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

Science.gov (United States)

2013-04-04

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

Feasibility of AmbulanCe-Based Telemedicine (FACT) Study : Safety, Feasibility and Reliability of Third Generation Ambulance Telemedicine

NARCIS (Netherlands)

Yperzeele, Laetitia; Van Hooff, Robbert-Jan; De Smedt, Ann; Espinoza, Alexis Valenzuela; Van Dyck, Rita; Van de Casseye, Rohny; Convents, Andre; Hubloue, Ives; Lauwaert, Door; De Keyser, Jacques; Brouns, Raf

2014-01-01

Background: Telemedicine is currently mainly applied as an in-hospital service, but this technology also holds potential to improve emergency care in the prehospital arena. We report on the safety, feasibility and reliability of in-ambulance teleconsultation using a telemedicine system of the third

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.

Pharmacogenetics of drug-induced arrhythmias : a feasibility study using spontaneous adverse drug reactions reporting data

NARCIS (Netherlands)

De Bruin, Marie L; van Puijenbroek, Eugene P; Bracke, Madelon; Hoes, Arno W; Leufkens, Hubert G M

PURPOSE: The bottleneck in pharmacogenetic research on rare adverse drug reactions (ADR) is retrieval of patients. Spontaneous reports of ADRs may form a useful source of patients. We investigated the feasibility of a pharmacogenetic study, in which cases were selected from the database of a

Drug safety: withdrawn medications are only part of the picture.

Science.gov (United States)

Rawson, Nigel S B

2016-02-13

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 However, withdrawn medications are only one part of the picture about how regulatory agencies manage drug risks.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

Intra-Target Microdosing - A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans.

Science.gov (United States)

Burt, T; MacLeod, D; Lee, K; Santoro, A; DeMasi, D K; Hawk, T; Feinglos, M; Rowland, M; Noveck, R J

2017-09-01

Intra-Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first-in-human (FIH) testing of new molecular entities (NMEs). ITM combines intra-target drug delivery and "microdosing," the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic-level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers received insulin microdose into the radial artery or full therapeutic dose intravenously in separate visits. Insulin and glucose levels were similar between systemic administration and ITM administration in the ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral hand but not in the contralateral hand. Positron emission tomography (PET) imaging of 18 F-fluorodeoxyglucose (FDG) uptake demonstrated differences between the ipsilateral and contralateral arms. The procedures were safe and well-tolerated. Results are consistent with ITM proof-of-concept (POC) and demonstrate the ethical, regulatory, and logistical feasibility of the approach. © 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Safety and efficacy of drugs in pregnancy.

Science.gov (United States)

Knoppert, David

2011-01-01

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

Safety, feasibility and efficacy of a rapid ART initiation in pregnancy ...

African Journals Online (AJOL)

Safety, feasibility and efficacy of a rapid ART initiation in pregnancy pilot programme in Cape Town, South Africa. S Black, R Zulliger, L Myer, R Marcus, S Jeneker, R Taliep, D Pienaar, R Wood, L-G Bekker ...

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

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...

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...

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...

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...

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...

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...

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

Science.gov (United States)

2012-12-19

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

Intra‐Target Microdosing – A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans

Science.gov (United States)

MacLeod, D; Lee, K; Santoro, A; DeMasi, DK; Hawk, T; Feinglos, M; Rowland, M; Noveck, RJ

2017-01-01

Abstract Intra‐Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first‐in‐human (FIH) testing of new molecular entities (NMEs). ITM combines intra‐target drug delivery and “microdosing,” the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic‐level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers received insulin microdose into the radial artery or full therapeutic dose intravenously in separate visits. Insulin and glucose levels were similar between systemic administration and ITM administration in the ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral hand but not in the contralateral hand. Positron emission tomography (PET) imaging of 18F‐fluorodeoxyglucose (FDG) uptake demonstrated differences between the ipsilateral and contralateral arms. The procedures were safe and well‐tolerated. Results are consistent with ITM proof‐of‐concept (POC) and demonstrate the ethical, regulatory, and logistical feasibility of the approach. PMID:28689370

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

Science.gov (United States)

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

2013-05-01

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

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...

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.

Feasibility and safety of augmented reality-assisted urological surgery using smartglass.

Science.gov (United States)

Borgmann, H; Rodríguez Socarrás, M; Salem, J; Tsaur, I; Gomez Rivas, J; Barret, E; Tortolero, L

2017-06-01

To assess the feasibility, safety and usefulness of augmented reality-assisted urological surgery using smartglass (SG). Seven urological surgeons (3 board urologists and 4 urology residents) performed augmented reality-assisted urological surgery using SG for 10 different types of operations and a total of 31 urological operations. Feasibility was assessed using technical metadata (number of photographs taken/number of videos recorded/video time recorded) and structured interviews with the urologists on their use of SG. Safety was evaluated by recording complications and grading according to the Clavien-Dindo classification. Usefulness of SG for urological surgery was queried in structured interviews and in a survey. The implementation of SG use during urological surgery was feasible with no intrinsic (technical defect) or extrinsic (inability to control the SG function) obstacles being observed. SG use was safe as no grade 3-5 complications occurred for the series of 31 urological surgeries of different complexities. Technical applications of SG included taking photographs/recording videos for teaching and documentation, hands-free teleconsultation, reviewing patients' medical records and images and searching the internet for health information. Overall usefulness of SG for urological surgery was rated as very high by 43 % and high by 29 % of surgeons. Augmented reality-assisted urological surgery using SG is both feasible and safe and also provides several useful functions for urological surgeons. Further developments and investigations are required in the near future to harvest the great potential of this exciting technology for urological surgery.

Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

Science.gov (United States)

Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

2016-12-15

Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

A Quantitative Feasibility Study on Potential Safety Improvement Effects of Advanced Safety Features in APR-1400 when Applied to OPR-1000

Energy Technology Data Exchange (ETDEWEB)

Ualikhan Zhiyenbayev [KAIST, Daejeon (Korea, Republic of); Chung, Dae Wook [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2015-10-15

This study aims to test the feasibility of the applications using Probabilistic Safety Assessment (PSA). Particularly, three of those advanced safety features are selected as follows: 1. Providing an additional Emergency Diesel Generator (EDG); 2. Increasing the capacity of Class 1E batteries; 3. Placing a Refueling Water Storage Tank (RWST) inside containment, i.e., change from RWST to IRWST. The Advanced Power Reactor 1400 (APR-1400) adopts several advanced safety features compared to its predecessor, the Optimized Power Reactor 1000 (OPR-1000), which includes an additional Emergency Diesel Generator, increase in battery capacity, in-containment refueling water storage tank (IRWST), and so on. Considering the remarkable advantages of these safety features in safety improvement and the design similarities between APR-1400 and OPR-1000, it is feasible to apply key advanced safety features of APR-1400 to OPR-1000 to enhance the safety. The selected safety features are incorporated into OPR-1000 PSA model using the Advanced Information Management System (AIMS) for PSA and CDFs are re-evaluated for each application and combination of three applications. Based on current results, it is concluded that three of key advanced safety features of APR-1400 can be effectively applied to OPR-1000, resulting in considerable safety improvement. In aggregate, three advanced safety features, which are an additional EDG, increased battery capacity and IRWST, can reduce the CDF of OPR-1000 by more than 15% when applied altogether.

A Quantitative Feasibility Study on Potential Safety Improvement Effects of Advanced Safety Features in APR-1400 when Applied to OPR-1000

International Nuclear Information System (INIS)

Ualikhan Zhiyenbayev; Chung, Dae Wook

2015-01-01

This study aims to test the feasibility of the applications using Probabilistic Safety Assessment (PSA). Particularly, three of those advanced safety features are selected as follows: 1. Providing an additional Emergency Diesel Generator (EDG); 2. Increasing the capacity of Class 1E batteries; 3. Placing a Refueling Water Storage Tank (RWST) inside containment, i.e., change from RWST to IRWST. The Advanced Power Reactor 1400 (APR-1400) adopts several advanced safety features compared to its predecessor, the Optimized Power Reactor 1000 (OPR-1000), which includes an additional Emergency Diesel Generator, increase in battery capacity, in-containment refueling water storage tank (IRWST), and so on. Considering the remarkable advantages of these safety features in safety improvement and the design similarities between APR-1400 and OPR-1000, it is feasible to apply key advanced safety features of APR-1400 to OPR-1000 to enhance the safety. The selected safety features are incorporated into OPR-1000 PSA model using the Advanced Information Management System (AIMS) for PSA and CDFs are re-evaluated for each application and combination of three applications. Based on current results, it is concluded that three of key advanced safety features of APR-1400 can be effectively applied to OPR-1000, resulting in considerable safety improvement. In aggregate, three advanced safety features, which are an additional EDG, increased battery capacity and IRWST, can reduce the CDF of OPR-1000 by more than 15% when applied altogether

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

Science.gov (United States)

2013-06-19

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

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.

Determining animal drug combinations based on efficacy and safety.

Science.gov (United States)

Kratzer, D D; Geng, S

1986-08-01

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

Combined leadless pacemaker and subcutaneous implantable defibrillator therapy: feasibility, safety, and performance

NARCIS (Netherlands)

Tjong, F. V. Y.; Brouwer, T. F.; Smeding, L.; Kooiman, K. M.; de Groot, J. R.; Ligon, D.; Sanghera, R.; Schalij, M. J.; Wilde, A. A. M.; Knops, R. E.

2016-01-01

The subcutaneous implantable cardioverter-defibrillator (S-ICD) and leadless pacemaker (LP) are evolving technologies that do not require intracardiac leads. However, interactions between these two devices are unexplored. We investigated the feasibility, safety, and performance of combined LP and

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

Science.gov (United States)

Treister, Roi; Trudeau, Jeremiah J; Van Inwegen, Richard; Jones, Judith K; Katz, Nathaniel P

2016-12-01

Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651). © 2016 American Academy of Addiction Psychiatry.

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...

Working towards consensus on methods used to elicit participant-reported safety data in uncomplicated malaria clinical drug studies: a Delphi technique study.

Science.gov (United States)

Mandimika, Nyaradzo; Barnes, Karen I; Chandler, Clare I R; Pace, Cheryl; Allen, Elizabeth N

2017-01-28

Eliciting adverse event (AE) and non-study medication data reports from clinical research participants is integral to evaluating drug safety. However, using different methods to question participants yields inconsistent results, compromising the interpretation, comparison and pooling of data across studies. This is particularly important given the widespread use of anti-malarials in vulnerable populations, and their increasing use in healthy, but at-risk individuals, as preventive treatment or to reduce malaria transmission. Experienced and knowledgeable anti-malarial drug clinical researchers were invited to participate in a Delphi technique study, to facilitate consensus on what are considered optimal (relevant, important and feasible) methods, tools, and approaches for detecting participant-reported AE and non-study medication data in uncomplicated malaria treatment studies. Of 72 invited, 25, 16 and 10 panellists responded to the first, second and third rounds of the Delphi, respectively. Overall, 68% (68/100) of all questioning items presented for rating achieved consensus. When asking general questions about health, panellists agreed on the utility of a question/concept about any change in health, taking care to ensure that such questions/concepts do not imply causality. Eighty-nine percent (39/44) of specific signs and symptoms questions were rated as optimal. For non-study medications, a general question and most structured questioning items were considered an optimal approach. The use of mobile phones, patient diaries, rating scales as well as openly engaging with participants to discuss concerns were also considered optimal complementary data-elicitation tools. This study succeeded in reaching consensus within a section of the anti-malarial drug clinical research community about using a general question concept, and structured questions for eliciting data about AEs and non-study medication reports. The concepts and items considered in this Delphi to be

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...

77 FR 2606 - Pipeline Safety: Random Drug Testing Rate

Science.gov (United States)

2012-01-18

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

75 FR 9018 - Pipeline Safety: Random Drug Testing Rate

Science.gov (United States)

2010-02-26

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

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…

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.

Echocardiography-based hemodynamic management of left ventricular diastolic dysfunction: a feasibility and safety study.

Science.gov (United States)

Shillcutt, Sasha K; Montzingo, Candice R; Agrawal, Ankit; Khaleel, Maseeha S; Therrien, Stacey L; Thomas, Walker R; Porter, Thomas R; Brakke, Tara R

2014-11-01

Patients with left ventricular diastolic dysfunction (LVDD) are at increased risk of postoperative adverse events. The primary aim of this study was to evaluate the safety and feasibility of using echocardiography-guided hemodynamic management (EGHEM) during surgery in subjects with LVDD compared to conventional management. The feasibility of using echocardiography to direct a treatment algorithm and clinical outcomes were compared for safety between groups. Subjects were screened for LVDD by preoperative transthoracic echocardiography (TTE) and randomized to the conventional or EGHEM group. Subjects in EGHEM received hemodynamic management based on left ventricular filling patterns on transesophageal echocardiography (TEE). Primary outcomes measured were the feasibility to obtain TEE images and follow a TEE-based treatment algorithm. Safety outcomes also compared the following clinical differences between groups: length of hospitalization, incidence of atrial fibrillation, congestive heart failure (CHF), myocardial infarction, cerebrovascular accident, transient ischemic attack and renal failure measured 30 days postoperatively. Population consisted of 28 surgical subjects (14 in conventional group and 14 in EGHEM group). Mean subject age was 73.4 ± 6.7 years (36% male) in conventional group and 65.9 ± 14.4 years (36% male) in EGHEM group. Procedures included orthopedic (conventional = 29%, EGHEM 36%), general (conventional = 50%, EGHEM = 36%), vascular (conventional = 7%, EGHEM = 21%), and thoracic (conventional = 14%, EGHEM = 7%). There was no statistically significant difference in adverse clinical events between the 2 groups. The EGHEM group had less CHF, atrial fibrillation, and shorter length of stay. Echocardiography-guided hemodynamic management of patients with LVDD during surgery is feasible and may be a safe alternative to conventional management. © 2014, Wiley Periodicals, Inc.

Safety learning from drugs of the same class

DEFF Research Database (Denmark)

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

2012-01-01

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

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.

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.

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.

The SHIELD (Safety & Health Improvement: Enhancing Law Enforcement Departments Study: Feasibility and Findings

Directory of Open Access Journals (Sweden)

Kerry Stephen Kuehl

2014-05-01

Full Text Available This randomized prospective trial aimed to assess the feasibility and efficacy of a team-based worksite health and safety intervention for law enforcement personnel. Four-hundred and eight subjects were enrolled and half were randomized to meet participants met for weekly, peer-led sessions delivered from a scripted team-based health and safety curriculum. Curriculum addressed: exercise, nutrition, stress, sleep, body weight, injury, and other unhealthy lifestyle behaviours such as smoking and heavy alcohol use. Health and safety questionnaires administered before and after the intervention found significant improvements for increased fruit and vegetable consumption, overall healthy eating, increased sleep quantity and sleep quality, and reduced personal stress.

Feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus™ for frail elderly: study protocol for a feasibility trial.

Science.gov (United States)

Gomes, Gisele Cristine Vieira; Bacha, Jéssica Maria Ribeiro; do Socorro Simões, Maria; Lin, Sumika Mori; Viveiro, Larissa Alamino Pereira; Varise, Eliana Maria; Filho, Wilson Jacob; Pompeu, José Eduardo

2017-01-01

Frailty can be defined as a medical syndrome with multiple causes and contributors, characterized by diminished strength and endurance and reduced physiological function that increases the vulnerability to develop functional dependency and/or death. Studies have shown that the most commonly studied exercise protocol for frail older adults is the multimodal training. Interactive video games (IVGs) involve tasks in virtual environments that combine physical and cognitive demands in an attractive and challenging way. The aim of this study will be to evaluate the feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus TM (NWFP) for frail older adults. The study is a randomized controlled, parallel group, feasibility trial. Participants will be randomly assigned to the experimental group (EG) and control group (CG). The EG will participate in 14 training sessions, each lasting 50 min, twice a week. In each training session, the participants will play five games, with three attempts at each game. The first attempt will be performed with the assistance of a physical therapist to correct the movements and posture of the patients and subsequent attempts will be performed independently. Scores achieved in the games will be recorded. The participants will be evaluated by a blinded physical therapist at three moments: before and after intervention and 30 days after the end of the intervention (follow-up). We will assess the feasibility, acceptability, safety, and clinical outcomes (postural control, gait, cognition, quality of life, mood, and fear of falling). Due to the deficiencies in multiple systems, studies have shown that multimodal interventions including motor-cognitive stimulation can improve the mobility of frail elderly adults. IVGs, among them the NWFP, are considered as a multimodal motor-cognitive intervention that can potentially improve motor and cognitive functions in the frail elderly. However, there is still no evidence

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

Science.gov (United States)

1980-06-01

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

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

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

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.

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...

Therapeutic drug monitoring to individualize the dosing of pazopanib: a pharmacokinetic feasibility study

NARCIS (Netherlands)

Wit, D. de; Erp, N. van; Hartigh, J. den; Wolterbeek, R..; Hollander-van Deursen, M. den; Labots, M.; Guchelaar (LUMC), H.J.; Verheul, H.M.; Gelderblom, H.

2015-01-01

BACKGROUND: Patients treated with the standard dose of pazopanib show a large interpatient variability in drug exposure defined as the area under the plasma concentration-time curve (AUC0-24h). The primary objective of this study was to evaluate the feasibility of pharmacokinetics (PK)-guided

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

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

NARCIS (Netherlands)

Hernández, J.F.

2015-01-01

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

Practices, patients and (imperfect data - feasibility of a randomised controlled clinical drug trial in German general practices

Directory of Open Access Journals (Sweden)

Hummers-Pradier Eva

2011-04-01

Full Text Available Abstract Background Randomised controlled clinical (drug trials supply high quality evidence for therapeutic strategies in primary care. Until now, experience with drug trials in German general practice has been sparse. In 2007/2008, the authors conducted an investigator-initiated, non-commercial, double-blind, randomised controlled pilot trial (HWI-01 to assess the clinical equivalence of ibuprofen and ciprofloxacin in the treatment of uncomplicated urinary tract infection (UTI. Here, we report the feasibility of this trial in German general practices and the implementation of Good Clinical Practice (GCP standards as defined by the International Conference on Harmonisation (ICH in mainly inexperienced general practices. Methods This report is based on the experience of the HWI-01 study conducted in 29 German general practices. Feasibility was defined by 1 successful practice recruitment, 2 sufficient patient recruitment, 3 complete and accurate data collection and 4 appropriate protection of patient safety. Results The final practice recruitment rate was 18%. In these practices, 79 of 195 screened UTI patients were enrolled. Recruitment differed strongly between practices (range 0-12, mean 2.8 patients per practice and was below the recruitment goal of approximately 100 patients. As anticipated, practice nurses became the key figures in the screening und recruitment of patients. Clinical trial demands, in particular for completing symptom questionnaires, documentation of source data and reporting of adverse events, did not agree well with GPs' documentation habits and required support from study nurses. In many cases, GPs and practice staff seemed to be overwhelmed by the amount of information and regulations. No sudden unexpected serious adverse reactions (SUSARs were observed during the trial. Conclusions To enable drug trials in general practice, it is necessary to adapt the setup of clinical research infrastructure to the needs of GPs and

Long-term safety and feasibility of three-vessel multimodality intravascular imaging in patients with ST-elevation myocardial infarction

DEFF Research Database (Denmark)

Taniwaki, Masanori; Radu, Maria D; Garcia-Garcia, Hector M

2015-01-01

We assessed the feasibility and the procedural and long-term safety of intracoronary (i.c) imaging for documentary purposes with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI in the s......We assessed the feasibility and the procedural and long-term safety of intracoronary (i.c) imaging for documentary purposes with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI...... in the setting of IBIS-4 study. IBIS4 (NCT00962416) is a prospective cohort study conducted at five European centers including 103 STEMI patients who underwent serial three-vessel coronary imaging during primary PCI and at 13 months. The feasibility parameter was successful imaging, defined as the number...... of pullbacks suitable for analysis. Safety parameters included the frequency of peri-procedural complications, and major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and any clinically-indicated revascularization at 2 years. Clinical outcomes were compared...

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

Science.gov (United States)

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

2017-12-01

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

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

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.

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

Science.gov (United States)

Allan, M C

1992-01-01

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

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.

Feasibility and safety of general anesthesia for bronchial thermoplasty: a description of early 10 treatments.

Science.gov (United States)

Aizawa, Mariko; Ishihara, Satoshi; Yokoyama, Takeshi; Katayama, Katsuyuki

2018-03-20

Bronchial thermoplasty (BT) is a recently introduced bronchoscopic treatment for patients with asthma refractory to pharmacotherapy. Intraprocedural sedation management is important for successful performance of BT. However, the results of general anesthesia in patients undergoing BT have not been well described. The aim of this study was to evaluate the feasibility and safety of general anesthesia in patients undergoing BT. We retrospectively reviewed the records of 10 consecutive BT treatments performed under general anesthesia in 4 patients. The feasibility outcomes were coughing and body movement during the procedure, procedure abandonment, and the relative frequency of thermal activation failure. The safety outcomes were bronchospasm and hypoxemia during the procedure, respiratory symptoms, and the need for oxygen after the procedure. Coughing occurred in two treatments. Neither body movement nor procedure abandonment occurred in any treatments. Neither intraprocedural bronchospasm nor hypoxemia occurred in any treatments. Respiratory symptoms occurred in 7 of 10 treatments within 1 day after the procedure and resolved within 4 days, which is comparable with a previous report. These results indicate that general anesthesia is feasible and safe for patients undergoing BT.

Direct transcatheter aortic valve implantation with self-expandable bioprosthesis: Feasibility and safety

Energy Technology Data Exchange (ETDEWEB)

Fiorina, Claudia, E-mail: clafiorina@yahoo.it [Cardiac Catheterization Laboratory, Cardiothoracic Department, Spedali Civili, Brescia (Italy); Maffeo, Diego; Curello, Salvatore [Cardiac Catheterization Laboratory, Cardiothoracic Department, Spedali Civili, Brescia (Italy); Lipartiti, Felicia [Division of Cardiology, Cardiothoracic Department, Spedali Civili, Brescia (Italy); Chizzola, Giuliano [Cardiac Catheterization Laboratory, Cardiothoracic Department, Spedali Civili, Brescia (Italy); D' Aloia, Antonio [Division of Cardiology, Cardiothoracic Department, Spedali Civili, Brescia (Italy); Adamo, Marianna [Cardiac Catheterization Laboratory, Cardiothoracic Department, Spedali Civili, Brescia (Italy); Mastropierro, Rosy [Division of Cardiothoracic Anestesiology, Cardiothoracic Department, Spedali Civili, Brescia (Italy); Gavazzi, Emanuele [Department of Radiology, University of Brescia, Spedali Civili, Brescia (Italy); Ciccarese, Camilla; Chiari, Ermanna [Division of Cardiology, Cardiothoracic Department, Spedali Civili, Brescia (Italy); Ettori, Federica [Cardiac Catheterization Laboratory, Cardiothoracic Department, Spedali Civili, Brescia (Italy)

2014-06-15

Background: Balloon valvuloplasty has been considered a mandatory step of the transcatheter aortic valve implantation (TAVI), although it is not without risk. The aim of this work was to evaluate the feasibility and safety of TAVI performed without pre-dilation (direct TAVI) of the stenosed aortic valve. Material and Methods: Between June 2012 and June 2013, 55 consecutive TAVI performed without pre-dilation at our institution using the self-expandable CoreValve prosthesis (Medtronic, Minneapolis, MN) were analyzed and compared with 45 pre-dilated TAVI performed the previous year. Inclusion criteria were a symptomatic and severe aortic stenosis. Exclusion criteria were defined as presence of pure aortic regurgitation, degenerated surgical bioprosthesis or bicuspid aortic valve and prior procedure of balloon aortic valvuloplasty performed as a bridge to TAVI. Results: High-burden calcification in the device landing zone, assessed by CT scan, was found in most of the patients. The valve size implanted was similar in both groups. Device success was higher in direct TAVI (85% vs. 64%, p = 0.014), mostly driven by a significant lower incidence of paravalvular leak (PVL ≥2; 9% vs. 33%, p = 0.02). Safety combined end point at 30 days was similar in both groups. Conclusion: Compared to TAVI with pre-dilation, direct TAVI is feasible regardless of the presence of bulky calcified aortic valve and the valve size implanted. Device success was higher in direct TAVI, mostly driven by a lower incidence of paravalvular leak. Safety at 30 days was similar in two groups.

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...

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

Feasibility of mini-tablets as a flexible drug delivery tool.

Science.gov (United States)

Mitra, Biplob; Chang, Jessica; Wu, Sy-Juen; Wolfe, Chad N; Ternik, Robert L; Gunter, Thomas Z; Victor, Michael C

2017-06-15

Mini-tablets have potential applications as a flexible drug delivery tool in addition to their generally perceived use as multi-particulates. That is, mini-tablets could provide flexibility in dose finding studies and/or allow for combination therapies in the clinic. Moreover, mini-tablets with well controlled quality attributes could be a prudent choice for administering solid dosage forms as a single unit or composite of multiple mini-tablets in patient populations with swallowing difficulties (e.g., pediatric and geriatric populations). This work demonstrated drug substance particle size and concentration ranges that achieve acceptable mini-tablet quality attributes for use as a single or composite dosage unit. Immediate release and orally disintegrating mini-tablet formulations with 30μm to 350μm (particle size d 90 ) acetaminophen and Compap™ L (90% acetaminophen) at concentrations equivalent to 6.7% and 26.7% acetaminophen were evaluated. Mini-tablets achieved acceptable weight variability, tensile strength, friability, and disintegration time at a reasonable solid fraction for each formulation. The content uniformity was acceptable for mini-tablets of 6.7% formulations with ≤170μm drug substance, mini-tablets of all 26.7% formulations, and composite dosage units containing five or more mini-tablets of any formulation. Results supported the manufacturing feasibility of quality mini-tablets, and their applicability as a flexible drug delivery tool. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug safety: Pregnancy rating classifications and controversies.

Science.gov (United States)

Wilmer, Erin; Chai, Sandy; Kroumpouzos, George

2016-01-01

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

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.

Feasibility, Safety, and Compliance in a Randomized Controlled Trial of Physical Therapy for Parkinson's Disease

Directory of Open Access Journals (Sweden)

Jennifer L. McGinley

2012-01-01

Full Text Available Both efficacy and clinical feasibility deserve consideration in translation of research outcomes. This study evaluated the feasibility of rehabilitation programs within the context of a large randomized controlled trial of physical therapy. Ambulant participants with Parkinson's disease (PD (n=210 were randomized into three groups: (1 progressive strength training (PST; (2 movement strategy training (MST; or (3 control (“life skills”. PST and MST included fall prevention education. Feasibility was evaluated in terms of safety, retention, adherence, and compliance measures. Time to first fall during the intervention phase did not differ across groups, and adverse effects were minimal. Retention was high; only eight participants withdrew during or after the intervention phase. Strong adherence (attendance >80% did not differ between groups (P=.435. Compliance in the therapy groups was high. All three programs proved feasible, suggesting they may be safely implemented for people with PD in community-based clinical practice.

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

Science.gov (United States)

1980-06-01

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

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

Science.gov (United States)

2011-10-14

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

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

Science.gov (United States)

Cruz, Jennifer L; Brown, Jamie N

2015-06-01

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

Analyzing research trends on drug safety using topic modeling.

Science.gov (United States)

Zou, Chen

2018-04-06

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

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...

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

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

Science.gov (United States)

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

2012-01-01

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

Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling

DEFF Research Database (Denmark)

Kammersgaard, L P; Rasmussen, B H; Jørgensen, Henrik Stig

2000-01-01

Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients...

Feasibility of Using Soccer and Job Training to Prevent Drug Abuse and HIV.

Science.gov (United States)

Rotheram-Borus, Mary Jane; Tomlinson, Mark; Durkin, Andrew; Baird, Kelly; DeCelles, Jeff; Swendeman, Dallas

2016-09-01

Many young, South African men use alcohol and drugs and have multiple partners, but avoid health care settings-the primary site for delivery of HIV intervention activities. To identify the feasibility of engaging men in HIV testing and reducing substance use with soccer and vocational training programs. In two Cape Town neighborhoods, all unemployed men aged 18-25 years were recruited and randomized by neighborhood to: (1) an immediate intervention condition with access to a soccer program, random rapid diagnostic tests (RDT) for alcohol and drug use, and an opportunity to enter a vocational training program (n = 72); or (2) a delayed control condition (n = 70). Young men were assessed at baseline and 6 months later by an independent team. Almost all young men in the two neighborhoods participated (98 %); 85 % attended at least one practice (M = 42.3, SD = 34.4); 71 % typically attended practice. Access to job training was provided to the 35 young men with the most on-time arrivals at practice, drug-free RDT, and no red cards for violence. The percentage of young men agreeing to complete RDT at soccer increased significantly over time; RDTs with evidence of alcohol and drug use decreased over time. At the pre-post assessments, the frequency of substance use decreased; and employment and income increased in the immediate condition compared to the delayed condition. HIV testing rates, health care contacts, sexual behaviors, HIV knowledge, condom use and attitudes towards women were similar over time. Alternative engagement strategies are critical pathways to prevent HIV among young men. This feasibility study shows that soccer and job training offer such an alternative, and suggest that a more robust evaluation of this intervention strategy be pursued.

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

Science.gov (United States)

McGivern, Jered V; Ebert, Allison D

2014-04-01

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

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

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

Science.gov (United States)

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

2016-02-01

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

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.

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

Science.gov (United States)

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

2011-04-01

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

The Feasibility of Interventions to Reduce HIV Risk and Drug Use among Heterosexual Methamphetamine Users.

Science.gov (United States)

Corsi, Karen F; Lehman, Wayne E; Min, Sung-Joon; Lance, Shannon P; Speer, Nicole; Booth, Robert E; Shoptaw, Steve

2012-06-04

This paper reports on a feasibility study that examined contingency management among out-of-treatment, heterosexual methamphetamine users and the reduction of drug use and HIV risk. Fifty-eight meth users were recruited through street outreach in Denver from November 2006 through March 2007. The low sample size reflects that this was a pilot study to see if CM is feasible in an out-of-treatment, street-recruited population of meth users. Secondary aims were to examine if reductions and drug use and risk behavior could be found. Subjects were randomly assigned to contingency management (CM) or CM plus strengths-based case management (CM/SBCM), with follow-up at 4 and 8 months. Participants were primarily White (90%), 52% male and averaged 38 years old. Eighty-three percent attended at least one CM session, with 29% attending at least fifteen. All participants reduced meth use significantly at follow-up. Those who attended more sessions submitted more stimulant-free urines than those who attended fewer sessions. Participants assigned to CM/SBCM attended more sessions and earned more vouchers than clients in CM. Similarly, participants reported reduced needle-sharing and sex risk. Findings demonstrate that CM and SBCM may help meth users reduce drug use and HIV risk.

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

Science.gov (United States)

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

2017-11-01

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

Safety and feasibility of fasting in combination with platinum-based chemotherapy.

Science.gov (United States)

Dorff, Tanya B; Groshen, Susan; Garcia, Agustin; Shah, Manali; Tsao-Wei, Denice; Pham, Huyen; Cheng, Chia-Wei; Brandhorst, Sebastian; Cohen, Pinchas; Wei, Min; Longo, Valter; Quinn, David I

2016-06-10

Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. NCT00936364 , registered propectively on July 9, 2009.

Safety and feasibility of fasting in combination with platinum-based chemotherapy

International Nuclear Information System (INIS)

Dorff, Tanya B.; Groshen, Susan; Garcia, Agustin; Shah, Manali; Tsao-Wei, Denice; Pham, Huyen; Cheng, Chia-Wei; Brandhorst, Sebastian; Cohen, Pinchas; Wei, Min; Longo, Valter; Quinn, David I.

2016-01-01

Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. Clinicaltrials.gov: NCT00936364, registered propectively on July 9, 2009. The online version of this article (doi:10.1186/s12885-016-2370-6) contains supplementary material, which is available to authorized users

Drug education in bolivian schools: A feasibility study for cross-cultural application of a preventive curricular unit

Science.gov (United States)

Gonzalez, Gerardo M.; Moreno, Veronica Kaune

1995-11-01

The purpose of this study was to test the feasibility of adapting and implementing in La Paz, Bolivia a drug education course originally developed for use in the middle schools in the United States. On the basis of teacher and student evaluations, it was concluded that the unit is a viable, culturally relevant and effective method of drug education in the public and private schools in La Paz. Implications for the prevention of other health-related problems and for implementation of a demandreduction strategy to prevent drug abuse throughout the Americas are discussed.

Feasibility study of applying the passive safety system concept to fusion–fission hybrid reactor

International Nuclear Information System (INIS)

Yu, Zhang-cheng; Xie, Heng

2014-01-01

The fusion–fission hybrid reactor can produce energy, breed nuclear fuel, and handle the nuclear waste, etc., with the fusion neutron source striking the subcritical blanket. The passive safety system consists of passive residual heat removal system, passive safety injection system and automatic depressurization system was adopted into the fusion–fission hybrid reactor in this paper. Modeling and nodalization of primary loop, partial secondary loop and passive core cooling system for the fusion–fission hybrid reactor using relap5 were conducted and small break LOCA on cold leg was analyzed. The results of key transient parameters indicated that the actuation of passive safety system could mitigate the accidental consequence of the 4-inch cold leg small break LOCA on cold leg in the early time effectively. It is feasible to apply the passive safety system concept to fusion–fission hybrid reactor. The minimum collapsed liquid level had great increase if doubling the volume of CMTs to increase its coolant injection and had no increase if doubling the volume of ACCs

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...

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.

Feasibility of AmbulanCe-Based Telemedicine (FACT study: safety, feasibility and reliability of third generation in-ambulance telemedicine.

Directory of Open Access Journals (Sweden)

Laetitia Yperzeele

Full Text Available Telemedicine is currently mainly applied as an in-hospital service, but this technology also holds potential to improve emergency care in the prehospital arena. We report on the safety, feasibility and reliability of in-ambulance teleconsultation using a telemedicine system of the third generation.A routine ambulance was equipped with a system for real-time bidirectional audio-video communication, automated transmission of vital parameters, glycemia and electronic patient identification. All patients ( ≥ 18 years transported during emergency missions by a Prehospital Intervention Team of the Universitair Ziekenhuis Brussel were eligible for inclusion. To guarantee mobility and to facilitate 24/7 availability, the teleconsultants used lightweight laptop computers to access a dedicated telemedicine platform, which also provided functionalities for neurological assessment, electronic reporting and prehospital notification of the in-hospital team. Key registrations included any safety issue, mobile connectivity, communication of patient information, audiovisual quality, user-friendliness and accuracy of the prehospital diagnosis.Prehospital teleconsultation was obtained in 41 out of 43 cases (95.3%. The success rates for communication of blood pressure, heart rate, blood oxygen saturation, glycemia, and electronic patient identification were 78.7%, 84.8%, 80.6%, 64.0%, and 84.2%. A preliminary prehospital diagnosis was formulated in 90.2%, with satisfactory agreement with final in-hospital diagnoses. Communication of a prehospital report to the in-hospital team was successful in 94.7% and prenotification of the in-hospital team via SMS in 90.2%. Failures resulted mainly from limited mobile connectivity and to a lesser extent from software, hardware or human error. The user acceptance was high.Ambulance-based telemedicine of the third generation is safe, feasible and reliable but further research and development, especially with regard to high

Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast.

Science.gov (United States)

Miller, Jessica A; Thompson, Patricia A; Hakim, Iman A; Lopez, Ana Maria; Thomson, Cynthia A; Chew, Wade; Hsu, Chiu-Hsieh; Chow, H-H Sherry

2012-10-01

Limonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy. We conducted a mouse disposition study to determine whether limonene would be bio available in the mammary tissue after topical application. SKH-1 mice received topical or oral administration of limonene in the form of orange oil every day for 4 weeks. Plasma and mammary pads were collected 4 hrs after the final dosing. We also conducted an exploratory clinical study to evaluate the safety and feasibility of topically applied limonene in the form of orange oil to the breast. Healthy women were recruited to apply orange oil containing massage oil to their breasts daily for four weeks. Safety and feasibility were assessed by reported adverse events, clinical labs, and usage compliance. Pre and post-intervention nipple aspirate fluid (NAF) and plasma were collected for limonene concentration determination. The mouse disposition study showed that topical and oral orange oil administration resulted in similar mammary tissue disposition of limonene with no clinical signs of toxicity. In the clinical study, the topical application of limonene containing massage oil to the breast was found to be safe with high levels of usage compliance for daily application, although NAF and plasma limonene concentrations were not significantly changed after the massage oil application. Our studies showed that limonene is bio available in mammary tissue after topical orange oil application in mice and this novel route of administration to the breast is safe and feasible in healthy women.

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.

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.

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

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

Feasibility study for the adoption of POSRV for KNGR safety depressurization system

International Nuclear Information System (INIS)

Kwon, Young Min; Lim, Hong Sik; Song, Jin Ho; Sim, Suk Ku; Park, Jong Kyun

1999-03-01

The Korean Next Generation Reactor (KNGR) adopted an advanced design feature of safety depressurization system(SDS) to rapidly de pressurize the reactor coolant system(RCS) in case of beyond design basis events of severe accidents, or a highly unlikely event of a total loss of feedwater (TLOFW) to both steam generators. Two design approaches were considered for the KNGR SDS design. The use of bleed valves similar to those of ABB-CE's system 80+ is design option 1, while in design option 2, the Power Operated Safety Relief valve (POSRV) is considered to provide the combined function of overpressure protection and rapid depressurization. The purpose of this report is to investigate the feasibility of adoption of French SebimPOSRVs for KNGR SDS (design option 2). This report provides the methodology to analyze the TLOFW event with Sebim valves and presents the results of thermal hydraulic analyses using a best-estimate version CEFLASH-4AS/REM for the TLOFW event with feed and bleed. The analyses were performed using a preliminary KNGR design data. For design option 2, if the operator opens two out of the three Sebim valves in conjunction with the four HPSI pumps before a hot leg saturation condition, the decay heat removal and core inventory make-up function can be successfully accomplished. The results of the present investigation demonstrate that the two design options are both feasible to mitigate the consequences of the TLOFW event with a sufficient margin. (Author). 22 refs., 3 tabs., 19 figs

[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.

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

NARCIS (Netherlands)

Dellicour, S.O.M.C.

2014-01-01

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

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

DEFF Research Database (Denmark)

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

2017-01-01

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

Technical feasibility and reliability of passive safety systems of AC600

International Nuclear Information System (INIS)

Niu, W.; Zeng, X.

1996-01-01

The first step conceptual design of the 600 MWe advanced PWR (AC-600) has been finished by the Nuclear Power Institute of China. Experiments on the passive system of AC-600 are being carried out, and are expected to be completed next year. The main research emphases of AC-600 conceptual design include the advanced core, the passive safety system and simplification. The design objective of AC-600 is that the safety, reliability, maintainability, operation cost and construction period are all improved upon compared to those of PWR plant. One of important means to achieve the objective is using a passive system, which has the following functions whenever its operation is required: providing the reactor core with enough coolant when others fail to make up the lost coolant; reactor residual heat removal; cooling and reducing pressure in the containment and preventing radioactive substances from being released into the environment after occurrence of accident (e.g. LOCA). The system should meet the single failure criterion, and keep operating when a single active component or passive component breaks down during the first 72 hour period after occurrence of accident, or in the long period following the 72 hour period. The passive safety system of AC-600 is composed of the primary safety injection system, the secondary emergency core residual heat removal system and the containment cooling system. The design of the system follows some relevant rules and criteria used by current PWR plant. The system has the ability to bear single failure, two complete separate subsystems are considered, each designed for 100% working capacity. Normal operation is separate from safety operation and avoids cross coupling and interference between systems, improves the reliability of components, and makes it easy to maintain, inspect and test the system. The paper discusses the technical feasibility and reliability of the passive safety system of AC-600, and some issues and test plans are also

Technical feasibility and reliability of passive safety systems of AC600

Energy Technology Data Exchange (ETDEWEB)

Niu, W; Zeng, X [Nuclear Power Inst. of China, Chendu (China)

1996-12-01

The first step conceptual design of the 600 MWe advanced PWR (AC-600) has been finished. Experiments on the passive system of AC-600 are being carried out, and are expected to be completed next year. The main research emphases of AC-600 conceptual design include the advanced core, the passive safety system and simplification. The design objective of AC-600 is that the safety, reliability, maintainability, operation cost and construction period are all improved upon compared to those of PWR plant. One of important means to achieve the objective is using a passive system, which has the following functions whenever its operation is required: providing the reactor core with enough coolant when others fail to make up the lost coolant; reactor residual heat removal; cooling and reducing pressure in the containment and preventing radioactive substances from being released into the environment after occurrence of accident (e.g. LOCA). The system should meet the single failure criterion, and keep operating when a single active component or passive component breaks down during the first 72 hour period after occurrence of accident, or in the long period following the 72 hour period. The passive safety system of AC-600 is composed of the primary safety injection system, the secondary emergency core residual heat removal system and the containment cooling system. The design of the system follows some relevant rules and criteria used by current PWR plant. The system has the ability to bear single failure, two complete separate subsystems are considered, each designed for 100% working capacity. Normal operation is separate from safety operation and avoids cross coupling and interference between systems, improves the reliability of components, and makes it easy to maintain, inspect and test the system. The paper discusses the technical feasibility and reliability of the passive safety system of AC-600, and some issues and test plans are also involved. (author). 3 figs, 1 tab.

Safety and Feasibility of Using the Second-Generation Pillcam Colon Capsule to Assess Active Colonic Crohn's Disease

NARCIS (Netherlands)

D'Haens, Geert; Löwenberg, Mark; Samaan, Mark A.; Franchimont, Denis; Ponsioen, Cyriel; van den Brink, Gijs R.; Fockens, Paul; Bossuyt, Peter; Amininejad, Leila; Rajamannar, Gopalan; Lensink, Elsemieke M.; van Gossum, Andre M.

2015-01-01

The second-generation Pillcam Colon Capsule Endoscope (PCCE-2; Given Imaging Ltd, Yoqneam, Israel) is an ingestible capsule for visualization of the colon. We performed a multicenter pilot study to assess its safety and feasibility in evaluating the severity of Crohn's disease (CD). In a prospective

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

Feasibility and safety of virtual-reality-based early neurocognitive stimulation in critically ill patients.

Science.gov (United States)

Turon, Marc; Fernandez-Gonzalo, Sol; Jodar, Mercè; Gomà, Gemma; Montanya, Jaume; Hernando, David; Bailón, Raquel; de Haro, Candelaria; Gomez-Simon, Victor; Lopez-Aguilar, Josefina; Magrans, Rudys; Martinez-Perez, Melcior; Oliva, Joan Carles; Blanch, Lluís

2017-12-01

Growing evidence suggests that critical illness often results in significant long-term neurocognitive impairments in one-third of survivors. Although these neurocognitive impairments are long-lasting and devastating for survivors, rehabilitation rarely occurs during or after critical illness. Our aim is to describe an early neurocognitive stimulation intervention based on virtual reality for patients who are critically ill and to present the results of a proof-of-concept study testing the feasibility, safety, and suitability of this intervention. Twenty critically ill adult patients undergoing or having undergone mechanical ventilation for ≥24 h received daily 20-min neurocognitive stimulation sessions when awake and alert during their ICU stay. The difficulty of the exercises included in the sessions progressively increased over successive sessions. Physiological data were recorded before, during, and after each session. Safety was assessed through heart rate, peripheral oxygen saturation, and respiratory rate. Heart rate variability analysis, an indirect measure of autonomic activity sensitive to cognitive demands, was used to assess the efficacy of the exercises in stimulating attention and working memory. Patients successfully completed the sessions on most days. No sessions were stopped early for safety concerns, and no adverse events occurred. Heart rate variability analysis showed that the exercises stimulated attention and working memory. Critically ill patients considered the sessions enjoyable and relaxing without being overly fatiguing. The results in this proof-of-concept study suggest that a virtual-reality-based neurocognitive intervention is feasible, safe, and tolerable, stimulating cognitive functions and satisfying critically ill patients. Future studies will evaluate the impact of interventions on neurocognitive outcomes. Trial registration Clinical trials.gov identifier: NCT02078206.

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

DEFF Research Database (Denmark)

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

2016-01-01

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

Safety and feasibility audit of a home-based drug-transitioning approach for patients with pulmonary arterial hypertension: an observational study.

Science.gov (United States)

Dawson, A; Reddecliffe, S; Coghlan, C; Schreiber, B E; Coghlan, J G

2018-04-01

Newer endothelin receptor antagonists (ERAs) used to treat patients with pulmonary arterial hypertension (PAH) are associated with fewer drug-drug interactions than bosentan and require less monitoring. This, combined with a pharmacokinetic basis for improved efficacy, means there may be a clinical rationale for changing therapies. However, this can be challenging and few data on its safety in patients with PAH are available. At the Royal Free Hospital in London, UK, home-based medication transitioning has been standard practice since 2009 to avoid unnecessary hospital visits for patients, unless there is a clinical imperative. In this audit of standard practice we evaluated the consequences of adopting such a strategy when transitioning PAH patients between ERA therapies. Using a Clinical Nurse Specialist-led, home-based transitioning strategy, 92 patients with PAH were transitioned from bosentan to macitentan or ambrisentan. Observational data were analysed retrospectively. The majority of patients were female with PAH associated with connective tissue disease and their ERA was changed in the hope of improving efficacy. The process was well tolerated with no adverse events associated with the process. Seventeen patients died during the study (macitentan, n = 5; ambrisentan, n = 12). None of the deaths was considered related to ERA treatment. The majority of patients remained clinically stable, based on WHO functional class and exercise capacity. An established home-based transitioning strategy can be adopted safely for patients with PAH changing ERA therapies. Most patients remained stable and the therapy change was well tolerated.

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

Science.gov (United States)

Frost Widnes, Sofia K; Schjøtt, Jan

2008-01-01

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

E-learning to improve the drug prescribing in the hospitalized elderly patients: the ELICADHE feasibility pilot study.

Science.gov (United States)

Franchi, C; Mari, D; Tettamanti, M; Pasina, L; Djade, C D; Mannucci, P M; Onder, G; Bernabei, R; Gussoni, G; Bonassi, S; Nobili, A

2014-08-01

E-learning is an efficient and cost-effective educational method. This study aimed at evaluating the feasibility of an educational e-learning intervention, focused on teaching geriatric pharmacology and notions of comprehensive geriatric assessment, to improve drug prescribing to hospitalized elderly patients. Eight geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control. Clinicians of the two groups had to complete a specific per group e-learning program in 30 days. Then, ten patients (aged ≥75 years) had to be consecutively enrolled collecting clinical data at hospital admission, discharge, and 3 months later. The quality of prescription was evaluated comparing the prevalence of potentially inappropriate medications through Beer's criteria and of potential drug-drug interactions through a specific computerized database. The study feasibility was confirmed by the high percentage (90 %) of clinicians who completed the e-learning program, the recruitment, and follow-up of all planned patients. The intervention was well accepted by all participating clinicians who judged positively (a mean score of >3 points on a scale of 5 points: 0 = useless; 5 = most useful) the specific contents, the methodology applied, the clinical relevance and utility of e-learning contents and tools for the evaluation of the appropriateness of drug prescribing. The pilot study met all the requested goals. The main study is currently ongoing and is planned to finish on July 2015.

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...

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

Science.gov (United States)

2011-08-01

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

A modular, prospective, semi-automated drug safety monitoring system for use in a distributed data environment.

Science.gov (United States)

Gagne, Joshua J; Wang, Shirley V; Rassen, Jeremy A; Schneeweiss, Sebastian

2014-06-01

The aim of this study was to develop and test a semi-automated process for conducting routine active safety monitoring for new drugs in a network of electronic healthcare databases. We built a modular program that semi-automatically performs cohort identification, confounding adjustment, diagnostic checks, aggregation and effect estimation across multiple databases, and application of a sequential alerting algorithm. During beta-testing, we applied the system to five databases to evaluate nine examples emulating prospective monitoring with retrospective data (five pairs for which we expected signals, two negative controls, and two examples for which it was uncertain whether a signal would be expected): cerivastatin versus atorvastatin and rhabdomyolysis; paroxetine versus tricyclic antidepressants and gastrointestinal bleed; lisinopril versus angiotensin receptor blockers and angioedema; ciprofloxacin versus macrolide antibiotics and Achilles tendon rupture; rofecoxib versus non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) and myocardial infarction; telithromycin versus azithromycin and hepatotoxicity; rosuvastatin versus atorvastatin and diabetes and rhabdomyolysis; and celecoxib versus ns-NSAIDs and myocardial infarction. We describe the program, the necessary inputs, and the assumed data environment. In beta-testing, the system generated four alerts, all among positive control examples (i.e., lisinopril and angioedema; rofecoxib and myocardial infarction; ciprofloxacin and tendon rupture; and cerivastatin and rhabdomyolysis). Sequential effect estimates for each example were consistent in direction and magnitude with existing literature. Beta-testing across nine drug-outcome examples demonstrated the feasibility of the proposed semi-automated prospective monitoring approach. In retrospective assessments, the system identified an increased risk of myocardial infarction with rofecoxib and an increased risk of rhabdomyolysis with cerivastatin years

Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions

Directory of Open Access Journals (Sweden)

Ethan L Matz

2018-01-01

Full Text Available Purpose: Autologous platelet rich plasma (PRP is used increasingly in a variety of settings. PRP injections have been used for decades to improve angiogenesis and wound healing. They have also been offered commercially in urology with little to no data on safety or efficacy. PRP could theoretically improve multiple urologic conditions, such as erectile dysfunction (ED, Peyronie's disease (PD, and stress urinary incontinence (SUI. A concern with PRP, however, is early washout, a situation potentially avoided by conversion to platelet rich fibrin matrix (PRFM. Before clinical trials can be performed, safety analysis is desirable. We reviewed an initial series of patients receiving PRFM for urologic pathology to assess safety and feasibility. Materials and Methods: Data were reviewed for patients treated with PRFM at our center from November 2012 to July 2017. Patients were observed immediately post-injection and at follow-up for complications and tolerability. Where applicable, International Index of Erectile Function (IIEF-5 scores were reviewed before and after injections for ED and/or PD. Pad use data was collected pre/post injection for SUI. Results: Seventeen patients were identified, with a mean receipt of 2.1 injections per patient. Post-procedural minor adverse events were seen in 3 men, consisting of mild pain at injection site and mild penile bruising. No patients experienced complications at follow-up. No decline was observed in men completing pre/post IIEF-5 evaluations. Conclusions: PRFM appears to be a safe and feasible treatment modality in patients with urologic disease. Further placebo-controlled trials are warranted.

Safety and efficacy of generic drugs with respect to brand formulation

OpenAIRE

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

2013-01-01

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

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

Science.gov (United States)

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

2013-12-01

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

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.

Feasibility studies of safety assessment methods for programmable automation systems. Final report of the AVV project

International Nuclear Information System (INIS)

Haapanen, P.; Maskuniitty, M.; Pulkkinen, U.; Heikkinen, J.; Korhonen, J.; Tuulari, E.

1995-10-01

Feasibility studies of two different groups of methodologies for safety assessment of programmable automation systems has been executed at the Technical Research Centre of Finland (VTT). The studies concerned the dynamic testing methods and the fault tree (FT) and failure mode and effects analysis (FMEA) methods. In order to get real experience in the application of these methods, an experimental testing of two realistic pilot systems were executed and a FT/FMEA analysis of a programmable safety function accomplished. The purpose of the studies was not to assess the object systems, but to get experience in the application of methods and assess their potentials and development needs. (46 refs., 21 figs.)

Documentation of pediatric drug safety in manufacturers' product monographs: a cross-sectional evaluation of the canadian compendium of pharmaceuticals and specialities.

Science.gov (United States)

Uppal, Navjeet K; Dupuis, Lee L; Parshuram, Christopher S

2008-01-01

To describe the provision of pediatric drug safety information in a national formulary of manufacturers' drug product monographs. We performed a cross-sectional evaluation of comprehensive product monographs contained in the 2005 Canadian Compendium of Pharmaceuticals and Specialities (CPS). We abstracted data describing indications for prescription, statements about pediatric safety, available preparations, and provision of dosing guidelines. For each monograph we classified pediatric safety data as either present, present but limited or absent. We then described the pediatric safety data in CPS monographs for drugs listed in the published formulary of the Hospital for Sick Children, Toronto, Ontario, Canada. A total of 2232 product monographs were screened; 684 were excluded and 1548 (66%) were further analyzed. 1462 (94%) had indications that did not exclude children. Pediatric safety information was present in 592 (38%), present but limited in 148 (10%), and absent in 808 (52%) drug monographs. Safety statements were absent in 224 (14%) drug monographs that provided both dosing guidelines and formulations suitable for administration to children, and in 214 (52%) of 411 drugs in the pediatric hospital formulary. We evaluated a widely available national source of pediatric prescribing information. Safety data for children was not mentioned in more than half of the product monographs. Moreover, the provision of safety data was discordant with indications for prescription, the availability of pediatric formulations, and dosing guidelines within the monographs, and with inclusion in a pediatric hospital formulary. Our study suggests that the presentation of pediatric safety data in drug product monographs can be improved to better inform prescribing and to optimize pharmacotherapy in children.

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

Science.gov (United States)

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

2015-02-13

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

MR cholangiopancreatography in children: feasibility, safety, and initial experience

International Nuclear Information System (INIS)

Delaney, Lisa; Karmazyn, Boaz; Akisik, M.F.; Jennings, S.G.; Applegate, Kimberly E.

2008-01-01

The indications for MR cholangiopancreatography (MRCP) in children, and its safety and findings, might differ from those in adults and are not well described. To investigate the safety, feasibility, and accuracy of MRCP in children. We reviewed all prospective MRCP reports, noting the indication, the use of secretin, endoscopic retrograde cholangiopancreatography (ERCP) findings, and patient outcomes. Two readers reviewed each MRCP study by consensus to rate duct visualization and compare pancreatic duct sizes before and after secretin administration (paired t-test). The likelihood of a normal versus an abnormal MRCP study was compared by gender, pancreatitis as the primary indication, secretin use, and whether ERCP was performed (Fisher's exact test), as well as age (t-test). A total of 85 MRCP studies were performed in children (mean age 10.3 years), most commonly for evaluation of pancreatitis (n=47, 55%); 41 (48%) used secretin and 39 (46%) used a negative oral contrast agent. Of the 85 studies, 72 (85%) had excellent image quality and 43 were normal. ERCP was performed after 16 of the 85 MRCP studies (19%); the diagnoses were concordant with those of MRCP in 13 (81%). There were 42 abnormal MRCP studies, and these were more likely to be in girls (P=0.03) and in children who had undergone ERCP (P<0.01). Secretin and the negative oral contrast agent were well-tolerated. Secretin improved duct visualization (P<0.001). MRCP safely and accurately depicted pancreaticobiliary anatomy in children. The use of secretin improved visualization of the pancreatic duct. (orig.)

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...

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

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

Science.gov (United States)

Meier, Brian P; Lappas, Courtney M

2016-11-01

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

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.

Incorporation of in silico biodegradability screening in early drug development--a feasible approach?

Science.gov (United States)

Steger-Hartmann, Thomas; Länge, Reinhard; Heuck, Klaus

2011-05-01

The concentration of a pharmaceutical found in the environment is determined by the amount used by the patient, the excretion and metabolism pattern, and eventually by its persistence. Biological degradation or persistence of a pharmaceutical is experimentally tested rather late in the development of a pharmaceutical, often shortly before submission of the dossier to regulatory authorities. To investigate whether the aspect of persistence of a compound could be assessed early during drug development, we investigated whether biodegradation of pharmaceuticals could be predicted with the help of in silico tools. To assess the value of in silico prediction, we collected results for the OECD 301 degradation test ("ready biodegradability") of 42 drugs or drug synthesis intermediates and compared them to the prediction of the in silico tool BIOWIN. Of these compounds, 38 were predictable with BIOWIN, which is a module of the Estimation Programs Interface (EPI) Suite™ provided by the US EPA. The program failed to predict the two drugs which proved to be readily biodegradable in the degradation tests. On the other hand, BIOWIN predicted two compounds to be readily biodegradable which, however, proved to be persistent in the test setting. The comparison of experimental data with the predicted one resulted in a specificity of 94% and a sensitivity of 0%. The results of this study do not indicate that application of the biodegradation prediction tool BIOWIN is a feasible approach to assess the ready biodegradability during early drug development.

Feasibility and safety of fiber optic micro-imaging in canine peripheral airways.

Directory of Open Access Journals (Sweden)

Yijun Liu

Full Text Available PURPOSE: To assess the feasibility and safety of imaging canine peripheral airways (0.05. Comparing pre-manipulation and post-manipulation values, SpO2 (F = 13.06, P<0.05 and PaO2 (F = 3.01, P = 0.01 were decreased, whereas RR (F = 3.85, P<0.05 was elevated during the manipulation. (3 Self-limited bleeding was observed in one dog; severe bleeding or other complications did not occur. CONCLUSION: Although the new apparatus had little effect on SpO2, PaO2 and RR, it can probe into small peripheral airways (<1 mm, which may provide a new platform for the early diagnosis of bronchiolar diseases.

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

Science.gov (United States)

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

2009-12-01

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

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

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.

Feasibility, safety and outcomes of playing Kinect Adventures!™ for people with Parkinson's disease: a pilot study.

Science.gov (United States)

Pompeu, J E; Arduini, L A; Botelho, A R; Fonseca, M B F; Pompeu, S M A A; Torriani-Pasin, C; Deutsch, J E

2014-06-01

To assess the feasibility, safety and outcomes of playing Microsoft Kinect Adventures™ for people with Parkinson's disease in order to guide the design of a randomised clinical trial. Single-group, blinded trial. Rehabilitation Center of São Camilo University, Brazil. Seven patients (six males, one female) with Parkinson's disease (Hoehn and Yahr Stages 2 and 3). Fourteen 60-minute sessions, three times per week, playing four games of Kinect Adventures! The feasibility and safety outcomes were patients' game performance and adverse events, respectively. The clinical outcomes were the 6-minute walk test, Balance Evaluation System Test, Dynamic Gait Index and Parkinson's Disease Questionnaire (PDQ-39). Patients' scores for the four games showed improvement. The mean [standard deviation (SD)] scores in the first and last sessions of the Space Pop game were 151 (36) and 198 (29), respectively [mean (SD) difference 47 (7), 95% confidence interval 15 to 79]. There were no adverse events. Improvements were also seen in the 6-minute walk test, Balance Evaluation System Test, Dynamic Gait Index and PDQ-39 following training. Kinect-based training was safe and feasible for people with Parkinson's disease (Hoehn and Yahr Stages 2 and 3). Patients improved their scores for all four games. No serious adverse events occurred during training with Kinect Adventures!, which promoted improvement in activities (balance and gait), body functions (cardiopulmonary aptitude) and participation (quality of life). Copyright © 2013 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Safety Improvements on Wood Chippers Currently in Use: A Study on Feasibility in the Italian Context

Directory of Open Access Journals (Sweden)

Giorgia Bagagiolo

2017-12-01

Full Text Available Following formal opposition by France, the harmonized safety standards regarding manually-loaded wood chippers (EN 13525:2005+A2:2009 which presumed compliance with the Essential Health and Safety Requirements (EHSR required by the Machine Directive (Directive 2006/42/EC, have recently been withdrawn, and a new draft of the standard is currently under revision. In order to assess the potential impact of the expected future harmonized standards within the Italian context, this study has examined the main issues in implementing EHSRs on wood chippers already being used. Safety issues regarding wood chippers already in use were identified in an analysis of the draft standard, through the observation of a number of case studies, and qualitative analysis of the essential technical interventions. A number of agricultural and forestry operators and companies participated in the study, pointing out the technical and economic obstacle facing the safety features requested by the pending new standard. It emerged that the main safety issues concerned the implementation of the reverse function, the stop bar, and the protective devices, the infeed chute dimension, the emergency stop function, and the designated feeding area. The possibility of adopting such solutions mainly depends on technical feasibility and costs, but an important role is also played by the attitude towards safety and a lack of adequate information regarding safety obligations and procedures among users.

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

Science.gov (United States)

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

2017-01-01

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

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

DEFF Research Database (Denmark)

Dybdahl, Torben; Andersen, Morten; Søndergaard, Jens

2004-01-01

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

How do pharmaceutical companies handle consumer adverse drug reaction reports? An overview based on a survey of French drug safety managers and officers.

Science.gov (United States)

Fleuranceau-Morel, P

2002-01-01

It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side-effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e-mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated

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

NARCIS (Netherlands)

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

2016-01-01

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

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.

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...

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.

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.

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.

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

Science.gov (United States)

Mackey, Tim K

2012-01-01

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

Drug waste minimisation and cost-containment in Medical Oncology: Two-year results of a feasibility study

Directory of Open Access Journals (Sweden)

Mansutti Mauro

2008-04-01

Full Text Available Abstract Background Cost-containment strategies are required to face the challenge of rising drug expenditures in Oncology. Drug wastage leads to economic loss, but little is known about the size of the problem in this field. Methods Starting January 2005 we introduced a day-to-day monitoring of drug wastage and an accurate assessment of its costs. An internal protocol for waste minimisation was developed, consisting of four corrective measures: 1. A rational, per pathology distribution of chemotherapy sessions over the week. 2. The use of multi-dose vials. 3. A reasonable rounding of drug dosages. 4. The selection of the most convenient vial size, depending on drug unit pricing. Results Baseline analysis focused on 29 drugs over one year. Considering their unit price and waste amount, a major impact on expense was found to be attributable to six drugs: cetuximab, docetaxel, gemcitabine, oxaliplatin, pemetrexed and trastuzumab. The economic loss due to their waste equaled 4.8% of the annual drug expenditure. After the study protocol was started, the expense due to unused drugs showed a meaningful 45% reduction throughout 2006. Conclusion Our experience confirms the economic relevance of waste minimisation and may represent a feasible model in addressing this issue. A centralised unit of drug processing, the availability of a computerised physician order entry system and an active involvement of the staff play a key role in allowing waste reduction and a consequent, substantial cost-saving.

Safety and feasibility of inpatient exercise training in pediatric heart failure: a preliminary report.

Science.gov (United States)

McBride, Michael G; Binder, Tracy Jo; Paridon, Stephen M

2007-01-01

To determine the safety and feasibility of an inpatient exercise training program for a group of pediatric heart transplantation candidates on multiple inotropic support. Children with end-stage heart disease often require heart transplantation. Currently, no data exist on the safety and feasibility of an inpatient exercise training program in pediatric patients awaiting heart transplantation while on inotropic support. Twenty ambulatory patients (11 male; age, 13.6 +/- 3.2 years) were admitted, listed, and subsequently enrolled into an exercise training program while awaiting heart transplantation. Patient diagnoses consisted of dilated cardiomyopathy (n = 15), restrictive cardiomyopathy (n = 1), and failing single-ventricle physiology (n = 4). Inotropic support consisted of a combination of dobutamine, dopamine, or milrinone. Exercise sessions were scheduled three times a week lasting from 30 to 60 minutes and consisted of aerobic and musculoskeletal conditioning. Over 6.2 +/- 4.2 months, 1,251 of a possible 1,508 exercise training sessions were conducted, with a total of 615 hours (26.3 +/- 2.7 min/session) dedicated to low-intensity aerobic exercise. Reasons for noncompliance included a change in medical status, staffing, or patient cooperation. Two adverse episodes (seizures) occurred, neither of which resulted in termination from the program. No adverse episodes of hypotension or significant complex arrhythmias occurred. No complication of medication administration or loss of intravenous access occurred. Data from this study indicate that pediatric patients on inotropic support as a result of systemic ventricular or biventricular heart failure can safely participate in exercise training programs with relatively moderate to high compliance.

Feasibility and Safety of Pressurized Intraperitoneal Aerosol Chemotherapy for Peritoneal Carcinomatosis: A Retrospective Cohort Study

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Martin Hübner

2017-01-01

Full Text Available Background. Pressurized intraperitoneal aerosol chemotherapy (PIPAC has been introduced as a novel repeatable treatment for peritoneal carcinomatosis. The available evidence from the pioneer center suggests good tolerance and high response rates, but independent confirmation is needed. A single-center cohort was analyzed one year after implementation for feasibility and safety. Methods. PIPAC was started in January 2015, and every patient was entered into a prospective database. This retrospective analysis included all consecutive patients operated until April 2016 with emphasis on surgical feasibility and early postoperative outcomes. Results. Forty-two patients (M : F = 8 : 34, median age 66 (59–73 years with 91 PIPAC procedures in total (4×: 1,  3×: 17,  2×: 12, and  1×: 12 were analyzed. Abdominal accessibility rate was 95% (42/44; laparoscopic access was not feasible in 2 patients with previous HIPEC. Median initial peritoneal carcinomatosis index (PCI was 10 (IQR 5–17. Median operation time was 94 min (89–108 with no learning curve observed. One PIPAC application was postponed due to intraoperative intestinal lesion. Overall morbidity was 9% with 7 minor complications (Clavien I-II and one PIPAC-unrelated postoperative mortality. Median postoperative hospital stay was 3 days (2-3. Conclusion. Repetitive PIPAC is feasible in most patients with refractory carcinomatosis of various origins. Intraoperative complications and postoperative morbidity rates were low. This encourages prospective studies assessing oncological efficacy.

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

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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.

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

DEFF Research Database (Denmark)

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

2014-01-01

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

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

Science.gov (United States)

2010-06-25

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

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

OpenAIRE

Castleden, C M; Pickles, H

1988-01-01

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

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...

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

International Nuclear Information System (INIS)

Boyd, Ian W.

2002-01-01

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

CRASH - Community Road Accident System Homepage : feasibility study on a European Road Safety Information System, financially supported by the European Commission.

NARCIS (Netherlands)

Brouwer, M. Poppe, F. Blokpoel, A. & Kars, V.

2000-01-01

This report is the result of a feasibility study, financially supported by the European Commission. The study investigated the possibilities for the development and maintenance of a European Road Safety Information System with relevant and internationally comparable information. Recommendations on

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

Science.gov (United States)

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

2013-09-01

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

Environmental, Safety, and Health Plan for the remedial investigation/feasibility study at Oak Ridge National Laboratory, Oak Ridge, Tennessee

International Nuclear Information System (INIS)

1993-05-01

This Environmental, Safety, and Health (ES ampersand H) Plan presents the concepts and methodologies to be followed during the remedial investigation/feasibility study (RI/FS) for Oak Ridge National Laboratory (ORNL) to protect the health and safety of employees, the public, and the environment. This ES ampersand H Plan acts as a management extension for ORNL and Martin Marietta Energy Systems, Inc. (Energy Systems) to direct and control implementation of the project ES ampersand H program. The subsections that follow describe the program philosophy, requirements, quality assurance measures, and methods for applying the ES ampersand H program to individual waste area grouping (WAG) remedial investigations. Hazardous work permits (HWPs) will be used to provide task-specific health and safety requirements

TryCYCLE: A Prospective Study of the Safety and Feasibility of Early In-Bed Cycling in Mechanically Ventilated Patients.

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Michelle E Kho

Full Text Available The objective of this study was to assess the safety and feasibility of in-bed cycling started within the first 4 days of mechanical ventilation (MV to inform a future randomized clinical trial.We conducted a 33-patient prospective cohort study in a 21-bed adult academic medical-surgical intensive care unit (ICU in Hamilton, ON, Canada. We included adult patients (≥ 18 years receiving MV who walked independently pre-ICU. Our intervention was 30 minutes of in-bed supine cycling 6 days/week in the ICU. Our primary outcome was Safety (termination, measured as events prompting cycling termination; secondary Safety (disconnection or dislodgement outcomes included catheter/tube dislodgements. Feasibility was measured as consent rate and fidelity to intervention. For our primary outcome, we calculated the binary proportion and 95% confidence interval (CI.From 10/2013-8/2014, we obtained consent from 34 of 37 patients approached (91.9%, 33 of whom received in-bed cycling. Of those who cycled, 16(48.4% were female, the mean (SD age was 65.8(12.2 years, and APACHE II score was 24.3(6.7; 29(87.9% had medical admitting diagnoses. Cycling termination was infrequent (2.0%, 95% CI: 0.8%-4.9% and no device dislodgements occurred. Cycling began a median [IQR] of 3 [2, 4] days after ICU admission; patients received 5 [3, 8] cycling sessions with a median duration of 30.7 [21.6, 30.8] minutes per session. During 205 total cycling sessions, patients were receiving invasive MV (150 [73.1%], vasopressors (6 [2.9%], sedative or analgesic infusions (77 [37.6%] and dialysis (4 [2.0%].Early cycling within the first 4 days of MV among hemodynamically stable patients is safe and feasible. Research to evaluate the effect of early cycling on patient function is warranted.Clinicaltrials.gov: NCT01885442.

Feasibility study of silica sol as the carrier of a hydrophobic drug in aqueous solution using enrofloxacin as the model

International Nuclear Information System (INIS)

Song Meirong; Song Junling; Ning Aimin; Cui Baoan; Cui Shumin; Zhou Yaobing; An Wankai; Dong Xuesong; Zhang Gege

2010-01-01

The aim of this study was to determine the feasibility of using silica sol to carry a hydrophobic drug in aqueous solution. Enrofloxacin, which was selected as the model drug because it is a broad-spectrum antibiotic drug with poor solubility in water, was adsorbed onto silica sol in aqueous solution during cooling from 60 deg. C to room temperature. The drug-loaded silica sol was characterized by transmission electron microscopy, Fourier transform infrared spectrum, thermal gravimetric analysis and ultraviolet-visible light spectroscopy. The results showed that enrofloxacin was adsorbed by silica sol without degradation at a loading of 15.23 wt.%. In contrast to the rapid release from pure enrofloxacin, the drug-loaded silica sol showed a slower release over a longer time. Kinetics analysis suggested the drug release from silica sol was mainly a diffusion-controlled process. Therefore, silica sol can be used to carry a hydrophobic drug in aqueous solution for controlled drug delivery.

Assuring consumer safety without animal testing: a feasibility case study for skin sensitisation.

Science.gov (United States)

Maxwell, Gavin; Aleksic, Maja; Aptula, Aynur; Carmichael, Paul; Fentem, Julia; Gilmour, Nicola; Mackay, Cameron; Pease, Camilla; Pendlington, Ruth; Reynolds, Fiona; Scott, Daniel; Warner, Guy; Westmoreland, Carl

2008-11-01

Allergic Contact Dermatitis (ACD; chemical-induced skin sensitisation) represents a key consumer safety endpoint for the cosmetics industry. At present, animal tests (predominantly the mouse Local Lymph Node Assay) are used to generate skin sensitisation hazard data for use in consumer safety risk assessments. An animal testing ban on chemicals to be used in cosmetics will come into effect in the European Union (EU) from March 2009. This animal testing ban is also linked to an EU marketing ban on products containing any ingredients that have been subsequently tested in animals, from March 2009 or March 2013, depending on the toxicological endpoint of concern. Consequently, the testing of cosmetic ingredients in animals for their potential to induce skin sensitisation will be subject to an EU marketing ban, from March 2013 onwards. Our conceptual framework and strategy to deliver a non-animal approach to consumer safety risk assessment can be summarised as an evaluation of new technologies (e.g. 'omics', informatics), leading to the development of new non-animal (in silico and in vitro) predictive models for the generation and interpretation of new forms of hazard characterisation data, followed by the development of new risk assessment approaches to integrate these new forms of data and information in the context of human exposure. Following the principles of the conceptual framework, we have been investigating existing and developing new technologies, models and approaches, in order to explore the feasibility of delivering consumer safety risk assessment decisions in the absence of new animal data. We present here our progress in implementing this conceptual framework, with the skin sensitisation endpoint used as a case study. 2008 FRAME.

Field validity and feasibility of four techniques for the detection of Trichuris in simians: a model for monitoring drug efficacy in public health?

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Bruno Levecke

Full Text Available BACKGROUND: Soil-transmitted helminths, such as Trichuris trichiura, are of major concern in public health. Current efforts to control these helminth infections involve periodic mass treatment in endemic areas. Since these large-scale interventions are likely to intensify, monitoring the drug efficacy will become indispensible. However, studies comparing detection techniques based on sensitivity, fecal egg counts (FEC, feasibility for mass diagnosis and drug efficacy estimates are scarce. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the ether-based concentration, the Parasep Solvent Free (SF, the McMaster and the FLOTAC techniques were compared based on both validity and feasibility for the detection of Trichuris eggs in 100 fecal samples of nonhuman primates. In addition, the drug efficacy estimates of quantitative techniques was examined using a statistical simulation. Trichuris eggs were found in 47% of the samples. FLOTAC was the most sensitive technique (100%, followed by the Parasep SF (83.0% [95% confidence interval (CI: 82.4-83.6%] and the ether-based concentration technique (76.6% [95% CI: 75.8-77.3%]. McMaster was the least sensitive (61.7% [95% CI: 60.7-62.6%] and failed to detect low FEC. The quantitative comparison revealed a positive correlation between the four techniques (Rs = 0.85-0.93; p<0.0001. However, the ether-based concentration technique and the Parasep SF detected significantly fewer eggs than both the McMaster and the FLOTAC (p<0.0083. Overall, the McMaster was the most feasible technique (3.9 min/sample for preparing, reading and cleaning of the apparatus, followed by the ether-based concentration technique (7.7 min/sample and the FLOTAC (9.8 min/sample. Parasep SF was the least feasible (17.7 min/sample. The simulation revealed that the sensitivity is less important for monitoring drug efficacy and that both FLOTAC and McMaster were reliable estimators. CONCLUSIONS/SIGNIFICANCE: The results of this study

Intra?Target Microdosing ? A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans

OpenAIRE

Burt, T; MacLeod, D; Lee, K; Santoro, A; DeMasi, DK; Hawk, T; Feinglos, M; Rowland, M; Noveck, RJ

2017-01-01

Intra-target microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first-in-human (FIH) testing of new molecular entities (NMEs). ITM combines intra-target drug delivery and "microdosing," the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic-level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers receive...

Feasibility, safety, acceptability, and preliminary efficacy of measurement-based care depression treatment for HIV patients in Bamenda, Cameroon.

Science.gov (United States)

Pence, Brian W; Gaynes, Bradley N; Atashili, Julius; O'Donnell, Julie K; Kats, Dmitry; Whetten, Kathryn; Njamnshi, Alfred K; Mbu, Tabenyang; Kefie, Charles; Asanji, Shantal; Ndumbe, Peter

2014-06-01

Depression affects 18-30 % of HIV-infected patients in Africa and is associated with greater stigma, lower antiretroviral adherence, and faster disease progression. However, the region's health system capacity to effectively identify and treat depression is limited. Task-shifting models may help address this large mental health treatment gap. Measurement-Based Care (MBC) is a task-shifting model in which a Depression Care Manager guides a non-psychiatric (e.g., HIV) provider in prescribing and managing antidepressant treatment. We adapted MBC for depressed HIV-infected patients in Cameroon and completed a pilot study to assess feasibility, safety, acceptability, and preliminary efficacy. We enrolled 55 participants; all started amitriptyline 25-50 mg daily at baseline. By 12 weeks, most remained at 50 mg daily (range 25-125 mg). Median (interquartile range) PHQ-9 depressive severity scores declined from 13 (12-16) (baseline) to 2 (0-3) (week 12); 87 % achieved depression remission (PHQ-9 feasibility, safety, acceptability, and preliminary efficacy in this uncontrolled pilot study. Further research should assess whether MBC could improve adherence and HIV outcomes in this setting.

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

Science.gov (United States)

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

2017-12-18

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

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

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

DEFF Research Database (Denmark)

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

2018-01-01

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

A comparative analysis of drug safety withdrawals in the UK and the US (1971-1992): implications for current regulatory thinking and policy.

Science.gov (United States)

Abraham, John; Davis, Courtney

2005-09-01

By going beyond individual case studies and solely quantitative surveys, this paper systematically examines why there were over twice as many new prescription drugs withdrawn from the market on grounds of safety in the UK as there were in the US between 1971 and 1992. Drawing on interviews with regulators, industry scientists and others involved, and on regulatory data never before accessed outside governments and companies, five key hypotheses which might explain this difference in drug safety withdrawals are analysed. These are: (1) simply because the UK approved more new drugs than the US; (2) because of an industrial corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3) because British regulators were more vigilant at spotting post-marketing safety problems than their US counterparts; (4) because the slowness of the US in approving new drugs enabled regulators there to learn from, and avoid, safety problems that had already emerged in the UK or European market; and (5) because more stringent regulation in the US meant that they approved fewer unsafe drugs on to the market in the first place. It is concluded that the main explanation for fewer drug safety withdrawals in the US is that the regulatory agency there applied more stringent pre-market review and/or standards, which took longer than UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering the US market. Contrary to the claims frequently made by the pharmaceutical industry and regulatory agencies on both sides of the Atlantic, these results imply that it is likely that acceleration of regulatory review times in the US and the UK since the early 1990s is compromising drug safety.

Effects of acute exercise on drug craving, self-esteem, mood and affect in adults with poly-substance dependence: Feasibility and preliminary findings.

Science.gov (United States)

Ellingsen, Maren Mikkelsen; Johannesen, Sunniva Launes; Martinsen, Egil W; Hallgren, Mats

2018-06-04

Novel treatments for substance use disorders are needed. Acute bouts of exercise can improve mood states in non-clinical populations, but effects in those with poly-substance dependence are understudied. We examined the feasibility and short-term effects of three types of exercise on drug cravings, self-esteem, mood and positive/negative affect in nine poly-drug-dependent inpatients. Using a cross-over design, changes in the four study outcomes were assessed immediately before exercise and on four separate occasions post-exercise (immediately after, then at 1, 2 and 4 h post-exercise) enabling patterns of change over time (analysis of covariance) to be observed. Participants were willing and able to engage in different non-laboratory based exercises. Football was associated with non-significant short-term reductions in drug cravings. A similar trend was seen for circuit-training, but not walking. Football and circuit-training were associated with brief improvements in mood and positive/negative affect. No adverse events were reported. Football, circuit training and walking are feasible therapeutic activities for inpatients with poly-substance dependence. Controlled trials are needed to determine the long-term effects of these activities. © 2018 Australasian Professional Society on Alcohol and other Drugs.

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

Directory of Open Access Journals (Sweden)

Prasad Thota

2018-01-01

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

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

Science.gov (United States)

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

2017-04-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

Bladder tissue engineering using biocompatible nanofibrous electrospun constructs: feasibility and safety investigation.

Science.gov (United States)

Shakhssalim, Nasser; Dehghan, Mohammad Mehdi; Moghadasali, Reza; Soltani, Mohammad Hossein; Shabani, Iman; Soleimani, Masoud

2012-01-01

To investigate the feasibility and safety of using biocompatible, nanofibrous electrospun polycaprolactone (PCL) and combination of polylactic acid (PLLA) and PCL mats in a canine model. Plasma-treated electrospun unseeded mats were implanted in three dogs. The first dog was sacrificed after 3 months and the second and third ones after 4 months, and then, the graft was examined macroscopically with subsequent morphological and histochemical evaluation. Both films showed high levels of cell infiltration and tissue formation, but body response to PLLA/PCL mat in comparison to PCL mat was very low. All three implantation models showed the same light microscopic morphology, immunohistochemistry, and scanning electron microscopy results; nevertheless, only the PCL/PLLA model showed favorable clinical results. Based on these data, nanofibrous PLLA/PCL scaffolding could be a suitable material for the bladder tissue engineering; however, it deserves further investigations.

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

Sponsors’ and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials

Science.gov (United States)

Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

2017-01-01

Background/aims: The Food and Drug Administration’s final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. Methods: In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative–nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. Results: The investigative site’s responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors’“filtering” of

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

Safety and feasibility of transcranial direct current stimulation in amyotrophic lateral sclerosis - a pilot study with a single subject experimental design.

Science.gov (United States)

Madhavan, Sangeetha; Sivaramakrishnan, Anjali; Bond, Sam; Jiang, Qin Li

2018-02-28

Transcranial direct current stimulation (tDCS) has been explored as a neuromodulatory tool to prime motor function in several neurological disorders. Studies using tDCS in amyotrophic lateral sclerosis (ALS) are limited. We investigated the safety, feasibility and effects of long-term tDCS in an individual with ALS. A 36-year-old male diagnosed with clinically definite ALS received 12 sessions each of anodal, sham, and cathodal tDCS. Outcome measures included disease progression (revised ALS functional rating scale (ALSFRS-R)), clinical measures of endurance and mobility, and corticomotor excitability. No adverse events or change in disease progression were noticed during the study. Small improvement in gait speed (15% increase) was noticed with anodal tDCS only. This case study demonstrates the safety and feasibility of long-term facilitatory and inhibitory tDCS on a single participant with ALS. This study serves as a guideline for implementing tDCS in future ALS trials.

Prediction of adverse drug reactions using decision tree modeling.

Science.gov (United States)

Hammann, F; Gutmann, H; Vogt, N; Helma, C; Drewe, J

2010-07-01

Drug safety is of great importance to public health. The detrimental effects of drugs not only limit their application but also cause suffering in individual patients and evoke distrust of pharmacotherapy. For the purpose of identifying drugs that could be suspected of causing adverse reactions, we present a structure-activity relationship analysis of adverse drug reactions (ADRs) in the central nervous system (CNS), liver, and kidney, and also of allergic reactions, for a broad variety of drugs (n = 507) from the Swiss drug registry. Using decision tree induction, a machine learning method, we determined the chemical, physical, and structural properties of compounds that predispose them to causing ADRs. The models had high predictive accuracies (78.9-90.2%) for allergic, renal, CNS, and hepatic ADRs. We show the feasibility of predicting complex end-organ effects using simple models that involve no expensive computations and that can be used (i) in the selection of the compound during the drug discovery stage, (ii) to understand how drugs interact with the target organ systems, and (iii) for generating alerts in postmarketing drug surveillance and pharmacovigilance.

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

Science.gov (United States)

Roth, Sanford H

2011-01-01

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

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

Science.gov (United States)

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

2011-11-01

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

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.

Feasibility of a Video-Based Advance Care Planning Website to Facilitate Group Visits among Diverse Adults from a Safety-Net Health System.

Science.gov (United States)

Zapata, Carly; Lum, Hillary D; Wistar, Emily; Horton, Claire; Sudore, Rebecca L

2018-02-20

Primary care providers in safety-net settings often do not have time to discuss advance care planning (ACP). Group visits (GV) may be an efficient means to provide ACP education. To assess the feasibility and impact of a video-based website to facilitate GVs to engage diverse adults in ACP. Feasibility pilot among patients who were ≥55 years of age from two primary care clinics in a Northern California safety-net setting. Participants attended two 90-minute GVs and viewed the five steps of the movie version of the PREPARE website ( www.prepareforyourcare.org ) concerning surrogates, values, and discussing wishes in video format. Two clinician facilitators were available to encourage participation. We assessed pre-to-post ACP knowledge, whether participants designated a surrogate or completed an advance directive (AD), and acceptability of GVs and PREPARE materials. We conducted two GVs with 22 participants. Mean age was 64 years (±7), 55% were women, 73% nonwhite, and 55% had limited literacy. Knowledge improved about surrogate designation (46% correct pre vs. 85% post, p = 0.01) and discussing decisions with others (59% vs. 90%, p = 0.01). Surrogate designation increased (48% vs. 85%, p = 0.01) and there was a trend toward AD completion (9% vs. 24%, p = 0.21). Participants rated the GVs and PREPARE materials a mean of 8 (±3.1) on a 10-point acceptability scale. Using the PREPARE movie to facilitate ACP GVs for diverse adults in safety net, primary care settings is feasible and shows potential for increasing ACP engagement.

Feasibility and Safety Assessment for Advanced Reactor Concepts Using Vented Fuel

International Nuclear Information System (INIS)

Klein, Andrew; Lenhof, Renae; Deason, Wesley; Harter, Jackson

2015-01-01

Recent interest in fast reactor technology has led to renewed analysis of past reactor concepts such as Gas Fast Reactors and Sodium Fast Reactors. In an effort to make these reactors more economic, the fuel is required to stay in the reactor for extended periods of time; the longer the fuel stays within the core, the more fertile material is converted into usable fissile material. However, as burnup of the fuel-rod increases, so does the internal pressure buildup due to gaseous fission products. In order to reach the 30 year lifetime requirements of some reactor designs, the fuel pins must have a vented-type design to allow the buildup of fission products to escape. The present work aims to progress the understanding of the feasibility and safety issues related to gas reactors that incorporate vented fuel. The work was separated into three different work-scopes: 1. Quantitatively determine fission gas release from uranium carbide in a representative helium cooled fast reactor; 2. Model the fission gas behavior, transport, and collection in a Fission Product Vent System; and, 3. Perform a safety analysis of the Fission Product Vent System. Each task relied on results from the previous task, culminating in a limited scope Probabilistic Risk Assessment (PRA) of the Fission Product Vent System. Within each task, many key parameters lack the fidelity needed for comprehensive or accurate analysis. In the process of completing each task, the data or methods that were lacking were identified and compiled in a Gap Analysis included at the end of the report.

Feasibility and Safety Assessment for Advanced Reactor Concepts Using Vented Fuel

Energy Technology Data Exchange (ETDEWEB)

Klein, Andrew [Oregon State Univ., Corvallis, OR (United States). Nuclear Engineering and Radiation Health Physics; Matthews, Topher [Oregon State Univ., Corvallis, OR (United States); Lenhof, Renae [Oregon State Univ., Corvallis, OR (United States); Deason, Wesley [Oregon State Univ., Corvallis, OR (United States); Harter, Jackson [Oregon State Univ., Corvallis, OR (United States)

2015-01-16

Recent interest in fast reactor technology has led to renewed analysis of past reactor concepts such as Gas Fast Reactors and Sodium Fast Reactors. In an effort to make these reactors more economic, the fuel is required to stay in the reactor for extended periods of time; the longer the fuel stays within the core, the more fertile material is converted into usable fissile material. However, as burnup of the fuel-rod increases, so does the internal pressure buildup due to gaseous fission products. In order to reach the 30 year lifetime requirements of some reactor designs, the fuel pins must have a vented-type design to allow the buildup of fission products to escape. The present work aims to progress the understanding of the feasibility and safety issues related to gas reactors that incorporate vented fuel. The work was separated into three different work-scopes: 1. Quantitatively determine fission gas release from uranium carbide in a representative helium cooled fast reactor; 2. Model the fission gas behavior, transport, and collection in a Fission Product Vent System; and, 3. Perform a safety analysis of the Fission Product Vent System. Each task relied on results from the previous task, culminating in a limited scope Probabilistic Risk Assessment (PRA) of the Fission Product Vent System. Within each task, many key parameters lack the fidelity needed for comprehensive or accurate analysis. In the process of completing each task, the data or methods that were lacking were identified and compiled in a Gap Analysis included at the end of the report.

Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia.

Science.gov (United States)

Titano, J J; Biederman, D M; Marinelli, B S; Patel, R S; Kim, E; Tabori, N E; Nowakowski, F S; Lookstein, R A; Fischman, A M

2016-05-01

Transradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions. Patients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications. From July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µL (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6% with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9%) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1%) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups. Transradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.

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

A systematic review and meta-analysis of the safety, feasibility and effect of exercise in women with stage II+ breast cancer.

Science.gov (United States)

Singh, Ben; Spence, Rosalind R; Steele, Megan L; Sandler, Carolina X; Peake, Jonathan M; Hayes, Sandra C

2018-05-03

To systematically evaluate the safety, feasibility and effect of exercise among women with stage II+ breast cancer. CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, Science Direct and SPORTDiscus were searched for articles published prior to March 1, 2017. Randomised, controlled, exercise trials involving at least 50% of women diagnosed with stage II+ breast cancer were included. Risk of bias was assessed and adverse event severity was classified using the Common Terminology Criteria. Feasibility was evaluated by computing median (range) recruitment, withdrawal and adherence rates. Meta-analyses were performed to evaluate exercise safety and effects on health outcomes only. The influence of intervention characteristics (mode, supervision, duration and timing) on exercise outcomes were also explored. There were no differences in adverse events between exercise and usual care (risk difference: feasibility outcomes were similar, irrespective of exercise mode, supervision, duration, or timing. Effects of exercise for quality of life, fitness, fatigue, strength, anxiety, depression, body mass index and waist circumference compared with usual care were significant (standardised mean difference range: 0.17-0.77, pfeasibility and effects of exercise for those with stage II+ breast cancer, suggesting that national and international exercise guidelines appear generalizable to women with local, regional and distant breast cancer. Copyright © 2018. Published by Elsevier Inc.

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.

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.

Feasibility and cost analysis of programmatic implementation of ...

African Journals Online (AJOL)

Objectives: Detection of Multi-drug resistant tuberculosis in Nigeria still remains a challenge. We evaluated the feasibility of programmatic implementation of the Microscopic-Observation Drug Susceptibility (MODS) assay, a rapid culture and drug susceptibility testing technique for drug susceptibility testing in a low resource ...

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

Science.gov (United States)

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel

2016-01-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID:27278929

Organized polysaccharide fibers as stable drug carriers

Science.gov (United States)

Janaswamy, Srinivas; Gill, Kristin L.; Campanella, Osvaldo H.; Pinal, Rodolfo

2013-01-01

Many challenges arise during the development of new drug carrier systems, and paramount among them are safety, solubility and controlled release requirements. Although synthetic polymers are effective, the possibility of side effects imposes restrictions on their acceptable use and dose limits. Thus, a new drug carrier system that is safe to handle and free from side effects is very much in need and food grade polysaccharides stand tall as worthy alternatives. Herein, we demonstrate for the first time the feasibility of sodium iota-carrageenan fibers and their distinctive water pockets to embed and release a wide variety of drug molecules. Structural analysis has revealed the existence of crystalline network in the fibers even after encapsulating the drug molecules, and iota-carrageenan maintains its characteristic and reproducible double helical structure suggesting that the composites thus produced are reminiscent of cocrystals. The melting properties of iota-carrageenan:drug complexes are distinctly different from those of either drug or iota-carrageenan fiber. The encapsulated drugs are released in a sustained manner from the fiber matrix. Overall, our research provides an elegant opportunity for developing effective drug carriers with stable network toward enhancing and/or controlling bioavailability and extending shelf-life of drug molecules using GRAS excipients, food polysaccharides, that are inexpensive and non–toxic. PMID:23544530

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.

Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis.

Science.gov (United States)

Robella, Manuela; Vaira, Marco; De Simone, Michele

2016-04-29

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. It has been proved to be safe and feasible if performed as an exclusive treatment in patients affected by peritoneal carcinomatosis. The first results in patients treated with PIPAC associated with systemic chemotherapy are presented. Between June 2015 and February 2016, 57 PIPAC applications with oxaliplatin or cisplatin + doxorubicin every 6 weeks at 37 °C and 12 mmHg for 30 min were performed. Forty PIPAC procedures performed in 14 patients were included in this study; thirteen patients were undergoing systemic chemotherapy with a wash-out interval of at least 2 weeks before and 1 week after each PIPAC. Safety, tolerability, and postoperative complications were assessed by collection of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) 2. Forty PIPAC administrations were performed in 14 patients with no major perioperative complications. CTCAE grades 1 and 2 were observed after six and eight procedures, respectively, for abdominal pain and nausea. Renal and hepatic functions were not impaired; no cumulative renal toxicity was observed after repeated PIPAC procedures in association with systemic chemotherapy. These preliminary data show that the association of PIPAC and systemic chemotherapy does not induce significant hepatic and renal toxicity. It allows inclusion of patients with extraperitoneal disease or at a high risk of developing it. Further studies are needed to assess whether this combination therapy could become part of the standard treatment for peritoneal carcinomatosis.

Sentinel lymph node biopsy in endometrial cancer-Feasibility, safety and lymphatic complications.

Science.gov (United States)

Geppert, Barbara; Lönnerfors, Céline; Bollino, Michele; Persson, Jan

2018-03-01

To compare the rate of lymphatic complications in women with endometrial cancer undergoing sentinel lymph node biopsy versus a full pelvic and infrarenal paraaortic lymphadenectomy, and to examine the overall feasibility and safety of the former. A prospective study of 188 patients with endometrial cancer planned for robotic surgery. Indocyanine green was used to identify the sentinel lymph nodes. In low-risk patients the lymphadenectomy was restricted to removal of sentinel lymph nodes whereas in high-risk patients also a full lymphadenectomy was performed. The impact of the extent of the lymphadenectomy on the rate of complications was evaluated. The bilateral detection rate of sentinel lymph nodes was 96% after cervical tracer injection. No intraoperative complication was associated with the sentinel lymph node biopsy per se. Compared with hysterectomy alone, the additional average operative time for removal of sentinel lymph nodes was 33min whereas 91min were saved compared with a full pelvic and paraaortic lymphadenectomy. Sentinel lymph node biopsy alone resulted in a lower incidence of leg lymphedema than infrarenal paraaortic and pelvic lymphadenectomy (1.3% vs 18.1%, p=0.0003). The high feasibility, the absence of intraoperative complications and the low risk of lymphatic complications supports implementing detection of sentinel lymph nodes in low-risk endometrial cancer patients. Given that available preliminary data on sensitivity and false negative rates in high-risk patients are confirmed in further studies, we also believe that the reduction in lymphatic complications and operative time strongly motivates the sentinel lymph node concept in high-risk endometrial cancer. Copyright © 2017. Published by Elsevier Inc.

Drug Safety: Managing Multiple Drugs

Science.gov (United States)

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

Pressure-controlled intermittent coronary sinus occlusion (PICSO) in acute ST-segment elevation myocardial infarction: results of the Prepare RAMSES safety and feasibility study

NARCIS (Netherlands)

van de Hoef, Tim P.; Nijveldt, Robin; van der Ent, Martin; Neunteufl, Thomas; Meuwissen, Martijn; Khattab, Ahmed; Berger, Rudolf; Kuijt, Wichert J.; Wykrzykowska, Joanna; Tijssen, Jan G. P.; van Rossum, Albert C.; Stone, Gregg W.; Piek, Jan J.

2015-01-01

Pressure-controlled intermittent coronary sinus occlusion (PICSO) may improve myocardial perfusion after pPCI. We evaluated the safety and feasibility of PICSO after pPCI for STEMI, and explored its effects on infarct size and myocardial function. Thirty patients were enrolled following successful

Novel Percutaneous Radiofrequency Ablation of Portal Vein Tumor Thrombus: Safety and Feasibility

Energy Technology Data Exchange (ETDEWEB)

Mizandari, Malkhaz [High Technology Medical Center, Tbilisi State Medical University (Georgia); Ao, Guokun [The 309 Hospital of People' s Liberation Army, Department on Oncology (China); Zhang Yaojun; Feng Xi [Imperial College London, Department of Surgery and Cancer (United Kingdom); Shen Qiang [The First Minimally Invasive Department of Eastern Hepatobiliary Surgery Hospital (China); Chen Minshan [Cancer Centre of Sun Yat-Sen University, Department of Hepatobiliary Surgery (China); Lau, Wan Yee [Chinese University of Hong Kong, Department of Surgery, Faculty of Medicine (Hong Kong); Nicholls, Joanna; Jiao Long; Habib, Nagy, E-mail: nagy.habib@imperial.ac.uk [Imperial College London, Department of Surgery and Cancer (United Kingdom)

2013-02-15

We report our experience of the safety of partial recanalization of the portal vein using a novel endovascular radiofrequency (RF) catheter for portal vein tumor thrombosis. Six patients with liver cancer and tumor thrombus in the portal vein underwent percutaneous intravascular radiofrequency ablation (RFA) using an endovascular bipolar RF device. A 0.035-inch guidewire was introduced into a tributary of the portal vein and through which a 5G guide catheter was introduced into the main portal vein. After manipulation of the guide catheter over the thrombus under digital subtraction angiography, the endovascular RF device was inserted and activated around the thrombus. There were no observed technique specific complications, such as hemorrhage, vessel perforation, or infection. Post-RFA portography showed partial recanalization of portal vein. RFA of portal vein tumor thrombus in patients with hepatocellular carcinoma is technically feasible and warrants further investigation to assess efficacy compared with current recanalization techniques.

Safety and feasibility of transcranial direct current stimulation in pediatric hemiparesis: randomized controlled preliminary study.

Science.gov (United States)

Gillick, Bernadette T; Feyma, Tim; Menk, Jeremiah; Usset, Michelle; Vaith, Amy; Wood, Teddi Jean; Worthington, Rebecca; Krach, Linda E

2015-03-01

Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that has shown improved adult stroke outcomes. Applying tDCS in children with congenital hemiparesis has not yet been explored. The primary objective of this study was to explore the safety and feasibility of single-session tDCS through an adverse events profile and symptom assessment within a double-blind, randomized placebo-controlled preliminary study in children with congenital hemiparesis. A secondary objective was to assess the stability of hand and cognitive function. A double-blind, randomized placebo-controlled pretest/posttest/follow-up study was conducted. The study was conducted in a university pediatric research laboratory. Thirteen children, ages 7 to 18 years, with congenital hemiparesis participated. Adverse events/safety assessment and hand function were measured. Participants were randomly assigned to either an intervention group or a control group, with safety and functional assessments at pretest, at posttest on the same day, and at a 1-week follow-up session. An intervention of 10 minutes of 0.7 mA tDCS was applied to bilateral primary motor cortices. The tDCS intervention was considered safe if there was no individual decline of 25% or group decline of 2 standard deviations for motor evoked potentials (MEPs) and behavioral data and no report of adverse events. No major adverse events were found, including no seizures. Two participants did not complete the study due to lack of MEP and discomfort. For the 11 participants who completed the study, group differences in MEPs and behavioral data did not exceed 2 standard deviations in those who received the tDCS (n=5) and those in the control group (n=6). The study was completed without the need for stopping per medical monitor and biostatisticial analysis. A limitation of the study was the small sample size, with data available for 11 participants. Based on the results of this study, tDCS appears to be safe

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

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

First series of total robotic hysterectomy (TRH) using new integrated table motion for the da Vinci Xi: feasibility, safety and efficacy.

Science.gov (United States)

Giannini, Andrea; Russo, Eleonora; Mannella, Paolo; Palla, Giulia; Pisaneschi, Silvia; Cecchi, Elena; Maremmani, Michele; Morelli, Luca; Perutelli, Alessandra; Cela, Vito; Melfi, Franca; Simoncini, Tommaso

2017-08-01

To present the first case series of total robotic hysterectomy (TRH), using integrated table motion (ITM), which is a new feature comprising a unique operating table by Trumpf Medical that communicates wirelessly with the da Vinci Xi surgical system. ITM has been specifically developed to improve multiquadrant robotic surgery such as that conducted in colorectal surgery. Between May and October 2015, a prospective post-market study was conducted on ITM in the EU in 40 cases from different specialties. The gynecological study group comprised 12 patients. Primary endpoints were ITM feasibility, safety and efficacy. Ten patients underwent TRH. Mean number of ITM moves was three during TRH; there were 31 instances of table moves in the ten procedures. Twenty-eight of 31 ITM moves were made to gain internal exposure. The endoscope remained inserted during 29 of the 31 table movements (94%), while the instruments remained inserted during 27 of the 31 moves (87%). No external instrument collisions or other problems related to the operating table were noted. There were no ITM safety-related observations and no adverse events. This preliminary study demonstrated the feasibility, safety and efficacy of ITM for the da Vinci Xi surgical system in TRH. ITM was safe, with no adverse events related to its use. Further studies will be useful to define the real role and potential benefit of ITM in gynecological surgery.

Feasibility evaluation of 3 automated cellular drug screening assays on a robotic workstation.

Science.gov (United States)

Soikkeli, Anne; Sempio, Cristina; Kaukonen, Ann Marie; Urtti, Arto; Hirvonen, Jouni; Yliperttula, Marjo

2010-01-01

This study presents the implementation and optimization of 3 cell-based assays on a TECAN Genesis workstation-the Caspase-Glo 3/7 and sulforhodamine B (SRB) screening assays and the mechanistic Caco-2 permeability protocol-and evaluates their feasibility for automation. During implementation, the dispensing speed to add drug solutions and fixative trichloroacetic acid and the aspiration speed to remove the supernatant immediately after fixation were optimized. Decontamination steps for cleaning the tips and pipetting tubing were also added. The automated Caspase-Glo 3/7 screen was successfully optimized with Caco-2 cells (Z' 0.7, signal-to-base ratio [S/B] 1.7) but not with DU-145 cells. In contrast, the automated SRB screen was successfully optimized with the DU-145 cells (Z' 0.8, S/B 2.4) but not with the Caco-2 cells (Z' -0.8, S/B 1.4). The automated bidirectional Caco-2 permeability experiments separated successfully low- and high-permeability compounds (Z' 0.8, S/B 84.2) and passive drug permeation from efflux-mediated transport (Z' 0.5, S/B 8.6). Of the assays, the homogeneous Caspase-Glo 3/7 assay benefits the most from automation, but also the heterogeneous SRB assay and Caco-2 permeability experiments gain advantages from automation.

The French underground research laboratory program, contribution to the feasibility and safety studies of geological disposal

International Nuclear Information System (INIS)

Hoorelbeke, J.M.; Niezborala, J.M.; Ben Slimane, K.

2001-01-01

The paper presents the content of the research program to be performed during the construction and the operation of the National Agency for Radioactive Waste Management's (ANDRA) underground laboratory, located in the east of France. The general architecture of the program is presented. Emphasis is put on an iterative process, the purpose of which is mainly to: Prepare site behavior models before starting each phase of the field work (bore hole drilling, shaft sinking, construction of underground galleries, specific experiments); Test and check each model through actual observations and measurements; Adjust the models to take into account the results of the former phase and predict the results expected during the following one. All these models, after validation, will be exploited during the assessment of the safety related performance of the components of the potential repository as well as the whole facility; Obtain necessary data related to the feasibility study of the disposal facility (mechanical design, thermal design, etc.,) and its safety assessment. The relationship between the experimental program, the conceptual design program and the safety evaluation program is explained in order to reach the project objectives which is the final document set to be provided to French authorities in 2006 according to the French law of December 1991. (author)

Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia

International Nuclear Information System (INIS)

Titano, J. J.; Biederman, D. M.; Marinelli, B. S.; Patel, R. S.; Kim, E.; Tabori, N. E.; Nowakowski, F. S.; Lookstein, R. A.; Fischman, A. M.

2016-01-01

PurposeTransradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions.Methods and MaterialsPatients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications.ResultsFrom July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µL (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6 % with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9 %) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1 %) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups.ConclusionsTransradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.

Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia

Energy Technology Data Exchange (ETDEWEB)

Titano, J. J., E-mail: joseph.titano@mountsinai.org; Biederman, D. M., E-mail: derek.biederman@mountsinai.org; Marinelli, B. S., E-mail: brett.marinelli@exchange.mssm.edu; Patel, R. S., E-mail: rahul.patel@mountsinai.org; Kim, E., E-mail: edward.kim@mountsinai.org; Tabori, N. E., E-mail: nora.tabori@mountsinai.org; Nowakowski, F. S., E-mail: scott.nowakowski@mountsinai.org; Lookstein, R. A., E-mail: robert.lookstein@mountsinai.org; Fischman, A. M., E-mail: aaron.fischman@mountsinai.org [Icahn School of Medicine at Mount Sinai, Department of Interventional Radiology (United States)

2016-05-15

PurposeTransradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions.Methods and MaterialsPatients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications.ResultsFrom July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µL (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6 % with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9 %) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1 %) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups.ConclusionsTransradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.

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

DEFF Research Database (Denmark)

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

2015-01-01

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

Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke.

Science.gov (United States)

Dawson, Jesse; Pierce, David; Dixit, Anand; Kimberley, Teresa J; Robertson, Michele; Tarver, Brent; Hilmi, Omar; McLean, John; Forbes, Kirsten; Kilgard, Michael P; Rennaker, Robert L; Cramer, Steven C; Walters, Matthew; Engineer, Navzer

2016-01-01

Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke. Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl-Meyer Assessment-Upper Extremity). Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, -0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6). This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01669161. © 2015 The Authors.

Feasibility and Safety of Endovascular Stripping of Totally Implantable Venous Access Devices

International Nuclear Information System (INIS)

Heye, Sam; Maleux, Geert; Goossens, G. A.; Vaninbroukx, Johan; Jerôme, M.; Stas, M.

2012-01-01

Purpose: To evaluate the safety and feasibility of percutaneous stripping of totally implantable venous access devices (TIVAD) in case of catheter-related sleeve and to report a technique to free the catheter tip from vessel wall adherence. Materials and Methods: A total of 37 stripping procedures in 35 patients (14 men, 40%, and 21 women, 60%, mean age 53 ± 14 years) were reviewed. Totally implantable venous access devices were implanted because of malignancy in most cases (85.7%). Catheter-related sleeve was confirmed as cause of persistent catheter dysfunction despite instillation of thrombolytics. A technique to mobilize the catheter tip from the vessel wall was used when stripping with the snare catheter was impossible. Technical success, complication rate, and outcome were noted. Results: A total of 55.9% (n = 19) of the 34 technically successful procedures (91.9%) could be done with the snare catheter. In 15 cases (44.1%), additional maneuvers to free the TIVAD’s tip from the vessel wall were needed. Success rate was not significantly lower before (72.4%) than after (96.7%) implementation of the new technique (P = 0.09). No complications were observed. Follow-up was available in 67.6% of cases. Recurrent catheter dysfunction was found in 17 TIVADs (78.3%) at a mean of 137.7 days and a median of 105 days. Conclusions: Stripping of TIVADs is technically feasible and safe, with an overall success rate of 91.9%. Additional endovascular techniques to mobilize the distal catheter tip from the wall of the superior vena cava or right atrium to allow encircling the TIVAD tip with the snare catheter may be needed in 44.1% of cases.

Mining FDA drug labels for medical conditions.

Science.gov (United States)

Li, Qi; Deleger, Louise; Lingren, Todd; Zhai, Haijun; Kaiser, Megan; Stoutenborough, Laura; Jegga, Anil G; Cohen, Kevin Bretonnel; Solti, Imre

2013-04-24

Cincinnati Children's Hospital Medical Center (CCHMC) has built the initial Natural Language Processing (NLP) component to extract medications with their corresponding medical conditions (Indications, Contraindications, Overdosage, and Adverse Reactions) as triples of medication-related information ([(1) drug name]-[(2) medical condition]-[(3) LOINC section header]) for an intelligent database system, in order to improve patient safety and the quality of health care. The Food and Drug Administration's (FDA) drug labels are used to demonstrate the feasibility of building the triples as an intelligent database system task. This paper discusses a hybrid NLP system, called AutoMCExtractor, to collect medical conditions (including disease/disorder and sign/symptom) from drug labels published by the FDA. Altogether, 6,611 medical conditions in a manually-annotated gold standard were used for the system evaluation. The pre-processing step extracted the plain text from XML file and detected eight related LOINC sections (e.g. Adverse Reactions, Warnings and Precautions) for medical condition extraction. Conditional Random Fields (CRF) classifiers, trained on token, linguistic, and semantic features, were then used for medical condition extraction. Lastly, dictionary-based post-processing corrected boundary-detection errors of the CRF step. We evaluated the AutoMCExtractor on manually-annotated FDA drug labels and report the results on both token and span levels. Precision, recall, and F-measure were 0.90, 0.81, and 0.85, respectively, for the span level exact match; for the token-level evaluation, precision, recall, and F-measure were 0.92, 0.73, and 0.82, respectively. The results demonstrate that (1) medical conditions can be extracted from FDA drug labels with high performance; and (2) it is feasible to develop a framework for an intelligent database system.

Catheter-Based Measurements of Absolute Coronary Blood Flow and Microvascular Resistance: Feasibility, Safety, and Reproducibility in Humans.

Science.gov (United States)

Xaplanteris, Panagiotis; Fournier, Stephane; Keulards, Daniëlle C J; Adjedj, Julien; Ciccarelli, Giovanni; Milkas, Anastasios; Pellicano, Mariano; Van't Veer, Marcel; Barbato, Emanuele; Pijls, Nico H J; De Bruyne, Bernard

2018-03-01

The principle of continuous thermodilution can be used to calculate absolute coronary blood flow and microvascular resistance (R). The aim of the study is to explore the safety, feasibility, and reproducibility of coronary blood flow and R measurements as measured by continuous thermodilution in humans. Absolute coronary flow and R can be calculated by thermodilution by infusing saline at room temperature through a dedicated monorail catheter. The temperature of saline as it enters the vessel, the temperature of blood and saline mixed in the distal part of the vessel, and the distal coronary pressure were measured by a pressure/temperature sensor-tipped guidewire. The feasibility and safety of the method were tested in 135 patients who were referred for coronary angiography. No significant adverse events were observed; in 11 (8.1%) patients, bradycardia and concomitant atrioventricular block appeared transiently and were reversed immediately on interruption of the infusion. The reproducibility of measurements was tested in a subgroup of 80 patients (129 arteries). Duplicate measurements had a strong correlation both for coronary blood flow (ρ=0.841, P <0.001; intraclass correlation coefficient=0.89, P <0.001) and R (ρ=0.780, P <0.001; intraclass correlation coefficient=0.89, P <0.001). In Bland-Altman plots, there was no significant bias or asymmetry. Absolute coronary blood flow (in L/min) and R (in mm Hg/L/min or Wood units) can be safely and reproducibly measured with continuous thermodilution. This approach constitutes a new opportunity for the study of the coronary microcirculation. © 2018 American Heart Association, Inc.

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

Science.gov (United States)

Castleden, C M; Pickles, H

1988-10-01

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

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

Directory of Open Access Journals (Sweden)

Roth SH

2011-05-01

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

Drug repurposing based on drug-drug interaction.

Science.gov (United States)

Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

2015-02-01

Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

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.

[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).

Safety and feasibility of liver resection with continued antiplatelet therapy using aspirin.

Science.gov (United States)

Monden, Kazuteru; Sadamori, Hiroshi; Hioki, Masayoshi; Ohno, Satoshi; Saneto, Hiromi; Ueki, Toru; Yabushita, Kazuhisa; Ono, Kazumi; Sakaguchi, Kousaku; Takakura, Norihisa

2017-07-01

Aspirin is widely used for the secondary prevention of ischemic stroke and cardiovascular disease. Perioperative aspirin may decrease thrombotic morbidity, but may also increase hemorrhagic morbidity. In particular, liver resection carries risks of bleeding, leading to higher risks of hemorrhagic morbidity. Our institution has continued aspirin therapy perioperatively in patients undergoing liver resection. This study examined the safety and feasibility of liver resection while continuing aspirin. We retrospectively evaluated 378 patients who underwent liver resection between January 2010 and January 2016. Patients were grouped according to preoperative aspirin prescription: patients with aspirin therapy (aspirin users, n = 31); and patients without use of aspirin (aspirin non-users, n = 347). Aspirin users were significantly older (P aspirin users than among aspirin non-users, no significant difference was identified. No postoperative hemorrhage was seen among aspirin users. Liver resection can be safely performed while continuing aspirin therapy without increasing hemorrhagic morbidity. Our results suggest that interruption of aspirin therapy is unnecessary for patients undergoing liver resection. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Feasibility and safety of prehospital administration of bivalirudin in patients with ST-elevation myocardial infarction

DEFF Research Database (Denmark)

Sejersten, Maria; Nielsen, Søren Loumann; Engstrøm, Thomas

2009-01-01

undergoing angiography with no difference between groups. Bivalirudin was easy to administer in the prehospital setting and did not affect the prehospital run times. In conclusion, the results suggest that prehospital bivalirudin administration is as safe and effective as heparin in the treatment of patients...... of this preliminary study was to describe the feasibility and safety of a switch from prehospital administration of unfractionated heparin to bivalirudin in ST-elevation acute myocardial infarction (STEMI) patients referred for primary percutaneous coronary intervention. Patients with STEMI treated with a 1-mg...... patients (59%) receiving bivalirudin and 72 receiving heparin were followed during hospitalization. The baseline characteristics and prehospital treatment times were comparable between the 2 groups. The thrombolysis in myocardial infarction flow before and after primary percutaneous coronary intervention...

Drug safety evaluation of defibrotide.

Science.gov (United States)

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

2013-01-01

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

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

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.

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

The feasibility and safety of thoracoscopic surgery under epidural and/or local anesthesia for spontaneous pneumothorax: a meta-analysis.

Science.gov (United States)

Chen, Wei; Zhang, Chenlei; Wang, Gebang; Li, Zhengjun; Wang, Hailong; Liu, Hongxu

2017-09-01

The aim of this study was to compare thoracoscopic surgery for spontaneous pneumothorax under epidural and/or local anesthesia (ELA) with that under general anesthesia and prove the feasibility and safety of thoracoscopic surgery under ELA for spontaneous pneumothorax. Relevant studies were searched in five databases from their date of publication to June 2016. We collected and analyzed the data concerning operative time, hospital stay, complications, air leak, recurrence and perioperative mortality. A forest plot was performed to compare the differences between the two groups. There were no significant differences between the ELA group and the general anesthesia (GA) group in operative time, hospital stay, complications, air leak or recurrence. There were 6 deaths reported in two studies. However, patients in the ELA group had significantly shorter global operating room time. Our study demonstrated that ELA, in comparison with GA, is feasible and safe for thoracoscopic surgery of spontaneous pneumothorax.

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...

Safety of Therapeutic Fever Induction in Cancer Patients Using Approved PAMP Drugs

Directory of Open Access Journals (Sweden)

Uwe Rudolf Max Reuter

2018-04-01

Full Text Available William Coley, between 1895 and 1936, treated hundreds of cancer patients using infusions of fever inducing bacerial extracts. Similar experiments were done by Klyuyeva and co-workers in the 1940ies in Russia using trypanosoma extracts. Many remissions and cures were reported. We have conjectured that pathogen associated molecular pattern substances (PAMP are the molecular explanation for the beneficial treatments in both groups. We could show that a combination of PAMP can eradicate solid tumours in cancer mice if applied several times. Accordingly, we suggested to combine PAMP containing approved drugs to treat cancer patients using a protocol similar to the old fever induction regimen. In this retrospective phase-1 study we report on the fever induction capacity and safety of applications of bacterial extracts, combinations of bacterial extracts with approved drugs, and combinations of approved drugs in 131 mainly cancer patients. Adverse reactions were those which can be expected during a feverish infection and mild. Over 523 fever inductions, no severe adverse reaction was observed.

Environmental, Safety, and Health Plan for the remedial investigation/feasibility study at Oak Ridge National Laboratory, Oak Ridge, Tennessee. Revision 1, Environmental Restoration Program

Energy Technology Data Exchange (ETDEWEB)

Davis, C. M.; El-Messidi, O. E.; Cowser, D. K.; Kannard, J. R.; Carvin, R. T.; Will, III, A. S.; Clark, Jr., C.; Garland, S. B.

1993-05-01

This Environmental, Safety, and Health (ES&H) Plan presents the concepts and methodologies to be followed during the remedial investigation/feasibility study (RI/FS) for Oak Ridge National Laboratory (ORNL) to protect the health and safety of employees, the public, and the environment. This ES&H Plan acts as a management extension for ORNL and Martin Marietta Energy Systems, Inc. (Energy Systems) to direct and control implementation of the project ES&H program. The subsections that follow describe the program philosophy, requirements, quality assurance measures, and methods for applying the ES&H program to individual waste area grouping (WAG) remedial investigations. Hazardous work permits (HWPs) will be used to provide task-specific health and safety requirements.

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

Science.gov (United States)

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

2016-12-12

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

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

Science.gov (United States)

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

2017-02-01

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

78 FR 23273 - Determination That the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug...

Science.gov (United States)

2013-04-18

... mitigation strategy (REMS) http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationfor... Blueprint for Prescriber Education for Extended- Release and Long-Acting Opioid Analgesics'' ( http://www...

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

Science.gov (United States)

Gentili, Marta; Pozzi, Marco; Peeters, Gabrielle; Radice, Sonia; Carnovale, Carla

2018-02-06

Knowledge of drugs safety collected during the pre-marketing phase is inevitably limited because the randomized clinical trials (RCTs) are rarely designed to evaluate safety. The small and selective groups of enrolled individuals and the limited duration of trials may hamper the ability to characterize fully the safety profiles of drugs. Additionally, information about rare adverse drug reactions (ADRs) in special groups is often incomplete or not available for most of the drugs commonly used in the daily clinical practice. In the paediatric setting several highimpact safety issues have emerged. Hence, in recent years, there has been a call for improved post-marketing pharmacoepidemiological studies, in which cohorts of patients are monitored for sufficient time in order to determine the precise risk-benefit ratio. In this review, we discuss the current available strategies enhancing the post-marketing monitoring activities of the drugs in the paediatric setting and define criteria whereby they can provide valuable information to improve the management of therapy in daily clinical practice including both safety and efficacy aspects. The strategies we cover include the signal detection using international pharmacovigilance and/or healthcare databases, the promotion of active surveillance initiatives which can generate complete, informative data sets for the signal detection and systematic review/meta-analysis. Together, these methods provide a comprehensive picture of causality and risk improving the management of therapy in a paediatric setting and they should be considered as a unique tool to be integrated with post-marketing activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cervical cancer screening: Safety, acceptability, and feasibility of a single-visit approach in Bulawayo, Zimbabwe.

Science.gov (United States)

Fallala, Muriel S; Mash, Robert

2015-05-05

Cervical cancer is the commonest cancer amongst African women, and yet preventative services are often inadequate. The purpose of the study was to assess the safety, acceptability and feasibility of visual inspection with acetic acid and cervicography (VIAC) followed by cryotherapy or a loop electrical excision procedure (LEEP) at a single visit for prevention of cancer of the cervix. The United Bulawayo Hospital, Zimbabwe. The study was descriptive, using retrospective data extracted from electronic medical records of women attending the VIAC clinic. Over 24 months 4641 women visited the clinic and were screened for cervical cancer using VIAC. Cryotherapy or LEEP was offered immediately to those that screened positive. Treated women were followed up at three months and one year. The rate of positive results on VIAC testing was 10.8%. Of those who were eligible, 17.0% received immediate cryotherapy, 44.1% received immediate LEEP, 1.9% delayed treatment, and 37.0% were referred to a gynaecologist. No major complications were recorded after cryotherapy or LEEP. Amongst those treated 99.5% expressed satisfaction with their experience. Only 3.2% of those treated at the clinic had a positive result on VIAC one year later. The service was shown to be feasible to sustain over time with the necessary consumables. There were no service-related treatment postponements and the clinic staff and facility were able to meet the demand for the service. A single-visit approach using VIAC, followed by cryotherapy or LEEP, proved to be safe, acceptable and feasible in an urban African setting in Bulawayo, Zimbabwe. Outcomes a year later suggested that treatment had been effective.

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

Science.gov (United States)

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

2013-12-01

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

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.

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

Science.gov (United States)

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

2012-09-01

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

Cardiopulmonary Exercise Testing in Patients with Asymptomatic or Equivocal Symptomatic Aortic Stenosis: Feasibility, Reproducibility, Safety and Information Obtained on Exercise Physiology.

Science.gov (United States)

van Le, Douet; Jensen, Gunnar Vagn Hagemann; Carstensen, Steen; Kjøller-Hansen, Lars

2016-01-01

The aim of this study was to determine the feasibility, reproducibility, safety and information obtained on exercise physiology from cardiopulmonary exercise testing (CPX) in patients with aortic stenosis. Patients with an aortic valve area (AVA) exercise, lower peak heart rate and FEV1, and higher VE/VCO2, but not by AVA index. Equivocal symptomatic status and a low gradient but high valvulo-arterial impedance were associated with a lower pVO2, but not with an inability to increase stroke volume. In total, 18 patients were referred for valve replacement. At 1 year, no cardiovascular deaths had occurred. CPX was feasible and reproducible and provided comprehensive data on exercise physiology. A CPX-guided treatment strategy was safe up to 1 year. © 2015 S. Karger AG, Basel.

Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

Science.gov (United States)

Wilkes, Denise M; Orillosa, Susan J; Hustak, Erik C; Williams, Courtney G; Doulatram, Gulshan R; Solanki, Daneshvari R; Garcia, Eduardo A; Huang, Li-Yen M

2017-06-13

The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Retrospective review of medical records. Private and academic pain clinic practices. Chronic noncancer pain patients. We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (microdose therapy was feasible, safe, and cost-effective in the outpatient setting. 2017 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.

Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma

International Nuclear Information System (INIS)

Saulnier Sholler, Giselle L; Bond, Jeffrey P; Bergendahl, Genevieve; Dutta, Akshita; Dragon, Julie

2015-01-01

The primary objective of the study was to evaluate the feasibility and safety of a process which would utilize genome-wide expression data from tumor biopsies to support individualized treatment decisions. Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%. Molecular profiling may provide data which will enable the practitioner to select the most appropriate therapeutic option for individual patients, thus improving outcomes. Sixteen patients with neuroblastoma were enrolled of which fourteen were eligible for this study. Feasibility was defined as completion of tumor biopsy, pathological evaluation, RNA quality control, gene expression profiling, bioinformatics analysis, generation of a drug prediction report, molecular tumor board yielding a treatment plan, independent medical monitor review, and treatment initiation within a 21 day period. All eligible biopsies passed histopathology and RNA quality control. Expression profiling by microarray and RNA sequencing were mutually validated. The average time from biopsy to report generation was 5.9 days and from biopsy to initiation of treatment was 12.4 days. No serious adverse events were observed and all adverse events were expected. Clinical benefit was seen in 64% of patients as stabilization of disease for at least one cycle of therapy or partial response. The overall response rate was 7% and the progression free survival was 59 days. This study demonstrates the feasibility and safety of performing real-time genomic profiling to guide treatment decision making for pediatric neuroblastoma patients

Feasibility, safety, and efficacy of aerobic training in pretreated patients with metastatic breast cancer: A randomized controlled trial.

Science.gov (United States)

Scott, Jessica M; Iyengar, Neil M; Nilsen, Tormod S; Michalski, Meghan; Thomas, Samantha M; Herndon, James; Sasso, John; Yu, Anthony; Chandarlapaty, Sarat; Dang, Chau T; Comen, Elizabeth A; Dickler, Maura N; Peppercorn, Jeffrey M; Jones, Lee W

2018-04-06

The investigation of exercise training in metastatic breast cancer has received minimal attention. This study determined the feasibility and safety of aerobic training in metastatic breast cancer. Sixty-five women (age, 21-80 years) with metastatic (stage IV) breast cancer (57% were receiving chemotherapy, and >40% had ≥ 2 lines of prior therapy) were allocated to an aerobic training group (n = 33) or a stretching group (n = 32). Aerobic training consisted of 36 supervised treadmill walking sessions delivered thrice weekly between 55% and 80% of peak oxygen consumption (VO 2peak ) for 12 consecutive weeks. Stretching was matched to aerobic training with respect to location, frequency, duration, and intervention length. The primary endpoint was aerobic training feasibility, which was a priori defined as the lost to follow-up (LTF) rate (aerobic training was LTF, whereas the mean attendance rate was 63% ± 30%. The rates of permanent discontinuation and dose modification were 27% and 49%, respectively. Intention-to-treat analyses indicated improvements in PROs, which favored the attention control group (P values > .05). Per protocol analyses indicated that 14 of 33 patients (42%) receiving aerobic training had acceptable tolerability (relative dose intensity ≥ 70%), and this led to improvements in VO 2peak and functional capacity (P values Aerobic training at the dose and schedule tested is safe but not feasible for a significant proportion of patients with metastatic breast cancer. The acceptable feasibility and promising benefit for select patients warrant further evaluation in a dose-finding phase 1/2 study. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Feasibility and Safety of Overtubes for PEG-Tube Placement in Patients with Head and Neck Cancer

Directory of Open Access Journals (Sweden)

Crispin O. Musumba

2015-01-01

Full Text Available Background. Percutaneous endoscopic gastrostomy (PEG placement using the “pull” technique is commonly utilized for providing nutritional support in head and neck cancer (HNC patients, but it may be complicated by peristomal metastasis in up to 3% of patients. Overtube-assisted PEG placement might reduce this risk. However, this technique has not been systemically studied for this purpose to date. Methods. Retrospective analysis of consecutive patients with HNC who underwent overtube-assisted PEG placement at Westmead Hospital, Australia, between June 2011 and December 2013. Data were extracted from patients’ endoscopy reports and case notes. We present our technique for PEG insertion and discuss the feasibility and safety of this method. Results. In all 53 patients studied, the PEG tubes were successfully placed using 25 cm long flexible overtubes, in 89% prophylactically (before commencing curative chemoradiotherapy, and in 11% reactively (for treatment of tumor related dysphagia or weight loss. During a median follow-up period of 16 months, 3 (5.7% patients developed peristomal infection and 3 others developed self-limiting peristomal pain. There were no cases of overtube-related adverse events or overt cutaneous metastases observed. Conclusions. Overtube-assisted PEG placement in patients with HNC is a feasible, simple, and safe technique and might be effective for preventing cutaneous metastasis.

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

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.

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.

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.

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

Science.gov (United States)

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

2018-01-01

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

Feasibility and Safety of a Powered Exoskeleton for Assisted Walking for Persons With Multiple Sclerosis: A Single-Group Preliminary Study.

Science.gov (United States)

Kozlowski, Allan J; Fabian, Michelle; Lad, Dipan; Delgado, Andrew D

2017-07-01

To examine the feasibility, safety, and secondary benefit potential of exoskeleton-assisted walking with one device for persons with multiple sclerosis (MS). Single-group longitudinal preliminary study with 8-week baseline, 8-week intervention, and 4-week follow-up. Outpatient MS clinic, tertiary care hospital. Participants (N=13; age range, 38-62y) were mostly women with Expanded Disability Status Scale scores ranging from 5.5 to 7.0. Exoskeleton-assisted walk training. Primary outcomes were accessibility (enrollment/screen pass), tolerability (completion/dropout), learnability (time to event for standing, walking, and sitting with little or no assistance), acceptability (satisfaction on the device subscale of the Quebec User Evaluation of Satisfaction with Assistive Technology version 2), and safety (event rates standardized to person-time exposure in the powered exoskeleton). Secondary outcomes were walking without the device (timed 25-foot walk test and 6-minute walk test distance), spasticity (Modified Ashworth Scale), and health-related quality of life (Patient-Reported Outcomes Measurement and Information System pain interference and Quality of Life in Neurological Conditions fatigue, sleep disturbance, depression, and positive affect and well-being). The device was accessible to 11 and tolerated by 5 participants. Learnability was moderate, with 5 to 15 sessions required to walk with minimal assistance. Safety was good; the highest adverse event rate was for skin issues at 151 per 1000 hours' exposure. Acceptability ranged from not very satisfied to very satisfied. Participants who walked routinely improved qualitatively on sitting, standing, or walking posture. Two participants improved and 2 worsened on ≥1 quality of life domain. The pattern of spasticity scores may indicate potential benefit. The device appeared feasible and safe for about a third of our sample, for whom routine exoskeleton-assisted walking may offer secondary benefits. Copyright �

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

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

Science.gov (United States)

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

2016-01-01

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

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

NIR spectrometry for counterfeit drug detection - A feasibility study

DEFF Research Database (Denmark)

Rodionova, O.Y.; Houmøller, Lars P.; Pomerantsev, A.L.

2005-01-01

for mathematical data processing for false drugs detection is demonstrated. Also, multivariate hyperspectral image analysis is applied providing additional diagnostic information. Hyperspectral imaging is becoming a useful diagnostic tool for identifying non-homogeneous spatial regions of drug formulation. Two...... types of drugs are used to demonstrate the applicability of these approaches....

Feasibility, safety and effectiveness of combining home based malaria management and seasonal malaria chemoprevention in children less than 10 years in Senegal

DEFF Research Database (Denmark)

Tine, Roger C K; Ndour, Cheikh T; Faye, Babacar

2014-01-01

Home-based management of malaria (HMM) may improve access to diagnostic testing and treatment with artemisinin combination therapy (ACT). In the Sahel region, seasonal malaria chemoprevention (SMC) is now recommended for the prevention of malaria in children. It is likely that combinations...... of antimalarial interventions can reduce the malaria burden. This study assessed the feasibility, effectiveness and safety of combining SMC and HMM delivered by community health workers (CHWs)....

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

Science.gov (United States)

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

2012-01-01

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

Feasibility, safety and tolerability of accelerated dobutamine stress echocardiography

Directory of Open Access Journals (Sweden)

Pavaci Herribert

2007-11-01

Full Text Available Abstract A continuous infusion of a single high dose of dobutamine has been, recently, suggested as a simple and effective protocol of stress echocardiography. The present study assesses the feasibility, safety, and tolerability of an accelerated dobutamine stress protocol performed in patients with suspected or known coronary artery disease. Two hundred sixty five consecutive patients underwent accelerated dobutamine stress echocardiography: the dobutamine was administered at a constant dose of 50 μg/kg/min for up to 10 minutes. The mean weight-adjusted cumulative dose of dobutamine used was 330 ± 105.24 μg/kg. Total duration of dobutamine infusion was 6.6 ± 2.1 min. Heart rate rose from 69.9 ± 12.1 to 123.1 ± 22.1 beats/min at peak with a concomitant change in systolic blood pressure (127.6 ± 18.1 vs. 167.6 ± 45.0 mmHg. Dobutamine administration produced a rapid increase in heart rate (9.4 ± 5.9 beats/min2. The side effects were similar to those described with the standard protocol; the most common were frequent premature ventricular complexes (21.5%, frequent premature atrial complexes (1.5% and non sustained ventricular tachycardia (1.5%; among non cardiac symptoms the most frequent were nausea (3.4%, headache (1.1% and symptomatic hypotension (1.1%. No major side effects were observed during the test. Our data demonstrate that a continous infusion of a single high dose of dobutamine is a safe and well tolerated method of performing stress echocardiography in patients with suspected or known coronary artery disease. This new protocol requires the administration of lower cumulative dobutamine dose than standard protocol and results in a significant reduction in test time.

Feasibility and Safety of a Transthoracic Pneumostoma Airway Bypass in Severe Emphysema Patients.

Science.gov (United States)

Snell, Gregory I; Holsworth, Lynda; Khorramnia, Sadie; Westall, Glen P; Williams, Trevor J; Marasco, Silvana; Gooi, Julian H

2017-01-01

Emphysema is characterised by airflow obstruction, hyperinflation, and resultant dyspnoea. It is worth investigating whether decompression improves lung mechanics and enhances quality of life (QoL). The purpose of this study was to describe the feasibility and safety of creating a transthoracic pneumostoma to enable lung reduction. A transthoracic 10-mm diameter Portaero Access Tube (Portaero™, Cupertino, CA, USA) was implanted via a third intercostal space incision in 15 severe emphysema patients [mean age 63 years, forced expiratory volume in 1 s 54% predicted, diffusing capacity for carbon monoxide 31% predicted, residual volume 246% predicted, Six-Minute Walk Test 296 m]. Four weeks later, an 8-mm Portaero Disposable Tube (3-8 cm in length) was substituted and changed daily thereafter. The targeted primary endpoints were a ≥12% increase in forced expiratory volume in 1 s and a decrease of ≥4 points in Saint George's Respiratory Questionnaire score at 6 months. Sixteen procedures were performed on 15 patients, complicated by 1 intercostal haemorrhage, 1 pneumothorax, and universal mild surgical emphysema. Early patency issues were common, but often responded to external endoscopic debridement or argon plasma laser. Three-month patency was achieved in 9 of 15 patients, and 6 of these had long-term patency (mean of 4 years). Patency was associated with potentially useful long-term improvements or stability in spirometry, residual volume, and QoL. However, the primary endpoints were not met at 6 months. The creation and maintenance of a transthoracic pneumostoma appears feasible and safe in patients with severe emphysema. Further studies refining patient selection (perhaps via chest computed tomography collateral ventilation and fissure assessments), techniques, and tube materials are suggested. © 2017 S. Karger AG, Basel.

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.

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.

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:

A feasibility study on the extended cycle from the point of view of Non-LOCA safety analysis

International Nuclear Information System (INIS)

Lee, Chul Sin; Kim, Hee Chul; Kim, Jeong Jin; Baek, Seung Su; Lee, Byung Il; Jeon, Tae Hyun; Lee, Jeong Chan

1996-06-01

Extended cycle operation has many advantages as compared with standard cycle operation (12 months) from the viewpoint of operators' exposure to radiation dose, man-power for maintenance and the production of nuclear waste. And it is more economic than the standard cycle operation. If the extended cycle operation is adopted in the CE type nuclear plant, the effective management and enhancement of operation capability could be expected. A feasibility study on the extended cycle operation should be performed. The purpose of this technical report is to perform safety analysis using the design data for Yonggwang Nuclear Plant (YGN) 3 and 4 extended cycle operation and to evaluate qualitatively and quantitatively the safety related design basis events to verify the satisfaction of the safety criteria. Boron dilution and steam line break accidents were found to be most influenced by the change of physics data due to the adaptation of the extended cycle operation. For boron dilution accident, source range monitor ratio of 3.07 for YGN 3 cycle 2 was decreased to 2.92. The 3D reactivity feedback effect due to the local heatup in the vicinity of stuck CEA was credited in the analysis of steam line break. No return-to-power occurred for the steam line break with offsite power available and return-to-power occurred for the steam line break with loss of offsite power. For the steam line break with loss of offsite power, the safety margin was preserved with respect to fuel performance (DNB and LHGR) despite the return-to-power. 6 tabs., 10 figs., 5 refs. (Author) .new

Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

Science.gov (United States)

Ocana, Alberto; Ethier, Josee-Lyne; Díez-González, Laura; Corrales-Sánchez, Verónica; Srikanthan, Amirrtha; Gascón-Escribano, María J; Templeton, Arnoud J; Vera-Badillo, Francisco; Seruga, Bostjan; Niraula, Saroj; Pandiella, Atanasio; Amir, Eitan

2015-11-24

Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.

Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir (I): a drug use investigation.

Science.gov (United States)

Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

2014-11-01

Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. We conducted a drug use investigation of peramivir from October 2010 to February 2012 and evaluated its safety and effectiveness under routine clinical settings. We collected data of 1309 patients from 189 facilities across Japan and examined safety in 1174 patients and effectiveness in 1158 patients. In total, 143 adverse events were observed with an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87% (22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR was reported as serious. ADR onset was within 3 days after the start of peramivir administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither patient characteristics nor treatment factors appeared to significantly affect drug safety. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. The present study demonstrates the safety and effectiveness of peramivir under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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.

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

Science.gov (United States)

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

2013-12-01

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

75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

Science.gov (United States)

2010-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...

Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy

Directory of Open Access Journals (Sweden)

Lee Young-Ho

2012-03-01

Full Text Available Abstract Backgrounds We conducted a pilot study of the infusion of intravenous autologous cord blood (CB in children with cerebral palsy (CP to assess the safety and feasibility of the procedure as well as its potential efficacy in countering neurological impairment. Methods Patients diagnosed with CP were enrolled in this study if their parents had elected to bank their CB at birth. Cryopreserved CB units were thawed and infused intravenously over 10~20 minutes. We assessed potential efficacy over 6 months by brain magnetic resonance imaging (MRI-diffusion tensor imaging (DTI, brain perfusion single-photon emission computed tomography (SPECT, and various evaluation tools for motor and cognitive functions. Results Twenty patients received autologous CB infusion and were evaluated. The types of CP were as follows: 11 quadriplegics, 6 hemiplegics, and 3 diplegics. Infusion was generally well-tolerated, although 5 patients experienced temporary nausea, hemoglobinuria, or urticaria during intravenous infusion. Diverse neurological domains improved in 5 patients (25% as assessed with developmental evaluation tools as well as by fractional anisotropy values in brain MRI-DTI. The neurologic improvement occurred significantly in patients with diplegia or hemiplegia rather than quadriplegia. Conclusions Autologous CB infusion is safe and feasible, and has yielded potential benefits in children with CP.

Safety, feasibility, and acceptability of visual inspection with acetic acid and immediate treatment with cryotherapy in rural Laos.

Science.gov (United States)

Phongsavan, Keokedthong; Phengsavanh, Alongkone; Wahlström, Rolf; Marions, Lena

2011-09-01

To assess the safety, acceptability, and feasibility of visual inspection with acetic acid (VIA) followed by immediate treatment with cryotherapy as a single-visit approach for the prevention of cervical cancer among women in rural Laos. In 2009, women from 2 provinces in Laos were recruited for cervical cancer screening using VIA. If the inspection of the cervix showed a well-defined acetowhite lesion close to the os, immediate cryotherapy was offered. Of the 1926 women who were included, 134 (7.0%) tested positive on VIA. Of these, 113 (84.3%) underwent immediate cryotherapy and none declined treatment. One year after immediate cryotherapy, 77 (68.1%) women returned for a follow-up assessment and 68 (88.3%) were now VIA-negative. There was no report of a major complication during or after treatment. The acceptance of both VIA and cryotherapy was high. Visual inspection with acetic acid is a simple test that requires minimal infrastructure and expenditure. Integration of VIA with cryotherapy at the primary care level may constitute a feasible program for the prevention of cervical cancer in Laos. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Prescription Drugs, Over-the-Counter Drugs, Supplements and Herbal Products

Science.gov (United States)

... at risk? Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... the-counter drugs, supplements and herbal products Prescription drugs, over-the-counter drugs, supplements and herbal products ...

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

Science.gov (United States)

Munkhdalai, Tsendsuren; Liu, Feifan; Yu, Hong

2018-04-25

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

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

Science.gov (United States)

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

2017-02-01

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

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

Science.gov (United States)

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

2009-08-01

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

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.

77 FR 44256 - Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510...

Science.gov (United States)

2012-07-27

...] Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510(k... serious and sometimes fatal consequences to patients. This guidance provides recommendations to 510(k... unintended connections between enteral and nonenteral devices. This draft guidance is not final nor is it in...

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.

da Vinci robot-assisted keyhole neurosurgery: a cadaver study on feasibility and safety.

Science.gov (United States)

Marcus, Hani J; Hughes-Hallett, Archie; Cundy, Thomas P; Yang, Guang-Zhong; Darzi, Ara; Nandi, Dipankar

2015-04-01

The goal of this cadaver study was to evaluate the feasibility and safety of da Vinci robot-assisted keyhole neurosurgery. Several keyhole craniotomies were fashioned including supraorbital subfrontal, retrosigmoid and supracerebellar infratentorial. In each case, a simple durotomy was performed, and the flap was retracted. The da Vinci surgical system was then used to perform arachnoid dissection towards the deep-seated intracranial cisterns. It was not possible to simultaneously pass the 12-mm endoscope and instruments through the keyhole craniotomy in any of the approaches performed, limiting visualization. The articulated instruments provided greater dexterity than existing tools, but the instrument arms could not be placed in parallel through the keyhole craniotomy and, therefore, could not be advanced to the deep cisterns without significant clashing. The da Vinci console offered considerable ergonomic advantages over the existing operating room arrangement, allowing the operating surgeon to remain non-sterile and seated comfortably throughout the procedure. However, the lack of haptic feedback was a notable limitation. In conclusion, while robotic platforms have the potential to greatly enhance the performance of transcranial approaches, there is strong justification for research into next-generation robots, better suited to keyhole neurosurgery.

Feasibility and safety of endoscopic submucosal dissection for lower rectal tumors with hemorrhoids.

Science.gov (United States)

Tanaka, Shinwa; Toyonaga, Takashi; Morita, Yoshinori; Hoshi, Namiko; Ishida, Tsukasa; Ohara, Yoshiko; Yoshizaki, Tetsuya; Kawara, Fumiaki; Umegaki, Eiji; Azuma, Takeshi

2016-07-21

To evaluate the feasibility and safety of endoscopic submucosal dissection (ESD) for lower rectal lesions with hemorrhoids. The outcome of ESD for 23 lesions with hemorrhoids (hemorrhoid group) was compared with that of 48 lesions without hemorrhoids extending to the dentate line (non-hemorrhoid group) during the same study period. Median operation times (ranges) in the hemorrhoid and non-hemorrhoid groups were 121 (51-390) and 130 (28-540) min. The en bloc resection rate and the curative resection rate in the hemorrhoid group were 96% and 83%, and they were 100% and 90% in the non-hemorrhoid group, respectively. In terms of adverse events, perforation and postoperative bleeding did not occur in both groups. In terms of the clinical course of hemorrhoids after ESD, the rate of complete recovery of hemorrhoids after ESD in lesions with resection of more than 90% was significantly higher than that in lesions with resection of less than 90%. ESD on lower rectal lesions with hemorrhoids could be performed safely, similarly to that on rectal lesions extending to the dentate line without hemorrhoids. In addition, all hemorrhoids after ESD improved to various degrees, depending on the resection range.

Data-driven drug safety signal detection methods in pharmacovigilance using electronic primary care records: A population based study

Directory of Open Access Journals (Sweden)

Shang-Ming Zhou

2017-04-01

Data-driven analytic methods are a valuable aid to signal detection of ADEs from large electronic health records for drug safety monitoring. This study finds the methods can detect known ADE and so could potentially be used to detect unknown ADE.

[HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals].

Science.gov (United States)

Gyalrong-Steur, Miriam; Kellermann, Anita; Bernard, Rudolf; Berndt, Georg; Bindemann, Meike; Nusser-Rothermundt, Elfriede; Amann, Steffen; Brakebusch, Myga; Brüggmann, Jörg; Tydecks, Eva; Müller, Markus; Dörje, Frank; Kochs, Eberhard; Riedel, Rainer

2017-04-01

In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands

Safety of Reiki Therapy for Newborns at Risk for Neonatal Abstinence Syndrome

Science.gov (United States)

Wright-Esber, Sandra; Zupancic, Julie; Gargiulo, Deb; Woodall, Patricia

2018-01-01

The incidence of opioid abuse and subsequent drug withdrawal is exponentially on the rise in the United States for many populations including newborns who are born to drug-addicted mothers. These newborns often exhibit symptoms of neonatal abstinence syndrome (NAS) within 24 to 72 hours of birth. Treatment of NAS includes monitoring of withdrawal symptoms, managing physiological parameters, and the use of supportive and pharmacologic treatments. Although a few randomized controlled trials exist, studies on supportive intervention are generally limited by small sample sizes, case study reports, expert opinions, and descriptive design. Few studies address the safety of Reiki for newborns at risk for NAS using neonatal parameters. This pilot study addresses feasibility and demonstrates that Reiki is safe when administered to this high-risk population. Considerations for future studies are discussed. PMID:29315084

Status of conceptual safety design study of Japanese sodium-cooled fast reactor

International Nuclear Information System (INIS)

Kubo, Shigenobu; Kurisaka, Kenichi; Niwa, Hajime; Shimakawa, Yoshio

2005-01-01

In this paper, the current conceptual safety design and related evaluation of Japanese Sodium-cooled Fast Reactor which is studied in the framework of the Feasibility Study (FS) on commercialized Fast Reactor Cycle Systems in Japan are described. The purpose of the safety design is to establish a feasible safety concept of FBR which aims at a sustainable energy source of the next generations. The safety targets and the safety design principle are set aiming at realizing worldwide acceptability of the safety level. The basic safety design concept, which can meet the safety targets, was formulated taking along with the defense-in-depth philosophy as the basic safety design principle. In order to cope with wide range of energy and resource demands, there are some various designs both of oxide and metal fuel for JSFR. Some analytical results of typical design basis events, design extension conditions and core damage frequency estimation show the feasibility of the safety design concept for them. (author)

Cervical cancer prevention: safety, acceptability, and feasibility of a single-visit approach in Accra, Ghana.

Science.gov (United States)

Blumenthal, Paul D; Gaffikin, Lynne; Deganus, Sylvia; Lewis, Robbyn; Emerson, Mark; Adadevoh, Sydney

2007-04-01

The purpose of this study was to assess the safety and acceptability of a single-visit approach to cervical cancer prevention combining visual inspection of the cervix with acetic acid wash (VIA) and cryotherapy. The study was observational. Nine clinicians were trained in VIA and cryotherapy. Over 18 months 3665 women were VIA-tested. If positive and eligible, cryotherapy was offered immediately. Treated women were followed-up at 3 months and 1 year. The test-positive rate was 13.2%. Of those eligible, 70.2% and 21% received immediate or delayed treatment, respectively. No major complications were recorded, and 5.6% presented for a perceived problem post-cryotherapy. Among those treated over 90% expressed satisfaction with their experience, and 96% had an indentifiable squamo-columnar junction. Only 2.6% (6/232) were test positive, 1-year posttreatment. A single-visit approach using VIA and cryotherapy proved to be safe, acceptable, and feasible in an urban African setting.

Multimodal impairment-based physical therapy for the treatment of patients with post-concussion syndrome: A retrospective analysis on safety and feasibility.

Science.gov (United States)

Grabowski, Patrick; Wilson, John; Walker, Alyssa; Enz, Dan; Wang, Sijian

2017-01-01

Demonstrate implementation, safety and feasibility of multimodal, impairment-based physical therapy (PT) combining vestibular/oculomotor and cervical rehabilitation with sub-symptom threshold exercise for the treatment of patients with post-concussion syndrome (PCS). University hospital outpatient sports medicine facility. Twenty-five patients (12-20 years old) meeting World Health Organization criteria for PCS following sport-related concussion referred for supervised PT consisting of sub-symptom cardiovascular exercise, vestibular/oculomotor and cervical spine rehabilitation. Retrospective cohort. Post-Concussion Symptom Scale (PCSS) total score, maximum symptom-free heart rate (SFHR) during graded exercise testing (GXT), GXT duration, balance error scoring system (BESS) score, and number of adverse events. Patients demonstrated a statistically significant decreasing trend (p feasibility for future clinical trials to determine viable treatment approaches to reduce symptoms and improve function while avoiding negative repercussions of physical inactivity and premature return to full activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

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...

Initial experience with a robotically operated video optical telescopic-microscope in cranial neurosurgery: feasibility, safety, and clinical applications.

Science.gov (United States)

Gonen, Lior; Chakravarthi, Srikant S; Monroy-Sosa, Alejandro; Celix, Juanita M; Kojis, Nathaniel; Singh, Maharaj; Jennings, Jonathan; Fukui, Melanie B; Rovin, Richard A; Kassam, Amin B

2017-05-01

OBJECTIVE The move toward better, more effective optical visualization in the field of neurosurgery has been a focus of technological innovation. In this study, the authors' objectives are to describe the feasibility and safety of a new robotic optical platform, namely, the robotically operated video optical telescopic-microscope (ROVOT-m), in cranial microsurgical applications. METHODS A prospective database comprising patients who underwent a cranial procedure between April 2015 and September 2016 was queried, and the first 200 patients who met the inclusion criteria were selected as the cohort for a retrospective chart review. Only adults who underwent microsurgical procedures in which the ROVOT-m was used were considered for the study. Preoperative, intraoperative, and postoperative data were retrieved from electronic medical records. The authors address the feasibility and safety of the ROVOT-m by studying various intraoperative variables and by reporting perioperative morbidity and mortality, respectively. To assess the learning curve, cranial procedures were categorized into 6 progressively increasing complexity groups. The main categories of pathology were I) intracerebral hemorrhages (ICHs); II) intraaxial tumors involving noneloquent regions or noncomplex extraaxial tumors; III) intraaxial tumors involving eloquent regions; IV) skull base pathologies; V) intraventricular lesions; and VI) cerebrovascular lesions. In addition, the entire cohort was evenly divided into early and late cohorts. RESULTS The patient cohort comprised 104 female (52%) and 96 male (48%) patients with a mean age of 56.7 years. The most common pathological entities encountered were neoplastic lesions (153, 76.5%), followed by ICH (20, 10%). The distribution of cases by complexity categories was 11.5%, 36.5%, 22%, 20%, 3.5%, and 6.5% for Categories I, II, II, IV, V, and VI, respectively. In all 200 cases, the surgical goal was achieved without the need for intraoperative conversion

Safety and feasibility of STAT RAD: Improvement of a novel rapid tomotherapy-based radiation therapy workflow by failure mode and effects analysis.

Science.gov (United States)

Jones, Ryan T; Handsfield, Lydia; Read, Paul W; Wilson, David D; Van Ausdal, Ray; Schlesinger, David J; Siebers, Jeffrey V; Chen, Quan

2015-01-01

The clinical challenge of radiation therapy (RT) for painful bone metastases requires clinicians to consider both treatment efficacy and patient prognosis when selecting a radiation therapy regimen. The traditional RT workflow requires several weeks for common palliative RT schedules of 30 Gy in 10 fractions or 20 Gy in 5 fractions. At our institution, we have created a new RT workflow termed "STAT RAD" that allows clinicians to perform computed tomographic (CT) simulation, planning, and highly conformal single fraction treatment delivery within 2 hours. In this study, we evaluate the safety and feasibility of the STAT RAD workflow. A failure mode and effects analysis (FMEA) was performed on the STAT RAD workflow, including development of a process map, identification of potential failure modes, description of the cause and effect, temporal occurrence, and team member involvement in each failure mode, and examination of existing safety controls. A risk probability number (RPN) was calculated for each failure mode. As necessary, workflow adjustments were then made to safeguard failure modes of significant RPN values. After workflow alterations, RPN numbers were again recomputed. A total of 72 potential failure modes were identified in the pre-FMEA STAT RAD workflow, of which 22 met the RPN threshold for clinical significance. Workflow adjustments included the addition of a team member checklist, changing simulation from megavoltage CT to kilovoltage CT, alteration of patient-specific quality assurance testing, and allocating increased time for critical workflow steps. After these modifications, only 1 failure mode maintained RPN significance; patient motion after alignment or during treatment. Performing the FMEA for the STAT RAD workflow before clinical implementation has significantly strengthened the safety and feasibility of STAT RAD. The FMEA proved a valuable evaluation tool, identifying potential problem areas so that we could create a safer workflow

Feasibility of applying the life history calendar in a population of chronic opioid users to identify patterns of drug use and addiction treatment.

Science.gov (United States)

Fikowski, Jill; Marchand, Kirsten; Palis, Heather; Oviedo-Joekes, Eugenia

2014-01-01

Uncovering patterns of drug use and treatment access is essential to improving treatment for opioid dependence. The life history calendar (LHC) could be a valuable instrument for capturing time-sensitive data on lifetime patterns of drug use and addiction treatment. This study describes the methodology applied when collecting data using the LHC in a sample of individuals with long-term opioid dependence and aims to identify specific factors that impact the feasibility of administering the LHC interview. In this study, the LHC allowed important events such as births, intimate relationships, housing, or incarcerations to become reference points for recalling details surrounding drug use and treatment access. The paper concludes that the administration of the LHC was a resource-intensive process and required special attention to interviewer training and experience with the study population. These factors should be considered and integrated into study plans by researchers using the LHC in addiction research.

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

Science.gov (United States)

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

2014-06-01

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

Safety and feasibility of transcranial direct current stimulation (tDCS) combined with sensorimotor retraining in chronic low back pain: a protocol for a pilot randomised controlled trial.

Science.gov (United States)

Ouellette, Adam Louis; Liston, Matthew B; Chang, Wei-Ju; Walton, David M; Wand, Benedict Martin; Schabrun, Siobhan M

2017-08-21

Chronic low back pain (LBP) is a common and costly health problem yet current treatments demonstrate at best, small effects. The concurrent application of treatments with synergistic clinical and mechanistic effects may improve outcomes in chronic LBP. This pilot trial aims to (1) determine the feasibility, safety and perceived patient response to a combined transcranial direct current stimulation (tDCS) and sensorimotor retraining intervention in chronic LBP and (2) provide data to support a sample size calculation for a fully powered trial should trends of effectiveness be present. A pilot randomised, assessor and participant-blind, sham-controlled trial will be conducted. Eighty participants with chronic LBP will be randomly allocated to receive either (1) active tDCS + sensorimotor retraining or (2) sham tDCS + sensorimotor retraining. tDCS (active or sham) will be applied to the primary motor cortex for 20 min immediately prior to 60 min of supervised sensorimotor retraining twice per week for 10 weeks. Participants in both groups will complete home exercises three times per week. Feasibility, safety, pain, disability and pain system function will be assessed immediately before and after the 10-week intervention. Analysis of feasibility and safety will be performed using descriptive statistics. Statistical analyses will be conducted based on intention-to-treat and per protocol and will be used to determine trends for effectiveness. Ethical approval has been gained from the institutional human research ethics committee (H10184). Written informed consent will be provided by all participants. Results from this pilot study will be submitted for publication in peer-reviewed journals. ACTRN12616000624482. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques.

Science.gov (United States)

Kirtane, Ameya R; Rothenberger, Meghan K; Frieberg, Abby; Nephew, Karla; Schultz-Darken, Nancy; Schmidt, Thomas; Reimann, Thomas; Haase, Ashley T; Panyam, Jayanth

2017-07-01

The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of ∼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Radiation processing of flue gases: Guidelines for feasibility studies

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-12-01

The aim of this publication is to facilitate the performance of feasibility studies for Electron Beam flue gas cleanup projects by providing guidelines to conduct these studies and compiling information on the state of the art. This document summarizes the contents of a feasibility study; discusses the main items in plant construction, measurement and control systems, radiation safety and building construction; and lists the required economic data for internationally funded projects.

Radiation processing of flue gases: Guidelines for feasibility studies

International Nuclear Information System (INIS)

2000-12-01

The aim of this publication is to facilitate the performance of feasibility studies for Electron Beam flue gas cleanup projects by providing guidelines to conduct these studies and compiling information on the state of the art. This document summarizes the contents of a feasibility study; discusses the main items in plant construction, measurement and control systems, radiation safety and building construction; and lists the required economic data for internationally funded projects

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

Science.gov (United States)

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

2017-05-04

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

Safety prediction for basic components of safety-critical software based on static testing

International Nuclear Information System (INIS)

Son, H.S.; Seong, P.H.

2000-01-01

The purpose of this work is to develop a safety prediction method, with which we can predict the risk of software components based on static testing results at the early development stage. The predictive model combines the major factor with the quality factor for the components, which are calculated based on the measures proposed in this work. The application to a safety-critical software system demonstrates the feasibility of the safety prediction method. (authors)

Using resources for scientific-driven pharmacovigilance: from many product safety documents to one product safety master file.

Science.gov (United States)

Furlan, Giovanni

2012-08-01

Current regulations require a description of the overall safety profile or the specific risks of a drug in multiple documents such as the Periodic and Development Safety Update Reports, Risk Management Plans (RMPs) and Signal Detection Reports. In a resource-constrained world, the need for preparing multiple documents reporting the same information results in shifting the focus from a thorough scientific and medical evaluation of the available data to maintaining compliance with regulatory timelines. Since the aim of drug safety is to understand and characterize product issues to take adequate risk minimization measures rather than to comply with bureaucratic requirements, there is the need to avoid redundancy. In order to identify core drug safety activities that need to be undertaken to protect patient safety and reduce the number of documents reporting the results of these activities, the author has reviewed the main topics included in the drug safety guidelines and templates. The topics and sources that need to be taken into account in the main regulatory documents have been found to greatly overlap and, in the future, as a result of the new Periodic Safety Update Report structure and requirements, in the author's opinion this overlap is likely to further increase. Many of the identified inter-document differences seemed to be substantially formal. The Development Safety Update Report, for example, requires separate presentation of the safety issues emerging from different sources followed by an overall evaluation of each safety issue. The RMP, instead, requires a detailed description of the safety issues without separate presentation of the evidence derived from each source. To some extent, however, the individual documents require an in-depth analysis of different aspects; the RMP, for example, requires an epidemiological description of the indication for which the drug is used and its risks. At the time of writing this article, this is not specifically

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

Science.gov (United States)

Day, Richard O; Williams, Kenneth M

2007-01-01

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

Cooking Healthy, Eating Smart (CHES): Evaluating the feasibility of using volunteers to deliver nutrition and food safety education to rural older adults

Science.gov (United States)

Getty, Morgan

Due to their limited resources, rural, older adults in the United States are at risk for poor diet-related health outcomes. Nutrition education is a key component in improving health outcomes in older adults. Cooking Healthy, Eating Smart (CHES) is a nine-lesson curriculum designed to teach rural, older adults culturally appropriate nutrition and food safety information. Funding to hire health professionals to deliver such a curriculum is limited, presenting the need to explore a less expensive mode of dissemination. In this community-based, participatory research study, a formative evaluation and feasibility study were conducted to examine the use of volunteers to deliver a nutrition and food safety curriculum to rural, older adults in South Carolina. Seven focus groups were conducted with members of the South Carolina Family and Community Leaders (SCFCL) and members of the American Association of Retired Persons (AARP) in the four regions of South Carolina to explore barriers and facilitators of volunteers delivering CHES (N=65 participants). The focus group findings informed the development of the volunteer training manual. A comparative case study method was used to examine the feasibility of a volunteer-based approach by observing and describing the delivery of CHES by two groups of volunteers in SC. The case study findings, including volunteer knowledge change, self-efficacy change, curriculum experience, program experience, and project team observations of volunteers indicated that using volunteers to deliver CHES is a plausible approach with the assistance of paid staff or project team members.

Hydrogen system (hydrogen fuels feasibility)

International Nuclear Information System (INIS)

Guarna, S.

1991-07-01

This feasibility study on the production and use of hydrogen fuels for industry and domestic purposes includes the following aspects: physical and chemical properties of hydrogen; production methods steam reforming of natural gas, hydrolysis of water; liquid and gaseous hydrogen transportation and storage (hydrogen-hydride technology); environmental impacts, safety and economics of hydrogen fuel cells for power generation and hydrogen automotive fuels; relevant international research programs

NTRE extended life feasibility assessment

Science.gov (United States)

Results of a feasibility analysis of a long life, reusable nuclear thermal rocket engine are presented in text and graph form. Two engine/reactor concepts are addressed: the Particle Bed Reactor (PBR) design and the Commonwealth of Independent States (CIS) concept. Engine design, integration, reliability, and safety are addressed by various members of the NTRE team from Aerojet Propulsion Division, Energopool (Russia), and Babcock & Wilcox.

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.

Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications.

Directory of Open Access Journals (Sweden)

Lin-Chau Chang

Full Text Available Standardised MedDRA Queries (SMQs have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA and Biologics License Application (BLA submissions to the United States Food and Drug Administration (USFDA.We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed.A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59% of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18% of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated. Most searches (75% of 227 searches with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process.SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications.

Science.gov (United States)

Chang, Lin-Chau; Mahmood, Riaz; Qureshi, Samina; Breder, Christopher D

2017-01-01

Standardised MedDRA Queries (SMQs) have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA) and Biologics License Application (BLA) submissions to the United States Food and Drug Administration (USFDA). We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs) of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed. A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59%) of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18%) of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated). Most searches (75% of 227 searches) with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process. SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

Safety and feasibility of the robotic platform in the management of surgical sequelae of chronic pancreatitis.

Science.gov (United States)

Hamad, Ahmad; Zenati, Mazen S; Nguyen, Trang K; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

2018-02-01

The application of minimally invasive surgery to chronic pancreatitis (CP) procedures is uncommon. Our objective was to report the safety and feasibility of the robotic approach in the treatment of surgical sequelae of CP, and provide insights into the technique, tricks, and pitfalls associated with the application of robotics to this challenging disease entity. A retrospective review of a prospectively maintained database of patients undergoing robotic-assisted resections and/or drainage procedures for CP at the University of Pittsburgh between May 2009 and January 2017 was performed. A video of a robotic Frey procedure is also shown. Of 812 robotic pancreatic resections and reconstructions 39 were for CP indications. These included 11 total pancreatectomies [with and without auto islet transplantation], 8 Puestow procedures, 4 Frey procedures, 6 pancreaticoduodenectomies, and 10 distal pancreatectomies. Median age was 49, and 41% of the patients were female. The most common etiology for CP was idiopathic pancreatitis (n = 16, 46%). Median operative time was 324 min with a median estimated blood loss of 250 ml. None of the patients required conversion to laparotomy. A Clavien III-IV complication rate was experienced by 5 (13%) patients, including one reoperation. Excluding the eleven patients who underwent TP, rate of clinically relevant postoperative pancreatic fistula was 7% (Grade B = 2, Grade C = 0). No 30 or 90 day mortalities were recorded. The median length of hospital stay was 7 days. Use of the robotic platform is safe and feasible when tackling complex pancreatic resections for sequelae of chronic pancreatitis.

Safety and feasibility of modified chair-yoga on functional outcome among elderly at risk for falls

Directory of Open Access Journals (Sweden)

Mary Lou Galantino

2012-01-01

Full Text Available Falls are among the most common problems affecting older adults. At least 50% of those over the age of 80 fall annually. The goal of this pilot study was to assess the safety and feasibility of structured yoga in an elderly population with fall risk. Seniors at risk for falls were identified and enrolled in a single arm pilot trial. A chair based yoga program was provided twice a week for 8 weeks. The program was designed from previously published pilot data. A battery of validated instruments was administered at baseline and week eight and was used to identify which instruments may be sensitive to change as a result of a yoga program. Among sixteen seniors (median age of 88 with a previous history of falls, 87% provided data for assessment at the end of the intervention. Two patients withdrew, one due to a fall outside the institution and the other due to lack of time and interest. There were no adverse events during the yoga sessions. Paired-t tests compared pre-post changes and gains were noted in Fear of Falling (5.27 to 2.60; P = 0.029 and SPPB sit to stand subscale (0.31 to 1.00; P =.022. Improved trends were noted in anxiety and the timed up and go assessments. We found the modified chair-yoga program is safe and recruitment is feasible. Our data suggests that yoga may be beneficial in improving mobility and reducing fear of falling which warrants additional research via randomized controlled trial.

Safety prediction for basic components of safety critical software based on static testing

International Nuclear Information System (INIS)

Son, H.S.; Seong, P.H.

2001-01-01

The purpose of this work is to develop a safety prediction method, with which we can predict the risk of software components based on static testing results at the early development stage. The predictive model combines the major factor with the quality factor for the components, both of which are calculated based on the measures proposed in this work. The application to a safety-critical software system demonstrates the feasibility of the safety prediction method. (authors)

Ion Prostate Irradiation (IPI) – a pilot study to establish the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique

International Nuclear Information System (INIS)

Habl, Gregor; Herfarth, Klaus; Hatiboglu, Gencay; Edler, Lutz; Uhl, Matthias; Krause, Sonja; Roethke, Matthias; Schlemmer, Heinz P; Hadaschik, Boris; Debus, Juergen

2014-01-01

Due to physical characteristics, ions like protons or carbon ions can administer the dose to the target volume more efficiently than photons since the dose can be lowered at the surrounding normal tissue. Radiation biological considerations are based on the assumption that the α/β value for prostate cancer cells is 1.5 Gy, so that a biologically more effective dose could be administered due to hypofractionation without increasing risks of late effects of bladder (α/β = 4.0) and rectum (α/β = 3.9). The IPI study is a prospective randomized phase II study exploring the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique. The study is designed to enroll 92 patients with localized prostate cancer. Primary aim is the assessment of the safety and feasibility of the study treatment on the basis of incidence grade III and IV NCI-CTC-AE (v. 4.02) toxicity and/or the dropout of the patient from the planned therapy due to any reason. Secondary endpoints are PSA-progression free survival (PSA-PFS), overall survival (OS) and quality-of-life (QoL). This pilot study aims at the evaluation of the safety and feasibility of hypofractionated irradiation of the prostate with protons and carbon ions in prostate cancer patients in an active beam technique. Additionally, the safety results will be compared with Japanese results recently published for carbon ion irradiation. Due to the missing data of protons in this hypofractionated scheme, an in depth evaluation of the toxicity will be created to gain basic data for a following comparison study with carbon ion irradiation. Clinical Trial Identifier: http://clinicaltrials.gov/show/NCT01641185 (clinicaltrials.gov)

Animal Product Safety Information

Science.gov (United States)

... Home Animal & Veterinary Safety & Health Product Safety Information Product Safety Information Share Tweet Linkedin Pin it More ... to report adverse experiences with veterinary drugs. Additional Product Information Questions and Answers: Evanger’s Dog and Cat ...

[Significance of re-evaluation and development of Chinese herbal drugs].

Science.gov (United States)

Gao, Yue; Ma, Zengchun; Zhang, Boli

2012-01-01

The research of new herbal drugs involves in new herbal drugs development and renew the old drugs. It is necessary to research new herbal drugs based on the theory of traditional Chinese medicine (TCM). The current development of famous TCM focuses on the manufacture process, quality control standards, material basis and clinical research. But system management of security evaluation is deficient, the relevant system for the safety assessment TCM has not been established. The causes of security problems, security risks, target organ of toxicity, weak link of safety evaluation, and ideas of safety evaluation are discussed in this paper. The toxicology research of chinese herbal drugs is necessary based on standard of good laboratory practices (GLP), the characteristic of Chinese herbal drugs is necessary to be fully integrated into safety evaluation. The safety of new drug research is necessary to be integrated throughout the entire process. Famous Chinese medicine safety research must be paid more attention in the future.

Feasibility study and uncertainties in the validation of an existing safety-related control circuit with the ISO 13849-1:2006 design standard

International Nuclear Information System (INIS)

Jocelyn, Sabrina; Baudoin, James; Chinniah, Yuvin; Charpentier, Philippe

2014-01-01

In industry, machine users and people who modify or integrate equipment often have to evaluate the safety level of a safety-related control circuit that they have not necessarily designed. The modifications or integrations may involve work to make an existing machine that does not comply with normative or regulatory specifications safe. However, how can a circuit performing a safety function be validated a posteriori? Is the validation exercise feasible? What are the difficulties and limitations of such a procedure? The aim of this article is to answer these questions by presenting a validation study of a safety function of an existing machine. A plastic injection molding machine is used for this study, as well as standard ISO 13849-1:2006. Validation consists of performing an a posteriori (post-design) estimation of the performance level of the safety function. The procedure is studied for two contexts of use of the machine: in industry, and in laboratory. The calculations required by the ISO standard were done using Excel, followed by SIStema software. It is shown that, based on the context of use, the estimated performance level was different for the same safety-related circuit. The variability in the results is explained by the assumptions made by the person undertaking the validation without the involvement of the machine designer. - Highlights: • Validation of the performance level of a safety function is undertaken. • An injection molding machine and ISO 13849-1:2006 standard are used for the procedure. • The procedure is undertaken for two contexts of use of the machine. • In this study, the performance level depends on the context of use. • The assumptions made throughout the study partially explain this difference

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

Directory of Open Access Journals (Sweden)

Zhou EH

2017-03-01

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

Patient safety incident reports related to traditional Japanese Kampo medicines: medication errors and adverse drug events in a university hospital for a ten-year period.

Science.gov (United States)

Shimada, Yutaka; Fujimoto, Makoto; Nogami, Tatsuya; Watari, Hidetoshi; Kitahara, Hideyuki; Misawa, Hiroki; Kimbara, Yoshiyuki

2017-12-21

Kampo medicine is traditional Japanese medicine, which originated in ancient traditional Chinese medicine, but was introduced and developed uniquely in Japan. Today, Kampo medicines are integrated into the Japanese national health care system. Incident reporting systems are currently being widely used to collect information about patient safety incidents that occur in hospitals. However, no investigations have been conducted regarding patient safety incident reports related to Kampo medicines. The aim of this study was to survey and analyse incident reports related to Kampo medicines in a Japanese university hospital to improve future patient safety. We selected incident reports related to Kampo medicines filed in Toyama University Hospital from May 2007 to April 2017, and investigated them in terms of medication errors and adverse drug events. Out of 21,324 total incident reports filed in the 10-year survey period, we discovered 108 Kampo medicine-related incident reports. However, five cases were redundantly reported; thus, the number of actual incidents was 103. Of those, 99 incidents were classified as medication errors (77 administration errors, 15 dispensing errors, and 7 prescribing errors), and four were adverse drug events, namely Kampo medicine-induced interstitial pneumonia. The Kampo medicine (crude drug) that was thought to induce interstitial pneumonia in all four cases was Scutellariae Radix, which is consistent with past reports. According to the incident severity classification system recommended by the National University Hospital Council of Japan, of the 99 medication errors, 10 incidents were classified as level 0 (an error occurred, but the patient was not affected) and 89 incidents were level 1 (an error occurred that affected the patient, but did not cause harm). Of the four adverse drug events, two incidents were classified as level 2 (patient was transiently harmed, but required no treatment), and two incidents were level 3b (patient was

Pediatric Drug Safety Signal Detection: A New Drug–Event Reference Set for Performance Testing of Data-Mining Methods and Systems

NARCIS (Netherlands)

O.U. Osokogu (Osemeke); F. Fregonese (Federica); C. Ferrajolo (Carmen); K.M.C. Verhamme (Katia); S. de Bie (Sandra); G. Jong (Geert’t); M. Catapano (Mariana); D. Weibel (Daniel); F. Kaguelidou (Florentia); W.M. Bramer (Wichor); Y. Hsia (Yingfen); I. Wong (Ian); M. Gazarian (Madlen); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

2015-01-01

textabstractBackground: Better evidence regarding drug safety in the pediatric population might be generated from existing data sources such as spontaneous reporting systems and electronic healthcare records. The Global Research in Paediatrics (GRiP)–Network of Excellence aims to develop

Feasibility and safety of GliaSite brachytherapy in treatment of CNS tumors following neurosurgical resection

Directory of Open Access Journals (Sweden)

Wernicke A

2010-01-01

Full Text Available Purpose: To investigate feasibility and safety of GliaSite brachytherapy for treatment of central nervous system (CNS tumors following neurosurgical resection. We report mature results of long-term follow-up, outcomes and toxicity. Materials and Methods: In the period from 2004 to 2007, 10 consecutive adult patients with recurrent, newly diagnosed, and metastatic brain malignancies underwent GliaSite brachytherapy following maximally safe neurosurgical resection. While 6/10 (60% patients were treated for recurrence, having previously been treated with external beam radiotherapy (EBRT, 4/10 (40% received radiotherapy (RT for the first time. A median dose of 52.0 Gy (range, 45.0 - 60.0 Gy was prescribed to 0.5 cm - 1.0 cm from the balloon surface. Radiation Therapy Oncology Group (RTOG criteria were used to assess toxicities associated with this technique. Follow-up was assessed with MRI scans and was available on all enrolled patients. Results: Median follow-up was 38 months (range, 18 - 57 months. Mean size of GliaSite balloon was 3.4 cm (range, 2.0 - 4.0 cm. Median survival was 14.0 months for the entire cohort after the treatment. The 17.6 and 16.0 months average survival for newly diagnosed and recurrent high grade gliomas (HGG, respectively, translated into a three-month improvement in survival in patients with newly diagnosed HGG compared to historical controls (P = 0.033. There were no RTOG grades 3 or 4 acute or late toxicities. Follow-up magnetic resonance imaging (MRI imaging did not identify radiation necrosis. Conclusions: Our data indicate that treatment with GliaSite brachytherapy is feasible, safe and renders acceptable local control, acute and long-term toxicities. We are embarking on testing larger numbers of patients with this treatment modality.

TIA triage in emergency department using acute MRI (TIA-TEAM): a feasibility and safety study.

Science.gov (United States)

Vora, Nirali; Tung, Christie E; Mlynash, Michael; Garcia, Madelleine; Kemp, Stephanie; Kleinman, Jonathan; Zaharchuk, Greg; Albers, Gregory; Olivot, Jean-Marc

2015-04-01

Positive diffusion weighted imaging (DWI) on MRI is associated with increased recurrent stroke risk in TIA patients. Acute MRI aids in TIA risk stratification and diagnosis. To evaluate the feasibility and safety of TIA triage directly from the emergency department (ED) with acute MRI and neurological consultation. Consecutive ED TIA patients assessed by a neurologist underwent acute MRI/MRA of head/neck per protocol and were hospitalized if positive DWI, symptomatic vessel stenosis, or per clinical judgment. Stroke neurologist adjudicated the final TIA diagnosis as definite, possible, or not a cerebrovascular event. Stroke recurrence rates were calculated at 7, 90, 365 days and compared with predicted stroke rates derived from historical DWI and ABCD(2) score data. One hundred twenty-nine enrolled patients had a mean age of 69 years (± 17) and median ABCD(2) score of 3 (interquartile range [IQR] 3-4). During triage, 112 (87%) patients underwent acute MRI after a median of 16 h (IQR 10-23) from symptom onset. No patients experienced a recurrent event before imaging. Twenty-four (21%) had positive DWI and 8 (7%) had symptomatic vessel stenosis. Of the total cohort, 83 (64%) were discharged and 46 (36%) were hospitalized. By one-year follow-up, one patient in each group had experienced a stroke. Of 92 patients with MRI and index cerebrovascular event, recurrent stroke rates were 1.1% at 7 and 90 days. These were similar to predicted recurrence rates. TIA triage in the ED using a protocol with neurological consultation and acute MRI is feasible and safe. The majority of patients were discharged without hospitalization and rates of recurrent stroke were not higher than predicted. © 2014 World Stroke Organization.

Feasibility and safety of a novel in vivo model to assess playground falls in children.

Science.gov (United States)

Ehrlich, Peter F; Young, Justin G; Ulin, Sheryl; Wooley, Charles; Armstrong, Thomas J; Buschmann, Bethany; Galecki, Andrzej; Ashton-Miller, James A

2013-07-01

Falls are the leading cause of nonfatal unintentional injuries among hospitalized children with playground equipment accounting for more than 50%. National standards for playground rung and rail design exist, but there a lack of in vivo models available to test these standards. We developed a novel in vivo model to test rung and rail design. We report the feasibility and safety of the model. A device was built to simulate children hanging onto a playground bar until their hand slips off. This was defined as breakaway strength. The handle unit was mounted on a vertical cable that was mechanically raised and lowered using a linear actuator controlled by the experimenter. The unit was padded and contained a video camera that recorded the posture of the hand during each trial. Breakaway force and torque were recorded as they held onto the handle by LabView software. In addition, standard anthropometrics and grip strength were recorded. Biomedical engineering approved the device. There were 425 eligible students aged 5 years to 11 years. Of these, 93% (397) participated (212 males and 185 females). Ninety-nine percent (396 of 397) completed all three experimental stations, one declined because of fear. There were no injuries and no falls. Average time to complete the study was 22 ± 0.5 minutes. Ninety-one percent of participants were right handed; the ethnicity was representative of the local area with 79% being white. Mean ± SD height, weight, and body mass index for the 397 participants were 1.28 ± 0.11 m, 28.0 ± 8.12 kg, and 16.31 ± 2.59 kg/m², respectively. Hand size, grip strength, and maximum breakaway force increased with age. This model is safe and feasible and maybe a viable method to assess rung and rail design for playgrounds.

Investigating drug repositioning opportunities in FDA drug labels through topic modeling.

Science.gov (United States)

Bisgin, Halil; Liu, Zhichao; Kelly, Reagan; Fang, Hong; Xu, Xiaowei; Tong, Weida

2012-01-01

Drug repositioning offers an opportunity to revitalize the slowing drug discovery pipeline by finding new uses for currently existing drugs. Our hypothesis is that drugs sharing similar side effect profiles are likely to be effective for the same disease, and thus repositioning opportunities can be identified by finding drug pairs with similar side effects documented in U.S. Food and Drug Administration (FDA) approved drug labels. The safety information in the drug labels is usually obtained in the clinical trial and augmented with the observations in the post-market use of the drug. Therefore, our drug repositioning approach can take the advantage of more comprehensive safety information comparing with conventional de novo approach. A probabilistic topic model was constructed based on the terms in the Medical Dictionary for Regulatory Activities (MedDRA) that appeared in the Boxed Warning, Warnings and Precautions, and Adverse Reactions sections of the labels of 870 drugs. Fifty-two unique topics, each containing a set of terms, were identified by using topic modeling. The resulting probabilistic topic associations were used to measure the distance (similarity) between drugs. The success of the proposed model was evaluated by comparing a drug and its nearest neighbor (i.e., a drug pair) for common indications found in the Indications and Usage Section of the drug labels. Given a drug with more than three indications, the model yielded a 75% recall, meaning 75% of drug pairs shared one or more common indications. This is significantly higher than the 22% recall rate achieved by random selection. Additionally, the recall rate grows rapidly as the number of drug indications increases and reaches 84% for drugs with 11 indications. The analysis also demonstrated that 65 drugs with a Boxed Warning, which indicates significant risk of serious and possibly life-threatening adverse effects, might be replaced with safer alternatives that do not have a Boxed Warning. In

A multiple biomarker assay for quality assessment of botanical drugs using a versatile microfluidic chip.

Science.gov (United States)

Li, Zhen-Hao; Ai, Ni; Yu, Lawrence X; Qian, Zhong-Zhi; Cheng, Yi-Yu

2017-09-25

Quality control is critical for ensuring the safety and effectiveness of drugs. Current quality control method for botanical drugs is mainly based on chemical testing. However, chemical testing alone may not be sufficient as it may not capture all constituents of botanical drugs. Therefore, it is necessary to establish a bioassay correlating with the drug's known mechanism of action to ensure its potency and activity. Herein we developed a multiple biomarker assay to assess the quality of botanicals using microfluidics, where enzyme inhibition was employed to indicate the drug's activity and thereby evaluate biological consistency. This approach was exemplified on QiShenYiQi Pills using thrombin and angiotensin converting enzyme as "quality biomarkers". Our results demonstrated that there existed variations in potency across different batches of the intermediates and preparations. Compared with chromatographic fingerprinting, the bioassay provided better discrimination ability for some abnormal samples. Moreover, the chip could function as "affinity chromatography" to identify bioactive phytochemicals bound to the enzymes. This work proposed a multiple-biomarker strategy for quality assessment of botanical drugs, while demonstrating for the first time the feasibility of microfluidics in this field.

Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

Science.gov (United States)

Labib, Gihan

2018-01-01

Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

Intravenous recombinant tissue plasminogen activator for acute ischemic stroke: a feasibility and safety study

Directory of Open Access Journals (Sweden)

Sadeghi-Hokmabadi E

2016-10-01

Full Text Available Elyar Sadeghi-Hokmabadi, Mehdi Farhoudi, Aliakbar Taheraghdam, Mazyar Hashemilar, Daryous Savadi-Osguei, Reza Rikhtegar, Kaveh Mehrvar, Ehsan Sharifipour, Parisa Youhanaee, Reshad Mirnour Neurosciences Research Center, Neurology Department, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan, Iran Background: In developing countries, intravenous thrombolysis (IVT is available at a limited number of centers. This study aimed to assess the feasibility and safety of IVT at Tabriz Imam Reza Hospital. Methods: In a prospective study, over a 55-month period, any patient at the hospital for whom stroke code had been activated was enrolled in the study. Data on demographic characteristics, stroke risk factors, admission blood pressure, blood tests, findings of brain computed tomography (CT scans, time of symtom onset, time of arrival to the emergency department, time of stroke code activation, time of CT scan examination, and the time of recombinant tissue plasminogen activator administration were recorded. National Institutes of Health Stroke Scale assessments were performed before IVT bolus, at 36 hours, at either 7 days or discharge (which ever one was earlier, and at 3-month follow-up. Brain CT scans were done for all patients before and 24 hours after the treatment. Results: Stroke code was activated for 407 patients and IVT was done in 168 patients. The rate of functional independence (modified Rankin Scale [mRS] 0–1 at 3 months was 39.2% (62/158. The mortality rate at day 7 was 6% (10/168. Hemorrhagic transformation was noted in 16 patients (9.5%. Symptomatic intracranial hemorrhage occurred in 5 (3%, all of which were fatal. One case of severe urinary bleeding and one other fatal case of severe angioedema were observed. Conclusion: During the first 4–5 years of administration of IVT in the hospital, it was found to be feasible and safe, but to increase the efficacy, poststroke care should be more organized and a stroke center

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.

Value of preapproval safety data in predicting postapproval hepatic safety and assessing the legitimacy of class warning.

Science.gov (United States)

Lin, Yeong-Liang; Wu, Ya-Chi; Gau, Churn-Shiouh; Lin, Min-Shung

2012-02-01

The objective of this study was to systematically evaluate whether preapproval safety data for nonhepatotoxic drugs and hepatotoxic drugs can be compared to improve preapproval prediction of postapproval hepatic safety and to assess the legitimacy of applying class warnings. Drugs within a therapeutic class that included at least one drug that had been withdrawn from the market because of liver toxicity or had a warning of potential liver toxicity issued by major regulatory agencies, and at least one drug free from such regulatory action, were identified and divided into two groups: drugs with and drugs without regulatory action. Preapproval clinical data [including the elevation rates of alanine aminotransferse (ALT) and withdrawal due to liver toxicity, the number of patients with combined elevation of ALT and bilirubin, and liver failure] and nonclinical data (including chemical structures, metabolic pathways, and other significant findings in animal studies) were compared between the two groups. Six drug classes were assessed in this study: thiazolidinediones, cyclooxygenase-2 inhibitors, fluoroquinolones, catechol-O-methyltransferase (COMT) inhibitors, leukotriene receptor inhibitors, and endothelin receptor antagonists. In two classes (COMT inhibitors and endothelin receptor antagonists), drugs with regulatory action had significantly higher rates of ALT elevation of more than threefold and greater numbers of patients with combined elevation of ALT and bilirubin than drugs without regulatory action. Drugs with regulatory action also had chemical structures or metabolic pathways associated with the toxicity. The legitimacy of class warnings was refuted in all six classes of drugs. Preapproval safety data may help predict postapproval hepatic safety and can be used to assess the legitimacy of applying class warnings.

Risk patterns in drug safety study using relative times by accelerated failure time models when proportional hazards assumption is questionable : an illustrative case study of cancer risk of patients on glucose-lowering therapies

NARCIS (Netherlands)

Ng, Edmond S-W; Klungel, Olaf H; Groenwold, Rolf H H; van Staa, Tjeerd-Pieter

2015-01-01

Observational drug safety studies may be susceptible to confounding or protopathic bias. This bias may cause a spurious relationship between drug exposure and adverse side effect when none exists and may lead to unwarranted safety alerts. The spurious relationship may manifest itself through

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)

Development of novel, 384-well high-throughput assay panels for human drug transporters: drug interaction and safety assessment in support of discovery research.

Science.gov (United States)

Tang, Huaping; Shen, Ding Ren; Han, Yong-Hae; Kong, Yan; Balimane, Praveen; Marino, Anthony; Gao, Mian; Wu, Sophie; Xie, Dianlin; Soars, Matthew G; O'Connell, Jonathan C; Rodrigues, A David; Zhang, Litao; Cvijic, Mary Ellen

2013-10-01

Transporter proteins are known to play a critical role in affecting the overall absorption, distribution, metabolism, and excretion characteristics of drug candidates. In addition to efflux transporters (P-gp, BCRP, MRP2, etc.) that limit absorption, there has been a renewed interest in influx transporters at the renal (OATs, OCTs) and hepatic (OATPs, BSEP, NTCP, etc.) organ level that can cause significant clinical drug-drug interactions (DDIs). Several of these transporters are also critical for hepatobiliary disposition of bilirubin and bile acid/salts, and their inhibition is directly implicated in hepatic toxicities. Regulatory agencies took action to address transporter-mediated DDI with the goal of ensuring drug safety in the clinic and on the market. To meet regulatory requirements, advanced bioassay technology and automation solutions were implemented for high-throughput transporter screening to provide structure-activity relationship within lead optimization. To enhance capacity, several functional assay formats were miniaturized to 384-well throughput including novel fluorescence-based uptake and efflux inhibition assays using high-content image analysis as well as cell-based radioactive uptake and vesicle-based efflux inhibition assays. This high-throughput capability enabled a paradigm shift from studying transporter-related issues in the development space to identifying and dialing out these concerns early on in discovery for enhanced mechanism-based efficacy while circumventing DDIs and transporter toxicities.

Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial.

Science.gov (United States)

Gómez-Barrena, Enrique; Rosset, Philippe; Gebhard, Florian; Hernigou, Philippe; Baldini, Nicola; Rouard, Helène; Sensebé, Luc; Gonzalo-Daganzo, Rosa M; Giordano, Rosaria; Padilla-Eguiluz, Norma; García-Rey, Eduardo; Cordero-Ampuero, José; Rubio-Suárez, Juan Carlos; Stanovici, Julien; Ehrnthaller, Christian; Huber-Lang, Markus; Flouzat-Lachaniette, Charles Henri; Chevallier, Nathalie; Donati, Davide Maria; Ciapetti, Gabriela; Fleury, Sandrine; Fernandez, Manuel-Nicolás; Cabrera, José-Rafael; Avendaño-Solá, Cristina; Montemurro, Tiziana; Panaitescu, Carmen; Veronesi, Elena; Rojewski, Markus Thomas; Lotfi, Ramin; Dominici, Massimo; Schrezenmeier, Hubert; Layrolle, Pierre

2018-03-19

ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Surgical procedures performed in the neonatal intensive care unit on critically ill neonates: feasibility and safety

International Nuclear Information System (INIS)

Mallick, M.S.; Jado, A.M.; Al-Bassam, A.R.

2008-01-01

Transferring unstable, ill neonates to and from the operating rooms carries significant risks and can lead to morbidity. We report on our experience in performing certain procedures in critically ill neonates in the neonatal intensive care unit (NICU). We examined the feasibility and safety for such an approach. All surgical procedures performed in the NICU between January 1999 and December 2005 were analyzed in terms of demographic data, diagnosis, preoperative stability of the patient, procedures performed, complications and outcome. Operations were performed at beside in the NICU in critically ill, unstable neonates who needed emergency surgery, in neonates of low birth weight (<1000 gm) and in neonates on special equipments like higher frequency ventilators and nitrous oxide. Thirty-seven surgical procedures were performed including 12 laparotomies, bowel resection and stomies, 7 repairs of congenital diaphragmatic hernias, 4 ligations of patent ductus arteriosus and various others. Birth weights ranged between 850 gm and 3500 gm (mean 2000 gm). Gestational age ranged between 25 to 42 weeks (mean, 33 weeks). Age at surgery was between 1 to 30 days (mean, 30 days). Preoperatively, 19 patients (51.3%) were on inotropic support and all were intubated and mechanically ventilated. There was no mortality related to surgical procedures. Postoperatively, one patient developed wound infection and disruption. Performing major surgical procedures in the NICU is both feasible and safe. It is useful in very low birth weight, critically ill neonates who have definite risk attached to transfer to the operating room. No special area is needed in the NICU to perform complication-free surgery, but designing an operating room within the NICU will be ideal. (author)

Nanotechnology inspired advanced engineering fundamentals for optimizing drug delivery.

Science.gov (United States)

Kassem, Ahmed Alaa

2018-02-06

Drug toxicity and inefficacy are commonly experienced problems with drug therapy failure. To face these problems, extensive research work took place aiming to design new dosage forms for drug delivery especially nanoparticulate systems. These systems are designed to increase the quantity of the therapeutic molecule delivered to the desired site concurrently with reduced side effects. In order to achieve this objective, nanocarriers must principally display suitable drug vehiculization abilities and a controlled biological destiny of drug molecules. Only the intelligent design of the nanomedicine will accomplish these fundamentals. The present review article is dedicated to the discussion of the important fundamentals to be considered in the fabrication of nanomedicines. These include the therapeutic agent, the nanocarrier and the functionalization moieties. Special consideration is devoted to the explanation and compilation of highly potential fabrication approaches assisting how to control the in vivo destiny of the nanomedicine. Finally, some nanotechnology-based drug delivery systems, for the development of nanomedicine, are also discussed. The nanotechnology-based drug delivery systems showed remarkable outcomes based on passive and active targeting as well as improvement of the drug pharmacodynamic and pharmacokinetic profiles. Multifunctional nanocarrier concept affords a revolutionary drug delivery approach for maximizing the efficacy, safety and monitoring the biological fate of the therapeutic molecule. Nanomedicines may enhance the efficacy of therapeutic molecules and reduce their toxic effects. Meanwhile, further research works are required to rightly optimize (and define) the effectiveness, nanotoxicity, in vivo destiny and feasibility of these nanomedicines which, from a preclinical standpoint, are actually promising. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Feasibility study of component risk ranking for plant maintenance

International Nuclear Information System (INIS)

Ushijima, Koji; Yonebayashi, Kenji; Narumiya, Yoshiyuki; Sakata, Kaoru; Kumano, Tetsuji

1999-01-01

Nuclear power is the base load electricity source in Japan, and reduction of operation and maintenance cost maintaining or improving plant safety is one of the major issues. Recently, Risk Informed Management (RIM) is focused as a solution. In this paper, the outline regarding feasibility study of component risk ranking for plant maintenance for a typical Japanese PWR plant is described. A feasibility study of component risk raking for plant maintenance optimization is performed on check valves and motor-operated valves. Risk ranking is performed in two steps using probabilistic analysis (quantitative method) for risk ranking of components, and deterministic examination (qualitative method) for component review. In this study, plant components are ranked from the viewpoint of plant safety / reliability, and the applicability for maintenance is assessed. As a result, distribution of maintenance resources using risk ranking is considered effective. (author)

Local rhBMP-12 on an Absorbable Collagen Sponge as an Adjuvant Therapy for Rotator Cuff Repair - A Phase 1, Randomized, Standard of Care Control, Multicenter Study: Safety and Feasibility.

Science.gov (United States)

Greiner, Stefan; Ide, Junji; Van Noort, Arthur; Mochizuki, Yu; Ochi, Hiroshi; Marraffino, Shannon; Sridharan, Sudhakar; Rudicel, Sally; Itoi, Eiji

2015-08-01

Recombinant human bone morphogenetic protein-12 (rhBMP-12) has been shown to induce tendon and ligament formation in rats and to improve tendon healing; however, the safety and feasibility of implanting rhBMP-12/absorbable collagen sponge (ACS) in humans are not known. To investigate the safety and feasibility of rhBMP-12 on an ACS as an adjuvant therapy in open rotator cuff repair. Randomized controlled trial; Level of evidence, 2. This study consisted of 20 patients with full-thickness rotator cuff tears. Patients were randomized either to standard of care (SOC) treatment (open rotator cuff repair) or to receive 0.015 mg/mL rhBMP-12/ACS and SOC treatment during their open rotator cuff repair (rhBMP-12/ACS group) at a rate of 1/4 SOC/rhBMP-12/ACS. The feasibility of implanting the product and the safety of the product were evaluated during the 1-year follow-up period. The evaluation involved up to 10 postoperative visits, which included physical examinations, radiographs, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans with an emphasis on heterotopic ossification (HO), pharmacokinetics, immunogenicity, laboratory evaluations, and local and systemic adverse events at specified time points. Small amounts of HO were seen on follow-up CT scans in 10 of 16 patients in the rhBMP-12/ACS group and in 2 of 3 patients in the SOC group. HO did not increase at 26 weeks and was not associated with any adverse events or unsatisfactory clinical outcomes. Pharmacokinetics demonstrated that circulating levels of rhBMP-12 were not detectable after administration. Five of 16 patients showed a postoperative immunogenic response but did not show any correlating adverse events. Complete healing of the rotator cuff was observed in 14 of 16 patients; 2 of 16 imaging results could not be analyzed because of artifacts in the rhBMP-12 group on MRI scans. In the SOC group, 1 of 4 patients showed a retear at 12 weeks after surgery. The use of rhBMP-12/ACS has been shown

Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay.

Science.gov (United States)

Alley, M C; Scudiero, D A; Monks, A; Hursey, M L; Czerwinski, M J; Fine, D L; Abbott, B J; Mayo, J G; Shoemaker, R H; Boyd, M R

1988-02-01

For the past 30 years strategies for the preclinical discovery and development of potential anticancer agents have been based largely upon the testing of agents in mice bearing transplantable leukemias and solid tumors derived from a limited number of murine as well as human sources. The feasibility of implementing an alternate approach, namely combined in vitro/in vivo screening for selective cytotoxicity among panels of human tumor cell lines derived from a broad spectrum of human solid tumors is under investigation. A group of 30 cell lines acquired from a variety of sources and representing 8 lung cancer pathologies as well as 76 cell lines representing 10 other categories of human cancer (carcinomas of colon, breast, kidney, prostate, ovary, head and neck; glioma; leukemia; melanoma; and sarcoma) have exhibited acceptable growth characteristics and suitable colorimetric profiles in a single, standard culture medium. Measurements of in vitro growth in microculture wells by cell-mediated reduction of tetrazolium showed excellent correlation (0.89 less than r2 less than 0.98) with measurements of cellular protein in adherent cell line cultures as well as viable cell count in suspension cell line cultures (0.94 less than r2 less than 0.99). Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.

Drug development: from concept to marketing!

Science.gov (United States)

Tamimi, Nihad A M; Ellis, Peter

2009-01-01

Drug development is an expensive, long and high-risk business taking 10-15 years and is associated with a high attrition rate. It is driven by medical need, disease prevalence and the likelihood of success. Drug candidate selection is an iterative process between chemistry and biology, refining the molecular properties until a compound suitable for advancing to man is found. Typically, about one in a thousand synthesised compounds is ever selected for progression to the clinic. Prior to administration to humans, the pharmacology and biochemistry of the drug is established using an extensive range of in vitro and in vivo test procedures. It is also a regulatory requirement that the drug is administered to animals to assess its safety. Later-stage animal testing is also required to assess carcinogenicity and effects on the reproductive system. Clinical phases of drug development include phase I in healthy volunteers to assess primarily pharmacokinetics, safety and toleration, phase II in a cohort of patients with the target disease to establish efficacy and dose-response relationship and large-scale phase III studies to confirm safety and efficacy. Experience tells us that approximately only 1 in 10 drugs that start the clinical phase will make it to the market. Each drug must demonstrate safety and efficacy in the intended patient population and its benefits must outweigh its risks before it will be approved by the regulatory agencies. Strict regulatory standards govern the conduct of pre-clinical and clinical trials as well as the manufacturing of pharmaceutical products. The assessment of the new medicinal product's safety continues beyond the initial drug approval through post-marketing monitoring of adverse events. Copyright 2009 S. Karger AG, Basel.

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.

Innovations in Post-Marketing Safety Research

NARCIS (Netherlands)

Stefánsdóttir, G.

2012-01-01

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

Balanced Propofol Sedation in Patients Undergoing EUS-FNA: A Pilot Study to Assess Feasibility and Safety

Directory of Open Access Journals (Sweden)

N. Pagano

2011-01-01

Full Text Available Introduction and aims. Balanced propofol sedation (BPS administered by gastroenterologists has gained popularity in endoscopic procedures. Few studies exist about the safety of this approach during endosonography with fine needle aspiration (EUS-FNA. We assessed the safety of BPS in EUS-FNA. Materials and methods. 112 consecutive patients, referred to our unit to perform EUS-FNA, from February 2008 to December 2009, were sedated with BPS. A second gastroenterologist administered the drugs and monitorized the patient. Results. All the 112 patients (62 males, mean age 58.35 completed the examination. The mean dose of midazolam and propofol was, respectively, of 2.1 mg (range 1–4 mg and 350 mg (range 180–400. All patients received oxygen with a mean flux of 4 liter/minute (range 2–6 liters/minute. The mean recovery time after procedure was 25 minutes (range 18–45 minutes. No major complications related to sedation were registered during all procedures. The oxygen saturation of all patients never reduced to less than 85%. Blood systolic pressure during and after the procedure never reduced to less than 100 mmHg. Conclusions. In our experience BPS administered by non-anaesthesiologists provided safe and successful sedation in patients undergoing EUS-FNA.

Safety and Feasibility of a Ketamine Package to Support Emergency and Essential Surgery in Kenya when No Anesthetist is Available: An Analysis of 1216 Consecutive Operative Procedures.

Science.gov (United States)

Burke, Thomas F; Suarez, Sebastian; Sessler, Daniel I; Senay, Ayla; Yusufali, Taha; Masaki, Charles; Guha, Moytrayee; Rogo, Debora; Jani, Pankaj; Nelson, Brett D; Rogo, Khama

2017-12-01

Lack of access to emergency and essential surgery is widespread in low- and middle-income countries. Scarce anesthesia services contribute to this unmet need. The aim of this study was to evaluate the safety and feasibility of the Every Second Matters for Emergency and Essential Surgery-Ketamine (ESM-Ketamine) package for emergency and essential procedures when no anesthetist was available. From November 2013 to September 2017, the ESM-Ketamine package was used for patients requiring emergency or life-improving surgeries in fifteen selected facilities across Kenya when no anesthetist was available. A mixed-methods approach was used to assess safety and feasibility of the ESM-Ketamine package, including demand, acceptability, and practicality. The primary outcome was ketamine-related adverse events. Key-informant interviews captured perceptions of providers, hospital administrators, and surgeons/proceduralists. Non-anesthetist mid-level providers used ESM-Ketamine for 1216 surgical procedures across the fifteen study facilities. The median ketamine dose was 2.1 mg/kg. Brief (30 s) oxygen desaturations occurred in seven patients (0.6%). There were 157 (13%) reported cases of hallucinations and agitation which were treated with diazepam. All patients recovered uneventfully, and no ketamine-related deaths were reported. Twenty-seven key-informant interviews showed strong support for the program with four main themes: financial considerations, provision of services, staff impact, and scaling considerations. The ESM-Ketamine package appears safe and feasible and is capable of expanding access to emergency and essential surgeries in rural Kenya when no anesthetist is available.

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease

DEFF Research Database (Denmark)

Chaparro, M; Verreth, A; Lobaton, T

2018-01-01

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs...... in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non......-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox...

75 FR 77798 - Interpretation of OSHA's Provisions for Feasible Administrative or Engineering Controls of...

Science.gov (United States)

2010-12-14

... DEPARTMENT OF LABOR Occupational Safety and Health Administration [Docket No. OSHA-2010-0032] 29 CFR Parts 1910 and 1926 Interpretation of OSHA's Provisions for Feasible Administrative or Engineering Controls of Occupational Noise AGENCY: Occupational Safety and Health Administration (OSHA), Labor. ACTION...

Index to Drug-Specific Information

Science.gov (United States)

... Postmarket Drug Safety Information for Patients and Providers Index to Drug-Specific Information Share Tweet Linkedin Pin ... options Linkedin Pin it Email Print Note: This Index does not include all FDA approved drugs. It ...

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.

Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

International Nuclear Information System (INIS)

Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y.

2014-01-01

The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

Energy Technology Data Exchange (ETDEWEB)

Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y., E-mail: frank.hsieh@nextcea.com

2014-09-15

The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

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

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

Dobutamine stress MRI. Part I. Safety and feasibility of dobutamine cardiovascular magnetic resonance in patients suspected of myocardial ischemia

International Nuclear Information System (INIS)

Kuijpers, Dirkjan; Janssen, Caroline H.C.; Oudkerk, Matthijs; Dijkman, Paul R.M. van

2004-01-01

The aim of the study was to evaluate safety and feasibility of dobutamine cardiovascular magnetic resonance (CMR) in patients with proven or suspected coronary artery disease. Dobutamine CMR was evaluated retrospectively in 400 consecutive patients with suspicion of myocardial ischemia. Dobutamine was infused using an incremental protocol up to 40 μg/kg body weight per minute. All anti-anginal medication was stopped 4 days before the CMR study and infusion time of dobutamine was 6 min per stage. Hemodynamic data, CMR findings and side effects were reported. Patients with contraindications to CMR (metallic implants and claustrophobia) were excluded from analysis. Dobutamine CMR was successfully performed in 355 (89%) patients. Forty-five (11%) patients could not be investigated adequately because of non-cardiac side effects in 29 (7%) and cardiac side effects in 16 (4%) patients. Hypotension (1.5%) and arrhythmias (1%) were the most frequent cardiac side effects. One patient developed a severe complication (ventricular fibrillation) at the end of the study. There were no myocardial infarctions or fatal complications of the stress test. The most frequent non-cardiac side effects were nausea, vomiting and claustrophobia. Age >70 years, prior myocardial infarction and rest wall motion abnormalities showed no significant differences with side effects (P>0.05). Dobutamine CMR is safe and feasible in patients with suspicion of myocardial ischemia. (orig.)

Dobutamine stress MRI. Part I. Safety and feasibility of dobutamine cardiovascular magnetic resonance in patients suspected of myocardial ischemia.

Science.gov (United States)

Kuijpers, Dirkjan; Janssen, Caroline H C; van Dijkman, Paul R M; Oudkerk, Matthijs

2004-10-01

The aim of the study was to evaluate safety and feasibility of dobutamine cardiovascular magnetic resonance (CMR) in patients with proven or suspected coronary artery disease. Dobutamine CMR was evaluated retrospectively in 400 consecutive patients with suspicion of myocardial ischemia. Dobutamine was infused using an incremental protocol up to 40 microg/kg body weight per minute. All anti-anginal medication was stopped 4 days before the CMR study and infusion time of dobutamine was 6 min per stage. Hemodynamic data, CMR findings and side effects were reported. Patients with contraindications to CMR (metallic implants and claustrophobia) were excluded from analysis. Dobutamine CMR was successfully performed in 355 (89%) patients. Forty-five (11%) patients could not be investigated adequately because of non-cardiac side effects in 29 (7%) and cardiac side effects in 16 (4%) patients. Hypotension (1.5%) and arrhythmias (1%) were the most frequent cardiac side effects. One patient developed a severe complication (ventricular fibrillation) at the end of the study. There were no myocardial infarctions or fatal complications of the stress test. The most frequent non-cardiac side effects were nausea, vomiting and claustrophobia. Age >70 years, prior myocardial infarction and rest wall motion abnormalities showed no significant differences with side effects (P>0.05). Dobutamine CMR is safe and feasible in patients with suspicion of myocardial ischemia. Copyright 2004 Springer-Verlag

Dobutamine stress MRI. Part I. Safety and feasibility of dobutamine cardiovascular magnetic resonance in patients suspected of myocardial ischemia

Energy Technology Data Exchange (ETDEWEB)

Kuijpers, Dirkjan [State University and Academic Hospital Groningen, Department of Radiology, Groningen (Netherlands); Bronovo Hospital, Department of Radiology and Cardiology, Bronovolaan 1, P.O. Box 96900, The Hague (Netherlands); Janssen, Caroline H.C.; Oudkerk, Matthijs [State University and Academic Hospital Groningen, Department of Radiology, Groningen (Netherlands); Dijkman, Paul R.M. van [Bronovo Hospital, Department of Radiology and Cardiology, Bronovolaan 1, P.O. Box 96900, The Hague (Netherlands)

2004-10-01

The aim of the study was to evaluate safety and feasibility of dobutamine cardiovascular magnetic resonance (CMR) in patients with proven or suspected coronary artery disease. Dobutamine CMR was evaluated retrospectively in 400 consecutive patients with suspicion of myocardial ischemia. Dobutamine was infused using an incremental protocol up to 40 {mu}g/kg body weight per minute. All anti-anginal medication was stopped 4 days before the CMR study and infusion time of dobutamine was 6 min per stage. Hemodynamic data, CMR findings and side effects were reported. Patients with contraindications to CMR (metallic implants and claustrophobia) were excluded from analysis. Dobutamine CMR was successfully performed in 355 (89%) patients. Forty-five (11%) patients could not be investigated adequately because of non-cardiac side effects in 29 (7%) and cardiac side effects in 16 (4%) patients. Hypotension (1.5%) and arrhythmias (1%) were the most frequent cardiac side effects. One patient developed a severe complication (ventricular fibrillation) at the end of the study. There were no myocardial infarctions or fatal complications of the stress test. The most frequent non-cardiac side effects were nausea, vomiting and claustrophobia. Age >70 years, prior myocardial infarction and rest wall motion abnormalities showed no significant differences with side effects (P>0.05). Dobutamine CMR is safe and feasible in patients with suspicion of myocardial ischemia. (orig.)

Application of Model Animals in the Study of Drug Toxicology

Science.gov (United States)

Song, Yagang; Miao, Mingsan

2018-01-01

Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

Nuclear safety regulation on nuclear safety equipment activities in relation to human and organizational factors

International Nuclear Information System (INIS)

Li Tianshu

2013-01-01

Based on years of knowledge in nuclear safety supervision and experience of investigating and dealing with violation events in repair welding of DFHM, this paper analyzes major faults in manufacturing and maintaining activities of nuclear safety equipment in relation to human and organizational factors. It could be deducted that human and organizational factors has definitely become key features in the development of nuclear energy and technology. Some feasible measures to reinforce supervision on nuclear safety equipment activities have also been proposed. (author)

Feasibility study on production of Co-60 in PHWR

Energy Technology Data Exchange (ETDEWEB)

Park, Kyung Bae; Han, Hyon Soo; Joo, Po Kook

2000-05-01

The purpose of this study is to analyze the safeties and the economics for Co-60 production from Wolsung PHWR and to verify the feasibility on the manufacturing of the final Co-60 source for industrial irradiation. The feasibility of reactor conversion was carried out with KEPCO collaboration. Through the site survey on the experience of Gentililly-2 in Canada, a feasibility of plant conversion, changes in design, equipment and tools for Co-60 production was verified. It was estimated that the reactor conversion would not impose adverse impact on plant safety. For the encapsulation of radiation source and storage of the final products, a modification of concrete hot cell at KAERI was primary concerns. The installation and improvement of facilities are needed to avoid cross contamination and extra radiation exposure. Main items for these are pressure gauge, separated HEPA filter the ceiling separation, extra-shielding and ceiling hoist system. At present, storage pool has got admission based on 400 kCi. But it is necessary to seismic analysis and design improvement of shielding to store 10 MCi (Co-60) which is the estimated Co-60 capacity produced by 3 PHWRs. According to present investigation, a production of Co-60 by PHWR and RIPE was seemed to be an economically feasible business and it was also expected that a joint venture will be able to realize by cooperation with MDS Nordion Co.

Feasibility study on production of Co-60 in PHWR

International Nuclear Information System (INIS)

Park, Kyung Bae; Han, Hyon Soo; Joo, Po Kook

2000-05-01

The purpose of this study is to analyze the safeties and the economics for Co-60 production from Wolsung PHWR and to verify the feasibility on the manufacturing of the final Co-60 source for industrial irradiation. The feasibility of reactor conversion was carried out with KEPCO collaboration. Through the site survey on the experience of Gentililly-2 in Canada, a feasibility of plant conversion, changes in design, equipment and tools for Co-60 production was verified. It was estimated that the reactor conversion would not impose adverse impact on plant safety. For the encapsulation of radiation source and storage of the final products, a modification of concrete hot cell at KAERI was primary concerns. The installation and improvement of facilities are needed to avoid cross contamination and extra radiation exposure. Main items for these are pressure gauge, separated HEPA filter the ceiling separation, extra-shielding and ceiling hoist system. At present, storage pool has got admission based on 400 kCi. But it is necessary to seismic analysis and design improvement of shielding to store 10 MCi (Co-60) which is the estimated Co-60 capacity produced by 3 PHWRs. According to present investigation, a production of Co-60 by PHWR and RIPE was seemed to be an economically feasible business and it was also expected that a joint venture will be able to realize by cooperation with MDS Nordion Co

Feasibility, tolerability and safety of pediatric hyperpolarized {sup 129}Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis

Energy Technology Data Exchange (ETDEWEB)

Walkup, Laura L.; Watters, Erin; Ruppert, Kai [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); Thomen, Robert P.; Woods, Jason C. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); Washington University in St. Louis, Department of Physics, St. Louis, MO (United States); Akinyi, Teckla G.; Cleveland, Zackary I. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); University of Cincinnati, Biomedical Engineering Program, Cincinnati, OH (United States); Clancy, John P. [Cincinnati Children' s Hospital Medical Center, Division of Pulmonary Medicine, Cincinnati, OH (United States)

2016-11-15

Hyperpolarized {sup 129}Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. To assess the feasibility, safety and tolerability of hyperpolarized {sup 129}Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. Seventeen healthy control subjects (ages 6-15 years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys) underwent {sup 129}Xe MRI, receiving up to three doses of {sup 129}Xe gas prepared by either a commercially available or a homebuilt {sup 129}Xe polarizer. Subject heart rate and SpO{sub 2} were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI. All children tolerated multiple doses of {sup 129}Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO{sub 2} (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO{sub 2} values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following {sup 129}Xe MRI, but all were deemed unrelated to the study. The feasibility, safety and tolerability of {sup 129}Xe MRI has been assessed in a small group of children as young as 6 years. SpO{sub 2} changes were consistent with the expected physiological effects of a short anoxic breath

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.

Projecting future drug expenditures--2009.

Science.gov (United States)

Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Doloresco, Fred; Martin, Patrick K; Blake, Sharon; Matusiak, Linda; Hunkler, Robert J; Schumock, Glen T

2009-02-01

Drug expenditure trends in 2007 and 2008, projected drug expenditures for 2009, and factors likely to influence drug expenditures are discussed. Various factors are likely to influence drug expenditures in 2009, including drugs in development, the diffusion of new drugs, drug safety concerns, generic drugs, Medicare Part D, and changes in the drug supply chain. The increasing availability of important generic drugs and drug safety concerns continue to moderate growth in drug expenditures. The drug supply chain remains dynamic and may influence drug expenditures, particularly in specialized therapeutic areas. Initial data suggest that the Medicare Part D benefit has influenced drug expenditures, but the ultimate impact of the benefit on drug expenditures remains unclear. From 2006 to 2007, total U.S. drug expenditures increased by 4.0%, with total spending rising from $276 billion to $287 billion. Drug expenditures in clinics continue to grow more rapidly than in other settings, with a 9.9% increase from 2006 to 2007. Hospital drug expenditures increased at a moderate rate of only 1.6% from 2006 to 2007; through the first nine months of 2008, hospital drug expenditures increased by only 2.8% compared with the same period in 2007. In 2009, we project a 0-2% increase in drug expenditures in outpatient settings, a 1-3% increase in expenditures for clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

The safety of treatment options available for gout.

Science.gov (United States)

Schlesinger, Naomi

2017-04-01

Gout is the most common inflammatory arthritis in humans. Gout treatment includes rapid initiation of anti-inflammatory medications for acute attacks and chronically treating with urate lowering drugs as well as chronic anti-inflammatory prophylaxis. Areas covered: This review aims to provide an overview and discussion of the safety concerns of current treatment options available for gout. Expert opinion: Gout is a curable disease with appropriate treatment. The advent of new therapies provides encouraging opportunities to improve gout management. However, clinicians should be aware of some of the safety concerns of medications used to treat acute and chronic gout. When prescribing medications for gout one has to be mindful of the presence of comorbidities commonly affecting gout patients that may affect drug safety and efficacy, especially in the elderly and in patients treated with multiple drugs. The benefits of gout drugs, usually, outweigh their safety concerns. Studies are needed in gout patients with chronic kidney disease and/or cardiovascular disease, so that escalation of dosing /combination of anti-inflammatory drugs needed to suppress gouty inflammation as well as escalation of dosing/combination of urate lowering drugs needed to achieve target serum urate level will lead to better understanding of gout treatment safety issues.

48 CFR 923.7001 - Nuclear safety.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Nuclear safety. 923.7001... ENVIRONMENT, CONSERVATION, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Environmental, Energy and Water Efficiency, Renewable Energy Technologies, and Occupational Safety Programs 923.7001 Nuclear safety. The DOE...

A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers

Directory of Open Access Journals (Sweden)

Oyoo George O

2011-03-01

Full Text Available Abstract Background Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers. Methods Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days. Results The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product were reported. The maximum concentration (Cmax was 160-200 nM and after 6 hours, the effective concentration (Ceff was Conclusion Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable Ceff of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.

A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery

International Nuclear Information System (INIS)

Harush-Frenkel, Oshrat; Bivas-Benita, Maytal; Nassar, Taher; Springer, Chaim; Sherman, Yoav; Avital, Avraham; Altschuler, Yoram; Borlak, Jurgen; Benita, Simon

2010-01-01

Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

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

Differentiating drugs by harm potential: the rational versus the feasible.

Science.gov (United States)

Kalant, H

1999-01-01

In an ideal harm reduction model, drugs would be ranked according to their potential to cause harm, with varying implications for control policies and interventions. In such a public health oriented approach, the maximum protection of the public from harm would be balanced with the least possible restriction of freedom. In reality, however, the accuracy and completeness of the necessary information for such a ranking is highly limited. Many other factors not readily incorporated in a rational model, such as values, beliefs, and traditions, also affect drug policy decisions. Thus, rather than relying on acquisition of the necessary knowledge, it may be preferable to focus efforts on developing effective nonlegal measures to reduce drug use and harm. [Translations are provided in the International Abstracts Section of this issue.

Development of NUMO safety case for geological disposal

International Nuclear Information System (INIS)

Suzuki, Satoru; Deguchi, Akira

2016-01-01

NUMO has developed a generic safety ease based on the latest knowledge to show the feasibility and safety of geological disposal in Japan. The NUMO safety case has been developed to provide a basic structure for subsequent safety cases that would be applied to any selected site, emphasising practical approaches and methodology, which will be applicable for the conditions/constraints during an actual siting process. This paper will provide a brief overview of the NUMO safety case. (author)

First-in-Human Ultrasound Molecular Imaging With a VEGFR2-Specific Ultrasound Molecular Contrast Agent (BR55) in Prostate Cancer: A Safety and Feasibility Pilot Study.

Science.gov (United States)

Smeenge, Martijn; Tranquart, François; Mannaerts, Christophe K; de Reijke, Theo M; van de Vijver, Marc J; Laguna, M Pilar; Pochon, Sibylle; de la Rosette, Jean J M C H; Wijkstra, Hessel

2017-07-01

BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-specific ultrasound molecular contrast agent (MCA), has shown promising results in multiple preclinical models regarding cancer imaging. In this first-in-human, phase 0, exploratory study, we investigated the feasibility and safety of the MCA for the detection of prostate cancer (PCa) in men using clinical standard technology. Imaging with the MCA was performed in 24 patients with biopsy-proven PCa scheduled for radical prostatectomy using a clinical ultrasound scanner at low acoustic power. Safety monitoring was done by physical examination, blood pressure and heart rate measurements, electrocardiogram, and blood sampling. As first-in-human study, MCA dosing and imaging protocol were necessarily fine-tuned along the enrollment to improve visualization. Imaging data were correlated with radical prostatectomy histopathology to analyze the detection rate of ultrasound molecular imaging with the MCA. Imaging with MCA doses of 0.03 and 0.05 mL/kg was adequate to obtain contrast enhancement images up to 30 minutes after administration. No serious adverse events or clinically meaningful changes in safety monitoring data were identified during or after administration. BR55 dosing and imaging were fine-tuned in the first 12 patients leading to 12 subsequent patients with an improved MCA dosing and imaging protocol. Twenty-three patients underwent radical prostatectomy. A total of 52 lesions were determined to be malignant by histopathology with 26 (50%) of them seen during BR55 imaging. In the 11 patients that were scanned with the improved protocol and underwent radical prostatectomy, a total of 28 malignant lesions were determined: 19 (68%) were seen during BR55 ultrasound molecular imaging, whereas 9 (32%) were not identified. Ultrasound molecular imaging with BR55 is feasible with clinical standard technology and demonstrated a good safety profile. Detectable levels of the MCA can be reached in patients

Prescription of hazardous drugs during pregnancy.

Science.gov (United States)

Malm, Heli; Martikainen, Jaana; Klaukka, Timo; Neuvonen, Pertti J

2004-01-01

Prescribing drugs to pregnant women requires the balancing of benefits and risks. Only a small proportion of drugs are known to be harmful to the fetus, but for the vast majority of drugs little evidence of fetal safety exists. To determine the prescription pattern of potentially and clearly harmful prescription drugs during pregnancy with reference to drug safety categorisation, and to define the drug groups primarily responsible for multiple drug use during pregnancy. A retrospective, register-based cohort study. Linkage of three nationwide registers in Finland. Data collection included prescription drugs purchased during the preconception period and each trimester in the pregnant cohort, and the corresponding time periods in the non-pregnant controls. The pregnancy safety categorisation was determined for each drug (Anatomic Therapeutic Chemical [ATC] code) by using the Swedish classification of approved medicinal products (Farmaceutiska Specialiteter i Sverige [FASS]) and if not available, the corresponding Australian (Australian Drug Evaluation Committee [ADEC]) or US categorisation (FDA). GROUPS STUDIED: Women applying for maternity support (maternal grants) during the year 1999 (n = 43 470) plus non-pregnant control women matched by age and hospital district (n = 43 470). In the pregnant cohort, 20.4% of women purchased at least one drug classified as potentially harmful during pregnancy, and 3.4% purchased at least one drug classified as clearly harmful. A significant decline occurred in the number of pregnant women purchasing potentially and clearly harmful drugs during the first trimester when compared with the preconception period, and the decline continued from the first to the second trimester. In the pregnant cohort, 107 (0.2%) women purchased at least ten different drugs during pregnancy. The drugs most commonly purchased in this group were topical corticosteroids and nasal preparations. The use of hazardous prescription drugs declines during

Spillover Effects of Drug Safety Warnings on Preventive Health Care Use

DEFF Research Database (Denmark)

Daysal, N. Meltem; Orsini, Chiara

2015-01-01

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

Pharmacist medication reviews to improve safety monitoring in primary care patients.

Science.gov (United States)

Gallimore, Casey E; Sokhal, Dimmy; Zeidler Schreiter, Elizabeth; Margolis, Amanda R

2016-06-01

Patients prescribed psychotropic medications within primary care are at risk of suboptimal monitoring. It is unknown whether pharmacists can improve medication safety through targeted monitoring of at risk populations. Access Community Health Centers implemented a quality improvement pilot project that included pharmacists on an integrated care team to provide medication reviews for patients. Aims were to determine whether inclusion of a pharmacist performing medication reviews within a primary care behavioral health (PCBH) practice is feasible and facilitates safe medication use. Pharmacists performed medication reviews of the electronic health record for patients referred for psychiatry consultation. Reviews were performed 1-3 months following consultation and focused on medications with known suboptimal monitoring rates. Reviews were documented within the EHR and routed to the primary care provider. Primary outcome measures were change in percentage up-to-date on monitoring and AIMS assessment, and at risk of experiencing drug interaction(s) between baseline and 3 months postreview. Secondary outcome was provider opinion of medication reviews collected via electronic survey. Reviews were performed for 144 patients. Three months postreview, percentage up-to-date on recommended monitoring increased 18% (p = .0001), at risk for drug interaction decreased 20% (p improved safety monitoring of psychotropic medications. Results identify key areas for improvement that other clinics considering integration of similar pharmacy services should consider. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Microneedle Patches as Drug and Vaccine Delivery Platform.

Science.gov (United States)

Li, Junwei; Zeng, Mingtao; Shan, Hu; Tong, Chunyi

2017-01-01

Transcutaneous delivery is the ideal method for delivering therapeutic reagents or vaccines into skin. With their promise of self-administration, cost-effective and high efficiency, microneedle patches have been studied intensively as therapeutic and vaccination delivery platform that replaces injection by syringe. This review aims to summarize the recent advancements of microneedle patches in application for drugs and vaccine delivery. We reviewed the most of recently published papers on microneedle patches, summarized their evolution, classification, state-of the-art capabilities and discussed promising application in drugs and vaccine delivery. With the rapid development of nanotechnology, microneedle patches have been improved by switching from undissolving to dissolving microneedles, and their safety has also improved dramatically. As a drug delivery tool, microneedle patches can deliver bioactive molecular of different physical size. Additionally, microneedle patches can be coated or encapsulate with DNA vaccine, subunit antigen, inactivated or live virus vaccine. Combining clinical results with the results of patient interview, microneedle patches are found to be feasible and are predicated to soon be acceptable for the medical service. In this review, we summarized the evolution, current and future application of microneedle patches as delivery vehicle for drugs and vaccines. Compared with traditional delivery tools, microneedle patches have many advantages, such as providing pain-free, non-invasive, convenient route for reagent administration and delivery, with no cold chain required for storage and transportation as well as decreasing sharp medical waste, needle-caused injury and transmission of blood-borne infectious disease in rural area. However, even though there are dramatic progress in preclinical investigation of microneedle patches, further testing will be required for clinical application. Further research should be implemented in multiple fields

Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

Directory of Open Access Journals (Sweden)

Apurv Patel

2016-01-01

Full Text Available The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients.

Drugs to be Discontinued

Data.gov (United States)

U.S. Department of Health & Human Services — Companies are required under Section 506C of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (as amended by the Food and Drug Administration Safety and...

Is clarithromycin a potential treatment for cachexia in people with lung cancer? A feasibility study.

Science.gov (United States)

Awan, Sarah; Crosby, Vincent; Potter, Vanessa; Hennig, Ivo; Baldwin, David; Ndlovu, Mehluli; Paradine, Sharon; Wilcock, Andrew

2017-02-01

Clarithromycin may improve cachexia and survival in non-small cell lung cancer (NSCLC), but adequately controlled data are lacking. This study was undertaken primarily to inform the feasibility and scale of a phase III trial. Eligible consenting patients with stage IV NSCLC and cachexia were to be randomized to receive either clarithromycin 250mg twice daily or placebo for eight weeks. Aspects of trial feasibility recorded included numbers eligible, approached and recruited, together with adherence and completion of treatment and assessments. Over 6 months, none of 125 patients identified fulfilled the entry criteria. The commonest reasons for ineligibility were the use of an excluded concurrent drug (45, 36%), brain metastases (22, 18%), poor performance status (21, 17%) and current chemotherapy (15, 12%). A phase III trial of clarithromycin using these entry criteria is not feasible in this setting. Other macrolides that have a lower risk of a drug-drug interaction may be more practical to pursue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Feasibility study on large pool-type LMFBR

International Nuclear Information System (INIS)

1984-01-01

A feasibility study has been conducted from 1981 FY to 1983 FY, in order to evaluate the feasibility of a large pool-type LMFBR under the Japanese seismic design condition and safety design condition, etc. This study was aimed to establish an original reactor structure concept which meets those design conditions especially required in Japan. In the first year, preceding design concepts had been reviewed and several concepts were originated to be suitable to Japan. For typical two of them being selected by preliminary analysis, test programs were planned. In the second year, more than twenty tests with basic models had been conducted under severe conditions, concurrently analytical approaches were promoted. In the last year, larger model tests were conducted and analytical methods have been verified concerning hydrodynamic effects on structure vibration, thermo-hydraulic behaviours in reactor plena and so on. Finally the reactor structure concepts for a large pool-type LMFBR have been acknowledged to be feasible in Japan. (author)

Deep Borehole Disposal Safety Analysis.

Energy Technology Data Exchange (ETDEWEB)

Freeze, Geoffrey A. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Stein, Emily [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Price, Laura L. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); MacKinnon, Robert J. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Tillman, Jack Bruce [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

2016-10-01

This report presents a preliminary safety analysis for the deep borehole disposal (DBD) concept, using a safety case framework. A safety case is an integrated collection of qualitative and quantitative arguments, evidence, and analyses that substantiate the safety, and the level of confidence in the safety, of a geologic repository. This safety case framework for DBD follows the outline of the elements of a safety case, and identifies the types of information that will be required to satisfy these elements. At this very preliminary phase of development, the DBD safety case focuses on the generic feasibility of the DBD concept. It is based on potential system designs, waste forms, engineering, and geologic conditions; however, no specific site or regulatory framework exists. It will progress to a site-specific safety case as the DBD concept advances into a site-specific phase, progressing through consent-based site selection and site investigation and characterization.

Feasibility of a seabed radionuclide transfer experiment (MISTE)

International Nuclear Information System (INIS)

Andrew, G.; Bourke, P.J.; Lever, D.A.; Taylor, B.L.

1984-12-01

This report presents an assessment of the feasibility at moderate cost, of in-situ measurement of radio-nuclide diffusion through soft sedimentary sea-bed. Its objective is to test and provide data for models of this phenomenon which may be used to assess the safety of burial of radioactive waste under the sea. (author)

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

Orphan drugs: trends and issues in drug development.

Science.gov (United States)

Rana, Proteesh; Chawla, Shalini

2018-04-12

Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.

Towards predictive cardiovascular safety : a systems pharmacology approach

NARCIS (Netherlands)

Snelder, Nelleke

2014-01-01

Cardiovascular safety issues related to changes in blood pressure, arise frequently in drug development. In the thesis “Towards predictive cardiovascular safety – a systems pharmacology approach”, a system-specific model is described to quantify drug effects on the interrelationship between mean

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

Directory of Open Access Journals (Sweden)

Giovanni Sotgiu

2015-03-01

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

Key issues for passive safety

International Nuclear Information System (INIS)

Hayns, M.R.

1996-01-01

The paper represents a summary of the introductory presentation made at this Advisory Group Meeting on the Technical Feasibility and Reliability of Passive Safety Systems. It was intended as an overview of our views on what are the key issues and what are the technical problems which might dominate any future developments of passive safety systems. It is, therefore, not a ''review paper'' as such and only record the highlights. (author)

Key issues for passive safety

Energy Technology Data Exchange (ETDEWEB)

Hayns, M R [AEA Technology, Harwell, Didcot (United Kingdom). European Institutions; Hicken, E F [Forschungszentrum Juelich GmbH (Germany)

1996-12-01

The paper represents a summary of the introductory presentation made at this Advisory Group Meeting on the Technical Feasibility and Reliability of Passive Safety Systems. It was intended as an overview of our views on what are the key issues and what are the technical problems which might dominate any future developments of passive safety systems. It is, therefore, not a ``review paper`` as such and only record the highlights. (author).

The Feasibility and Safety of Surgery in Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Study

Directory of Open Access Journals (Sweden)

Alexandra W. Elias

2017-06-01

Full Text Available Immune checkpoint inhibitors (ICI are revolutionizing care for cancer patients. The list of malignancies for which the Food and Drug Administration is granting approval is rapidly increasing. Furthermore, there is a concomitant increase in clinical trials incorporating ICI. However, the safety of ICI in patients undergoing surgery remains unclear. Herein, we assessed the safety of ICI in the perioperative setting at a single center. We conducted a retrospective review of patients who underwent planned surgery while receiving ICI in the perioperative setting from 2012 to 2016. We collected 30-day postoperative morbidity and mortality utilizing the Clavien–Dindo classification system. We identified 17 patients who received perioperative ICI in 22 operations. Patients were diagnosed with melanoma (n = 14, renal cell carcinoma (n = 2, and urothelial carcinoma (n = 1. Therapies included pembrolizumab (n = 10, ipilimumab (n = 5, atezolizumab (n = 5, and ipilimumab/nivolumab (n = 2. Procedures included cutaneous/subcutaneous resection (n = 6, lymph node resection (n = 5, small bowel resection (n = 5, abdominal wall resection (n = 3, other abdominal surgery (n = 3, orthopedic surgery (n = 1, hepatic resection (n = 1, and neurosurgery (n = 2. There were no Grade III–IV Clavien–Dindo complications. There was one death secondary to ventricular fibrillation in the setting of coronary artery disease. ICI appear safe in the perioperative setting, involving multiple different types of surgery, and likely do not need to be stopped in the perioperative setting. Further studies are warranted to confirm these findings.

Study protocol for the FITR Heart Study: Feasibility, safety, adherence, and efficacy of high intensity interval training in a hospital-initiated rehabilitation program for coronary heart disease.

Science.gov (United States)

Taylor, Jenna; Keating, Shelley E; Leveritt, Michael D; Holland, David J; Gomersall, Sjaan R; Coombes, Jeff S

2017-12-01

For decades, moderate intensity continuous training (MICT) has been the cornerstone of exercise prescription for cardiac rehabilitation (CR). High intensity interval training (HIIT) is now recognized in CR exercise guidelines as an appropriate and efficient modality for improving cardiorespiratory fitness, a strong predictor of mortality. However, the clinical application of HIIT in a real world CR setting, in terms of feasibility, safety, and long-term adherence, needs further investigation to address ongoing reservations. Furthermore, studies using objective measures of exercise intensity (such as heart rate; HR) have produced variable outcomes. Therefore we propose investigating the use of subjective measures (such as rating of perceived exertion (RPE)) for prescribing exercise intensity. One hundred adults with coronary artery disease (CAD) attending a hospital-initiated CR program will be randomized to 1) HIIT: 4 × 4 min high intensity intervals at 15-18 RPE interspersed with 3-min active recovery periods or 2) MICT: usual care exercise including 40 min continuous exercise at a moderate intensity corresponding to 11-13 RPE. Primary outcome is change in exercise capacity (peak VO 2 ) following 4 weeks of exercise training. Secondary outcome measures are: feasibility, safety, exercise adherence, body composition, vascular function, inflammatory markers, intrahepatic lipid, energy intake, and dietary behavior over 12-months; and visceral adipose tissue (VAT) following 12 weeks of exercise training. This study aims to address the ongoing concerns regarding the practicality and safety of HIIT in CR programs. We anticipate study findings will lead to the development of a standardized protocol to facilitate CR programs to incorporate HIIT as a standard exercise option for appropriate patients.

Feasibility and Safety of Local Treatment with Recombinant Human Tissue Factor Pathway Inhibitor in a Rat Model of Streptococcus pneumoniae Pneumonia.

Directory of Open Access Journals (Sweden)

Florry E van den Boogaard

Full Text Available Pulmonary coagulopathy is intrinsic to pulmonary injury including pneumonia. Anticoagulant strategies could benefit patients with pneumonia, but systemic administration of anticoagulant agents may lead to suboptimal local levels and may cause systemic hemorrhage. We hypothesized nebulization to provide a safer and more effective route for local administration of anticoagulants. Therefore, we aimed to examine feasibility and safety of nebulization of recombinant human tissue factor pathway inhibitor (rh-TFPI in a well-established rat model of Streptococcus (S. pneumoniae pneumonia. Thirty minutes before and every 6 hours after intratracheal instillation of S. pneumonia causing pneumonia, rats were subjected to local treatment with rh-TFPI or placebo, and sacrificed after 42 hours. Pneumonia was associated with local as well as systemic activation of coagulation. Nebulization of rh-TFPI resulted in high levels of rh-TFPI in bronchoalveolar lavage fluid, which was accompanied by an attenuation of pulmonary coagulation. Systemic rh-TFPI levels remained undetectable, and systemic TFPI activity and systemic coagulation were not affected. Histopathology revealed no bleeding in the lungs. We conclude that nebulization of rh-TFPI seems feasible and safe; local anticoagulant treatment with rh-TFPI attenuates pulmonary coagulation, while not affecting systemic coagulation in a rat model of S. pneumoniae pneumonia.

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.

Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis

Science.gov (United States)

Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; de Morales, José M. García Ruiz; Herreras, Jose M.; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

2017-01-01

Abstract Background: To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Methods: Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). Results: We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Conclusions: Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients. PMID:29049193

78 FR 38053 - Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug...

Science.gov (United States)

2013-06-25

... marketing for reasons other than safety or effectiveness. FDA will not begin procedures to withdraw approval... Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug...-610 were not withdrawn from sale for reasons of safety or effectiveness. This determination means that...

Safety, acceptability, and feasibility of a single-visit approach to cervical-cancer prevention in rural Thailand: a demonstration project.

Science.gov (United States)

Gaffikin, L; Blumenthal, P D; Emerson, M; Limpaphayom, K

2003-03-08

To increase screening and treatment coverage, innovative approaches to cervical-cancer prevention are being investigated in rural Thailand. We assessed the value of a single-visit approach combining visual inspection of the cervix with acetic acid wash (VIA) and cryotherapy. 12 trained nurses provided services in mobile (village health centre-based) and static (hospital-based) teams in four districts of Roi-et Province, Thailand. Over 7 months, 5999 women were tested by VIA. If they tested positive, after counselling about the benefits, potential risks, and probable side-effects they were offered cryotherapy. Data measuring safety, acceptability, feasibility, and effort to implement the programme were gathered. The VIA test-positive rate was 13.3% (798/5999), and 98.5% (609/618) of those eligible accepted immediate treatment. Overall, 756 women received cryotherapy, 629 (83.2%) of whom returned for their first follow-up visit. No major complications were recorded, and 33 (4.4%) of those treated returned for a perceived problem. Only 17 (2.2%) of the treated women needed clinical management other than reassurance about side-effects. Both VIA and cryotherapy were highly acceptable to the patients (over 95% expressed satisfaction with their experience). At their 1-year visit, the squamocolumnar junction was visible to the nurses, and the VIA test-negative rate was 94.3%. A single-visit approach with VIA and cryotherapy seems to be safe, acceptable, and feasible in rural Thailand, and is a potentially efficient method of cervical-cancer prevention in such settings.

Investigative safety science as a competitive advantage for Pharma.

Science.gov (United States)

Moggs, Jonathan; Moulin, Pierre; Pognan, Francois; Brees, Dominique; Leonard, Michele; Busch, Steve; Cordier, Andre; Heard, David J; Kammüller, Michael; Merz, Michael; Bouchard, Page; Chibout, Salah-Dine

2012-09-01

Following a US National Academy of Sciences report in 2007 entitled "Toxicity Testing of the 21st Century: a Vision and a Strategy," significant advances within translational drug safety sciences promise to revolutionize drug discovery and development. The purpose of this review is to outline why investigative safety science is a competitive advantage for the pharmaceutical industry. The article discusses the essential goals for modern investigative toxicologists including: cross-species target biology; molecular pathways of toxicity; and development of predictive tools, models and biomarkers that allow discovery researchers and clinicians to anticipate safety problems and plan ways to address them, earlier than ever before. Furthermore, the article emphasizes the importance of investigating unanticipated clinical safety signals through a combination of mechanistic preclinical studies and/or molecular characterization of clinical samples from affected organs. The traditional boundaries between pharma industry teams focusing on safety/efficacy and preclinical/clinical development are rapidly disappearing in favor of translational safety science-centric organizations with a vision of bringing more effective medicines forward safely and quickly. Comparative biology and mechanistic toxicology approaches facilitate: i) identifying translational safety biomarkers; ii) identifying new drug targets/indications; and iii) mitigating off-target toxicities. These value-adding safety science contributions will change traditional toxicologists from side-effect identifiers to drug development enablers.

Safety design philosophy of gas turbine high temperature reactor (GTHTR300)

International Nuclear Information System (INIS)

Katanishi, Shoji; Kunitomi, Kazuhiko

2003-01-01

Japan Atomic Energy Research Institute has been developing design studies of the Gas Turbine High Temperature Reactor (GTHTR300). The original safety design philosophy has also been discussed and fixed for the GTHTR300. One of the unique feature of the safety philosophy of the GTHTR300 is that a depressurization accident is postulated as a design basis accident in order to show the high level of safety characteristics, though its probability of occurrence is much lower than the probability range of design basis accident. Another feature of safety design is to adopt a double confinement that is one of the original concepts for the GTHTR300. By using a double confinement, a feasibility of safety design without containment vessel was clarified even in case of a depressurization accident. This article describes the safety design philosophy and some results of preliminary evaluations which were conducted in order to clarify the feasibility of original safety design of the GTHTR300. (author)

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

Directory of Open Access Journals (Sweden)

Kylie Thaler

2009-11-01

Full Text Available Kylie Thaler1, Divya V Chandiramani2, Richard A Hansen2, Gerald Gartlehner11Department for Evidence-based Medicine and Clinical Epidemiology, Danube University Krems, Krems, Austria; 2UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAObjective: 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

Biocompatible Polymer Nanoformulation To Improve the Release and Safety of a Drug Mimic Molecule Detectable via ICP-MS.

Science.gov (United States)

Ferrari, Raffaele; Talamini, Laura; Violatto, Martina Bruna; Giangregorio, Paola; Sponchioni, Mattia; Morbidelli, Massimo; Salmona, Mario; Bigini, Paolo; Moscatelli, Davide

2017-01-03

Fluorescent poly(ε-caprolactone)-based nanoparticles (NPs) have been synthesized and successfully loaded with a titanium organometallic compound as a mimic of a water-insoluble drug. The nature of this nanovector enabled us to combine the quantification of the metal in tissues after systemic administration in healthy immunocompetent mice by inductively coupled plasma mass spectroscopy (ICP-MS) followed by the visualization of NPs in organ sections by confocal microscopy. This innovative method of nanodrug screening has enabled us to elucidate the crucial parameters of their kinetics. The organometallic compound is a good mimic of most anticancer drugs, and this approach is an interesting starting point to design the relevance of a broad range of nanoformulations in terms of safety and targeted delivery of the cargoes.

Feasibility, tolerability and safety of pediatric hyperpolarized "1"2"9Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis

International Nuclear Information System (INIS)

Walkup, Laura L.; Watters, Erin; Ruppert, Kai; Thomen, Robert P.; Woods, Jason C.; Akinyi, Teckla G.; Cleveland, Zackary I.; Clancy, John P.

2016-01-01

Hyperpolarized "1"2"9Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. To assess the feasibility, safety and tolerability of hyperpolarized "1"2"9Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. Seventeen healthy control subjects (ages 6-15 years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys) underwent "1"2"9Xe MRI, receiving up to three doses of "1"2"9Xe gas prepared by either a commercially available or a homebuilt "1"2"9Xe polarizer. Subject heart rate and SpO_2 were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI. All children tolerated multiple doses of "1"2"9Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO_2 (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO_2 values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following "1"2"9Xe MRI, but all were deemed unrelated to the study. The feasibility, safety and tolerability of "1"2"9Xe MRI has been assessed in a small group of children as young as 6 years. SpO_2 changes were consistent with the expected physiological effects of a short anoxic breath-hold, and other mild side effects were

Transdermal drug delivery: feasibility for treatment of superficial bone stress fractures.

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Aghazadeh-Habashi, Ali; Yang, Yang; Tang, Kathy; Lőbenberg, Raimar; Doschak, Michael R

2015-12-01

Transdermal drug delivery offers the promise of effective drug therapy at selective sites of pathology whilst reducing systemic exposure to the pharmaceutical agents in off-target organs and tissues. However, that strategy is often limited to cells comprising superficial tissues of the body (rarely to deeper bony structures) and mostly indicated with small hydrophobic pharmacological agents, such as steroid hormones and anti-inflammatory gels to skin, muscle, and joints. Nonetheless, advances in transdermal liposomal formulation have rendered the ability to readily incorporate pharmacologically active hydrophilic drug molecules and small peptide biologics into transdermal dosage forms to impart the effective delivery of those bioactive agents across the skin barrier to underlying superficial tissue structures including bone, often enhanced by some form of electrical, chemical, and mechanical facilitation. In the following review, we evaluate transdermal drug delivery systems, with a particular focus on delivering therapeutic agents to treat superficial bone pain, notably stress fractures. We further introduce and discuss several small peptide hormones active in bone (such as calcitonins and parathyroid hormone) that have shown potential for transdermal delivery, often under the added augmentation of transdermal drug delivery systems that employ lipo/hydrophilicity, electric charge, and/or microprojection facilitation across the skin barrier.

Potential benefit of dolutegravir once daily: efficacy and safety

Directory of Open Access Journals (Sweden)

Fantauzzi A

2013-02-01

Full Text Available Alessandra Fantauzzi,1 Ombretta Turriziani,2 Ivano Mezzaroma11Department of Clinical Medicine, 2Department of Molecular Medicine, Sapienza, University of Rome, Rome, ItalyAbstract: The viral integrase enzyme has recently emerged as a primary alternative target to block HIV-1 replication, and integrase inhibitors are considered a pivotal new class of antiretroviral drugs. Dolutegravir is an investigational next-generation integrase inhibitor showing some novel and intriguing characteristics, ie, it has a favorable pharmacokinetic profile with a prolonged intracellular half-life, rendering feasible once-daily dosing without the need for ritonavir boosting and without regard to meals. Moreover, dolutegravir is primarily metabolized via uridine diphosphate glucuronosyltranferase 1A1, with a minor component of the cytochrome P450 3A4 isoform, thereby limiting drug–drug interactions. Furthermore, its metabolic profile enables coadministration with most of the other available antiretroviral agents without dose adjustment. Recent findings also demonstrate that dolutegravir has significant activity against HIV-1 isolates with resistance mutations associated with raltegravir and/or elvitegravir. The attributes of once-daily administration and the potential to treat integrase inhibitor-resistant viruses make dolutegravir an interesting and promising investigational drug. In this review, the main concerns about the efficacy and safety of dolutegravir as well as its resistance profile are explored by analysis of currently available data from preclinical and clinical studies.Keywords: antiretroviral drugs, HIV-1 integrase, integrase inhibitors, dolutegravir, once daily

Drug safety in pregnancy: utopia or achievable prospect? Risk information, risk research and advocacy in Teratology Information Services.

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Schaefer, Christof

2011-03-01

Even though from preclinical testing to drug risk labeling, the situation with drugs in pregnancy has improved substantially since the thalidomide scandal, there is still an increasing need to provide healthcare professionals and patients with updated individualized risk information for clinical decision making. For the majority of drugs, clinical experience is still insufficient with respect to their safety in pregnancy. There is often uncertainty in how to interpret the available scientific data. Based on 20 years of experience with Teratology Information Services (TIS) cooperating in the European Network of Teratology Information Services (ENTIS) methods of risk interpretation, follow-up of exposed pregnancies through the consultation process and their evaluation is discussed. Vitamin K antagonists, isotretinoin and angiotensin (AT) II-receptor-antagonists are presented as examples of misinterpretation of drug risks and subjects of research based on observational clinical data recorded in TIS. As many TIS are poorly funded, advocacy is necessary by establishing contacts with decision makers in health politics and administration, informing them of the high return in terms of health outcomes and cost savings provided by TIS as reference institutions in clinical teratology. © 2011 The Author. Congenital Anomalies © 2011 Japanese Teratology Society.

Best practice strategies to safeguard drug prescribing and drug administration: an anthology of expert views and opinions.

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Seidling, Hanna M; Stützle, Marion; Hoppe-Tichy, Torsten; Allenet, Benoît; Bedouch, Pierrick; Bonnabry, Pascal; Coleman, Jamie J; Fernandez-Llimos, Fernando; Lovis, Christian; Rei, Maria Jose; Störzinger, Dominic; Taylor, Lenka A; Pontefract, Sarah K; van den Bemt, Patricia M L A; van der Sijs, Heleen; Haefeli, Walter E

2016-04-01

While evidence on implementation of medication safety strategies is increasing, reasons for selecting and relinquishing distinct strategies and details on implementation are typically not shared in published literature. We aimed to collect and structure expert information resulting from implementing medication safety strategies to provide advice for decision-makers. Medication safety experts with clinical expertise from thirteen hospitals throughout twelve European and North American countries shared their experience in workshop meetings, on-site-visits and remote structured interviews. We performed an expert-based, in-depth assessment of implementation of best-practice strategies to improve drug prescribing and drug administration. Workflow, variability and recommended medication safety strategies in drug prescribing and drug administration processes. According to the experts, institutions chose strategies that targeted process steps known to be particularly error-prone in the respective setting. Often, the selection was channeled by local constraints such as the e-health equipment and critically modulated by national context factors. In our study, the experts favored electronic prescribing with clinical decision support and medication reconciliation as most promising interventions. They agreed that self-assessment and introduction of medication safety boards were crucial to satisfy the setting-specific differences and foster successful implementation. While general evidence for implementation of strategies to improve medication safety exists, successful selection and adaptation of a distinct strategy requires a thorough knowledge of the institute-specific constraints and an ongoing monitoring and adjustment of the implemented measures.

Drug-Drug/Drug-Excipient Compatibility Studies on Curcumin using Non-Thermal Methods

Directory of Open Access Journals (Sweden)

Moorthi Chidambaram

2014-05-01

Full Text Available Purpose: Curcumin is a hydrophobic polyphenol isolated from dried rhizome of turmeric. Clinical usefulness of curcumin in the treatment of cancer is limited due to poor aqueous solubility, hydrolytic degradation, metabolism, and poor oral bioavailability. To overcome these limitations, we proposed to fabricate curcumin-piperine, curcumin-quercetin and curcumin-silibinin loaded polymeric nanoformulation. However, unfavourable combinations of drug-drug and drug-excipient may result in interaction and rises the safety concern. Hence, the present study was aimed to assess the interaction of curcumin with excipients used in nanoformulations. Methods: Isothermal stress testing method was used to assess the compatibility of drug-drug/drug-excipient. Results: The combination of curcumin-piperine, curcumin-quercetin, curcumin-silibinin and the combination of other excipients with curcumin, piperine, quercetin and silibinin have not shown any significant physical and chemical instability. Conclusion: The study concludes that the curcumin, piperine, quercetin and silibinin is compatible with each other and with other excipients.

French PWR safety philosophy

International Nuclear Information System (INIS)

Conte, M.

1986-05-01

Increasing knowledge and lessons learned from starting and operating experience of French nuclear power plants, completed by the experience learned from the operation of foreign reactors, has contributed to the improvement of French PWR design and safety philosophy. Based on a deterministic approach, the French safety analysis was progressively completed by a probabilistic approach, each of them having possibilities and limits. As a consequence of the global risk objective set in 1977 for nuclear reactors, safety analysis was extended to the evaluation of events more complex than the conventional ones, and later to the evaluation of the feasibility of the offsite emergency plans in case of severe accidents

Predicting transporter-mediated drug interactions: Commentary on: "Pharmacokinetic evaluation of a drug transporter cocktail consisting of digoxin, furosemide, metformin and rosuvastatin" and "Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A".

Science.gov (United States)

Zhang, L; Sparreboom, A

2017-04-01

Transporters, expressed in various tissues, govern the absorption, distribution, metabolism, and excretion of drugs, and consequently their inherent safety and efficacy profiles. Drugs may interact with a transporter as a substrate and/or an inhibitor. Understanding transporter-mediated drug-drug interactions (DDIs), in addition to enzyme-mediated DDIs, is an integral part of risk assessment in drug development and regulatory review because the concomitant use of more than one medication in patients is common. © 2016 ASCPT.

21 CFR 610.11 - General safety.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false General safety. 610.11 Section 610.11 Food and... GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.11 General safety. A general safety test... for administration to humans. The general safety test is required in addition to other specific tests...

Measuring the impact of pharmacoepidemiologic research using altmetrics: A case study of a CNODES drug-safety article.

Science.gov (United States)

Gamble, J M; Traynor, Robyn L; Gruzd, Anatoliy; Mai, Philip; Dormuth, Colin R; Sketris, Ingrid S

2018-03-24

To provide an overview of altmetrics, including their potential benefits and limitations, how they may be obtained, and their role in assessing pharmacoepidemiologic research impact. Our review was informed by compiling relevant literature identified through searching multiple health research databases (PubMed, Embase, and CIHNAHL) and grey literature sources (websites, blogs, and reports). We demonstrate how pharmacoepidemiologists, in particular, may use altmetrics to understand scholarly impact and knowledge translation by providing a case study of a drug-safety study conducted by the Canadian Network of Observational Drug Effect Studies. A common approach to measuring research impact is the use of citation-based metrics, such as an article's citation count or a journal's impact factor. "Alternative" metrics, or altmetrics, are increasingly supported as a complementary measure of research uptake in the age of social media. Altmetrics are nontraditional indicators that capture a diverse set of traceable, online research-related artifacts including peer-reviewed publications and other research outputs (software, datasets, blogs, videos, posters, policy documents, presentations, social media posts, wiki entries, etc). Compared with traditional citation-based metrics, altmetrics take a more holistic view of research impact, attempting to capture the activity and engagement of both scholarly and nonscholarly communities. Despite the limited theoretical underpinnings, possible commercial influence, potential for gaming and manipulation, and numerous data quality-related issues, altmetrics are promising as a supplement to more traditional citation-based metrics because they can ingest and process a larger set of data points related to the flow and reach of scholarly communication from an expanded pool of stakeholders. Unlike citation-based metrics, altmetrics are not inherently rooted in the research publication process, which includes peer review; it is unclear to

Independent safety organization

International Nuclear Information System (INIS)

Kato, W.Y.; Weinstock, E.V.; Carew, J.F.; Cerbone, R.J.; Guppy, J.G.; Hall, R.E.; Taylor, J.H.

1985-01-01

Brookhaven National Laboratory has conducted a study on the need and feasibility of an independent organization to investigate significant safety events for the Office for Analysis and Evaluation of Operational Data, USNRC. The study consists of three parts: the need for an independent organization to investigate significant safety events, alternative organizations to conduct investigations, and legislative requirements. The determination of need was investigated by reviewing current NRC investigation practices, comparing aviation and nuclear industry practices, and interviewing a spectrum of representatives from the nuclear industry, the regulatory agency, and the public sector. The advantages and disadvantages of alternative independent organizations were studied, namely, an Office of Nuclear Safety headed by a director reporting to the Executive Director for Operations (EDO) of NRC; an Office of Nuclear Safety headed by a director reporting to the NRC Commissioners; a multi-member NTSB-type Nuclear Safety Board independent of the NRC. The costs associated with operating a Nuclear Safety Board were also included in the study. The legislative requirements, both new authority and changes to the existing NRC legislative authority, were studied. 134 references

Impact of ITER liquid metal design options on safety level and licensing - Sweden

International Nuclear Information System (INIS)

Harfors, C.; Devell, L.; Johansson, Kjell; Lundell, B.; Rolandsson, S.

1993-01-01

The safety level and licensability of five design options for ITER coolant, breeding material and structural material are assessed, with emphasis on some specified accident scenarios. The safety level is assessed in terms of barrier requirements and the feasibility to construct and qualify such a barrier. The licensability in Sweden of each design option is assessed based on the indicated safety level and on a judgement of the technical feasibility to construct and qualify the ITER tokamak itself, based on the selected design option. 20 refs

Systematic review and meta-analysis of feasibility, safety, and efficacy of a novel procedure: associating liver partition and portal vein ligation for staged hepatectomy.

Science.gov (United States)

Schadde, Erik; Schnitzbauer, Andreas A; Tschuor, Christoph; Raptis, Dimitri A; Bechstein, Wolf O; Clavien, Pierre-Alain

2015-09-01

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel strategy to resect liver tumors despite the small size of the liver remnant. It is an hepatectomy in two stages, with PVL and parenchymal transection during the first stage, which induces rapid growth of the remnant liver exceeding any other technique. Despite high postoperative morbidity and mortality in most reports, the technique was adopted by a number of surgeons. This systematic review explores current data regarding the feasibility, safety, and oncologic efficacy of ALPPS; the search strategy has been published online. A meta-analysis of hypertrophy, feasibility (ALPPS stage 2 performed), mortality, complications, and R0 (complete) resection was performed. A literature search revealed a total of 13 publications that met the search criteria, reporting data from 295 patients. Evidence levels were low, with the highest Oxford evidence level being 2c. The most common indication was colorectal liver metastasis in 203 patients. Hypertrophy in the meta-analysis was 84 %, feasibility (ALPPS stage 2 performed) 97 % (CI 94-99 %), 90-day mortality 11 % (CI 8-16 %), and complications grade IIIa or higher occured in 44 % (CI 38-50 %) of patients. A standardized reporting format for complications is lacking despite the widespread use of the Clavien-Dindo classification. Oncological outcome is not well-documented. The most common topics in the selected studies published were technical feasibility and indications for the procedures. Publication bias due to case-series and single-center reports is common. A systematic exploration of this novel operation with a rigid methodology, such as registry analyses and a randomized controlled trial, is highly advised.

How participation in a Drug Company-Managed Clinical Trial Influenced GPs’ Guideline Adherence and Drug Preference: A Register-Based study

DEFF Research Database (Denmark)

Andersen, Morten; Kragstrup, Jakob; Søndergaard, Jens

2005-01-01

21 st International Con ference on Pharmacoepidemiology and Therapeytic Risk Management, Nashville, Tennessee, USA, Abstract 187 i Pharmacoepidemiology and drug safety 2004;14:494......21 st International Con ference on Pharmacoepidemiology and Therapeytic Risk Management, Nashville, Tennessee, USA, Abstract 187 i Pharmacoepidemiology and drug safety 2004;14:494...

Feasibility of a Trial on Improvisational Music Therapy for Children with Autism Spectrum Disorder.

Science.gov (United States)

Geretsegger, Monika; Holck, Ulla; Bieleninik, Łucja; Gold, Christian

2016-01-01

To conduct generalizable, rigorously designed, adequately powered trials investigating music therapy and other complex interventions, it is essential that study procedures are feasible and acceptable for participants. To date, only limited evidence on feasibility of trial designs and strategies to facilitate study implementation is available in the music therapy literature. Using data from a subsample of a multi-center RCT on improvisational music therapy (IMT) for autism spectrum disorder (ASD), this study aims to evaluate feasibility of study procedures, evaluate safety, document concomitant treatment, and report consistency of individuals' trends over time in chosen outcome measures. Children with ASD aged between 4 years, 0 months, and 6 years, 11 months, were randomly assigned to one of three conditions: one (low intensity) vs. three weekly IMT sessions (high intensity) for five months vs. standard care. Feasibility was evaluated by examining recruitment, implementation of study conditions, assessment procedures, blinding, and retention; we also evaluated safety, concomitant treatment, and consistency of changes in standardized scales completed by blinded assessors and parents before and 5 months after randomization. Within this subsample (n = 15), recruitment rates, session attendance in the high-intensity condition, and consistency between outcome measures were lower than expected. Session attendance in the low-intensity and control conditions, treatment fidelity, measurement completion, blinding, retention, and safety met a priori thresholds for feasibility. By discussing strategies to improve recruitment and to minimize potential burden on study participants, referrers, and researchers, this study helps build knowledge about designing and implementing trials successfully. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Studying the Safety Impact of Autonomous Vehicles Using Simulation-Based Surrogate Safety Measures

OpenAIRE

Morando, Mark Mario; Tian, Qingyun; Truong, Long T.; Vu, Hai L.

2018-01-01

Autonomous vehicle (AV) technology has advanced rapidly in recent years with some automated features already available in vehicles on the market. AVs are expected to reduce traffic crashes as the majority of crashes are related to driver errors, fatigue, alcohol, or drugs. However, very little research has been conducted to estimate the safety impact of AVs. This paper aims to investigate the safety impacts of AVs using a simulation-based surrogate safety measure approach. To this end, safety...

Feasibility and safety of electrochemotherapy (ECT) in the pancreas: a pre-clinical investigation

International Nuclear Information System (INIS)

Girelli, Roberto; Prejanò, Simona; Cataldo, Ivana; Corbo, Vincenzo; Martini, Lucia; Scarpa, Aldo; Claudio, Bassi

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease generally refractory to standard chemotherapeutic agents; therefore improvements in anticancer therapies are mandatory. A major determinant of therapeutic resistance in PDAC is the poor drug delivery to neoplastic cells, mainly due to an extensive fibrotic reaction. Electroporation can be used in vivo to increase cancer cells’ local uptake of chemotherapeutics (electrochemotherapy, ECT), thus leading to an enhanced tumour response rate. In the present study, we evaluated the in vivo effects of reversible electroporation in normal pancreas in a rabbit experimental model. We also tested the effect of electroporation on pancreatic cancer cell lines in order to evaluate their increased sensitivity to chemotherapeutic agents. The application in vivo of the European Standard Operating Procedure of Electrochemotherapy (ESOPE) pulse protocol (1000 V/cm, 8 pulses, 100 μs, 5 KHz) was tested on the pancreas of normal New Zealand White Rabbits and short and long-term toxicity were assessed. PANC1 and MiaPaCa2 cell lines were tested for in vitro electrochemotherapy experiments with and without electroporation. Levels of cell permeabilization were determined by flow cytometry, whereas cell viability and drug (cisplatin and bleomycin) sensitivity of pulsed cells were measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium (MTS) assay. In healthy rabbits, neither systemic nor local toxic effects due to the electroporation procedure were observed, demonstrating the safety of the optimized electric parameters in the treatment of the pancreas in vivo. In parallel, we established an optimized protocol for ECT in vitro that determined an enhanced anti-cancer effect of bleomycin and cisplatin with respect to treatment without electroporation. Our data suggest that electroporation is a safe procedure in the treatment of PDAC because it does not affect normal pancreatic parenchyma

A Public-Private Consortium Advances Cardiac Safety Evaluation: Achievements of the HESI Cardiac Safety Technical Committee

Science.gov (United States)

The evaluation of cardiovascular side-effects is a critical element in the development of all new drugs and chemicals. Cardiac safety issues have been and continue to be a major cause of attrition and withdrawal due to Adverse Drug Reactions (ADRs) in pharmaceutical drug developm...

Pilot In Command: A Feasibility Assessment of Autonomous Flight Management Operations

Science.gov (United States)

Wing, David J.; Ballin, Mark G.; Krishnamurthy, Karthik

2004-01-01

Several years of NASA research have produced the air traffic management operational concept of Autonomous Flight Management with high potential for operational feasibility, significant system and user benefits, and safety. Among the chief potential benefits are demand-adaptive or scalable capacity, user flexibility and autonomy that may finally enable truly successful business strategies, and compatibility with current-day operations such that the implementation rate can be driven from within the user community. A concept summary of Autonomous Flight Management is provided, including a description of how these operations would integrate in shared airspace with existing ground-controlled flight operations. The mechanisms enabling the primary benefits are discussed, and key findings of a feasibility assessment of airborne autonomous operations are summarized. Concept characteristics that impact safety are presented, and the potential for initially implementing Autonomous Flight Management is discussed.

Improving safety-related knowledge, attitude and practices of nurses handling cytotoxic anticancer drug: pharmacists' experience in a general hospital, Malaysia.

Science.gov (United States)

Keat, Chan Huan; Sooaid, Nor Suhada; Yun, Cheng Yi; Sriraman, Malathi

2013-01-01

An increasing trend of cytotoxic drug use, mainly in cancer treatment, has increased the occupational exposure among the nurses. This study aimed to assess the change of nurses' safety-related knowledge as well as attitude levels and subsequently to assess the change of cytotoxic drug handling practices in wards after a series of pharmacist-based interventions. This prospective interventional study with a before and after design requested a single group of 96 nurses in 15 wards actively providing chemotherapy to answer a self-administered questionnaire. A performance checklist was then used to determine the compliance of all these wards with the recommended safety measures. The first and second assessments took 2 months respectively with a 9-month intervention period. Pharmacist-based interventions included a series of technical, educational and administrative support measures consisting of the initiation of closed-system cytotoxic drug reconstitution (CDR) services, courses, training workshops and guideline updates. The mean age of nurses was 32.2∓6.19 years. Most of them were female (93.8%) and married (72.9%). The mean knowledge score of nurses was significantly increased from 45.5∓10.52 to 73.4∓8.88 out of 100 (p<0.001) at the end of the second assessment. Overall, the mean practice score among the wards was improved from 7.6∓5.51 to 15.3∓2.55 out of 20 (p<0.001). The pharmacist-based interventions improved the knowledge, attitude and safe practices of nurses in cytotoxic drug handling. Further assessment may help to confirm the sustainability of the improved practices.

Drug development in neuropsychopharmacology.

Science.gov (United States)

Fritze, Jürgen

2008-03-01

Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

A study of software safety analysis system for safety-critical software

International Nuclear Information System (INIS)

Chang, H. S.; Shin, H. K.; Chang, Y. W.; Jung, J. C.; Kim, J. H.; Han, H. H.; Son, H. S.

2004-01-01

The core factors and requirements for the safety-critical software traced and the methodology adopted in each stage of software life cycle are presented. In concept phase, Failure Modes and Effects Analysis (FMEA) for the system has been performed. The feasibility evaluation of selected safety parameter was performed and Preliminary Hazards Analysis list was prepared using HAZOP(Hazard and Operability) technique. And the check list for management control has been produced via walk-through technique. Based on the evaluation of the check list, activities to be performed in requirement phase have been determined. In the design phase, hazard analysis has been performed to check the safety capability of the system with regard to safety software algorithm using Fault Tree Analysis (FTA). In the test phase, the test items based on FMEA have been checked for fitness guided by an accident scenario. The pressurizer low pressure trip algorithm has been selected to apply FTA method to software safety analysis as a sample. By applying CASE tool, the requirements traceability of safety critical system has been enhanced during all of software life cycle phases