Haeng; Kim, Su-Jin; Seong, Jong-Mi; Chung, Soo-Youn; Park, Byung-Joo

    2014-11-01

    Pharmacovigilance plays a vital role in ensuring that patients receive appropriate medical products that are safe and effective. This paper aims to describe the history of pharmacovigilance in Korea and introduce the establishment and goal of the KIDS. In Korea, the adverse drug reactions (ADR) reporting system was launched in 1988 by the Korea Ministry of Food and Drug Safety (MFDS) and spontaneous ADR reports have been collected from health care professionals and the general public. Although the ADR reporting system has begun, the reporting rate was very low in the first 10 years, and safety actions were done passively in response to the US Food and Drug Administration (FDA) or European Medicines Agency (EMA)'s safety alert and communications. Therefore, the Korea Institute of Drug Safety and Risk Management (KIDS) was established in April 2012 as a new initiative for pharmacovigilance. The KIDS will continue to contribute to the improvement of Korean pharmacovigilance by collecting, managing, and analyzing consumer-centered drug safety information. Copyright © 2014 John Wiley & Sons, Ltd.

  7. 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.

  8. 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.

  9. [Appropriate prescription, adherence and safety of non-steroidal anti-inflammatory drugs].

    Science.gov (United States)

    Sostres, Carlos; Lanas, Ángel

    2016-03-18

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most numerous category of drugs sharing the same mechanism of action and therapeutic activities (anti-inflammatory, analgesic and anti-pyretic). Despite having similar efficacy for pain relieve, the different available NSAIDs show variability in its safety profile. The risk of gastrointestinal and cardiovascular complications varies depending on the dose of NSAID and also the presence of different risk factors. It is necessary, therefore, an individualized case assessment before establishing the indication of the best NSAID for each patient, taking account of the best gastroprotection strategy. Improved prescription and enhanced treatment adherence are central objectives to reduce NSAID-related complications. A recent consensus of the Spanish Association of Gastroenterology and the Spanish societies of Cardiology and Rheumatology intends to promote the rational use of NSAIDs according to new recent studies. This review provides additional aspects to facilitate the optimal decision-making process in the routine use of these drugs in clinical practice. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  10. 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.

  11. Regional cooperation for transport of nuclear and radioactive material. Safety, security and safeguards related regulatory tasks concerning international spent fuel shipments

    International Nuclear Information System (INIS)

    Koblinger, László; Horváth, Kristóf

    2016-01-01

    The safety, security and safeguards related regulatory tasks of international spent fuel transports are to be performed according to international conventions; additionally, Hungary as a member state of the European Union shall comply with the relevant EURATOM requirements. The international requirements are reflected in the national legislations of the countries concerned by the transports of research reactor spent fuel under the Global Threat Reduction Initiative repatriation project. The successful realization of these shipments demanded long-lasting preparation with thorough cooperation and conduct with clockwork precision by the regulatory bodies within states and regionally

  12. The U.S. weapon-grade plutonium shipment. Safety and security concern for the ''Eurofab'' operation in France

    International Nuclear Information System (INIS)

    Marignac, Y.; Coeytaux, X.

    2004-09-01

    The present report is a comprehensive update based on a briefing published by W.I.S.E.-Paris in July 2003 on the US plan-also known as Eurofab- to have M.O.X. lead test assemblies fabricated in the French plant of ATPu, Cadarache. Based on recent developments, it discussed the specific risks raised by the unprecedented operation, in particular at the transport and fabrication stages. This analysis includes a joint assessment, by W.I.S.E.-Paris and Large and Associates, in response to the French Institute of radiation protection and nuclear safety (I.R.S.N.) criticism over the independent reports they previously published on this issue. (author)

  13. The safety regime concerning transboundary movement of radioactive waste and its compatibility with the trade regime of the WTO

    International Nuclear Information System (INIS)

    Strack, L.

    2004-01-01

    There is now extensive international law which regulates or prohibits the transboundary movement of radioactive waste. It seems likely that the trade restrictive provisions of the safety regime could be justified under the scope of Article X XI or X X GATT(general agreement on tariffs and trade). If a legitimate non proliferation issue were involved it is likely that any WTO (world trade organization) dispute settlement organ would allow governments the use of exceptions. Thus, the emerging international radioactive waste regime seems reconcilable under the WTO system. However, further clarification by the political, not the dispute settlement, institutions of the WTO would remove any remaining uncertainty by reaffirming the requirements of current law. Achieving sustainable development requires a coherent framework of global environment and economic governance. (N.C.)

  14. Decree of the President of the Republic of 31 July 1980 concerning the Higher Institute for Safety at Work (Section 23 of Act N0 833 of 1978)

    International Nuclear Information System (INIS)

    1980-01-01

    This Decree is important as respects nuclear energy insofar as the tasks of the Institute which are mainly of an advisory nature, also concern radiation protection and safety in connection with nuclear activities. It provides for an advisory role to be played by the Institute as regards health protection in the field of nuclear power generation and radioactive materials, including use of and trade in such materials. On the other hand, it does not affect the regulations governing the use of nuclear energy, in particular as concerns Act N 0 1240 of 1971 reorganising the CNEN, Act N 0 1860 of 1962 on the peaceful uses of nuclear energy, Presidential Decree N 0 185 of 1964 on radiation protection and the decrees implementing these tests (NEA) [fr

  15. 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

  16. 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

  17. Impact of a transient instability of the ecstasy market on health concerns and drug use patterns in The Netherlands

    NARCIS (Netherlands)

    Brunt, Tibor M.; Niesink, Raymond J. M.; van den Brink, Wim

    2012-01-01

    A recent decline in MDMA-like substances in ecstasy tablets has been reported by a number of countries in the European Union. This study describes the instability of the ecstasy market in The Netherlands during 2008 and 2009, and investigates whether this had any impact on drug testing or patterns

  18. “Is it still safe to eat traditional food?” Addressing traditional food safety concerns in aboriginal communities

    Energy Technology Data Exchange (ETDEWEB)

    Bordeleau, Serge, E-mail: Serge.Bordeleau@uqat.ca [Chaire de Recherche du Canada en Foresterie Autochtone, Université du Québec en Abitibi-Témiscamingue, 445 boul. de l' Université, Rouyn-Noranda, Québec J9X 5E4 (Canada); Chaire Industrielle CRSNG-UQAT-UQÀM en Aménagement Forestier Durable, Université du Québec en Abitibi-Témiscamingue, 445 boul. de l' Université, Rouyn-Noranda, Québec J9X 5E4 (Canada); Asselin, Hugo, E-mail: Hugo.Asselin@uqat.ca [Chaire de Recherche du Canada en Foresterie Autochtone, Université du Québec en Abitibi-Témiscamingue, 445 boul. de l' Université, Rouyn-Noranda, Québec J9X 5E4 (Canada); Chaire Industrielle CRSNG-UQAT-UQÀM en Aménagement Forestier Durable, Université du Québec en Abitibi-Témiscamingue, 445 boul. de l' Université, Rouyn-Noranda, Québec J9X 5E4 (Canada); and others

    2016-09-15

    Food insecurity is a growing concern for indigenous communities worldwide. While the risk of heavy metal contamination associated to wild food consumption has been extensively studied in the Arctic, data are scarce for the Boreal zone. This study addressed the concerns over possible heavy metal exposure through consumption of traditional food in four Anishnaabeg communities living in the Eastern North American boreal forest. Liver and meat samples were obtained from 196 snowshoe hares (Lepus americanus) trapped during winter 2012 across the traditional lands of the participating communities and within 56–156 km of a copper smelter. Interviews were conducted with 78 household heads to assess traditional food habits, focusing on snowshoe hare consumption. Concentrations in most meat and liver samples were below the detection limit for As, Co, Cr, Ni and Pb. Very few meat samples had detectable Cd and Hg concentrations, but liver samples had mean dry weight concentrations of 3.79 mg/kg and 0.15 mg/kg respectively. Distance and orientation from the smelter did not explain the variability between samples, but percent deciduous and mixed forest cover had a marginal negative effect on liver Cd, Cu and Zn concentrations. The estimated exposition risk from snowshoe hare consumption was low, although heavy consumers could slightly exceed recommended Hg doses. In accordance with the holistic perspective commonly adopted by indigenous people, the nutritional and sociocultural importance of traditional food must be considered in risk assessment. Traditional food plays a significant role in reducing and preventing serious health issues disproportionately affecting First Nations, such as obesity, diabetes, and cardiovascular diseases. Traditional consumption of snowshoe hare (Lepus americanus) entails low risk of heavy metal exposure if animals are tapped > 50 km from a point emission source (such as a copper smelter in the present study), if risk-increasing behaviours are

  19. “Is it still safe to eat traditional food?” Addressing traditional food safety concerns in aboriginal communities

    International Nuclear Information System (INIS)

    Bordeleau, Serge; Asselin, Hugo

    2016-01-01

    Food insecurity is a growing concern for indigenous communities worldwide. While the risk of heavy metal contamination associated to wild food consumption has been extensively studied in the Arctic, data are scarce for the Boreal zone. This study addressed the concerns over possible heavy metal exposure through consumption of traditional food in four Anishnaabeg communities living in the Eastern North American boreal forest. Liver and meat samples were obtained from 196 snowshoe hares (Lepus americanus) trapped during winter 2012 across the traditional lands of the participating communities and within 56–156 km of a copper smelter. Interviews were conducted with 78 household heads to assess traditional food habits, focusing on snowshoe hare consumption. Concentrations in most meat and liver samples were below the detection limit for As, Co, Cr, Ni and Pb. Very few meat samples had detectable Cd and Hg concentrations, but liver samples had mean dry weight concentrations of 3.79 mg/kg and 0.15 mg/kg respectively. Distance and orientation from the smelter did not explain the variability between samples, but percent deciduous and mixed forest cover had a marginal negative effect on liver Cd, Cu and Zn concentrations. The estimated exposition risk from snowshoe hare consumption was low, although heavy consumers could slightly exceed recommended Hg doses. In accordance with the holistic perspective commonly adopted by indigenous people, the nutritional and sociocultural importance of traditional food must be considered in risk assessment. Traditional food plays a significant role in reducing and preventing serious health issues disproportionately affecting First Nations, such as obesity, diabetes, and cardiovascular diseases. Traditional consumption of snowshoe hare (Lepus americanus) entails low risk of heavy metal exposure if animals are tapped > 50 km from a point emission source (such as a copper smelter in the present study), if risk-increasing behaviours are

  20. Radiation safety concerns for pregnant or breast feeding patients. The positions of the NCRP and the ICRP

    Energy Technology Data Exchange (ETDEWEB)

    Meinhold, C.B. [Brookhaven National Lab., Upton, NY (United States)

    1997-01-01

    For many years, protecting the fetus has been a concern of the National Council on Radiation Protection and Measurements (NCRP) and the International Commission on Radiological Protection (ICRP). Early recommendations focused on the possibility of a wide variety of detrimental developmental effects while later recommendations focused on the potential for severe mental retardation and/or reduction in the intelligence quotient (I.Q.). The latest recommendations also note that the risk of cancer for the fetus is probably two to three times greater per Sv than in the adult. For all these reasons, the NCRP and the ICRP have provided guidance to physicians on taking all reasonable steps to ascertain whether any woman requiring a radiological or nuclear medicine procedure is pregnant or nursing a child. The NCRP and the ICRP also advise the clinician to postpone such procedures until after delivery or cessation of nursing, if possible.

  1. Radiation safety concerns for pregnant or breast feeding patients. The positions of the NCRP and the ICRP

    International Nuclear Information System (INIS)

    Meinhold, C.B.

    1997-01-01

    For many years, protecting the fetus has been a concern of the National Council on Radiation Protection and Measurements (NCRP) and the International Commission on Radiological Protection (ICRP). Early recommendations focused on the possibility of a wide variety of detrimental developmental effects while later recommendations focused on the potential for severe mental retardation and/or reduction in the intelligence quotient (I.Q.). The latest recommendations also note that the risk of cancer for the fetus is probably two to three times greater per Sv than in the adult. For all these reasons, the NCRP and the ICRP have provided guidance to physicians on taking all reasonable steps to ascertain whether any woman requiring a radiological or nuclear medicine procedure is pregnant or nursing a child. The NCRP and the ICRP also advise the clinician to postpone such procedures until after delivery or cessation of nursing, if possible

  2. Depression longitudinally mediates the association of appearance concerns to ART non-adherence in HIV-infected individuals with a history of injection drug use.

    Science.gov (United States)

    Blashill, Aaron J; Gordon, Janna R; Safren, Steven A

    2014-02-01

    Appearance concerns are common among HIV-infected individuals, and previous cross-sectional and longitudinal data indicate that these concerns are associated with antiretroviral therapy (ART) non-adherence. However, to date, no known prospective data have explored the mechanism behind this relationship. Thus, the aim of the current study was to test depression severity as a prospective mediator of the relationship between appearance concerns and ART non-adherence in HIV-infected individuals with a history of injection drug use (IDU). Participants were 89 HIV-infected individuals with a history of IDU who participated in a prospective, randomized controlled trial of cognitive behavioral therapy for depression and medication adherence. Clinician-administered measures of depression severity and appearance concerns, along with electronic monitoring of ART non-adherence were included. Data were analyzed using longitudinal linear mixed-level modeling, and mediation was tested via the Monte Carlo Method of Assessing Mediation. Appearance concerns were predictive of depression severity, γ = .31, SE = .076, 95 % CI [.16, .46], t = 4.1, p = .0001, and depression severity was predictive of ART non-adherence, γ = 3.3, SE = 1.3, 95 % CI [.8, 5.8], t = 2.6, p = .01. The effect of appearance concerns on ART non-adherence, however, was significantly mediated by depression severity, γ = 1.02, 95 % CI [.21, 2.1]. Appearance concerns are associated with depression severity, which in turn is associated with ART non-adherence. Integrative interventions addressing appearance concerns, depression and ART adherence are needed, as this is one potential pathway towards worse health outcomes in HIV-infected individuals.

  3. Common Health, Safety and Environmental Concerns in Upstream Oil and Gas Sector: Implications for HSE Management in Ghana

    Directory of Open Access Journals (Sweden)

    Seth Oppong

    2014-01-01

    Full Text Available This paper explores the literature to identify common occupational injuries, diseases, and psychological wellbeing on oil rigs as well as the negative environmental impacts of the upstream oil and gas sector. It ends by making recommendations for effective health, safety, and environmental (HSE management. Review of the literature showed that contusion (bruise, cuts, and laceration are the commonest occupational injuries that workers on the oil rig suffer and that the injuries mostly affect the hand and finger, leg, and eyes of the offshore workers. These injuries were found to be caused mostly by direct stroke, jamming and overstrain. Similarly, accidental poisoning, musculoskeletal disorders, respiratory disorders and diseases of the digestive system were also documented as the commonest occupational diseases among offshore workers. The literature also shows that working offshore is associated with poorer psychological wellbeing or health; this is to say that offshore workers tend to experience higher levels of stress, burnout, anxiety, depression, low job satisfaction (particularly with the environmental conditions associated with their work, and sleep disorders. Finally, the literature review indicated that land-use problems, air pollution, acid rain, climate change, habitat disruption, environmental degradation, oil spills and leakages are some of environmental impacts of upstream oil production. This review was concluded by recommending some measures for the management of the HSE hazards associated with the oil and gas sector.

  4. Are There Potential Safety Problems Concerning the Use of Electronic Performance-Tracking Systems? The Experience of a Multisport Elite Club.

    Science.gov (United States)

    Medina, Daniel; Pons, Eduard; Gomez, Antonio; Guitart, Marc; Martin, Andres; Vazquez-Guerrero, Jairo; Camenforte, Ismael; Carles, Berta; Font, Roger

    2017-09-01

    Despite approval of the use of electronic performance-tracking systems (EPTSs) during competition by the International Football Association Board, other team-sport organizations and leagues have banned their use due to "safety concerns," with no evidence to support this assertion. The aim of the current brief report was to provide empirical evidence to support the widespread use of EPTSs across all sports by examining safety issues concerning their use in a multi-team-sport club. Five outdoor football teams (1st team, 2nd team, under 19 [U-19], under 18 [U-18], and 1st team female) and 3 indoor-sport (basketball, futsal, and handball) teams were monitored, accounting for a total of 63,734 h of training and 12,748 h of game time. A questionnaire was sent to all fitness coaches involved, and the clinical history was reviewed for every medical issue reported. Six minor chest contusions were recorded in female football goalkeepers wearing the frontal chest strap (3.17 episodes per 1000 training h). During training, 3 episodes of minor skin abrasion affecting the thoracic area due to wearing vests too tight were recorded in the U-19 football team (0.21 per 1000 h) and 2 episodes in U-18 (0.39 per 1000 h). It must be noted that none of these episodes resulted in lost days of training or games, and none required medical assistance. In conclusion, empirical evidence confirms that EPTSs are safe to use across team sports.

  5. [Drug supply and patient safety in long-term care facilities for the elderly].

    Science.gov (United States)

    Uhrhan, T; Schaefer, M

    2010-05-01

    Nursing home residents are a continuously growing population with a need for intense pharmacotherapy due to numerous comorbid conditions. Polypharmacy and the frequent use of psychotropic medication increase the risk of adverse drug events, which may result in risk of increased morbidity and mortality in frail, elderly patients. The requirement to solve individual therapeutic problems has to be supported by not only an adequate and need-based pharmaceutical supply but also by suitable organizational and logistic solutions. In the nursing home environment, ineffective communication between the various professional groups involved in medical treatment may lead to inappropriate or unintentional medication use. In the present survey, data and research results that are relevant to assess the medical treatment situation in long-term care facilities particularly with regard to the safety of pharmacotherapy are presented. The two problem areas of patient-customized therapy and the handling of pharmaceuticals in the context of institutional care are addressed separately.

  6. Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) Collies after oral administration.

    Science.gov (United States)

    Walther, Feli M; Paul, Allan J; Allan, Mark J; Roepke, Rainer K A; Nuernberger, Martin C

    2014-03-06

    Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. This study investigated the safety of oral administration of fluralaner at 3 times the highest expected clinical dose to Multi Drug Resistance Protein 1 (MDR1(-/-)) gene defect Collies. Sixteen Collies homozygous for the MDR1 deletion mutation were included in the study. Eight Collies received fluralaner chewable tablets once at a dose of 168 mg/kg; eight sham dosed Collies served as controls. All Collies were clinically observed until 28 days following treatment. No adverse events were observed subsequent to fluralaner treatment of MDR1(-/-) Collies at three times the highest expected clinical dose. Fluralaner chewable tablets are well tolerated in MDR1(-/-) Collies following oral administration.

  7. Resolute Integrity drug eluting stent safety and efficacy for the treatment of coronary artery disease

    Directory of Open Access Journals (Sweden)

    Burgos JD

    2013-02-01

    Full Text Available Jose D Burgos, Safa Farrag, Debabrata Mukherjee Department of Internal Medicine, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA Abstract: The need to develop a local antirestenotic mechanism to prevent in-stent thrombosis has driven the development of new generation stents. The Resolute Integrity® stent is a zotarolimus-eluting system with a new BioLinx™ polymer that allows a slower drug elution. Recently available data has shown the clinical efficacy and safety of this stent in randomized and observational studies. The Resolute Integrity stent system has demonstrated noninferiority when compared with other stents and holds the promise to treat more complex coronary lesions. Keywords: zotarolimus, BioLinx, coronary stenosis, stents, restensosis, stent thrombosis

  8. 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.

  9. Cardiovascular safety of non-steroidal anti-inflammatory drugs revisited.

    Science.gov (United States)

    Walker, Chris; Biasucci, Luigi M

    2018-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used to treat inflammatory pain for decades. More recently, newer NSAIDs were developed to target the inducible isoform of cyclooxygenase (COX), COX-2, with the aim of reducing gastrointestinal toxicity. While the COX-2 selective inhibitors were effective in reducing pain and gastrointestinal harm, they soon were associated with an increased risk of adverse cardiovascular events. Initially, the view emerged that selective inhibition of COX-2, and sparing of COX-1, was responsible for the increased cardiovascular harm observed. However, as more data from different human populations has become available this view has begun to be challenged. This review examines the current understanding of the role of prostaglandins and COX-1 and COX-2, particularly in platelets, the vasculature, and the kidney together with an overview of the cardiovascular and renal safety of both traditional NSAIDs and COX-2 selective inhibitors. Available data from active comparator randomized controlled trials, including the data from the PRECISION trial investigating the long term cardiovascular safety of patients exclusively with elevated baseline cardiovascular risk, are presented. The data, when considered holistically, support the idea that all NSAIDs carry some level of cardiovascular risk, be they traditional NSAIDs or COX-2 selective agents. There is also some evidence of heterogeneity of effect with NSAIDs particularly in relation to effects on blood pressure, with no clear demarcation based on the degree of COX-2 selectivity.

  10. Continuous versus group sequential analysis for post-market drug and vaccine safety surveillance.

    Science.gov (United States)

    Silva, I R; Kulldorff, M

    2015-09-01

    The use of sequential statistical analysis for post-market drug safety surveillance is quickly emerging. Both continuous and group sequential analysis have been used, but consensus is lacking as to when to use which approach. We compare the statistical performance of continuous and group sequential analysis in terms of type I error probability; statistical power; expected time to signal when the null hypothesis is rejected; and the sample size required to end surveillance without rejecting the null. We present a mathematical proposition to show that for any group sequential design there always exists a continuous sequential design that is uniformly better. As a consequence, it is shown that more frequent testing is always better. Additionally, for a Poisson based probability model and a flat rejection boundary in terms of the log likelihood ratio, we compare the performance of various continuous and group sequential designs. Using exact calculations, we found that, for the parameter settings used, there is always a continuous design with shorter expected time to signal than the best group design. The two key conclusions from this article are (i) that any post-market safety surveillance system should attempt to obtain data as frequently as possible, and (ii) that sequential testing should always be performed when new data arrives without deliberately waiting for additional data. © 2015, The International Biometric Society.

  11. Safety of epoietin beta-quinine drug combination in children with cerebral malaria in Mali.

    Science.gov (United States)

    Picot, Stéphane; Bienvenu, Anne-Lise; Konate, Salimata; Sissoko, Sibiri; Barry, Abdoulaye; Diarra, Elisabeth; Bamba, Karidiatou; Djimdé, Abdoulaye; Doumbo, Ogobara K

    2009-07-24

    Cerebral malaria carries an unacceptable case fatality rate in children despite timely and adequate chemotherapy. To improve the survival rate, adjunctive therapies previously tested mainly focused on the modulation of the inflammatory response, without definitive effect in humans. In this context, a new adjunctive strategy using a neuroprotective drug: erythropoietin (epoietin-beta, Epo) was proposed. An open-labelled study including cerebral malaria children (Blantyre coma score below 3) was conducted in Mali. The objective was to assess the short-term safety (seven days) of erythropoietin at high doses (1,500 U/kg/day during three days) combined to quinine. 35 patients with unrousable coma were included in the study. None of expected side effects of erythropoietin were observed during the seven days follow-up. No significant increase in the case fatality rate (7/35 patients) was observed compared to other studies with mortality rates ranging from 16 to 22% in similar endemic areas. These data provide the first evidence of the short-term safety of erythropoietin at high doses combined to quinine. A multicentre study is needed to assess the potential of Epo as an adjunctive therapy to increase the survival during cerebral malaria. CLINICAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT00697164.

  12. Drug safety evaluation of parathyroid hormone for hypocalcemia in patients with hypoparathyroidism.

    Science.gov (United States)

    Marcucci, Gemma; Della Pepa, Giuseppe; Brandi, Maria Luisa

    2017-05-01

    Hypoparathyroidism is a rare disorder characterized by low serum calcium levels and high serum phosphate levels, and low or inappropriately normal levels of parathyroid hormone (PTH). This disease is commonly treated with calcium supplements and active vitamin D metabolites or analogues, but large doses of these supplements are often utilized to relieve the symptoms caused by hypocalcemia, without guarantee of a physiological normalization of calcium-phosphate homeostasis. Areas covered: Several studies have investigated replacement therapy with recombinant human PTH [rhPTH (1-84) and rhPTH (1-34)] for subjects with hypoparathyroidism. In 2015, The Food and Drug Administration (FDA) approved, in the United States, rhPTH (1-84), named Natpara®, a bioenginerred rhPTH, for the management of chronic hypoparathyroidism not well controlled with conventional therapy. This article evaluates the safety and tolerability of rhPTH (1-84) in patients with chronic hypoparathyroidism, and also describes the studies conducted so far on rhPTH (1-34) used for chronic hypoparathyroidism. Expert opinion: The research done in this field has shown that replacement treatment with rhPTH is an attractive option for subjects with hypoparathyroidism who are unable to maintain stable and safe serum and urinary calcium levels. However, since therapy with rhPTH is a long-term management option in hypoparathyroidism, more long-term safety data are needed.

  13. Results of the 2013–2014 national roadside survey of alcohol and drug use by drivers : traffic safety facts : research note.

    Science.gov (United States)

    2015-02-01

    In 20132014, the National Highway Traffic Safety Administration conducted the most recent National Roadside Survey of Alcohol and Drug Use by Drivers.1 This voluntary and anonymous study is the second to collect data on drug use, presenting our fi...

  14. Safety of 5-Aminosalicylic Acid Derivatives in Patients with Sensitivity to Acetylsalicylic Acid and Nonsteroidal Anti-inflammatory Drugs.

    Science.gov (United States)

    Poh, Jennifer; Knowles, Sandra

    2014-01-01

    One of the cornerstones of the management of inflammatory bowel disease is the use of 5-aminosalicylic acid (5-ASA) compounds for treatment of flares and as maintenance therapy during remission. There are concerns about using 5-ASA in patients with a history of hypersensitivity to acetylsalicylic acid (ASA). To assess the literature with respect to the safety of 5-ASA compounds in patients with documented sensitivity to ASA or nonsteroidal anti-inflammatory drugs (NSAIDs). A literature search was conducted in the MEDLINE and Embase databases, using various search terms, including "aminosalicylic acids", "non-steroidal anti-inflammatory agents," "hypersensitivity", and "allergy". The search was limited to articles (of any study design) published in English. Abstracts, full articles, and reference lists from retrieved articles were assessed to identify further relevant literature. Of 485 citations identified in the initial search, 4 case reports were relevant to the study objective and were analyzed in detail. Three of the case reports described the successful use of 5-ASA compounds in patients with prior sensitivity to ASA or an NSAID. The fourth report described a reaction to 5-ASA in a patient who had previously tolerated ASA. All of the reports were limited by lack of investigation into the validity of the reported sensitivity to ASA or 5-ASA. There is a dearth of evidence demonstrating cross-reactivity between ASA or NSAID and 5-ASA. This lack of information may relate to the mechanism of action of 5-ASA. This agent controls inflammation by inhibiting prostaglandin E2 and leukotrienes. In contrast, ASA-induced or NSAID-induced reactions are due to inhibition of the cycloxygenase-1 enzyme and subsequent release of histamine and synthesis of leukotrienes. Further reports describing the safety of 5-ASA use in patients with sensitivity to ASA or NSAIDs are needed before safety in this situation can be definitively determined. In patients with sensitivity to ASA or

  15. EEG in non-clinical drug safety assessments: Current and emerging considerations.

    Science.gov (United States)

    Authier, Simon; Delatte, Marcus S; Kallman, Mary-Jeanne; Stevens, Joanne; Markgraf, Carrie

    2016-01-01

    Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in preclinical safety studies, pre-dose or post-dose EEG assessments are not. Industry practices as they relate to preclinical seizure liability and sleep assessments are not well characterized and the extent of preclinical EEG testing varies between organizations. In the current paper, we discuss the various aspects of preclinical EEG to characterize drug-induced seizure risk and sleep disturbances, as well as describe the use of these data in a regulatory context. An overview of EEG technology-its correct application and its limitations, as well as best practices for setting up the animal models is presented. Sleep and seizure detection are discussed in detail. A regulatory perspective on the use of EEG data is provided and, tying together the previous topics is a discussion of the translational aspects of EEG. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. The global counterfeit drug trade: patient safety and public health risks.

    Science.gov (United States)

    Mackey, Tim K; Liang, Bryan A

    2011-11-01

    Counterfeit drugs are a global problem with significant and well-documented consequences for global health and patient safety, including drug resistance and patient deaths. This multibillion-dollar industry does not respect geopolitical borders, and threatens public health in both rich and resource-poor nations alike. The epidemiology of counterfeits is also wide in breadth and scope, including thousands of counterfeit incidents per year, encompassing all types of therapeutic classes, and employing a complex global supply chain network enabling this illegal activity. In addition, information technologies available through the Internet and sales via online pharmacies have allowed the criminal element to thrive in an unregulated environment of anonymity, deception, and lack of adequate enforcement. Though recent global enforcement efforts have led to arrests of online counterfeit sellers, such actions have not stemmed supplies from illegal online sellers or kept up with their creativity in illegally selling their products. To address this issue, we propose a global policy framework utilizing public-private partnership models with centralized surveillance reporting that would enable cooperation and coordination to combat this global health crisis. Copyright © 2011 Wiley-Liss, Inc.

  17. 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)

  18. 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.

  19. Does Patient Reporting lead to Earlier Detection of Drug Safety Signals? : A Retrospective Comparison of Time to Reporting Between Patients and Healthcare Professionals in a Global Database

    NARCIS (Netherlands)

    Rolfes, Leàn; van Hunsel, Florence; Caster, Ola; Taavola, Henric; Taxis, Katja; van Puijenbroek, Eugène

    2018-01-01

    OBJECTIVE: To explore if there is a difference between patients and healthcare professionals (HCPs) in time to reporting drug-adverse drug reaction (ADR) associations which led to drug safety signals. DESIGN: This was a retrospective comparison of time to reporting selected drug-ADR associations

  20. Review of the Safety Concern Related to CANDU Moderator Temperature Distribution and Status of KAERI Moderator Circulation Test (MCT) Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, Bo W.; Kim, Hyoung T. [Severe Accident and PHWR Safety Research Division, Daejeon (Korea, Republic of); Kim, Tongbeum [University of the Witwatersrand, Johannesburg (South Africa); Im, Sunghyuk [KAIST, Daejeon (Korea, Republic of)

    2015-10-15

    threshold temperature and no further deformation is expected. Consequently, a sufficient condition to ensure fuel channel integrity following a large LOCA, is the avoidance of sustained calandria tubes dryout. If the moderator available subcooling at the onset of a large LOCA is greater than the subcooling requirements, a sustained calandria tube dryout is avoided. The temperature oscillations observed in reactor and in test measurements such as MTF need to be characterized and quantified to show that it does not jeopardize the currently available safety margins. Because of the importance of an accurate prediction of moderator temperature distributions and the related moderator subcooling, a 1/4 scaled-down moderator tank of a CANDU-6 reactor, called Moderator Circulation Test (MCT), was erected at KAERI and the current status of MCT experiment progress is described and further experiments are expected to be carried out to generate the experimental data necessary to validate the computer codes that will be used to analyze the accident analysis of operating CANDU-6 plants.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Identification of UV-absorbing extractables from rubber closures used in containers of injectable powder and safety assessment of leachables in the drug.

    Science.gov (United States)

    Wei, Yulei; Wu, Ying; Zhu, Tingli; Li, Zhiyan; Zhang, Yilan

    2017-05-10

    Rubber closures have been of great concern to regulatory authorities on account of their potential safety risks to patients. The aim of our work is to provide part of data about the compatibility of the injectable powder and its packaging materials for the drug registration. In this report, methodologies were established to study the system of the preparation. Firstly, three major extractables were isolated by semi-preparative HPLC method combined with silica gel-based chromatographic methods. NMR spectra including 1D NMR ( 1 H, 13 C, DEPT135) and 2D NMR (COSY, HSQC, HMBC) were introduced to identify the extractables, besides HPLC, GC-MS, ESI-MS/MS and HRMS. The extractables were determined to be N-(2-(2,2,4,4-tetramethylcyclohexyl)allyl) benzo[d]thiazol-2-amine (1), 2,6-Di-tert-butyl-4-methylphenol (2) and sulfur (3) respectively. Then, to address safety concerns, approaches including QSAR analysis, the TTC and comprehensive literature evaluation methods to toxicological safety evaluation of the target compounds were established, where the safety threshold such as TTC and PDE values were developed. Finally, the migration testing of the extractables were performed to assess the leaching behavior of the rubber closures. An optimized analysis method was proposed using SPE and HPLC with an ultraviolet detector, which demonstrated good linearity, acceptable accuracy and precision. The levels of the target compounds in the powder were measured and the calculated worst case exposure of extractable 2 exceeded the TTC limit of 1.5μg/day, indicating that the products may possess potential health risks to patients. In contrast to previous studies, various NMR techniques, which were rarely applied to identify unknown extractables from rubber closures in the literature, were discussed for the structural elucidation of rubber closures extractables. Among the target compounds, extractable 1 was a new compound, whose isolation and structural elucidation were first reported here

  6. Ptaquiloside, the major carcinogen of bracken fern, in the pooled raw milk of healthy sheep and goats: an underestimated, global concern of food safety.

    Science.gov (United States)

    Virgilio, Antonella; Sinisi, Annamaria; Russo, Valeria; Gerardo, Salvatore; Santoro, Adriano; Galeone, Aldo; Taglialatela-Scafati, Orazio; Roperto, Franco

    2015-05-20

    Bracken fern (Pteridium aquilinum) is a worldwide plant containing toxic substances, which represent an important chemical hazard for animals, including humans. Ptaquiloside, 1, a norsesquiterpenoid glucoside, is the major carcinogen of bracken detected in the food chain, particularly in the milk from farm animals. To date, ptaquiloside has been shown in the milk of cows feeding on a diet containing bracken fern. This is the first study that shows the systematic detection of ptaquiloside, 1, and reports its direct quantitation in pooled raw milk of healthy sheep and goats grazing on bracken. Ptaquiloside, 1, was detected by a sensitive method based on the chemical conversion of ptaquiloside, 1, into bromopterosine, 4, following gas chromatography-mass spectrometry (GC-MS) analysis. The presence of ptaquiloside, 1, possibly carcinogenic to humans, in the milk of healthy animals is an unknown potential health risk, thus representing a harmful and potential global concern of food safety.

  7. Evaluation of various ways to deliver information concerning non-steroidal anti-inflammatory drugs to osteoarthritis patients.

    Science.gov (United States)

    Gremeaux, V; Durand, S; Benaïm, C; Hérisson, C; Monleaud, J; Hansel, S; Coudeyre, E

    2013-02-01

    It is essential to provide complete information to patients using non-steroidal anti-inflammatory drugs (NSAIDs) because of the risk of side effects. Today, most healthcare professionals recommend and privilege oral information regarding NSAIDs. Evaluate the impact of three standardized NSAIDs information-delivery modalities on knowledge, anxiety and satisfaction of patients hospitalized in a Physical Medicine and Rehabilitation unit for debilitating and degenerative locomotor diseases. Randomized prospective study with an alternate month design. Two control groups were provided with only one type of information modality: written (information sheet) or oral (presentation). The intervention group received both modalities of information. The information included: the definition of NSAIDs, advantages and side effects, and practical advice regarding proper use. The main evaluation criterion was knowledge progression assessed by a specific questionnaire. Secondary criteria were anxiety evolution (STAI-Y questionnaire) and satisfaction related to the information delivered. One hundred and forty patients were included. Knowledge was improved in the three groups, with a greater score improvement in the group that received both modalities (P=0.05). No intergroup difference was noted on anxiety or satisfaction. Associating both information-delivery modalities (written+oral) contributes to improving knowledge but does not seem to have an impact on the anxiety of patients treated with NSAIDs for their degenerative locomotor disease. Using standardized information sheets with a validated content could help pharmacists in their role as healthcare education provider and effectively complement the information delivered orally. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. The impact of emerging safety and effectiveness evidence on the use of physician-administered drugs: the case of bevacizumab for breast cancer.

    Science.gov (United States)

    Conti, Rena M; Dusetzina, Stacie B; Herbert, Ann C; Berndt, Ernst R; Huskamp, Haiden A; Keating, Nancy L

    2013-07-01

    Spending on physician-administered drugs is high and uses not approved by the US Food and Drug Administration (FDA) are frequent. Although these drugs may be targets of future policy efforts to rationalize use, little is known regarding how physicians respond to emerging safety and effectiveness evidence. We analyzed changes in bevacizumab (Avastin) use for breast cancer in response to its market launch (February 2008), 2 FDA meetings reviewing data suggesting that its risks exceed its benefits (July 2010 and June 2011), and the FDA's withdrawal of approval (November 2011). Data from a population-based audit of oncologists' prescribing (IntrinsiQ Intellidose) were used to measure the monthly number of breast cancer patients treated with bevacizumab (January 2008-April 2012). The number of bevacizumab patients following each regulatory action was estimated using negative binomial regression, compared with patients before the first FDA meeting, adjusting for cancer stage, treatment line, patient age, and outpatient office affiliation. Bevacizumab use for breast cancer increased significantly after FDA approval. After all regulatory actions, there was a 65% decline (95% CI, 64%-65%) in use compared with the period before the first meeting. The largest decline was in the 6-month period after the first meeting (37%; 95% CI, 28%-47%). The rate of decline did not differ by patient or cancer characteristics and differed minimally by office affiliation. Bevacizumab use for breast cancer declined dramatically after FDA meetings and regulatory actions, a period without changes in guideline recommendations or insurance coverage. Physicians seem to be responsive to emerging evidence concerning physician-administered drug safety and effectiveness.

  9. Application of the threshold of toxicological concern approach for the safety evaluation of calendula flower (Calendula officinalis) petals and extracts used in cosmetic and personal care products.

    Science.gov (United States)

    Re, T A; Mooney, D; Antignac, E; Dufour, E; Bark, I; Srinivasan, V; Nohynek, G

    2009-06-01

    Calendula flower (Calendula officinalis) (CF) has been used in herbal medicine because of its anti-inflammatory activity. CF and C. officinalis extracts (CFE) are used as skin conditioning agents in cosmetics. Although data on dermal irritation and sensitization of CF and CFE's are available, the risk of subchronic systemic toxicity following dermal application has not been evaluated. The threshold of toxicological concern (TTC) is a pragmatic, risk assessment based approach that has gained regulatory acceptance for food and has been recently adapted to address cosmetic ingredient safety. The purpose of this paper is to determine if the safe use of CF and CFE can be established based upon the TTC class for each of its known constituents. For each constituent, the concentration in the plant, the molecular weight, and the estimated skin penetration potential were used to calculate a maximal daily systemic exposure which was then compared to its corresponding TTC class value. Since the composition of plant extracts are variable, back calculation was used to determine the maximum acceptable concentration of a given constituent in an extract of CF. This paper demonstrates the utility and practical application of the TTC concept when used as a tool in the safety evaluation of botanical extracts.

  10. Alternation of antiretroviral drug regimens for HIV infection. Efficacy, safety and tolerability at week 96 of the Swatch Study.

    Science.gov (United States)

    Negredo, Eugenia; Paredes, Roger; Peraire, Joaquim; Pedrol, Enric; Côté, Helene; Gel, Silvia; Fumoz, Carmina R; Ruiz, Lidia; Abril, Vicente; Rodriguez de Castro, Eduardo; Ochoa, Claudia; Martinez-Picado, Javier; Montaner, Julio; Rey-Joly, Celestino; Clotet, Bonaventura

    2004-12-01

    Alternation of antiretroviral drug regimens has been proposed as a novel treatment strategy for HIV infection. However, some concerns persist regarding antiviral efficacy, adherence, toxicity and resistance evolution in the long term. A total of 161 antiretroviral-naive HIV-1-infected patients were randomized to receive stavudine/didanosine/efavirenz (group A) or zidovudine/lamivudine/ nelfinavir (group B) or to alternate between the two regimens every 3 months starting with regimen A (group C). Antiviral efficacy, adherence, safety and tolerability were analysed every 12 weeks. After 96 weeks, time to virological failure was significantly delayed in the alternating regimen compared with the standards of care regimens. Virological suppression was seen in 46%, 48% and 58% of patients in groups A, B and C, respectively, in the intention-to-treat analysis and in 75%, 76% and 97% in the on-treatment analysis (A vs C: P=0.014; B vs C: P=0.016; A vs B: P=0.849). At the end of the study, 94% of patients in group A and 92% in groups B and C reported an adherence greater than 95%. Alternating therapy was associated with a similar impact on CD4+ counts in comparison with the standards of care regimens, as well as a lower mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio decrease in the mitochondrial substudy performed on 37 patients. The frequency and intensity of adverse events in the alternating group decreased during subsequent cycles. Our results favour the hypothesis that proactive therapy switching may delay the accumulation of resistance mutations. Moreover, the alternating regimen was well tolerated and adherence remained comparably high in all treatment groups. The lower mtDNA/nDNA ratio decrease observed in this group may imply a lower impact on mitochondrial toxicity than in standard regimens.

  11. Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

    Science.gov (United States)

    Stegemann, Sven

    2018-05-02

    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 are not medical or pharmaceutical experts, who have impaired health and potentially disabilities 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.

  12. The use of reimbursement data for timely monitoring of vaccination coverage: the example of human papillomavirus vaccine following public concerns about vaccine safety.

    Science.gov (United States)

    Fonteneau, Laure; Ragot, Marine; Parent du Châtelet, Isabelle; Guthmann, Jean-Paul; Lévy-Bruhl, Daniel

    2015-12-12

    Since 2011 public concerns about Human Papillomavirus (HPV) vaccination safety and efficacy arose in France. We explored the relevance of using vaccines reimbursement data to assess the impact of those public concerns on vaccination coverage. We used the Permanent Sample of Beneficiaries which was, at the time of the study, a representative sample of 1/97(th) health insurance beneficiaries of the main Social Security scheme, the General Health Insurance Scheme, covering approximately 77 % of the French resident population. We estimated HPV vaccination coverage among girls born between 1995 and 1999 at their 15(th), 16(th) and 17(th) birthday. The coverage for complete vaccination among 16 years old girls decreased from 26.5 % in the first semester of 2011 to 18.6 % in the first semester of 2014. HPV vaccination coverage was already low in 2011 and continued to decrease thereafter. Vaccines reimbursement data allowed us to reactively monitor the impact of the controversy on vaccination coverage and design counteracting measures.

  13. Finnish discourses of the stakeholders on development of the implementation of EU legislation concerned with occupational safety and health in computer work.

    Science.gov (United States)

    Niskanen, Toivo; Lehtelä, Jouni

    2015-01-01

    The overall research objective was to empirically develop the ideas around a system of occupational safety and health (OSH) practices in visual display unit (VDU) work, to describe their relationship with the OSH legislation and to explore how these best practices work to achieve positive results. The aim of the present study was to explore qualitative perceptions of the stakeholders (Finnish Employers' Associations, Employees Organizations and OSH Governmental Inspectorates) concerning the way that the OSH legislation on VDU work is being applied at work. Many stakeholders claim that technological advances require that in OSH the VDU legislation should be updated, especially that it should be clarified, e.g., when does the VDU worker have the right to obtain special eyeglasses needed for VDU work. Many stakeholders believe that additional guidelines concerning practical ergonomic arrangements in VDU work environment and eyeglasses of the VDU workers are needed. In VDU ergonomics, the co-operation between workplace and occupational health care professionals needs to be developed.

  14. 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

  15. A human liver microphysiology platform for investigating physiology, drug safety, and disease models.

    Science.gov (United States)

    Vernetti, Lawrence A; Senutovitch, Nina; Boltz, Robert; DeBiasio, Richard; Shun, Tong Ying; Gough, Albert; Taylor, D Lansing

    2016-01-01

    This paper describes the development and characterization of a microphysiology platform for drug safety and efficacy in liver models of disease that includes a human, 3D, microfluidic, four-cell, sequentially layered, self-assembly liver model (SQL-SAL); fluorescent protein biosensors for mechanistic readouts; as well as a microphysiology system database (MPS-Db) to manage, analyze, and model data. The goal of our approach is to create the simplest design in terms of cells, matrix materials, and microfluidic device parameters that will support a physiologically relevant liver model that is robust and reproducible for at least 28 days for stand-alone liver studies and microfluidic integration with other organs-on-chips. The current SQL-SAL uses primary human hepatocytes along with human endothelial (EA.hy926), immune (U937) and stellate (LX-2) cells in physiological ratios and is viable for at least 28 days under continuous flow. Approximately, 20% of primary hepatocytes and/or stellate cells contain fluorescent protein biosensors (called sentinel cells) to measure apoptosis, reactive oxygen species (ROS) and/or cell location by high content analysis (HCA). In addition, drugs, drug metabolites, albumin, urea and lactate dehydrogenase (LDH) are monitored in the efflux media. Exposure to 180 μM troglitazone or 210 μM nimesulide produced acute toxicity within 2-4 days, whereas 28 μM troglitazone produced a gradual and much delayed toxic response over 21 days, concordant with known mechanisms of toxicity, while 600 µM caffeine had no effect. Immune-mediated toxicity was demonstrated with trovafloxacin with lipopolysaccharide (LPS), but not levofloxacin with LPS. The SQL-SAL exhibited early fibrotic activation in response to 30 nM methotrexate, indicated by increased stellate cell migration, expression of alpha-smooth muscle actin and collagen, type 1, alpha 2. Data collected from the in vitro model can be integrated into a database with access to related

  16. 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

  17. Safety and effectiveness of colistin compared with tobramycin for multi-drug resistant Acinetobacter baumannii infections

    Directory of Open Access Journals (Sweden)

    Cohen Karen

    2009-03-01

    Full Text Available Abstract Background Nosocomial infections due to multi-drug resistant Acinetobacter baumannii are often treated with colistin, but there are few data comparing its safety and efficacy with other antimicrobials. Methods A retrospective cohort study of patients treated with colistin or tobramycin for A. baumannii infections in intensive care units (ICUs at Groote Schuur hospital. Colistin was used for A. baumannii isolates which were resistant to all other available antimicrobials. In the tobramycin group, 53% of the isolates were only susceptible to tobramycin and colistin. We assessed ICU mortality, nephrotoxicity and time to the first negative culture. Results 32 patients, with similar admission APACHE scores and serum creatinine, were treated with each antimicrobial. There were no significant differences between the colistin and tobramycin groups in ICU mortality (p = 0.54, nephrotoxicity (p = 0.67, change in creatinine from baseline to highest subsequent value (p = 0.11 and time to microbiological clearance (p = 0.75. The hazard ratio for total in-hospital survival in patients treated with colistin compared to tobramycin was 0.43 (95% CI 0.19 to 0.99. Conclusion Our study suggests that colistin and tobramycin have similar risks of nephrotoxicity and are equally efficacious. Colistin is an acceptable antibiotic for the treatment of A. baumanii infections when the organism is resistant to other available antimicrobials.

  18. 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.

  19. Safety

    CERN Multimedia

    2003-01-01

    Please note that the safety codes A9, A10 AND A11 (ex annexes of SAPOCO/42) entitled respectively "Safety responsibilities in the divisions" "The safety policy committee (SAPOCO) and safety officers' committees" and "Administrative procedure following a serious accident or incident" are available on the web at the following URLs: Code A9: http://edms.cern.ch/document/337016/LAST_RELEASED Code A10: http://edms.cern.ch/document/337019/LAST_RELEASED Code A11: http://edms.cern.ch/document/337026/LAST_RELEASED Paper copies can also be obtained from the TIS divisional secretariat, e-mail: tis.secretariat@cern.ch. TIS Secretariat

  20. 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.

  1. 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...

  2. 75 FR 32189 - Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety...

    Science.gov (United States)

    2010-06-07

    ..., GlaxoSmithKline, a drug approved for blood glucose control in adults with type 2 diabetes mellitus. Data... Outcome and Regulation of Glycemia in Diabetes (RECORD) Trial, observational data, health claims data, and...

  3. Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing.

    Science.gov (United States)

    Ortega, Francis A; Grandi, Eleonora; Krogh-Madsen, Trine; Christini, David J

    2017-01-01

    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.

  4. 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

  5. Safety and efficacy of drug eluting stents in patients with spontaneous coronary artery dissection.

    Science.gov (United States)

    Conrotto, Federico; D'Ascenzo, Fabrizio; Cerrato, Enrico; Fernández-Ortiz, Antonio; Gonzalo, Nieves; Macaya, Fernando; Tamburino, Corrado; Barbanti, Marco; van Lavieren, Martijn; Piek, Jan J; Applegate, Robert J; Latib, Azeem; Spinnler, Maria Teresa; Marzullo, Raffaella; Iannaccone, Mario; Pavani, Marco; Crimi, Gabriele; Fattori, Rossella; Chinaglia, Alessandra; Presbitero, Patrizia; Varbella, Ferdinando; Gaita, Fiorenzo; Escaned, Javier

    2017-07-01

    Given the different pathogenesis, use of drug eluting stent (DES) in patients with Spontaneous Coronary Artery Dissection SCAD may delay the healing of the dissected vessel. Aim of our study was to compare the safety and the efficacy of DES vs. bare metal stent (BMS) in a cohort of patients who underwent stenting for SCAD. Consecutive patients with SCAD between January 1995 and August 2014 were retrospectively identified in 12 centers and included. Major Adverse Cardiac Events (MACE) was the primary end point. A total of 238 SCAD patients were identified: of them 108 patients underwent PCI with DES or BMS. Overall 24 patients (22.2%) suffered an intra-procedural complication without any differences between the 2 groups. At median follow-up of 1201days (Inter Quartile Range 541-2760), incidence of the primary endpoint showed a trend towards less events in the DES-treated patients (38.7% vs. 25.9% p=0.14) mainly driven by the benefit of DES in terms of TVR (17.6% vs. 4%, p=0.08), mortality (16.8% vs. 9.3%, p=0.4), and MI rate (16% vs. 8.4%, p=0.33). STEMI at presentation (HR 6.4, CI 95% 1.29-31.9, p=0.02) but not kind of stent (HR 0.97, CI 95% 0.2-4.7, p=0.9) emerged as independently related to prognosis at multivariable analysis. In SCAD patients use of DES seems to be as safe as BMS with trend of better efficacy in the long term. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Analgesic efficacy and safety of nonsteroidal anti-inflammatory drugs after transurethral resection of prostate

    Directory of Open Access Journals (Sweden)

    Cengiz Kara

    2010-02-01

    Full Text Available OBJECTIVES: The aim of this study was to assess the analgesic efficacy and safety of nonsteroidal anti-inflammatory drugs (NSAIDs, administered as intramuscular diclofenac in comparison with intravenous paracetamol after transurethral resection of the prostate (TURP. MATERIALS AND METHODS: Fifty men, aged 55 to 75 years, undergoing TURP at our hospital were included in this study. Patients were divided randomly and prospectively into two groups (25 patients in each group. Group I (NSAID received 75 mg of diclofenac i.m. at the end of the operation followed by 75 mg of diclofenac i.m. for 24 hours (75 mg x 2 once a day = 150 mg/24 h postoperatively. The other group (Group II consisted of patients who received 1g/100 mL i.v. paracetamol 15 minutes twice daily as postoperative analgesia. Postoperative pain scores were evaluated at 30 minutes, 1, 2, 4 and 6 hours after administration of each analgesic, using a visual analogue scale (VAS. Furthermore, preoperative and postoperative hemoglobin (Hb levels and hemostatic variables (bleeding time, prothrombine time and the international normalized ratio?, i.e. the ratio of a patient's prothrombin time to a normal [control] sample were recorded in all patients. RESULTS: The pain score changes during a 4 hour period between the two groups was similar (p = 0.162. Thirty minutes after surgery, pain scores were high (> 3 cm in both groups and without differences between groups (p = 0.11 but 6 hours after surgery, pain scores were significantly higher with paracetamol compared to diclofenac (p < 0.05. No significant difference was observed between the groups regarding the amount of resected tissue, operating time, preoperative-postoperative Hb levels and hemostatic variables. In the both groups, no patient required blood transfusion postoperatively. CONCLUSIONS: NSAIDs are not a contraindication to TURP and should be used for the control of postoperative pain if indicated.

  7. Association between the use of anticholinergic antiparkinson drugs and safety and receptor drug-binding profiles of antipsychotic agents.

    Science.gov (United States)

    Gjerden, Pål; Slørdal, Lars; Bramness, Jørgen G

    2009-12-01

    The use of anticholinergic antiparkinson drugs is almost exclusively confined to treating antipsychotic-induced extrapyramidal side effects (EPS). We investigated the prevalence of concomitant prescription of anticholinergics as a proxy for antipsychotic-induced EPS and compared variance in prevalence with differences in the assumed mechanisms of action of antipsychotics on central nervous system (CNS) transmitter systems (i.e., receptor drug-binding profiles). We paid special attention to potential differences between typical and atypical antipsychotics. Data were drawn from the Norwegian Prescription Database on sales of antipsychotic and anticholinergic antiparkinson drugs to a total of 57,130 outpatients in 2004. We assessed concomitant dispensations of antipsychotic and anticholinergic drugs and correlated the prevalence of concomitantly prescribed anticholinergics to previously assessed receptor-binding profiles of antipsychotics. The concurrent use of anticholinergics varied between 0.4% and 26.0% for patients using a single antipsychotic agent. The prevalence of anticholinergic comedication was more than twice as high in patients using two or more antipsychotic drugs. Four typical antipsychotics (fluphenazine, zuclopenthixol, haloperidol, and perphenazine) were associated with higher concomitant use of anticholinergics than the rest. For the remaining 14 antipsychotic agents, the difference between typical and atypical antipsychotics was neither pronounced nor systematic. A high degree of D2-receptor antagonism and a high 5-HT2A/D2-receptor-affinity ratio coincided with the use of anticholinergics. The liability of antipsychotic drugs to cause EPS seemed to vary considerably and largely independently of the distinction between typical and atypical antipsychotics.

  8. 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.

  9. The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience

    Science.gov (United States)

    Shuster, Constantin; DeMarco, Mari L.; Rosenfeld, Gregory

    2016-01-01

    Background. Infliximab (IFX) therapeutic drug monitoring (TDM) allows for objective decision making in patients with inflammatory bowel disease (IBD) and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA) concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67%) and 2 (83%) had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P = 0.098). Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range. PMID:27957480

  10. The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience

    Directory of Open Access Journals (Sweden)

    Robert A. Mitchell

    2016-01-01

    Full Text Available Background. Infliximab (IFX therapeutic drug monitoring (TDM allows for objective decision making in patients with inflammatory bowel disease (IBD and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67% and 2 (83% had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P=0.098. Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range.

  11. Comparative efficacy and safety of oral antidiabetic drugs and insulin in treating gestational diabetes mellitus

    Science.gov (United States)

    Liang, Hui-ling; Ma, Shu-juan; Xiao, Yan-ni; Tan, Hong-zhuan

    2017-01-01

    Abstract Background: The safety and efficacy of different drugs in treatment of gestational diabetes mellitus (GDM) patients who could not maintain normal glucose level only through diet and exercise remains to be debated. We performed this network meta-analysis (NAM) to compare and rank different antidiabetic drugs in glucose level control and pregnancy outcomes in GDM patients. Methods: We searched PubMed, Cochrane Library, Web of Science, and Embase up to December 31, 2016. Randomized controlled trials (RCTs) related to different drugs in the treatment of GDM patients were enrolled. We extracted the relevant information and assessed the risk of bias with the Cochrane risk of bias tool. We did pair-wise meta-analyses using the fixed-effects model or random-effects model and then adopted random-effects NAM combining both direct and indirect evidence within a Bayesian framework, to calculate the odds ratio (OR) or standardized mean difference (SMD) and to draw a surface under the cumulative ranking curve of the neonatal and maternal outcomes of different treatments in GDM patients. Results: Thirty-two randomized controlled trials (RCTs) were included in this NAM, including 6 kinds of treatments (metformin, metformin plus insulin, insulin, glyburide, acarbose, and placebo). The results of the NAM showed that regarding the incidence of macrosomia and LGA, metformin had lower incidence than glyburide (OR, 0.5411 and 0.4177). In terms of the incidence of admission to the NICU, insulin had higher incidence compared with glyburide (OR, 1.844). As for the incidence of neonatal hypoglycemia, metformin had lower incidence than insulin and glyburide (OR, 0.6331 and 0.3898), and insulin was lower than glyburide (OR, 0.6236). For mean birth weight, metformin plus insulin was lower than insulin (SMD, -0.5806), glyburide (SMD, -0.7388), and placebo (SMD, -0.6649). Besides, metformin was observed to have lower birth weight than glyburide (SMD, 0.2591). As for weight gain

  12. 78 FR 49988 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules on Foreign Supplier...

    Science.gov (United States)

    2013-08-16

    .../Certification Bodies; Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA or we) is announcing a public meeting to discuss... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1 and 16 [Docket...

  13. 78 FR 6762 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Science.gov (United States)

    2013-01-31

    ... AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA) is announcing a public meeting to discuss the proposed rules to establish... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110...

  14. 78 FR 57320 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules on Foreign Supplier...

    Science.gov (United States)

    2013-09-18

    .../Certification Bodies; Public Meetings AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meetings. SUMMARY: The Food and Drug Administration (FDA or we) is announcing two public meetings to... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1 and 16 [Docket...

  15. 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...

  16. 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

  17. A comparison of safety and efficacy of cytotoxic versus molecularly targeted drugs in pediatric phase I solid tumor oncology trials.

    Science.gov (United States)

    Dorris, Kathleen; Liu, Chunyan; Li, Dandan; Hummel, Trent R; Wang, Xia; Perentesis, John; Kim, Mi-Ok; Fouladi, Maryam

    2017-03-01

    Prior reviews of phase I pediatric oncology trials involving primarily cytotoxic agents have reported objective response rates (ORRs) and toxic death rates of 7.9-9.6% and 0.5%, respectively. These data may not reflect safety and efficacy in phase I trials of molecularly targeted (targeted) drugs. A systematic review of pediatric phase I solid tumor trials published in 1990-2013 was performed. The published reports were evaluated for patient characteristics, toxicity information, and response numbers. A total of 143 phase I pediatric clinical trials enrolling 3,896 children involving 53 targeted and 48 cytotoxic drugs were identified. A meta-analysis demonstrated that the ORR is 2.1-fold higher with cytotoxic drugs (0.066 vs. 0.031 per subject; P = 0.007). By contrast, the pooled estimate of the stable disease rate (SDR) is similar for cytotoxic and targeted drugs (0.2 vs. 0.23 per subject; P = 0.27).  The pooled estimate of the dose-limiting toxicity rate is 1.8-fold larger with cytotoxic drugs (0.24 vs. 0.13 per subject; P = 0.0003). The hematologic grade 3-4 (G3/4) toxicity rate is 3.6-fold larger with cytotoxic drugs (0.43 vs. 0.12 per treatment course; P = 0.0001); however, the nonhematologic G3/4 toxicities and toxic deaths occur at similar rates for cytotoxic and targeted drugs. In phase I pediatric solid tumor trials, ORRs were significantly higher for cytotoxic versus targeted agents. SDRs were similar in targeted and cytotoxic drug trials. Patients treated with cytotoxic agents were more likely to experience hematologic G3/4 toxicities than those patients receiving targeted drugs. © 2016 Wiley Periodicals, Inc.

  18. 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.

  19. Inhaled pulmonary vasodilators for persistent pulmonary hypertension of the newborn: safety issues relating to drug administration and delivery devices

    Directory of Open Access Journals (Sweden)

    Cosa N

    2016-04-01

    Full Text Available Nathan Cosa,1 Edward Costa Jr2 1Department of Respiratory Care, Banner Desert Medical Center, Cardon Children's Medical Center, Mesa, AZ, 2Department of Medical Affairs, Mallinckrodt Pharmaceuticals, Hampton, NJ, USA Abstract: Treatment for persistent pulmonary hypertension of the newborn (PPHN aims to reduce pulmonary vascular resistance while maintaining systemic vascular resistance. Selective pulmonary vasodilation may be achieved by targeting pulmonary-specific pathways or by delivering vasodilators directly to the lungs. Abrupt withdrawal of a pulmonary vasodilator can cause rebound pulmonary hypertension. Therefore, use of consistent delivery systems that allow for careful monitoring of drug delivery is important. This manuscript reviews published studies of inhaled vasodilators used for treatment of PPHN and provides an overview of safety issues associated with drug delivery and delivery devices as they relate to the risk of rebound pulmonary hypertension. Off-label use of aerosolized prostacyclins and an aerosolized prostaglandin in neonates with PPHN has been reported; however, evidence from large randomized clinical trials is lacking. The amount of a given dose of aerosolized drug that is actually delivered to the lungs is often unknown, and the actual amount of drug deposited in the lungs can be affected by several factors, including patient size, nebulizer used, and placement of the nebulizer within the breathing circuit. Inhaled nitric oxide (iNO is the only pulmonary vasodilator approved by the US Food and Drug Administration for the treatment of PPHN. The iNO delivery device, INOmax DSIR®, is designed to constantly monitor NO, NO2, and O2 deliveries and is equipped with audible and visual alarms to alert providers of abrupt discontinuation and incorrect drug concentration. Other safety features of this device include two independent backup delivery systems, a backup drug cylinder, a battery that provides up to 6 hours of

  20. Bringing a genomic perspective to the safety of drug treatment in oncology

    OpenAIRE

    Innocenti, Federico

    2017-01-01

    This article describes the clinical relevance of toxicity of therapies administered to patients with cancer, putting the patient, rather than disease, at the center of the evaluation of safety of anti-cancer therapy. Hence, the implications of adverse events are described from the patient perspective, focusing on the impact of patient safety on quality of life and efficacy of treatment. Issues revolving around other types of safety, such as financial toxicity, are also discussed. The role pla...

  1. Proposition of resolution tending to create an inquiry commission concerning the safety conditions of the radiotherapy practices; Proposition de resolution tendant a creer une commission d'enquete concernant les conditions de securite des pratiques de radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-10-15

    Towards the number of radiotherapy acts made every year and the increase of the number of the revealed accidents, it is absolutely indispensable to have an feedback experience and an assessment of the existing means today to control the radioprotection. This work has to allow to give propositions to improve the radiotherapy quality and safety, and provide the patients safety before, during and after the ionizing radiation exposure. (N.C.)

  2. 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

  3. Efficacy and safety of anakinra for the treatment of rheumatoid arthritis: an update of the Oregon Drug Effectiveness Review Project

    Science.gov (United States)

    Thaler, Kylie; Chandiramani, Divya V; Hansen, Richard A; Gartlehner, Gerald

    2009-01-01

    Objective To systematically review the general and comparative efficacy and safety of anakinra for rheumatoid arthritis. Methods We searched MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 to April 2009. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database. For efficacy we included randomized controlled trials (RCTs) comparing anakinra with placebo or other biologics. For safety both experimental and observational studies were eligible. Two persons independently reviewed abstracts and full text articles and extracted relevant data. Results We included data from 3 RCTs comparing anakinra with placebo for rheumatoid arthritis (RA). The pooled relative risk (RR) of an ACR50 (American College of Rheumatology) response for anakinra compared with placebo is 2.28 (95% CI 1.41 to 3.67). Adjusted indirect comparisons of ACR50 response rates of anakinra and anti-TNF agents showed a RR of 0.67 (95% CI 0.38 to 1.17) favoring the anti-TNF drugs. This result did not reach statistical significance. For safety, we included 9 experimental and observational studies of 24 weeks to 3 years duration. Up to 30% of patients withdrew from the studies due to adverse events. 67.2% (95% CI 38.7 to 95.7) of patients experienced an injection site reaction. Conclusions Anakinra is an effective drug for treating RA. Indirect comparisons with adalimumab, etanercept and infliximab, however, showed a trend towards greater efficacy for the anti-TNF drugs. Anakinra also seems to be associated with comparably high rates of injection site reactions. These results should be taken into account when considering biologic therapy for patients with RA. PMID:20054439

  4. On-chip food safety monitoring: multi-analyte screening with imaging surface plasmon resonance-based biosensor

    NARCIS (Netherlands)

    Rebe, S.

    2010-01-01

    Food safety is an increasing health concern, recognised and promoted by many
    institutions across the globe. Food products can be contaminated with pathogenic
    microorganisms, environmental pollutants, veterinary drug residues, allergens and toxins.
    Public health concerns which have

  5. Evaluation of pharmaceutical concerns in Germany: frequency and potential reasons

    Directory of Open Access Journals (Sweden)

    Gradl G

    2016-09-01

    Full Text Available Background: Generic substitution can have unintended consequences. In Germany, brand name to generic or generic to generic switching is mainly driven by rebate contracts. Frequent switching may raise concerns about bio- and therapeutic equivalence. Expected patient confusion may result in compromised medication adherence or new onset of other drug-related problems. Since 2008, pharmacists are allowed to deviate from rebate contracts by denying substitution due to pharmaceutical concerns on an individual basis. Objectives: To explore the frequency of documented pharmaceutical concerns in Germany between July 2011 and December 2013 and to identify the medicines most frequently related to pharmaceutical concerns in 2013. Methods: We analyzed documented pharmaceutical concerns in all prescribed drugs at the expense of any statutory health insurance company requiring pharmacies’ generic substitution according to rebate contracts. Results: Since July 2011, the frequency of documented pharmaceutical concerns in relation to prescribed drug products with rebate contracts requiring substitution increased consistently and doubled between July 2011 and July 2013. Overall in 2013, the trend of the two previous years continued and reached approximately 1.5%. The most affected drugs/drug classes were thyroid hormones (in particular combinations with iodide; 15.9% followed by ondansetron (12.5%, and levothyroxine (11.3%. For all drugs/drug classes under investigation, product-, patient- or disease-related aspects could be identified which are potential reasons to deny substitution and to document pharmaceutical concerns. Conclusions: Although there is no electronic recording of the specific reasons for pharmaceutical concerns in claims data, our analyses support the assumption that pharmacists make use of this instrument based on individual clinical decisions and as required by contract. Pharmaceutical concerns are, therefore, an important instrument for

  6. 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.

  7. Review of the safety of nonsteroidal anti-inflammatory drugs and ...

    African Journals Online (AJOL)

    A systemic review found that NSAIDs were one of four drugs associated with the highest number of drug-related hospital admissions. The others were diuretics, anticoagulants and antiplatelet agents.1 A wide range of adverse events are caused by both selective and nonselective cyclo-oxygenase. (COX) inhibitors.

  8. Effects of Drugs and Alcohol on Behavior, Job Performance, and Workplace Safety

    Science.gov (United States)

    Elliott, Karen; Shelley, Kyna

    2006-01-01

    A study of records for 1 large U.S. company revealed that employees with positive drug screens were fired, whereas workers who self-disclosed drug/alcohol problems remained employed. Both groups were offered substance abuse intervention, and some previously fired workers were rehired after they received treatment. Accident results showed that…

  9. 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:

  10. 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...

  11. Investigation of the radiological safety concerns and medical history of the late Joseph T. Harding, former employee of the Paducah Gaseous Diffusion Plant

    CERN Document Server

    Vallario, E J

    1981-01-01

    An ex-employee's claims that inadequate enforcement of radiation safety regulations allowed excess radiation exposure thereby causing his deteriorating health was not substantiated by a thorough investigation.

  12. Investigation of the radiological safety concerns and medical history of the late Joseph T. Harding, former employee of the Paducah Gaseous Diffusion Plant

    International Nuclear Information System (INIS)

    Vallario, E.J.; Wolfe, H.R.

    1981-01-01

    An ex-employee's claims that inadequate enforcement of radiation safety regulations allowed excess radiation exposure thereby causing his deteriorating health was not substantiated by a thorough investigation

  13. Investigation of the radiological safety concerns and medical history of the late Joseph T. Harding, former employee of the Paducah Gaseous Diffusion Plant

    International Nuclear Information System (INIS)

    Vallario, E.J.; Wolfe, H.R.

    1981-03-01

    An ex-employee's claims that inadequate enforcement of radiation safety regulations allowed excess radiation exposure thereby causing his deteriorating health was not substantiated by a thorough investigation

  14. Guide to the declaration procedure and coding system for criteria concerning significant events related to safety, radiation protection or the environment, applicable to basic nuclear installations and the transport of radioactive materials

    International Nuclear Information System (INIS)

    Lacoste, Andre-Claude

    2005-01-01

    This guide notably contains various forms associated with the declaration of significant events, and explanations to fill them in: significant event declaration form for a basic nuclear installation, significant event declaration form for radioactive material transport, significant event report for a basic nuclear installation, significant event report for radioactive material transport, declaration criteria for significant events related to the safety of non-PWR basic nuclear installations, declaration criteria for significant events related to PWR safety, significant events declared further to events resulting in group 1 unavailability and non-compliance with technical operating specifications, declaration criteria for significant events concerning radiation protection for basic nuclear installations, declaration criteria for significant events concerning environmental protection, applicable to basic nuclear installations, and declaration criteria for significant events concerning radioactive material transport

  15. 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.

  16. Efficacy and Safety of Drug-Eluting Stents in the Real World: 8-Year Follow-Up

    Directory of Open Access Journals (Sweden)

    Denise Oliveira Pellegrini

    2014-09-01

    Full Text Available Background: 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. Objective: To evaluate the efficacy and safety of drug-eluting stents in the real world. Methods: 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. Results: 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®. Conclusion: 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.

  17. Efficacy and safety of drug-eluting stents in the real world: 8-year follow-up.

    Science.gov (United States)

    Pellegrini, Denise Oliveira; Gomes, Vitor Osório; Lasevitch, Ricardo; Smidt, Luis; Azeredo, Marco Aurélio; Ledur, Priscila; Bodanese, Rodrigo; Sinnott, Leonardo; Moriguchi, Emílio; Caramori, Paulo

    2014-09-01

    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.

  18. 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.

  19. Hazardous Drugs

    Science.gov (United States)

    ... and hazardous drugs in the workplace. Pharmacy . OSHA Hospital eTool. Reviews safety and health topics related to hazardous drugs including drug handling, administration, storage, and disposal. OSHA has identified worker exposure ...

  20. The effectiveness of risk communication regarding drug safety information: a nationwide survey by the Japanese public health insurance claims data.

    Science.gov (United States)

    Hagiwara, Hiromi; Nakano, Shun; Ogawa, Yoshihiro; Tohkin, Masahiro

    2015-06-01

    We evaluated the effectiveness of warning letters published by the pharmaceutical regulatory agency in Japan on communication of drug safety and risk by quantitative analysis of the national health insurance claims database (NHICD). We then explored what factors may have affected risk communication. We measured the implementation rate of the hepatitis virus-monitoring test among methotrexate (MTX)-treated patients; a warning letter had been issued regarding the use of MTX, as it apparently activates the hepatitis virus. Data from the NHICD, which include 99·3% of Japanese residents, were used. A total of 4,933,481 patients with rheumatoid arthritis (RA) (January-June, 2010) were the focus of this study. The implementation rate of the hepatitis virus-monitoring test increased from 1·4% before to 1·8% after the warning letter announcement. Logistic regression analysis suggested that the installation of a drug information management room is one of the important factors affecting risk communication. Further analysis revealed that the hepatitis virus monitoring rates in hospitals without drug information management rooms increased from 2·3% to 4·1% due to the issue of the warning letter. The warning letter from the regulatory agency plays an important role in risk communication in hospitals without drug information management rooms. © 2015 John Wiley & Sons Ltd.

  1. 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...

  2. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

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

  3. SAFETY

    CERN Multimedia

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

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

  4. 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.

  5. 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

  6. Safety and pharmacokinetics of the neuroprotective drug lubeluzole in patients with ischemic stroke

    NARCIS (Netherlands)

    De Keyser, J; Van De Velde, [No Value; Schellens, RLLA; Hantson, L; Tritsmans, L; Gheuens, J; Van Peer, A; Woestenborghs, R; Franke, CL; van Gorp, J

    1997-01-01

    A total of 22 patients with acute ischemic stroke participated in two randomized, single-masked, placebo-controlled studies that evaluated the safety and pharmacokinetics of single escalating intravenous doses of lubeluzole. The first dose of study medication in all patients was given within 6 hours

  7. Inhibition of EGF Uptake by Nephrotoxic Antisense Drugs In Vitro and Implications for Preclinical Safety Profiling

    Directory of Open Access Journals (Sweden)

    Annie Moisan

    2017-03-01

    Full Text Available Antisense oligonucleotide (AON therapeutics offer new avenues to pursue clinically relevant targets inaccessible with other technologies. Advances in improving AON affinity and stability by incorporation of high affinity nucleotides, such as locked nucleic acids (LNA, have sometimes been stifled by safety liabilities related to their accumulation in the kidney tubule. In an attempt to predict and understand the mechanisms of LNA-AON-induced renal tubular toxicity, we established human cell models that recapitulate in vivo behavior of pre-clinically and clinically unfavorable LNA-AON drug candidates. We identified elevation of extracellular epidermal growth factor (EGF as a robust and sensitive in vitro biomarker of LNA-AON-induced cytotoxicity in human kidney tubule epithelial cells. We report the time-dependent negative regulation of EGF uptake and EGF receptor (EGFR signaling by toxic but not innocuous LNA-AONs and revealed the importance of EGFR signaling in LNA-AON-mediated decrease in cellular activity. The robust EGF-based in vitro safety profiling of LNA-AON drug candidates presented here, together with a better understanding of the underlying molecular mechanisms, constitutes a significant step toward developing safer antisense therapeutics.

  8. 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.

  9. 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

    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...... associated with increased risk of ischemic stroke [hazard ratio 2·15 (95% confidence interval 1·66-2·79) and 2·37 (confidence interval 1·99-2·81), respectively]. Diclofenac was also associated with increased risk of hemorrhagic stroke and so was naproxen [hazard ratio 2·15 (confidence interval 1......·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....

  10. Drug safety surveillance using de-identified EMR and claims data: issues and challenges.

    Science.gov (United States)

    Nadkarni, Prakash M

    2010-01-01

    The author discusses the challenges of pharmacovigilance using electronic medical record and claims data. Use of ICD-9 encoded data has low sensitivity for detection of adverse drug events (ADEs), because it requires that an ADE escalate to major-complaint level before it can be identified, and because clinical symptomatology is relatively under-represented in ICD-9. A more appropriate vocabulary for ADE identification, SNOMED CT, awaits wider deployment. The narrative-text record of progress notes can potentially be used for more sensitive ADE detection. More effective surveillance will require the ability to grade ADEs by severity. Finally, access to online drug information that includes both a reliable hierarchy of drug families as well as structured information on existing ADEs can improve the focus and predictive ability of surveillance efforts.

  11. 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

  12. 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

  13. Investigation of the radiological safety concerns and medical history of the late Joseph T. Harding, former employee of the Paducah Gaseous Diffusion Plant

    Energy Technology Data Exchange (ETDEWEB)

    Vallario, E.J.; Wolfe, H.R.

    1981-03-01

    An ex-employee's claims that inadequate enforcement of radiation safety regulations allowed excess radiation exposure thereby causing his deteriorating health was not substantiated by a thorough investigation.

  14. 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 ty