Sample records for post approval study

  1. 77 FR 50514 - Post-Approval Studies 2012 Workshop: Design, Methodology, and Role in Evidence Appraisal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-21

    ...] Post-Approval Studies 2012 Workshop: Design, Methodology, and Role in Evidence Appraisal Throughout the... Administration (FDA) is announcing the following public workshop entitled ``Post-Approval Studies 2012 Workshop: Design, Methodology, and Role in Evidence Appraisal Throughout the Total Product Life Cycle.'' The topics...

  2. Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey.

    PubMed

    Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

    2015-01-01

    In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA's pre-market approval (PMA) pathway. We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives.

  3. Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey

    PubMed Central

    Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

    2015-01-01

    Background In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA’s pre-market approval (PMA) pathway. Methods and results We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Conclusion Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives. PMID:26060416

  4. 30 CFR 15.10 - Post-approval product audit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Post-approval product audit. 15.10 Section 15... General Provisions § 15.10 Post-approval product audit. (a) Approved explosives and sheathed explosive... observe any tests conducted during this audit. (c) An approved explosive or sheathed explosive unit shall...

  5. 23 CFR 1340.11 - Post-approval alterations to survey design.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Post-approval alterations to survey design. 1340.11... Post-approval alterations to survey design. After NHTSA approval of a survey design, States shall submit for NHTSA approval any proposed alteration to their survey design, including, but not limited to...

  6. 23 CFR 1340.11 - Post-approval alterations to survey design.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Post-approval alterations to survey design. 1340.11... Post-approval alterations to survey design. After NHTSA approval of a survey design, States shall submit for NHTSA approval any proposed alteration to their survey design, including, but not limited to...

  7. 23 CFR 1340.11 - Post-approval alterations to survey design.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Post-approval alterations to survey design. 1340.11... Post-approval alterations to survey design. After NHTSA approval of a survey design, States shall submit for NHTSA approval any proposed alteration to their survey design, including, but not limited to...

  8. 30 CFR 7.8 - Post-approval product audit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Post-approval product audit. 7.8 Section 7.8... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY General § 7.8 Post-approval product audit...-holder may observe any tests conducted during this audit. (c) An approved product shall be subject to...

  9. 30 CFR 250.282 - Do I have to conduct post-approval monitoring?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Do I have to conduct post-approval monitoring... OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Plans and Information Post-Approval Requirements for the Ep, Dpp, and Docd § 250.282 Do I have to conduct post-approval monitoring...

  10. 30 CFR 14.10 - Post-approval product audit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Post-approval product audit. 14.10 Section 14... General Provisions § 14.10 Post-approval product audit. (a) Approved conveyor belts will be subject to... applicant and other persons agreed upon by MSHA and the applicant may be present during audit tests and...

  11. 30 CFR 14.10 - Post-approval product audit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Post-approval product audit. 14.10 Section 14... General Provisions § 14.10 Post-approval product audit. (a) Approved conveyor belts will be subject to... applicant and other persons agreed upon by MSHA and the applicant may be present during audit tests and...

  12. 30 CFR 14.10 - Post-approval product audit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Post-approval product audit. 14.10 Section 14... General Provisions § 14.10 Post-approval product audit. (a) Approved conveyor belts will be subject to... applicant and other persons agreed upon by MSHA and the applicant may be present during audit tests and...

  13. 30 CFR 250.282 - Do I have to conduct post-approval monitoring?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false Do I have to conduct post-approval monitoring... ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL... conduct post-approval monitoring? After approving your EP, DPP, or DOCD, the Regional Supervisor may...

  14. 30 CFR 71.301 - Respirable dust control plan; approval by District Manager and posting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... District Manager and posting. 71.301 Section 71.301 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... plan; approval by District Manager and posting. (a) The District Manager will approve respirable dust control plans on a mine-by-mine basis. When approving respirable dust control plans, the District Manager...

  15. 42 CFR 84.310 - Post-approval testing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Respirators § 84.310 Post-approval testing. (a) NIOSH will periodically test the capacity and performance of units of approved CCERs. (b) NIOSH may test units that are new and/or units that have been deployed in... 42 Public Health 1 2014-10-01 2014-10-01 false Post-approval testing. 84.310 Section 84.310 Public...

  16. 42 CFR 84.310 - Post-approval testing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Respirators § 84.310 Post-approval testing. (a) NIOSH will periodically test the capacity and performance of units of approved CCERs. (b) NIOSH may test units that are new and/or units that have been deployed in... 42 Public Health 1 2013-10-01 2013-10-01 false Post-approval testing. 84.310 Section 84.310 Public...

  17. 42 CFR 84.310 - Post-approval testing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Respirators § 84.310 Post-approval testing. (a) NIOSH will periodically test the capacity and performance of units of approved CCERs. (b) NIOSH may test units that are new and/or units that have been deployed in... 42 Public Health 1 2012-10-01 2012-10-01 false Post-approval testing. 84.310 Section 84.310 Public...

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

    PubMed

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

    2017-06-01

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

  19. Post-trial period surveillance for randomised controlled cardiovascular studies: submitted protocols, consent forms and the role of the ethics board.

    PubMed

    Zia, Mohammad I; Heslegrave, Ronald; Newton, Gary E

    2011-12-01

    The post-trial period is the time period after the end of study drug administration. It is unclear whether post-trial arrangements for patient surveillance are routinely included in study protocols and consents, and whether research ethics boards (REB) consider the post-trial period. The objective was to determine whether trial protocols and consent forms reviewed by the REB describe procedures for post-trial period surveillance. An observational study of protocols of randomised trials of chronic therapies for cardiac conditions, approved by the REB of two academic institutions affiliated with the University of Toronto in Canada (University Health Network and Mount Sinai Hospital) from 1995 to 2007. Plans for patient surveillance in the post-trial period described in the protocol or in the consent form before and after REB approval were recorded. 42 studies were identified including 18 heart failure and 15 coronary artery disease trials. Only four studies planned a clinical visit after trial termination, and an additional three planned a telephone contact after trial completion. Five trials submitted consent forms to the REB with a discussion of the post-trial period. The majority of protocols and consent forms did not discuss plans for post-trial period surveillance. The post-trial period and the REB approval process could be improved by systematic follow-up being described in the protocol and consent form. The small number of trial protocols evaluated in the study may impair the degree to which the results can be generalised.

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

    PubMed

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

    2013-11-01

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

  1. Post-marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross-sectional study.

    PubMed

    Zeitoun, Jean-David; Baron, Gabriel; Vivot, Alexandre; Atal, Ignacio; Downing, Nicholas S; Ross, Joseph S; Ravaud, Philippe

    2018-01-15

    Post-marketing research in oncology has rarely been described. We aimed to characterize post-marketing trials for a consistent set of anticancer agents over a long period. We performed a cross-sectional analysis of post-marketing trials registered at ClinicalTrials.gov through September 2014 for novel anticancer agents approved by both the US Food and Drug Administration and the European Medicines Agency between 2005 and 2010. All relevant post-marketing trials were classified according to indication, primary outcome, starting date, sponsors, and planned enrollment. Supplemental indications were retrieved from regulatory documents and publication rate was assessed by two different methods. Ten novel anticancer agents were eligible: five were indicated for hematologic malignancies and the remaining five for solid cancers (three for kidney cancer). We identified 2,345 post-marketing trials; 1,362 (58.1%) targeted an indication other than the originally approved one. We observed extreme variations among drugs in both number of post-marketing trials (range 8-530) and overall population to be enrolled per trial (1-8,381). Post-marketing trials assessed almost all types of cancers, the three most frequently studied cancers being leukemia, kidney cancer and myeloma. In all, 6.6% of post-marketing trials had a clinical endpoint as a primary outcome, and 35.9% and 54.1% had a safety or surrogate endpoint, respectively, as a primary outcome. Nine drugs obtained approval for supplemental indications. The publication rate at 10 years was 12.3 to 26.1% depending on the analysis method. In conclusion, we found that post-marketing research in oncology is highly heterogeneous and the publication rate of launched trials is low. © 2017 UICC.

  2. 38 CFR 21.5250 - Courses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under 38 U.S.C. Chapter 32 Courses... paragraph (c)(1))—Course and licensing and certification test approval; jurisdiction and notices. (2... 21.4267—Approval of independent study. (17) Section 21.4268—Approval of licensing and certification...

  3. 38 CFR 21.5250 - Courses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under 38 U.S.C. Chapter 32 Courses... paragraph (c)(1))—Course and licensing and certification test approval; jurisdiction and notices. (2... 21.4267—Approval of independent study. (17) Section 21.4268—Approval of licensing and certification...

  4. 38 CFR 21.5250 - Courses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under 38 U.S.C. Chapter 32 Courses... paragraph (c)(1))—Course and licensing and certification test approval; jurisdiction and notices. (2... 21.4267—Approval of independent study. (17) Section 21.4268—Approval of licensing and certification...

  5. 38 CFR 21.5250 - Courses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under 38 U.S.C. Chapter 32 Courses... paragraph (c)(1))—Course and licensing and certification test approval; jurisdiction and notices. (2... 21.4267—Approval of independent study. (17) Section 21.4268—Approval of licensing and certification...

  6. 38 CFR 21.5250 - Courses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under 38 U.S.C. Chapter 32 Courses... paragraph (c)(1))—Course and licensing and certification test approval; jurisdiction and notices. (2... 21.4267—Approval of independent study. (17) Section 21.4268—Approval of licensing and certification...

  7. Post-approval Studies for Rare Disease Treatments and Orphan Drugs.

    PubMed

    Maier, William C; Christensen, Ronald A; Anderson, Patricia

    2017-01-01

    Drug development involves a multi-stage process of drug discovery, animal studies and human clinical trials to assess the safety and efficacy of new medications. Rare disease drug development involves a much smaller number of affected patients, a predominance of pediatric patients and more complicated disease presentation. Post-approval studies are designed to address several limitations associated with the rare disease clinical trials.National and international regulatory agencies in the US and Europe have adopted similar approaches to requirements post-approval data for rare diseases and orphan drug indications. The US FDA published guidance in 2011 and the European Medicines Agency in 2015.Post-approval studies for rare diseases include observational studies, pragmatic trials and randomized controlled studies. Observational studies include both original data collection studies and the use of secondary data (retrospective studies). Original data collection can address limitations of retrospective studies resulting from incomplete information in secondary data sources. Disease registries focus on detail about a broad range of patients with a rare disease while product-related registries focus on specific health care outcomes associated with a single product and may incorporate a comparator of an alternative therapy or therapies.Rare disease patients can be difficult to find and enroll in a registry using conventional physician based driven recruitment. The study process also needs to recognize changes in the patient's disease and lifestyle and adapt both the study design and methods over time. Many rare diseases have strong patient advocacy groups that can in aid the design and execution of rare disease registries.

  8. Comparison of the new Japanese legislation for expedited approval of regenerative medicine products with the existing systems in the USA and European Union.

    PubMed

    Jokura, Yoji; Yano, Kazuo; Yamato, Masayuki

    2018-02-01

    Legislation for expedited-approval pathways and programmes for drugs, biologics or medical devices has been enacted for rapid commercialization of innovative products in the United States of America (USA) and the European Union (EU). However, less innovative products are increasingly benefitting from these expedited-approval pathways, and obligations to collect and report post-marketing data on approved products are being bypassed frequently. The Japanese government recently enacted legislation for a new conditional and time-limited approval pathway dedicated to regenerative medicine products. The current study examines this new legislation and compares it with existing US and EU regulatory frameworks, with a particular focus on how it addresses the limitations of existing systems. Regulations, guidance documents and approval information were gathered from the websites of the respective authorities in the USA, the EU and Japan, and the systems were categorized through qualitative analysis. The pathways and programmes from each region were categorized into four groups, based on the requirement of pre- or post-marketing clinical data. Expedited-approval pathways in the USA and the EU provide similar qualification criteria, such as severity of target disease; however, such criteria are not specified for the new pathway in Japan. Only the Japanese pathway stipulates a time limitation on exceptional approval, requiring post-marketing study for conditional and time-limited products. Continuous improvement is necessary to solve previously addressed issues within the expedited-approval pathways and programmes and to ensure that innovative medical products are rigourously screened, but also readily available to patients in need. The time limitation of conditional approval could be a potential solution to some of these problems. Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd. Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-01

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

  11. 24 CFR 570.461 - Post-preliminary approval requirements; lead-based paint.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... requirements; lead-based paint. 570.461 Section 570.461 Housing and Urban Development Regulations Relating to... GRANTS Urban Development Action Grants § 570.461 Post-preliminary approval requirements; lead-based paint. The recipient may receive preliminary approval prior to the accomplishment of lead-based paint...

  12. 24 CFR 570.461 - Post-preliminary approval requirements; lead-based paint.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... requirements; lead-based paint. 570.461 Section 570.461 Housing and Urban Development Regulations Relating to... GRANTS Urban Development Action Grants § 570.461 Post-preliminary approval requirements; lead-based paint. The recipient may receive preliminary approval prior to the accomplishment of lead-based paint...

  13. 24 CFR 570.461 - Post-preliminary approval requirements; lead-based paint.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... requirements; lead-based paint. 570.461 Section 570.461 Housing and Urban Development Regulations Relating to... GRANTS Urban Development Action Grants § 570.461 Post-preliminary approval requirements; lead-based paint. The recipient may receive preliminary approval prior to the accomplishment of lead-based paint...

  14. 24 CFR 570.461 - Post-preliminary approval requirements; lead-based paint.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... requirements; lead-based paint. 570.461 Section 570.461 Housing and Urban Development Regulations Relating to... GRANTS Urban Development Action Grants § 570.461 Post-preliminary approval requirements; lead-based paint. The recipient may receive preliminary approval prior to the accomplishment of lead-based paint...

  15. 24 CFR 570.461 - Post-preliminary approval requirements; lead-based paint.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... requirements; lead-based paint. 570.461 Section 570.461 Housing and Urban Development Regulations Relating to... GRANTS Urban Development Action Grants § 570.461 Post-preliminary approval requirements; lead-based paint. The recipient may receive preliminary approval prior to the accomplishment of lead-based paint...

  16. What "likes" have got to do with it: Exposure to peers' alcohol-related posts and perceptions of injunctive drinking norms.

    PubMed

    Boyle, Sarah C; Smith, Daniel J; Earle, Andrew M; LaBrie, Joseph W

    2018-01-01

    Examine 1) whether observed social reinforcements (i.e., "likes") received by peers' alcohol-related social media posts are related to first-year college students' perceptions of peer approval for risky drinking behaviors; and 2) whether associations are moderated by students' alcohol use status. First-year university students (N = 296) completed an online survey in September, 2014. Participants reported their own alcohol use, friends' alcohol use, perceptions of the typical student's approval for risky drinking, and ranked 10 types of social media posts in terms of the relative numbers of "likes" received when posted by peers. Observed social reinforcement (i.e., "likes") for peers' alcohol-related posts predicted perceptions of peer approval for risky drinking behaviors among non-drinking students, but not drinking students. For first-year college students who have not yet initiated drinking, observing peers' alcohol-related posts to receive abundant "likes" may increase perceptions of peer approval for risky drinking.

  17. 30 CFR 550.282 - Do I have to conduct post-approval monitoring?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 2 2013-07-01 2013-07-01 false Do I have to conduct post-approval monitoring... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Plans and Information... monitoring? After approving your EP, DPP, or DOCD, the Regional Supervisor may direct you to conduct...

  18. 30 CFR 550.282 - Do I have to conduct post-approval monitoring?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 2 2014-07-01 2014-07-01 false Do I have to conduct post-approval monitoring... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Plans and Information... monitoring? After approving your EP, DPP, or DOCD, the Regional Supervisor may direct you to conduct...

  19. 30 CFR 550.282 - Do I have to conduct post-approval monitoring?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false Do I have to conduct post-approval monitoring... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Plans and Information... monitoring? After approving your EP, DPP, or DOCD, the Regional Supervisor may direct you to conduct...

  20. How Does Medical Device Regulation Perform in the United States and the European Union? A Systematic Review

    PubMed Central

    Kramer, Daniel B.; Xu, Shuai; Kesselheim, Aaron S.

    2012-01-01

    Background Policymakers and regulators in the United States (US) and the European Union (EU) are weighing reforms to their medical device approval and post-market surveillance systems. Data may be available that identify strengths and weakness of the approaches to medical device regulation in these settings. Methods and Findings We performed a systematic review to find empirical studies evaluating medical device regulation in the US or EU. We searched Medline using two nested categories that included medical devices and glossary terms attributable to the US Food and Drug Administration and the EU, following PRISMA guidelines for systematic reviews. We supplemented this search with a review of the US Government Accountability Office online database for reports on US Food and Drug Administration device regulation, consultations with local experts in the field, manual reference mining of selected articles, and Google searches using the same key terms used in the Medline search. We found studies of premarket evaluation and timing (n = 9), studies of device recalls (n = 8), and surveys of device manufacturers (n = 3). These studies provide evidence of quality problems in pre-market submissions in the US, provide conflicting views of device safety based largely on recall data, and relay perceptions of some industry leaders from self-surveys. Conclusions Few studies have quantitatively assessed medical device regulation in either the US or EU. Existing studies of US and EU device approval and post-market evaluation performance suggest that policy reforms are necessary for both systems, including improving classification of devices in the US and promoting transparency and post-market oversight in the EU. Assessment of regulatory performance in both settings is limited by lack of data on post-approval safety outcomes. Changes to these device approval and post-marketing systems must be accompanied by ongoing research to ensure that there is better assessment of what works in either setting. Please see later in the article for the Editors' Summary. PMID:22912563

  1. 13 CFR 302.18 - Post-approval requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Section 302.18 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE... Federal cost principles (collectively, “Post-Approval Requirements”). A Recipient's failure to comply with... Assistance award, or other adverse consequences to the Recipient. (b) Part 307 (Economic Adjustment...

  2. Utilizing national and international registries to enhance pre-market medical device regulatory evaluation.

    PubMed

    Yue, Lilly Q; Campbell, Gregory; Lu, Nelson; Xu, Yunling; Zuckerman, Bram

    2016-01-01

    Regulatory decisions are made based on the assessment of risk and benefit of medical devices at the time of pre-market approval and subsequently, when post-market risk-benefit balance needs reevaluation. Such assessments depend on scientific evidence obtained from pre-market studies, post-approval studies, post-market surveillance studies, patient perspective information, as well as other real world data such as national and international registries. Such registries provide real world evidence and are playing a more and more important role in enhancing the safety and effectiveness evaluation of medical devices. While these registries provide large quantities of data reflecting real world practice and can potentially reduce the cost of clinical trials, challenges arise concerning (1) data quality adequate for regulatory decision-making, (2) bias introduced at every stage and aspect of study, (3) scientific validity of study designs, and (4) reliability and interpretability of study results. This article will discuss related statistical and regulatory challenges and opportunities with examples encountered in medical device regulatory reviews.

  3. 13 CFR 307.6 - Economic Adjustment Assistance post-approval requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Economic Adjustment Assistance post-approval requirements. 307.6 Section 307.6 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE ECONOMIC ADJUSTMENT ASSISTANCE INVESTMENTS General § 307.6 Economic...

  4. 13 CFR 307.6 - Economic Adjustment Assistance post-approval requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Economic Adjustment Assistance post-approval requirements. 307.6 Section 307.6 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE ECONOMIC ADJUSTMENT ASSISTANCE INVESTMENTS General § 307.6 Economic...

  5. 13 CFR 307.6 - Economic Adjustment Assistance post-approval requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Economic Adjustment Assistance post-approval requirements. 307.6 Section 307.6 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE ECONOMIC ADJUSTMENT ASSISTANCE INVESTMENTS General § 307.6 Economic...

  6. 13 CFR 307.6 - Economic Adjustment Assistance post-approval requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Economic Adjustment Assistance post-approval requirements. 307.6 Section 307.6 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE ECONOMIC ADJUSTMENT ASSISTANCE INVESTMENTS General § 307.6 Economic...

  7. 13 CFR 307.6 - Economic Adjustment Assistance post-approval requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Economic Adjustment Assistance post-approval requirements. 307.6 Section 307.6 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE ECONOMIC ADJUSTMENT ASSISTANCE INVESTMENTS General § 307.6 Economic...

  8. Mitroflow DL Post Approval Study- North America

    ClinicalTrials.gov

    2017-12-04

    Aortic Stenosis; Aortic Regurgitation; Aortic Valve Insufficiency; Heart Valve Diseases; Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Heart Diseases; Pathological Conditions, Anatomical

  9. FDA Approvals - Cancer Currents Blog

    Cancer.gov

    Blog posts on cancer drugs and devices approved by the Food and Drug Administration—including summaries of the evidence to support the approvals and what they mean for patients—from NCI Cancer Currents.

  10. 76 FR 12213 - Agency Information Collection Activities; Extension of an Approved Information Collection Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-04

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

  11. 15 CFR 921.12 - Post site selection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... NOAA approval of a proposed site, the state may submit a request for funds to develop the draft... and biological characteristics of the site approved by NOAA necessary for providing EIS information to NOAA. The state's request for these post site selection funds must be accompanied by the information...

  12. 15 CFR 921.12 - Post site selection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... NOAA approval of a proposed site, the state may submit a request for funds to develop the draft... and biological characteristics of the site approved by NOAA necessary for providing EIS information to NOAA. The state's request for these post site selection funds must be accompanied by the information...

  13. 15 CFR 921.12 - Post site selection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... NOAA approval of a proposed site, the state may submit a request for funds to develop the draft... and biological characteristics of the site approved by NOAA necessary for providing EIS information to NOAA. The state's request for these post site selection funds must be accompanied by the information...

  14. 15 CFR 921.12 - Post site selection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... NOAA approval of a proposed site, the state may submit a request for funds to develop the draft... and biological characteristics of the site approved by NOAA necessary for providing EIS information to NOAA. The state's request for these post site selection funds must be accompanied by the information...

  15. 15 CFR 921.12 - Post site selection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... NOAA approval of a proposed site, the state may submit a request for funds to develop the draft... and biological characteristics of the site approved by NOAA necessary for providing EIS information to NOAA. The state's request for these post site selection funds must be accompanied by the information...

  16. Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain

    DTIC Science & Technology

    2013-10-01

    revised documents August Non-perishable Supplies ordered & received DUKE IRB approved study via expedited review September Submitted all revisions...2013 February March April May June July August September October HRPO request for revised, addtn’l docs VA approved protocol...A few candidate gene polymorphisms have been linked to pain susceptibility, including catechol-O-methyltranferase ( COMT ). This gene modulates

  17. 77 FR 22387 - Pipeline Safety: Information Collection Activities, Revision to Gas Transmission and Gathering...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... post- construction hydrostatic test of at least 1.25 times the maximum allowable operating pressure... a post-construction hydrostatic pressure test of at least 125% of the MAOP, and total miles of... approved under OMB control number 2137- 0522 and the hazardous liquid accident report is approved under OMB...

  18. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  19. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  20. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  1. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  2. 30 CFR 7.91 - Post-approval product audit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Diesel Engines Intended for Use in... except for cause, the approval holder shall make a diesel engine available for audit at no cost to MSHA. ...

  3. Summary of the EMA Joint Regulators/Industry QbD workshop (London, UK; 28-29 January 2014).

    PubMed

    Cook, Graham; France, Georges; Holte, Øyvind; Lorenti, Giampiero; Tainsh, David

    2016-01-01

    This paper summarizes the discussions and insights gained from the key themes that emerged during the Quality by Design (QbD) Workshop held at the European Medicines Agency (EMA) offices in London, UK, on 28-29 January 2014. Industry and regulators shared practical experiences from six case studies (five approved small molecule products and one phase 3 biotechnological product) based on QbD submissions by five companies (AstraZeneca, GlaxoSmithKline, Novartis, NovoNordisk, and Pfizer).The case studies covered a range of different development, regulatory submission, and post-approval aspects of QbD and were developed through confidential discussions between the company representatives and regulators. Key themes that emerged from the workshop discussions were: 1. presentation of information in submissions (development story and the presentation of information in marketing authorization applications; risk assessment and criticality); 2. development aspects (design space; use of models; control strategy); and 3. post-approval aspects (lifecycle management; dossier-quality system interactions; handling of deviations). Many aspects of QbD for biotechnological products are similar to small molecules, but there are some important differences highlighted in this paper.The final section of the paper discusses some proposals for future developments to address the issues that were identified. This paper summarizes the discussions and insights gained from the key themes that emerged during the Quality by Design (QbD) Workshop held at the European Medicines Agency offices in London, UK, on 28-29 January 2014. Industry and regulators shared practical experiences from six case studies (five approved small-molecule products and one phase 3 biotechnological product) based on QbD submissions by five companies (AstraZeneca, GlaxoSmithKline, Novartis, NovoNordisk, and Pfizer).The case studies covered a range of different development, regulatory submission, and post-approval aspects of QbD and were developed through confidential discussions between the company representatives and regulators. Key themes that emerged from the workshop discussions were: 1. presentation of information in submissions (development story and the presentation of information in marketing authorization applications; risk assessment and criticality); 2. development aspects (design space; use of models; control strategy); and 3. post-approval aspects (lifecycle management; dossier-quality system interactions; handling of deviations). Many aspects of QbD for biotechnological products are similar to small molecules, but there are some important differences highlighted in this paper.The final section of the paper discusses some proposals for future developments to address the issues that were identified. © PDA, Inc. 2016.

  4. 30 CFR 250.282 - Do I have to conduct post-approval monitoring?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false Do I have to conduct post-approval monitoring... OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Plans and... monitoring? The Regional Supervisor may direct you to conduct monitoring programs. You must retain copies of...

  5. 30 CFR 250.282 - Do I have to conduct post-approval monitoring?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 2 2013-07-01 2013-07-01 false Do I have to conduct post-approval monitoring... OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Plans and... monitoring? The Regional Supervisor may direct you to conduct monitoring programs. You must retain copies of...

  6. 30 CFR 250.282 - Do I have to conduct post-approval monitoring?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 2 2014-07-01 2014-07-01 false Do I have to conduct post-approval monitoring... OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Plans and... monitoring? The Regional Supervisor may direct you to conduct monitoring programs. You must retain copies of...

  7. Immunotherapy Combination Approved for Advanced Kidney Cancer

    Cancer.gov

    FDA has approved the combination of the immunotherapy drugs nivolumab (Opdivo) and ipilimumab (Yervoy) as an initial treatment for some patients with advanced kidney cancer. The approval is expected to immediately affect patient care, as this Cancer Currents post explains.

  8. 29 CFR 1952.10 - Requirements for approval of State posters.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Requirements for approval of State posters. 1952.10 Section... and Conditions § 1952.10 Requirements for approval of State posters. (a)(1) In order to inform..., States with approved plans shall develop and require employers to post a State poster meeting the...

  9. 29 CFR 1952.10 - Requirements for approval of State posters.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Requirements for approval of State posters. 1952.10 Section... and Conditions § 1952.10 Requirements for approval of State posters. (a)(1) In order to inform..., States with approved plans shall develop and require employers to post a State poster meeting the...

  10. 29 CFR 1952.10 - Requirements for approval of State posters.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Requirements for approval of State posters. 1952.10 Section... and Conditions § 1952.10 Requirements for approval of State posters. (a)(1) In order to inform..., States with approved plans shall develop and require employers to post a State poster meeting the...

  11. 29 CFR 1952.10 - Requirements for approval of State posters.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Requirements for approval of State posters. 1952.10 Section... and Conditions § 1952.10 Requirements for approval of State posters. (a)(1) In order to inform..., States with approved plans shall develop and require employers to post a State poster meeting the...

  12. 29 CFR 1952.10 - Requirements for approval of State posters.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Requirements for approval of State posters. 1952.10 Section... and Conditions § 1952.10 Requirements for approval of State posters. (a)(1) In order to inform..., States with approved plans shall develop and require employers to post a State poster meeting the...

  13. 34 CFR 686.21 - Calculation of a grant.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., a student's participation in a program of study abroad if it is approved for credit by the home... TEACH Grants for undergraduate and post-baccalaureate study may not exceed $16,000. (ii) The aggregate...

  14. 34 CFR 686.21 - Calculation of a grant.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., a student's participation in a program of study abroad if it is approved for credit by the home... TEACH Grants for undergraduate and post-baccalaureate study may not exceed $16,000. (ii) The aggregate...

  15. 34 CFR 686.21 - Calculation of a grant.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., a student's participation in a program of study abroad if it is approved for credit by the home... TEACH Grants for undergraduate and post-baccalaureate study may not exceed $16,000. (ii) The aggregate...

  16. Impact of a Step Therapy for Guanfacine Extended-Release on Medication Utilization and Health Care Expenditures Among Individuals Receiving Treatment for ADHD.

    PubMed

    Suehs, Brandon T; Sikirica, Vanja; Mudumby, Pallavi; Dufour, Robert; Patel, Nick C

    2015-09-01

    While step therapy (ST) policies are generally effective at reducing cost through the managed utilization of targeted medications, the clinical implications of ST policies are not clear and may vary across therapeutic areas. Guanfacine extended-release (GXR) is approved by the FDA for the treatment of attention-deficit/hyperactivity disorder (ADHD) as both monotherapy and adjunctive to stimulant treatment. At the introduction of GXR to the market, Humana implemented an ST policy on GXR requiring the documentation of previous treatment, intolerance, or contraindication to generic clonidine or guanfacine. To examine the impact of a GXR ST coverage determination (i.e., approved vs. denied) on medication utilization and health care costs among members of a commercial health plan with an ST policy for GXR.  This study was a retrospective cohort study of administrative claims data. Humana commercial members prescribed GXR who had an ST coverage determination review were identified. All members included in this analysis were required to be aged 6-17 years, have a diagnosis of ADHD or be receiving stimulant medication, have an ST coverage determination (index event) between September 1, 2009, and May 30, 2012, and have 6 months of pre- and post-index continuous enrollment. Members were assigned to either the approved or denied group based on the outcome of the ST coverage determination. Medical and pharmacy claims data were used to measure baseline demographic and clinical characteristics and to measure medication utilization and health care costs. Outcomes assessed during follow-up included ADHD medication use, proportion of days covered (PDC) with any ADHD medication treatment, time to first observed post-index ADHD treatment, and all-cause and mental health (MH)-related health care costs. Administrative costs associated with the coverage determination process were also estimated. Bivariate and multivariable adjusted analyses were conducted to compare medication utilization and health care costs between the approved and denied groups. A total of 642 members were included in the analysis (denied group n = 395 [61.5%], approved group n = 247 [38.5%]). The approved and denied groups were similar in terms of baseline demographics, provider characteristics, and baseline MH diagnoses, with the exception of anxiety disorders being more prevalent in the approved group compared with the denied group (18.2% vs. 10.6%, P = 0.006). A denied GXR coverage determination was associated with a greater percentage of members receiving no ADHD treatment post-index (13.9% vs. 3.2%, P  less than  0.001), greater mean [SD] number of days between index and first observed post-index ADHD medication claim (44.5 [59.6] vs. 17.6 [33.4], P  less than  0.001), and lower mean [SD] PDC with any ADHD medication post-index (0.59 [0.33] vs. 0.75 [0.26], P  less than  0.001). These findings remained statistically significant in multivariable regression models. Unadjusted pre-index median total health care costs and MH-related costs were greater among the approved group compared with the denied group (total health care: $1,582 vs. $1,465, P = 0.033; MH-related: $993 vs. $981, P = 0.020). Likewise, post-index median total health care and MH-related costs were greater among the approved group compared with the denied group (total: $2,056 vs. $1,420, P  less than  0.001; MH-related: $1,543 vs. $946, P  less than  0.001). After adjustment for potentially confounding covariates including pre-index costs, there were no statistically significant differences between the approved and denied groups in all-cause total health care (P = 0.393) or MH-related health care costs (P = 0.054).  The current study found that GXR coverage denial was associated with lower rate of ADHD medication utilization, greater delay in receiving ADHD medication, and lower PDC with ADHD medication. There were no differences observed between the approved and denied group in terms of all-cause total health care or MH-related total health care costs after controlling for potentially confounding variables. Prior to implementation in the ADHD therapeutic area and others, payers should consider the potentially unintended consequences of ST policies, including delay in treatment and undertreatment.

  17. Tisagenlecleucel (Kymriah) Approved to Treat Some Lymphomas

    Cancer.gov

    FDA has approved the CAR T-cell therapy tisagenlecleucel for adults with diffuse large B-cell lymphoma that is relapsed or refractory. Learn more about this new approval and how it may affect patients in this NCI Cancer Currents blog post.

  18. Vocations: The Link between Post-Compulsory Education and the Labour Market. What the Research Says For... Qualification & Approval Bodies

    ERIC Educational Resources Information Center

    Wheelahan, Leesa; Buchanan, John; Yu, Serena

    2015-01-01

    This summary pulls together the relevant key findings for qualification and approval bodies from the research program "Vocations: The Link between Post-Compulsory Education and the Labour Market." The program was comprised of three different strands: (1) pathways from VET in Schools, (2) pathways within and between vocational education…

  19. Abemaciclib gets new approval for breast cancer

    Cancer.gov

    DA has approved the CDK4/6 inhibitor abemaciclib (Verzenio) as a first-line treatment in some women with advanced or metastatic breast cancer. Under the approval, it must be used in combination with an aromatase inhibitor, as this Cancer Currents blog post explains.

  20. A decade of marketing approval of gene and cell-based therapies in the United States, European Union and Japan: An evaluation of regulatory decision-making.

    PubMed

    Coppens, D G M; de Wilde, S; Guchelaar, H J; De Bruin, M L; Leufkens, H G M; Meij, P; Hoekman, J

    2018-05-02

    There is a widely held expectation of clinical advance with the development of gene and cell-based therapies (GCTs). Yet, establishing benefits and risks is highly uncertain. We examine differences in decision-making for GCT approval between jurisdictions by comparing regulatory assessment procedures in the United States (US), European Union (EU) and Japan. A cohort of 18 assessment procedures was analyzed by comparing product characteristics, evidentiary and non-evidentiary factors considered for approval and post-marketing risk management. Product characteristics are very heterogeneous and only three products are marketed in multiple jurisdictions. Almost half of all approved GCTs received an orphan designation. Overall, confirmatory evidence or indications of clinical benefit were evident in US and EU applications, whereas in Japan approval was solely granted based on non-confirmatory evidence. Due to scientific uncertainties and safety risks, substantial post-marketing risk management activities were requested in the EU and Japan. EU and Japanese authorities often took unmet medical needs into consideration in decision-making for approval. These observations underline the effects of implemented legislation in these two jurisdictions that facilitate an adaptive approach to licensing. In the US, the recent assessments of two chimeric antigen receptor-T cell (CAR-T) products are suggestive of a trend toward a more permissive approach for GCT approval under recent reforms, in contrast to a more binary decision-making approach for previous approvals. It indicates that all three regulatory agencies are currently willing to take risks by approving GCTs with scientific uncertainties and safety risks, urging them to pay accurate attention to post-marketing risk management. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  1. 29 CFR 37.64 - What procedures must the Director follow when CRC has completed a post-approval compliance review?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true What procedures must the Director follow when CRC has completed a post-approval compliance review? 37.64 Section 37.64 Labor Office of the Secretary of Labor... (WIA) Compliance Procedures § 37.64 What procedures must the Director follow when CRC has completed a...

  2. Design and analysis of post-marketing research.

    PubMed

    Zhou, Xiao-Hua Andrew; Yang, Wei

    2013-07-01

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

  3. Normative feedback for parents of college students: piloting a parent based intervention to correct misperceptions of students' alcohol use and other parents' approval of drinking.

    PubMed

    Labrie, Joseph W; Napper, Lucy E; Hummer, Justin F

    2014-01-01

    Multi-component parent-based interventions (PBIs) provide a promising avenue for targeting alcohol use and related consequences in college students. Parents of college-aged children can have a significant influence on their children's alcohol use decisions. However, parents tend to underestimate their own child's alcohol use and overestimate other similar parents' approval of student drinking. These misperceptions could have important implications for parents' own attitudes and alcohol-related communication with their student. Targeting these misperceptions through normative feedback could help promote greater and more in-depth alcohol-related communication. The present study examines the potential efficacy of web-based alcohol-related normative feedback for parents of college students. A sample of 144 parents of college students received web-based normative feedback about students' alcohol use and approval, as well as other same-college parents' alcohol approval. Parents completed measures of perceived student alcohol use, student alcohol approval, other-parent alcohol approval, and intentions to discuss alcohol use both pre- and post-normative feedback. Post-feedback, parents reported stronger intentions to talk to their student about alcohol, were less confident in their knowledge of their students' alcohol use, and believed that their student drank in greater quantity and more frequently than pre-feedback. Parents also perceived other parents to be less approving of alcohol use after viewing normative feedback. These findings provide preliminary support for the use of web-based normative feedback for parents of college students. Given these promising results, further research developing and testing this approach merits attention. © 2013.

  4. Dabrafenib Plus Trametinib Approved for Melanoma, Thyroid Cancer

    Cancer.gov

    FDA recently approved the combination of dabrafenib (Taflinar) and trametinib (Mekinist) to treat some patients with melanoma and anaplastic thyroid cancer whose tumors have a mutation in the BRAF gene. As this Cancer Currents blog post explains, this is the first treatment approved specifically for anaplastic thyroid

  5. Partner approval and intention to use contraception among Zanzibari women presenting for post-abortion care.

    PubMed

    Esber, Allahna; Foraker, Randi E; Hemed, Maryam; Norris, Alison

    2014-07-01

    We examined the effect of partner approval of contraception on intention to use contraception among women obtaining post-abortion care in Zanzibar. Our data source was a 2010 survey of 193 women obtaining post-abortion care at a large public hospital in Zanzibar. We used multivariable logistic regression analysis to assess associations between partner approval and intention to use contraception. Overall, 23% of participants had used a contraceptive method in the past, and 66% reported intending to use contraception in the future. We found that partner approval of contraception and ever having used contraception in the past were each associated with intending to use contraception in the future. In the multivariable model, adjusting for past contraception use, partner approval of contraception was associated with 20 times the odds of intending to use contraception (odds ratio, 20.25; 95% confidence interval, 8.45-48.56). We found a strong association between partner approval and intention to use contraception. Efforts to support contraceptive use must include both male and female partners. Public health and educational efforts to increase contraceptive use must include men and be targeted to both male and female partners. Given that male partners are often not present when women obtain health care, creative efforts will be required to meet men in community settings. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain

    DTIC Science & Technology

    2014-10-01

    and meetings with VAMC nursing and all study personnel while awaiting CRADA approval from VAMC NOVEMBER Duke/VA CRADA approved; start of enrollment at...Duke patient enrollment MAY Numerous meetings at Duke (Investigational Drug Service, Limb Loss Clinical Nurse Specialist, in-patient team) to discuss...Dionne Apedjihoun, CRC met with Nancy Payne, Duke Clinical Nurse /Limb Loss Specialist to trouble shoot potential patient recruitment for in and out

  7. Ear Acupuncture for Post-Operative Pain Associated with Ambulatory Arthroscopic Knee Surgery: A Randomized Controlled Trial

    DTIC Science & Technology

    2014-01-14

    E7(/(3+21(180%(5 ,QFOXGHDUHDFRGH 14 Jan 2014 Final Report Ear acupuncture for post-operative pain associated with ambulatory arthroscopic...DISTRIBUTION A. Approved for public release: distribution unlimited. The purpose of this study is to compare ear acupuncture plus standard therapy versus...3298 Ear Acupuncture for Post-operative Pa111 Assoc1ated With Ambulatory Arthroscopic Knee Surgery A Randomized Controlled Trial ’• V ’’ ’-’ I

  8. Procedural trends, outcomes, and readmission rates pre-and post-FDA approval for MitraClip from the National Readmission Database (2013-14).

    PubMed

    Panaich, Sidakpal S; Arora, Shilpkumar; Badheka, Apurva; Kumar, Varun; Maor, Elad; Raphael, Claire; Deshmukh, Abhishek; Reeder, Guy; Eleid, Mackram; Rihal, Charanjit S

    2018-05-01

    There are sparse clinical data on the procedural trends, outcomes and readmission rates following FDA approval and expansion of Transcatheter mitral valve repair/MitraClip ® . Whether a complex new technology can be disseminated safely and quickly is controversial. The study cohort was derived from the National Readmission Data (NRD) 2013-14. MitraClip ® was identified using appropriate International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. The primary outcome was a composite of in-hospital mortality + procedural complications. Secondary outcome included 30-day readmissions. Hierarchical two level logistic models were used to evaluate study outcomes. Our analysis included 2003 MitraClip ® procedures. Overall in-hospital mortality was 3.9%. As expected, there was a significant increase in procedural volume post-FDA approval. Importantly, a corresponding downward trend in mortality and procedural complications was observed. Significant predictors of in-hospital mortality and procedural complications included the use of vasopressors (P <0.001) and hemodynamic support (P < 0.001). Higher hospital volume (≥10 MitraClips/year) was associated with lower in-hospital mortality and complications (P = 0.02). There were 304 (15.1%) 30-day readmissions, with heart failure being the most common cause of readmission. Elective procedures had lower in-hospital mortality (P < 0.001) and lower readmission rates (P = 0.011) compared with nonelective procedures. A significant increase in MitraClip ® procedural volumes occurred post-FDA approval. Overall morbidity and mortality were low and trended downwards. Hospital procedure volume ≥10 cases were associated with lower mortality and overall complication rates. These data suggest a successful roll out of a very complex novel structural heart procedure. © 2017 Wiley Periodicals, Inc.

  9. 38 CFR 21.9765 - Program of education approval.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Program of education... (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approval of Programs of Education § 21.9765 Program of education approval. VA may provide educational assistance for pursuit of a program of...

  10. 38 CFR 21.9765 - Program of education approval.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Program of education... (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approval of Programs of Education § 21.9765 Program of education approval. VA may provide educational assistance for pursuit of a program of...

  11. 38 CFR 21.9765 - Program of education approval.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Program of education... (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approval of Programs of Education § 21.9765 Program of education approval. VA may provide educational assistance for pursuit of a program of...

  12. 38 CFR 21.9765 - Program of education approval.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Program of education... (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approval of Programs of Education § 21.9765 Program of education approval. VA may provide educational assistance for pursuit of a program of...

  13. 38 CFR 21.9765 - Program of education approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Program of education... (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approval of Programs of Education § 21.9765 Program of education approval. VA may provide educational assistance for pursuit of a program of...

  14. A Retrospective Analysis of Pre-surgical Incisor Decompensation Attained in an Orthognathic Surgery Population

    DTIC Science & Technology

    2016-07-01

    owner. ~ GARY S. MAYNE, Maj, USAF, DC Tri-Service Orthodontic Residency Program Air Force Post Graduate Dental School Uniformed Services University...APPROVED: __________________________________________ Drew W. Fallis, D.D.S., M.S., Dean, Air Force Post-Graduate Dental School iii...Air Force Postgraduate Dental School, Joint Base San Antonio-Lackland, San Antonio, Texas, USA). Inclusion criteria for the study were 1

  15. 39 CFR 111.4 - Approval of the Director of the Federal Register.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Approval of the Director of the Federal Register. 111.4 Section 111.4 Postal Service UNITED STATES POSTAL SERVICE POST OFFICE SERVICES [DOMESTIC MAIL] GENERAL INFORMATION ON POSTAL SERVICE § 111.4 Approval of the Director of the Federal Register...

  16. 42 CFR 37.4 - Plans for chest roentgenographic examinations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... covered by the plan; (4) The name and location of the approved X-ray facility or facilities, and the... approval as the originally approved plan. (e) The operator must promptly display in a visible location on... NIOSH. The proposed plan or change in plan must remain posted in a visible location on the bulletin...

  17. $627 Million Gulf Spill Restoration Plan Approved | NOAA Gulf Spill

    Science.gov Websites

    Publications Press Releases Story Archive Home $627 Million Gulf Spill Restoration Plan Approved $627 Million Gulf Spill Restoration Plan Approved Bird landing on water share Posted on October 3, 2014 | Assessment Gulf of Mexico early restoration projects since the oil spill. The restoration plan includes 44

  18. Japanese Physicians' Views on Drug Post-Marketing Surveillance.

    PubMed

    Maeda, Kazuki; Katashima, Rumi; Ishizawa, Keisuke; Yanagawa, Hiroaki

    2015-12-01

    Registration trials leading to the approval of drugs are paramount in drug development. After approval, continuous efforts are necessary to ensure proper use of the approved drugs. In Japan, post-marketing surveillance (PMS) by drug companies is conducted in accordance with good post-marketing study practice (GPSP). Although the global standard for pharmacovigilance is incorporated into GPSP, attention has recently been focused on disassociating them. In this study, we examined physicians' views on PMS with the aim of conducting PMS more effectively. We retrospectively reviewed records between 2009 and 2013 from the institutional review board of Tokushima University Hospital, an academic hospital in rural Japan. The annual number of times PMS was performed was then determined. Next, we assessed physicians' attitudes toward drug PMS, including ethical issues, in a cross-sectional study using a questionnaire designed for this study. Five- and two-point scales were used. The questionnaire was distributed in 2014 to 221 physicians listed as investigators in PMS contracts. Of the 221 physicians, 103 (46.6%) responded to the questionnaire. About 50% of the respondents had experience writing PMS reports. Many of the physicians considered PMS to be important but burdensome. Furthermore, from the viewpoint of research ethics, many physicians considered it improper within the present PMS framework to collect and provide data beyond the scope of routine clinical practice without obtaining informed consent in the case of extra blood sampling, provision of images, monitoring and controlled studies. Beyond practical factors such as workload, attention should be given to establishing an ethical infrastructure and globally harmonized system with regard to the Japanese PMS system. Given the limitations of this single-institution study, further research is needed to collect information for developing a suitable infrastructure.

  19. 48 CFR 22.404-10 - Posting wage determinations and notice.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Posting wage... Contracts Involving Construction 22.404-10 Posting wage determinations and notice. The contractor must keep a copy of the applicable wage determination (and any approved additional classifications) posted at...

  20. FDA Approves Apalutamide for Prostate Cancer

    Cancer.gov

    Apalutamide (Erleada) is a hormone therapy that counteracts resistance to androgen deprivation therapy. Learn more about the FDA approval of apalutamide for men with castration-resistant nonmetastatic prostate cancer in this Cancer Currents blog post.

  1. Normative Feedback for Parents of College Students: Piloting a Parent Based Intervention to Correct Misperceptions of Students’ Alcohol Use and Other Parents’ Approval of Drinking

    PubMed Central

    LaBrie, Joseph W.; Napper, Lucy E.; Hummer, Justin F.

    2013-01-01

    Objective Multi-component parent-based interventions (PBIs) provide a promising avenue for targeting alcohol use and related consequences in college students. Parents of college-aged children can have a significant influence on their children’s alcohol use decisions. However, parents tend to underestimate their own child’s alcohol use and overestimate other similar parents’ approval of student drinking. These misperceptions could have important implications for parents’ own attitudes and alcohol-related communication with their student. Targeting these misperceptions through normative feedback could help promote greater and more in-depth alcohol-related communication. The present study examines the potential efficacy of web-based alcohol-related normative feedback for parents of college students. Method A sample of 144 parents of college students received web-based normative feedback about students’ alcohol use and approval, as well as other same-college parents’ alcohol approval. Parents completed measures of perceived student alcohol use, student alcohol approval, other-parent alcohol approval, and intentions to discuss alcohol use both pre- and post-normative feedback. Results Post-feedback, parents reported stronger intentions to talk to their student about alcohol, were less confident in their knowledge of their students’ alcohol use, and believed that their student drank in greater quantity and more frequently than pre-feedback. Parents also perceived other parents to be less approving of alcohol use after viewing normative feedback. Conclusions These findings provide preliminary support for the use of web-based normative feedback for parents of college students. Given these promising results, further research developing and testing this approach merits attention. PMID:24099892

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

    PubMed

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

    2015-06-01

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

  3. Biometric Identification Verification Technology Status and Feasibility Study

    DTIC Science & Technology

    1994-09-01

    L’., .- CONTRACT No. DNA 001 -93-C-01 37 Approved for public release;T distribution Is unlimited. ~v 94g’ Destroy this report when it is no longer...DISTRIBUI ION/AVAILABILITY STATEMENT 12b. DISTRIBUTION CODE Approved for public release; distribution is unlimited. 13. ABSTRACT (Maximurm 200 wvrds) DoD...guys." 4lie issue is then reduced to one of positive identification and control. Traditiozal~y, this has beeýu accomplished by posting a guard or entry

  4. Midwest Guardrail System (MGS) with southern yellow pine posts.

    DOT National Transportation Integrated Search

    2013-09-01

    The Midwest Guardrail System (MGS) has previously been approved for use with various alternative species of wood posts. However, Southern Yellow Pine (SYP) is the most common wood guardrail post material in the United States. The goal of this researc...

  5. 14 CFR 1264.135 - Post-hearing briefs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FRAUD CIVIL PENALTIES ACT OF 1986 § 1264.135 Post-hearing briefs. The presiding officer may require the parties to file post-hearing briefs. In any event, upon approval of the presiding officer, any party may... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Post-hearing briefs. 1264.135 Section 1264...

  6. 14 CFR 1264.135 - Post-hearing briefs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... FRAUD CIVIL PENALTIES ACT OF 1986 § 1264.135 Post-hearing briefs. The presiding officer may require the parties to file post-hearing briefs. In any event, upon approval of the presiding officer, any party may... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Post-hearing briefs. 1264.135 Section 1264...

  7. 14 CFR 1264.135 - Post-hearing briefs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... FRAUD CIVIL PENALTIES ACT OF 1986 § 1264.135 Post-hearing briefs. The presiding officer may require the parties to file post-hearing briefs. In any event, upon approval of the presiding officer, any party may... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Post-hearing briefs. 1264.135 Section 1264...

  8. 14 CFR 1264.135 - Post-hearing briefs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... FRAUD CIVIL PENALTIES ACT OF 1986 § 1264.135 Post-hearing briefs. The presiding officer may require the parties to file post-hearing briefs. In any event, upon approval of the presiding officer, any party may... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Post-hearing briefs. 1264.135 Section 1264...

  9. Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Postamputation Pain

    DTIC Science & Technology

    2015-10-01

    of Chronic Post -Am utation Pain Research Office Use Onl Continuin Review A roved: A. Study Status at the Durham VAMC: Please choose a response that...data from our other VIPER research grant2, demononstrating a 65% incidence of chronic post -amputation pain. This is consistent with historical...Scope of Practice document. No research may be continued beyond the designated approval period. Date: From: Investigator: Institutional Review Board

  10. 25 CFR 518.4 - What criteria must a tribe meet to receive a certificate of self-regulation?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Establishes or approves, and requires the posting of, rules of games; (xiv) Inspects games, tables, equipment... aids and tests such for compliance with standards; (xvi) Establishes or approves video surveillance...

  11. 25 CFR 518.4 - What criteria must a tribe meet to receive a certificate of self-regulation?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Establishes or approves, and requires the posting of, rules of games; (xiv) Inspects games, tables, equipment... aids and tests such for compliance with standards; (xvi) Establishes or approves video surveillance...

  12. 25 CFR 518.4 - What criteria must a tribe meet to receive a certificate of self-regulation?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Establishes or approves, and requires the posting of, rules of games; (xiv) Inspects games, tables, equipment... aids and tests such for compliance with standards; (xvi) Establishes or approves video surveillance...

  13. 25 CFR 518.4 - What criteria must a tribe meet to receive a certificate of self-regulation?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Establishes or approves, and requires the posting of, rules of games; (xiv) Inspects games, tables, equipment... aids and tests such for compliance with standards; (xvi) Establishes or approves video surveillance...

  14. Announcements under Renewable Fuel Standard

    EPA Pesticide Factsheets

    RFS program announcements are posted below by the calendar year in which the action was posted. Announcements will include rulemakings, responses to petitions, new pathway approvals, compliance deadlines, alternative plans, and among others.

  15. A Novel EphA4-Based Small Molecule-Based Therapeutic Strategy for Prevention and Treatment of Post-Traumatic Osteoarthritis

    DTIC Science & Technology

    2015-09-01

    first three months of the project, we successfully obtained approval for our Animal Component of Research Project (ACORP) from our local IACUC and...total number of animals . The approved ACORP and the amendment were submitted to ACURO for approval and final approval from the ACURO was secured on...the tibial plateau. The injury was produced using an “Instron” servohydraulic tester with the animal under inhalation anesthesia (3% isoflurane, 0.5

  16. 40 CFR 265.145 - Financial assurance for post-closure care.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of this section in accordance with § 265.145(h). (e) Financial test and corporate guarantee for post... closure and post-closure cost estimates to be covered by the test; (iv) Specify the date ending the owner... Regional Administrator may approve a decrease in the current post-closure cost estimate for which this test...

  17. 40 CFR 265.145 - Financial assurance for post-closure care.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of this section in accordance with § 265.145(h). (e) Financial test and corporate guarantee for post... closure and post-closure cost estimates to be covered by the test; (iv) Specify the date ending the owner... Regional Administrator may approve a decrease in the current post-closure cost estimate for which this test...

  18. 40 CFR 265.145 - Financial assurance for post-closure care.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of this section in accordance with § 265.145(h). (e) Financial test and corporate guarantee for post... closure and post-closure cost estimates to be covered by the test; (iv) Specify the date ending the owner... Regional Administrator may approve a decrease in the current post-closure cost estimate for which this test...

  19. 40 CFR 265.145 - Financial assurance for post-closure care.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of this section in accordance with § 265.145(h). (e) Financial test and corporate guarantee for post... closure and post-closure cost estimates to be covered by the test; (iv) Specify the date ending the owner... Regional Administrator may approve a decrease in the current post-closure cost estimate for which this test...

  20. 40 CFR 265.145 - Financial assurance for post-closure care.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of this section in accordance with § 265.145(h). (e) Financial test and corporate guarantee for post... closure and post-closure cost estimates to be covered by the test; (iv) Specify the date ending the owner... Regional Administrator may approve a decrease in the current post-closure cost estimate for which this test...

  1. 14 CFR § 1264.135 - Post-hearing briefs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... PROGRAM FRAUD CIVIL PENALTIES ACT OF 1986 § 1264.135 Post-hearing briefs. The presiding officer may require the parties to file post-hearing briefs. In any event, upon approval of the presiding officer, any... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Post-hearing briefs. § 1264.135 Section Â...

  2. 45 CFR 602.30 - Changes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION UNIFORM ADMINISTRATIVE... approved project. However, unless waived by the awarding agency, certain types of post-award changes in budgets and projects shall require the prior written approval of the awarding agency. (b) Relation to cost...

  3. 45 CFR 602.30 - Changes.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION UNIFORM ADMINISTRATIVE... approved project. However, unless waived by the awarding agency, certain types of post-award changes in budgets and projects shall require the prior written approval of the awarding agency. (b) Relation to cost...

  4. 45 CFR 602.30 - Changes.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION UNIFORM ADMINISTRATIVE... approved project. However, unless waived by the awarding agency, certain types of post-award changes in budgets and projects shall require the prior written approval of the awarding agency. (b) Relation to cost...

  5. FDA Expands Approval of Brentuximab for Hodgkin Lymphoma

    Cancer.gov

    The FDA has expanded the approved uses of brentuximab (Adcetris) in people with Hodgkin lymphoma. As this Cancer Currents post explains, it can now be used in combination with three chemotherapy drugs as an initial treatment in patients with advanced disease.

  6. Overview of the 2016 U.S. Food and Drug Administration Circulatory System Devices Advisory Panel Meeting on the Absorb Bioresorbable Vascular Scaffold System.

    PubMed

    Steinvil, Arie; Rogers, Toby; Torguson, Rebecca; Waksman, Ron

    2016-09-12

    This study aims to describe the discussions and recommendations made during the U.S. Food and Drug Administration (FDA) Circulatory System Device Panel pre-market approval application for the Absorb Bioresorbable Vascular Scaffold (BVS) System. The Absorb BVS System is a first-of-its-kind fully bioresorbable percutaneous coronary intervention technology. The absorb BVS was studied in the ABSORB III (A Clinical Evaluation of Absorb BVS, the Everolimus Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects with de Novo Native Coronary Artery Lesions) trial, the pivotal U.S. investigational device exemption trial. Observational report of the FDA Circulatory System Device Panel pre-market approval application meeting held on March 15, 2016. The U.S. FDA Circulatory System Device Panel members reviewed the ABSROB III trial outcomes and additional post hoc analyses presented by the sponsor and the FDA. The ABSORB III trial met the primary endpoint of noninferiority of Absorb BVS compared with the control, XIENCE drug-eluting stent, for target lesion failure at 1 year. Although a higher numerical trend for adverse outcomes was reported for the Absorb BVS, there were no statistical differences between Absorb BVS and XIENCE for any safety or effectiveness components for target lesion failure or for the secondary pre-specified outcomes. Panel members raised concerns with regard to the ABSORB III results and post hoc analyses focusing mainly on the noninferiority design of the trial, the apparent safety issues of the Absorb BVS in small vessels, the mismatch of visually versus intravascular imaging assessed vessel size found in ABSORB III and its implications on the adequate device labeling, the safety of Absorb BVS in specific patient and lesion subsets, and the post-approval commitments of the sponsor. Following panel discussions and the evidence presented, the panel voted for approval of the device. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. Characteristics of Clinical Studies Used for US Food and Drug Administration Approval of High-Risk Medical Device Supplements.

    PubMed

    Zheng, Sarah Y; Dhruva, Sanket S; Redberg, Rita F

    2017-08-15

    High-risk medical devices often undergo modifications, which are approved by the US Food and Drug Administration (FDA) through various kinds of premarket approval (PMA) supplements. There have been multiple high-profile recalls of devices approved as PMA supplements. To characterize the quality of the clinical studies and data (strength of evidence) used to support FDA approval of panel-track supplements (a type of PMA supplement pathway that is used for significant changes in a device or indication for use and always requires clinical data). Descriptive study of clinical studies supporting panel-track supplements approved by the FDA between April 19, 2006, and October 9, 2015. Panel-track supplement approval. Methodological quality of studies including randomization, blinding, type of controls, clinical vs surrogate primary end points, use of post hoc analyses, and reporting of age and sex. Eighty-three clinical studies supported the approval of 78 panel-track supplements, with 71 panel-track supplements (91%) supported by a single study. Of the 83 studies, 37 (45%) were randomized clinical trials and 25 (30%) were blinded. The median number of patients per study was 185 (interquartile range, 75-305), and the median follow-up duration was 180 days (interquartile range, 84-270 days). There were a total of 150 primary end points (mean [SD], 1.8 [1.2] per study), and 57 primary end points (38%) were compared with controls. Of primary end points with controls, 6 (11%) were retrospective controls and 51 (89%) were active controls. One hundred twenty-one primary end points (81%) were surrogate end points. Thirty-three studies (40%) did not report age and 25 (30%) did not report sex for all enrolled patients. The FDA required postapproval studies for 29 of 78 (37%) panel-track supplements. Among clinical studies used to support FDA approval of high-risk medical device modifications, fewer than half were randomized, blinded, or controlled, and most primary outcomes were based on surrogate end points. These findings suggest that the quality of studies and data evaluated to support approval by the FDA of modifications of high-risk devices should be improved.

  8. Innovation in the pharmaceutical industry: New estimates of R&D costs.

    PubMed

    DiMasi, Joseph A; Grabowski, Henry G; Hansen, Ronald W

    2016-05-01

    The research and development costs of 106 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug and biologics development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval. The estimated average out-of-pocket cost per approved new compound is $1395 million (2013 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a real discount rate of 10.5% yields a total pre-approval cost estimate of $2558 million (2013 dollars). When compared to the results of the previous study in this series, total capitalized costs were shown to have increased at an annual rate of 8.5% above general price inflation. Adding an estimate of post-approval R&D costs increases the cost estimate to $2870 million (2013 dollars). Copyright © 2016 Elsevier B.V. All rights reserved.

  9. 38 CFR 21.5150 - State approving agencies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false State approving agencies. 21.5150 Section 21.5150 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under...

  10. 38 CFR 21.5150 - State approving agencies.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false State approving agencies. 21.5150 Section 21.5150 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under...

  11. 38 CFR 21.5150 - State approving agencies.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false State approving agencies. 21.5150 Section 21.5150 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under...

  12. 38 CFR 21.5150 - State approving agencies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false State approving agencies. 21.5150 Section 21.5150 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under...

  13. 38 CFR 21.5150 - State approving agencies.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false State approving agencies. 21.5150 Section 21.5150 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-Vietnam Era Veterans' Educational Assistance Under...

  14. 50 CFR 697.27 - Trap transferability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Trap allocation transfers must be approved by the Regional Administrator before becoming effective. The Regional Administrator shall approve a transfer upon a showing by the involved permit holders of the... allocation to transfer, the Regional Administrator will calculate the seller's pre-transfer and post-transfer...

  15. 77 FR 36292 - Proposed Collection, Comments Requested: FBI National Academy Level III Evaluation; FBI National...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-18

    ... Questionnaire for Graduates, FBI National Academy Post-Course Questionnaire for Supervisors of Graduates ACTION...: Approval of a reinstated collection. 2. Title of the Forms: FBI National Academy Post-Course Questionnaire for Graduates. FBI National Academy Post-Course Questionnaire for Supervisors of Graduates. 3. Agency...

  16. 76 FR 14737 - Bureau of Educational and Cultural Affairs (ECA) Request for Grant Proposals: One Beat

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-17

    ... selected and provide contact information at posts to award recipient; Advise selected countries for... participants to ECA for review and approval; Inform posts of final selections. Program Development and... programs, and then advise posts on the application, recruitment and participant selection process. Outlines...

  17. Improving the postmarket surveillance of total joint arthroplasty devices.

    PubMed

    Mahomed, Nizar N; Syed, Khalid; Sledge, Clement B; Brennan, Troyen A; Liang, Matthew H

    2008-01-01

    To evaluate the FDA's approval process and postmarket surveillance strategies for THR devices. The FDA Center for Devices and Radiological Health (CDRH) 510k releasable database was used to document approved THR devices. The CDRH Medical Device Reporting data files were used to study the efficiency of the FDA's post-market surveillance system. Manufacturers were contacted to supply information regarding their implants. Medline was searched between 1966-1996 to determine the percentage of THR devices with published data on clinical outcomes. Between 1976 and 1996, 701 new THR devices were approved by the Substantial Equivalent (SE) route and 34 were approved on the basis of Premarket Approval PMA. The number of approvals doubled between 1991-1995 compared to 1976-1990. Seventy-four different manufacturers obtained approval to market THR devices. Only four manufacturers obtained approval via the PMA application. Under Mandatory Device Reporting all revision arthroplasties should be reported. Using data from 2 independent services for which we had US hospital discharge data in 1993 we estimate that only 3% of all revision THR were reported to the FDA. Manufacturers of hip implants failed to provide useful information. Medline search revealed only 15% of the approved THR devices had published data on outcomes. Current FDA premarket approval and postmarket surveillance strategies fail to provide information for evidence-based selection of THR devices. Recommendations are made to avert problems with device failures.

  18. 40 CFR 141.720 - Inactivation toolbox components.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... between the indicated values: Log credit = (0.0397 × (1.09757)Temp) × CT. (c) Site-specific study. The... this section on a site-specific basis. The State must base this approval on a site-specific study a... in this table are applicable only to post-filter applications of UV in filtered systems and to...

  19. 40 CFR 141.720 - Inactivation toolbox components.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... between the indicated values: Log credit = (0.0397 × (1.09757)Temp) × CT. (c) Site-specific study. The... this section on a site-specific basis. The State must base this approval on a site-specific study a... in this table are applicable only to post-filter applications of UV in filtered systems and to...

  20. 40 CFR 141.720 - Inactivation toolbox components.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... between the indicated values: Log credit = (0.0397 × (1.09757)Temp) × CT. (c) Site-specific study. The... this section on a site-specific basis. The State must base this approval on a site-specific study a... in this table are applicable only to post-filter applications of UV in filtered systems and to...

  1. 40 CFR 141.720 - Inactivation toolbox components.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... between the indicated values: Log credit = (0.0397 × (1.09757)Temp) × CT. (c) Site-specific study. The... this section on a site-specific basis. The State must base this approval on a site-specific study a... in this table are applicable only to post-filter applications of UV in filtered systems and to...

  2. Post-approval monitoring and oversight of U.S.-initiated human subjects research in resource-constrained countries.

    PubMed

    Brown, Brandon; Kinsler, Janni; Folayan, Morenike O; Allen, Karen; Cáceres, Carlos F

    2014-06-01

    The history of human subjects research and controversial procedures in relation to it has helped form the field of bioethics. Ethically questionable elements may be identified during research design, research implementation, management at the study site, or actions by a study's investigator or other staff. Post-approval monitoring (PAM) may prevent violations from occurring or enable their identification at an early stage. In U.S.-initiated human subjects research taking place in resource-constrained countries with limited development of research regulatory structures, arranging a site visit from a U.S. research ethics committee (REC) becomes difficult, thus creating a potential barrier to regulatory oversight by the parent REC. However, this barrier may be overcome through the use of digital technologies, since much of the world has at least remote access to the Internet. Empirical research is needed to pilot test the use of these technologies for research oversight to ensure the protection of human subjects taking part in research worldwide.

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

    PubMed Central

    2016-01-01

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

  4. 77 FR 66908 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-07

    ... Rule Change Relating to Post-Trade Transparency for Agency Pass-Through Mortgage- Backed Securities..., 2012, concerning an Order Granting Approval of Proposed Rule Change Relating to Post-Trade Transparency...

  5. Lack of proportionality. Seven specifications of public interest that override post-approval commercial interests on limited access to clinical data.

    PubMed

    Strech, Daniel; Littmann, Jasper

    2012-07-02

    For the protection of commercial interests, licensing bodies such as the EMA and health technology assessment institutions such as NICE restrict full access to unpublished evidence. Their respective policies on data transparency, however, lack a systematic account of (1) what kinds of commercial interests remain relevant after market approval has been granted, (2) what the specific types of public interest are that may override these commercial interests post approval, and, most importantly, (3) what criteria guide the trade-off between public interest and legitimate measures for the protection of commercial interest. Comparing potential commercial interests with seven specifications of relevant public interest reveals the lack of proportionality inherent in the current practices of EMA and NICE.

  6. 77 FR 8865 - Recent Postings of Broadly Applicable Alternative Test Methods

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... Applicable Alternative Test Methods AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of availability. SUMMARY: This notice announces the broadly applicable alternative test method approval decisions... INFORMATION CONTACT: An electronic copy of each alternative test method approval document is available on the...

  7. 75 FR 7593 - Recent Postings of Broadly Applicable Alternative Test Methods

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-22

    ... Applicable Alternative Test Methods AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of availability. SUMMARY: This notice announces the broadly applicable alternative test method approval decisions... electronic copy of each alternative test method approval document is available on EPA's Web site at http...

  8. 78 FR 11174 - Recent Postings of Broadly Applicable Alternative Test Methods

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ... Applicable Alternative Test Methods AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of availability. SUMMARY: This notice announces the broadly applicable alternative test method approval decisions... INFORMATION CONTACT: An electronic copy of each alternative test method approval document is available on the...

  9. Bariatric surgery in patients with bipolar spectrum disorders: Selection factors, post-operative visit attendance, and weight outcomes

    PubMed Central

    Friedman, Kelli E.; Applegate, Katherine; Portenier, Dana; McVay, Megan

    2017-01-01

    Background As many of 3% of bariatric surgery candidates are diagnosed with a bipolar spectrum disorder. Objectives 1) To describe differences between patients with bipolar spectrum disorders who are approved and not approved for surgery by the mental health evaluator. 2) To examine surgical outcomes of patients with bipolar spectrum disorders. Setting Academic medical center, United States. Methods A retrospective record review was conducted of consecutive patients who applied for bariatric surgery between 2004 and 2009. Patients diagnosed with bipolar spectrum disorders who were approved for surgery (n=42) were compared with patients with a bipolar spectrum disorder who were not approved (n=31) and to matched control surgical patients without a bipolar spectrum diagnosis (n=29) on a variety of characteristics and surgical outcomes. Results Of bariatric surgery candidates diagnosed with a bipolar spectrum disorder who applied for surgery, 57% were approved by the psychologist and 48% ultimately had surgery. Patients with a bipolar spectrum disorder who were approved for surgery were less likely to have had a previous psychiatric hospitalizations than those who were not approved for surgery. Bariatric surgery patients diagnosed with a bipolar spectrum disorder were less likely to attend follow-up care appointments 2 or more years post-surgery compared to matched patients without bipolar disorder. Among patients with available data, those with a bipolar spectrum disorder and matched patients had similar weight loss at 12 months (n=21 for bipolar, n=24 for matched controls) and at 2 or more years (mean=51 months; n=11 for bipolar, n=20 for matched controls). Conclusions Patients diagnosed with a bipolar spectrum disorder have a high rate of delay/denial for bariatric surgery based on the psychosocial evaluation and are less likely to attend medical follow-up care 2 or more years post-surgery. Carefully screened patients with bipolar disorder who engage in long-term follow-up care may benefit from bariatric surgery. PMID:28169206

  10. Contrasting clinical evidence for market authorisation of cardio-vascular devices in Europe and the USA: a systematic analysis of 10 devices based on Austrian pre-reimbursement assessments.

    PubMed

    Wild, Claudia; Erdös, Judit; Zechmeister, Ingrid

    2014-11-04

    European medical device regulation is under scrutiny and will be re-regulated with stricter rules concerning requirements for clinical evidence for high-risk medical devices. It is the aim of this study to analyse the differences between Europe and USA in dealing with risks and benefits of new cardio-vascular devices. Since no information is available on clinical data used by the Notified Body for CE-marking, data from Austrian pre-reimbursement assessments close to European market approval were used as proxy and compared with clinical data available at time of market approval by FDA in the USA. 10 cardio-vascular interventions with 27 newly CE approved medical devices were analysed. The time lag between market authorisation in Europe and in the USA is 3 to 7 years. Only 7 CE-marked devices also hold a FDA market approval, 7 further devices are in FDA approved ongoing efficacy trials. For 4 of the CE-marked devices the FDA market application or the approval-trial was either suspended due to efficacy or safety concerns or the approval was denied. Evidence available at time of CE-marking are most often case-series or small feasibility RCTs, while large RCTs and only in rare cases prospective cohort studies are the basis of FDA approvals. Additionally, the FDA often requires post-approval studies for high-risk devices. Market authorisation based on mature clinical data deriving from larger RCTs and longer follow-ups do not only change the perspective on the risk-benefit ratio, but also secures real patient benefit and safety and assures payers of investing only in truly innovative devices.

  11. 78 FR 67211 - Notice of Request for the Extension of a Currently Approved Information Collection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... Certifications and Assurances, that they will comply with pre-award and post-delivery audit requirements for..., Post-Delivery Audit Requirements Under Buy America DATES: Comments must be submitted before January 7... through Friday, except federal holidays. FOR FURTHER INFORMATION CONTACT: Pre-Award, Post-Delivery Audit...

  12. 29 CFR 1903.2 - Posting of notice; availability of the Act, regulations and applicable standards.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... has an approved poster informing employees of their protections and obligations as defined in § 1952.10 of this chapter, such poster, when posted by employers covered by the State plan, shall constitute...) Reproductions or facsimiles of such Federal or State posters shall constitute compliance with the posting...

  13. 29 CFR 1903.2 - Posting of notice; availability of the Act, regulations and applicable standards.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... has an approved poster informing employees of their protections and obligations as defined in § 1952.10 of this chapter, such poster, when posted by employers covered by the State plan, shall constitute...) Reproductions or facsimiles of such Federal or State posters shall constitute compliance with the posting...

  14. 29 CFR 1903.2 - Posting of notice; availability of the Act, regulations and applicable standards.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... has an approved poster informing employees of their protections and obligations as defined in § 1952.10 of this chapter, such poster, when posted by employers covered by the State plan, shall constitute...) Reproductions or facsimiles of such Federal or State posters shall constitute compliance with the posting...

  15. 29 CFR 1903.2 - Posting of notice; availability of the Act, regulations and applicable standards.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... has an approved poster informing employees of their protections and obligations as defined in § 1952.10 of this chapter, such poster, when posted by employers covered by the State plan, shall constitute...) Reproductions or facsimiles of such Federal or State posters shall constitute compliance with the posting...

  16. 29 CFR 1903.2 - Posting of notice; availability of the Act, regulations and applicable standards.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... has an approved poster informing employees of their protections and obligations as defined in § 1952.10 of this chapter, such poster, when posted by employers covered by the State plan, shall constitute...) Reproductions or facsimiles of such Federal or State posters shall constitute compliance with the posting...

  17. 46 CFR 154.1862 - Posting of speed reduction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Posting of speed reduction. 154.1862 Section 154.1862... STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Operations § 154.1862 Posting of speed reduction. If a speed reduction is specially approved by the Commandant under § 154.409, the master shall...

  18. 46 CFR 154.1862 - Posting of speed reduction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Posting of speed reduction. 154.1862 Section 154.1862... STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Operations § 154.1862 Posting of speed reduction. If a speed reduction is specially approved by the Commandant under § 154.409, the master shall...

  19. 7 CFR 1717.608 - RUS approval of contracts.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... engineering services, and in 7 CFR part 1726 for construction and procurement. (b) Large retail power contracts. RUS approval of contracts to sell electric power to retail customers is required only if the... AGRICULTURE POST-LOAN POLICIES AND PROCEDURES COMMON TO INSURED AND GUARANTEED ELECTRIC LOANS Operational...

  20. 7 CFR 1717.608 - RUS approval of contracts.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... engineering services, and in 7 CFR part 1726 for construction and procurement. (b) Large retail power contracts. RUS approval of contracts to sell electric power to retail customers is required only if the... AGRICULTURE POST-LOAN POLICIES AND PROCEDURES COMMON TO INSURED AND GUARANTEED ELECTRIC LOANS Operational...

  1. 7 CFR 1717.608 - RUS approval of contracts.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... engineering services, and in 7 CFR part 1726 for construction and procurement. (b) Large retail power contracts. RUS approval of contracts to sell electric power to retail customers is required only if the... AGRICULTURE POST-LOAN POLICIES AND PROCEDURES COMMON TO INSURED AND GUARANTEED ELECTRIC LOANS Operational...

  2. Rucaparib Approved as Maintenance Therapy for Ovarian Cancer

    Cancer.gov

    FDA has expanded its approval of rucaparib for women with ovarian, fallopian tube, or primary peritoneal cancer. As this Cancer Currents blog post explains, it can now be used to treat women with recurrent disease whose tumors shrank after subsequent treatment with a platinum-based chemotherapy.

  3. Coercion and Reconciliation: Post-Conflict Resolution After the American Civil War

    DTIC Science & Technology

    2016-05-26

    Approved for public release; distribution is unlimited Coercion and Reconciliation: Post -Conflict Resolution After the American Civil War A...Reconciliation: Post -Conflict Resolution After 5a. CONTRACT NUMBER The American Civil War 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...policies. The conclusion is that during post -conflict resolution, having a moderate coercive body to maintain security, while allowing for political

  4. The Effect of Post Traumatic Stress Disorder on Military Leadership: An Historical Perspective

    DTIC Science & Technology

    2011-05-19

    Post Traumatic Stress Disorder ( PTSD ) on military leadership. For over twenty years, the United States Army has used the Be...Introduction Multiple deployment cycles to Iraq and Afghanistan combat zones and the increase in Post - Traumatic Stress Disorder ( PTSD ) have resulted...Approved for Public Release; Distribution is Unlimited The Effect of Post Traumatic Stress Disorder on Military Leadership: An

  5. Cancer Nursing Education: Literature Review and Documentary Analysis.

    ERIC Educational Resources Information Center

    Langton, Helen; Blunden, Gillian; Hek, Gill

    The knowledge and skills needed by cancer nurses and the content and strategies of England's existing cancer nursing education programs were examined. The study included a comprehensive literature review and an analysis of course documents from selected English National Board-approved post-qualifying cancer nursing and palliative care courses…

  6. 38 CFR 21.9590 - Approved programs of education and courses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... licensing or certification test designed to help the individual maintain employment in a vocation or... VETERANS AFFAIRS (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approved Programs of... certification test, for which he or she is requesting reimbursement; or (5) Be an individual who has taken a...

  7. 38 CFR 21.9590 - Approved programs of education and courses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... licensing or certification test designed to help the individual maintain employment in a vocation or... VETERANS AFFAIRS (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approved Programs of... certification test, for which he or she is requesting reimbursement; or (5) Be an individual who has taken a...

  8. 38 CFR 21.9590 - Approved programs of education and courses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... licensing or certification test designed to help the individual maintain employment in a vocation or... VETERANS AFFAIRS (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approved Programs of... certification test, for which he or she is requesting reimbursement; or (5) Be an individual who has taken a...

  9. 38 CFR 21.9590 - Approved programs of education and courses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... licensing or certification test designed to help the individual maintain employment in a vocation or... VETERANS AFFAIRS (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approved Programs of... certification test, for which he or she is requesting reimbursement; or (5) Be an individual who has taken a...

  10. 78 FR 22877 - Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-17

    ... Bank has developed an electronic disbursement approval processing system for guaranteed lenders with... authorized by Ex-Im Bank and legal documentation has been completed, the lender will obtain and review the... application system (ExIm Online). Ex-Im Bank's action (approved or declined) will be posted on the lender's...

  11. 78 FR 10169 - Agency Information Collection Activities: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-13

    ... Bank has developed an electronic disbursement approval processing system for guaranteed lenders with... authorized by Ex-Im Bank and legal documentation has been completed, the lender will obtain and review the... application system (ExIm Online). Ex-Im Bank's action (approved or declined) will be posted on the lender's...

  12. 77 FR 11677 - Medicaid Program; Review and Approval Process for Section 1115 Demonstrations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-27

    ... experimental, pilot, and demonstration projects approved under section 1115 of the Social Security Act relating... selected provisions of section 1902 of the Act for experimental, pilot, or demonstration projects... application, and recommended that CMS allow the State to not post a complete application. The commenters noted...

  13. Constructing target product profiles (TPPs) to help vaccines overcome post-approval obstacles

    PubMed Central

    Lee, Bruce Y.; Burke, Donald S.

    2012-01-01

    As history has demonstrated, post-approval obstacles can impede a vaccine’s use and potentially lead to its withdrawal. Addressing these potential obstacles when changes in a vaccine’s technology can still be easily made may improve a vaccine’s chances of success. Augmented vaccine target product profiles (TPPs) can help vaccine scientists better understand and anticipate these obstacles and galvanize conversations among various vaccine stakeholders (e.g., scientists, marketers, business development managers, policy makers, public health officials, health care workers, third party payors, etc.) earlier in a vaccine’s development. PMID:19782109

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

    PubMed

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

    2010-08-01

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

  15. Post-Conflict Realities and the Future of Stability in Nepal

    DTIC Science & Technology

    2017-03-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release. Distribution is unlimited. POST -CONFLICT REALITIES AND THE...DATE March 2017 3. REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE POST -CONFLICT REALITIES AND THE FUTURE OF STABILITY IN... post -insurgency Nepal has failed to deliver on the promises of reform that brought it to power. The long-enduring social and economic grievances based

  16. 46 CFR 169.849 - Posting placards containing instructions for launching and inflating inflatable liferafts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Inspections § 169.849 Posting placards containing instructions for launching and inflating inflatable... accessible to the ship's company and guests approved placards containing instructions for launching and... determined by the Officer in Charge, Marine Inspection. ...

  17. 77 FR 67442 - Proposed Information Collections; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ... summarized in our request for Office of Management and Budget (OMB) approval of the relevant information... changes to these two forms, see the TTB announcement posted on the beer page of the TTB Web site at http://www.ttb.gov/beer/index.shtml . Type of Review: Revision of a currently approved collection. Affected...

  18. 50 CFR 648.11 - At-sea sea sampler/observer coverage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... approved observer service providers shall be distributed to vessel owners and shall be posted on the NMFS... writing to all observer service providers approved pursuant to paragraph (h) of this section, NMFS shall... from the intended sail date; and (4) Procurement of observer services by scallop vessels. (i) An owner...

  19. 75 FR 36099 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-24

    ... of the availability of safety and effectiveness summaries of approved PMAs through the Internet and... New Hampshire Ave., Bldg. 66, rm. 1650, Silver Spring, MD 20993, 301-796- 6570. SUPPLEMENTARY... and denials in the Federal Register. Instead, the agency now posts this information on the Internet on...

  20. 75 FR 54154 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... effectiveness summaries of approved PMAs through the Internet and the agency's Division of Dockets Management... and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 1650... Federal Register. Instead, the agency now posts this information on the Internet on FDA's home page at...

  1. 75 FR 72829 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-26

    ... and effectiveness summaries of approved PMAs through the Internet and the Agency's Division of Dockets..., Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg... Federal Register. Instead, the Agency now posts this information on the Internet on FDA's home page at...

  2. 17 CFR 40.3 - Voluntary submission of new products for Commission review and approval.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FUTURES TRADING COMMISSION PROVISIONS COMMON TO REGISTERED ENTITIES § 40.3 Voluntary submission of new...) Describe any agreements or contracts entered into with other parties that enable the registered entity to...) Certify that the registered entity posted a notice of its request for Commission approval of the new...

  3. 17 CFR 40.3 - Voluntary submission of new products for Commission review and approval.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FUTURES TRADING COMMISSION PROVISIONS COMMON TO REGISTERED ENTITIES § 40.3 Voluntary submission of new...) Describe any agreements or contracts entered into with other parties that enable the registered entity to...) Certify that the registered entity posted a notice of its request for Commission approval of the new...

  4. 17 CFR 40.3 - Voluntary submission of new products for Commission review and approval.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FUTURES TRADING COMMISSION PROVISIONS COMMON TO REGISTERED ENTITIES § 40.3 Voluntary submission of new...) Describe any agreements or contracts entered into with other parties that enable the registered entity to...) Certify that the registered entity posted a notice of its request for Commission approval of the new...

  5. Influence of site and operator characteristics on carotid artery stent outcomes: analysis of the CAPTURE 2 (Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events) clinical study.

    PubMed

    Gray, William A; Rosenfield, Kenneth A; Jaff, Michael R; Chaturvedi, Seemant; Peng, Lei; Verta, Patrick

    2011-02-01

    The aim of this study was to analyze the CAPTURE 2 (Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events) study for physician- or site-related variables associated with differential outcomes for carotid artery stenting (CAS). The CAPTURE 2 trial is an ongoing, prospective, nonrandomized, independently adjudicated, multicenter clinical study enrolling high-surgical-risk patients undergoing CAS. In this assessment of the CAPTURE 2 study, the American Heart Association carotid endarterectomy guideline limits were used to define acceptable site and physician CAS outcomes; therefore, the resulting population of nonoctogenarian, asymptomatic subjects in this analysis is confined to 3,388 (of the total 5,297) subjects treated at 180 U.S. hospitals by 459 operators between March 2006 and January 2009. The rates of death, stroke, and myocardial infarction and death and stroke (DS) at 30 days were 3.5% and 3.3%, respectively, for the full CAPTURE 2 study cohort and 2.9% and 2.7%, respectively, for the asymptomatic, nonoctogenarian subgroup. In this subgroup, two-thirds of sites (118 of 180, 66%) had no DS events. Within the remaining sites, an inverse relationship between event rates and hospital patient volume as well as between event rates and individual operator volume was observed. The DS rates trended lower for interventional cardiologists compared with other specialties. Outcomes from the largest prospectively gathered, independently adjudicated, multicenter CAS study indicate that CAS can be safely performed in a variety of hospital settings by physicians with various specialties. The most important determinant of perioperative CAS outcomes was both site and operator CAS volume. A threshold of 72 cases was found to be necessary for consistently achieving a DS rate below 3% in this later-phase single arm study; background era and non-study operator experience will affect this determination. (Second Phase of "Carotid RX ACCULINK/RX ACCUNET Post-Approval Trial to Uncover Unanticipated or Rare Events"; NCT00302237). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. Marriage Counselling in Australia: An Evaluation.

    ERIC Educational Resources Information Center

    Wolcott, Ilene; Glezer, Helen

    A study was conducted of the effectiveness of marriage counseling with respect to marital status and the long-term stability of relationships. Data were gathered from clients of approved Australian marriage counseling agencies (n=540) who took a pre-counseling survey during a 4-week period in October-November 1987 and a post-counseling survey 8…

  7. 75 FR 62541 - Agency Information Collection Request. 30-Day Public Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... coalitions' structure, funding, activities, impact, and outcomes post-funding. The survey design and content...) approval on a new collection to conduct a survey of community coalitions formerly funded by the Community... Human Services (DHHS). As part of the study, a one-time, self-administered survey will be administered...

  8. 75 FR 8983 - Notice of Proposed Information Collection for Public Comment: Housing Counseling Outcomes Study

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

    ... outcomes realized by clients of HUD-approved counseling agencies seeking assistance to either purchase a home (pre-purchase clients) or to resolve or prevent mortgage delinquency (post-purchase clients... about their counseling experience and their current housing situation. The purpose of this survey is to...

  9. 40 CFR Appendix A to Subpart C of... - Alternative Testing Methods Approved for Analyses Under the Safe Drinking Water Act

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Spectrometry (GC/MS) 525.3 24 Carbofuran High-performance liquid chromatography (HPLC) with post-column... (HPLC) with Post-Column Derivatization and Fluorescence Detection 6651 B 6651 B 6651 B-00, B-05... Chromatography/Mass Spectrometry (GC/MS) 525.3 24 Oxamyl High-performance liquid chromatography (HPLC) with post...

  10. 7 CFR 4274.332 - Post award requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., justifies different amounts, a reserve for bad debts of 6 percent of outstanding loans must be accumulated... Program (IRP) § 4274.332 Post award requirements. (a) Applicability. Intermediaries receiving loans under this program shall be governed by these regulations, the loan agreement, the approved work plan...

  11. 75 FR 6401 - Medical Devices Regulated by the Center for Biologics Evaluation and Research; Availability of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ... premarket approval applications (PMAs) that have been approved by the Center for Biologics Evaluation and Research (CBER). This list is intended to inform the public of the availability through the Internet and... post this information on the Internet at http://www.fda.gov . In addition, the regulations provide that...

  12. 76 FR 9281 - Approval and Promulgation of Air Quality Implementation Plans; Massachusetts; Revised Carbon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ... Massachusetts. This SIP submittal contains revisions to the carbon monoxide (CO) maintenance plan for Lowell... plan. The intended effect of this action is to propose approval of this revision to the Lowell CO..., 5 Post Office Square--Suite 100, (Mail code OEP05-2), Boston, MA 02109-3912. 5. Hand Delivery or...

  13. 40 CFR 52.1470 - Identification of plan.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...). 445.513 “Fossil fuel” defined 12/4/76 49 FR 11626 (3/27/84) Most recently approved version was... produced by burning of fossil fuels 10/31/05 73 FR 20536 (4/16/08) Most recently approved version was... for each source; form of application; issuance or denial; posting 5/4/06 77 FR 59321 (9/27/12...

  14. 77 FR 66844 - Federal Acquisition Regulation; Submission for OMB Review; Evaluation of Export Offers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-07

    ... Management and Budget (OMB) a request to review and approve an extension of a previously approved information... posted without change to http://www.regulations.gov , including any personal and/or business confidential... United States (CONUS) ports and offers are solicited on a free onboard (f.o.b.) origin or f.o.b...

  15. 42 CFR 37.4 - Plans for chest roentgenographic examinations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... name and location of the approved X-ray facility or facilities, and the approximate date(s) and time(s... shall promptly display in a visible location on the bulletin board at the mine its proposed plan or... posted in a visible location on the bulletin board until ALOSH either grants or denies approval of it at...

  16. 42 CFR 37.4 - Plans for chest roentgenographic examinations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... name and location of the approved X-ray facility or facilities, and the approximate date(s) and time(s... shall promptly display in a visible location on the bulletin board at the mine its proposed plan or... posted in a visible location on the bulletin board until ALOSH either grants or denies approval of it at...

  17. 42 CFR 37.4 - Plans for chest roentgenographic examinations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... name and location of the approved X-ray facility or facilities, and the approximate date(s) and time(s... shall promptly display in a visible location on the bulletin board at the mine its proposed plan or... posted in a visible location on the bulletin board until ALOSH either grants or denies approval of it at...

  18. [Study on the reform and improvement of the medical device registration system in China].

    PubMed

    Wang, Lanming

    2012-11-01

    Based on the theories of the Government Regulation and Administrative Licensure, aiming at the current situations of medical device registration system in China, some policy suggestions for future reform and improvement were provided as follows. (1) change the concepts of medical device registration administration. (2) perfect the regulations of medical device registration administration. (3) reform the medical device review organizational system. (4) Optimize the procedure of review and approval. (5) set up and maintain a professional team of review and approval staff. (6) reinforce the post-marketing supervision of medical devices. (7) foster and bring into play of the role of non-government organizations.

  19. [Consideration of clinical development for new anticancer drugs on Japan, proposal from approval reviewer].

    PubMed

    Urano, Tsutomu

    2007-02-01

    There become problems about a delay on clinical development of anticancer drug in Japan and drug lag. I consider causes and solutions of the problems from a position of drug approval reviewer. I think the drug lag may cause by stating later state in global clinical development or stagnation of clinical trial activities. To prevail against drug lag,it is necessary to attend to multinational clinical studies,and to mature Japanese clinical trial environment and post-market planning. Then, I believe that the most important point is to make a start on early stage of global clinical development.

  20. The Effects of Implementing a Classwide Peer Tutoring Model on Social Approvals and Disapprovals Emitted during Unstructured Free Time

    ERIC Educational Resources Information Center

    Lawson, Tracy Reilly; Trapenberg, Gabrielle

    2007-01-01

    This study tested a classwide peer tutoring model using rule-governed responding to teach tutors to accurately present learn units during social studies instruction using a multiple baseline across participants with pre and post intervention probes. Three students, aged 8 to 10, in a self-contained 3rd/4th grade CABAS[R] classroom participated in…

  1. 77 FR 65436 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-26

    ... Rule Change Relating to Post-Trade Transparency for Agency Pass-Through Mortgage- Backed Securities... to post-trade transparency for Agency Pass-Through Mortgage-Backed Securities (``MBS'') traded in.... 78o-3(b)(6). In approving the original TRACE rules, the Commission stated that price transparency...

  2. 22 CFR 96.51 - Post-adoption services in incoming cases.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

  3. 22 CFR 96.51 - Post-adoption services in incoming cases.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

  4. 22 CFR 96.51 - Post-adoption services in incoming cases.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

  5. 22 CFR 96.51 - Post-adoption services in incoming cases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

  6. 22 CFR 96.51 - Post-adoption services in incoming cases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

  7. 77 FR 528 - Self-Regulatory Organizations; The National Securities Clearing Corporation; Order Granting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-05

    ...-Regulatory Organizations; The National Securities Clearing Corporation; Order Granting Approval of a Proposed Rule Change To Amend Rules Relating To the Creation of a Service To Provide Post-Trade Information... trading activity of their organizations, their correspondent firms, or both through review of post-trade...

  8. 75 FR 75373 - Conduct of Employees and Former Employees; Exemption From Post-Employment Restrictions for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-03

    ...; Exemption From Post- Employment Restrictions for Communications Furnishing Scientific or Technological... of the executive branch may obtain approval from DOE to make communications to DOE solely for the... communications to DOE solely for the purpose of furnishing scientific or technological information during the...

  9. Use of a bibliometric literature review to assess medical research capacity in post-conflict and developing countries: Somaliland 1991-2013.

    PubMed

    Boyce, Ross; Rosch, Richard; Finlayson, Alexander; Handuleh, Djibril; Walhad, Said Ahmed; Whitwell, Susannah; Leather, Andy

    2015-11-01

    Effective healthcare systems require high-quality research to guide evidence-based interventions and strategic planning. In low- and middle-income countries, especially those emerging from violent conflict, research capacity often lags behind other aspects of health system development. Here, we sought to bibliometrically review health-related research output in Somaliland, a post-conflict self-declared, autonomous nation on the Horn of Africa, as a means of assessing research capacity. We reviewed articles on health-related research conducted in Somaliland between 1991 and 2013 that included a description of the experimental design, and articles were published in either a peer-reviewed journal or as part of a scholarly programme receiving formal review. We did not include policy or social science research that did not enrol or interact with subjects from Somaliland. Using online databases, all studies meeting minimum eligibility criteria were reviewed in regard to Somaliland-based co-authorship, topic of research and specific measures of quality. A total of 37 studies were included in this review. Of these, only 19 (51%) included co-authorship by Somaliland-based researchers. Of the 21 studies reporting ethical approval, 16 (64%) received approval from the Somalia or Somaliland Ministry of Health, while five received approval from a university or national commission. More than two-thirds of published research was limited to a few areas of investigation with most (19, 51%) following basic cross-sectional study designs. The number of articles published per year increased from 0 to 1 in the years 1991-2007 to a maximum of 8 in 2013. Research activity in Somaliland is extremely limited. Investigators from high-income countries have largely directed the research agenda in Somaliland; only half of the included studies list co-authors from institutions in Somaliland. Leadership and governance of health research in Somaliland is required to define national priorities, promote scholarly activity and guide the responsible conduct of research. The methods used here to assess research capacity may be generalisable to other low- and middle-income countries and post-conflict settings to measure the impact of research capacity-building efforts. © 2015 John Wiley & Sons Ltd.

  10. Real Time Cockpit Resource Management (CRM) Training

    DTIC Science & Technology

    2010-10-01

    to post-test. Table 4 Learning Scores for the Five Spiral 1 Classes Spiral 1 Class Pilots Sensors Pretest Posttest Difference Pretest Posttest ...results from the five Spiral 1 classes. Table 6 Pretest / Posttest Gain Scores Associated with Each Learning Test Item Test Item Class Item...SMALL BUSINESS INNOVATION RESEARCH (SBIR) PHASE II REPORT. Distribution A: Approved for public release; distribution unlimited. (Approval given

  11. 77 FR 42497 - Information Collection(s) Being Submitted for Review and Approval to the Office of Management and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-19

    ... officer (a post staffed 24 hours a day) in the FCC's Communications and Crisis Management Center in... Approval to the Office of Management and Budget (OMB) AGENCY: Federal Communications Commission. ACTION... comments to Nicholas A. Fraser, Office of Management and Budget (OMB), via fax at 202-395-5167 or via...

  12. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

    PubMed

    Krentz, A J; Fujioka, K; Hompesch, M

    2016-06-01

    Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs. © 2016 John Wiley & Sons Ltd.

  13. How drugs are developed and approved by the FDA: current process and future directions.

    PubMed

    Ciociola, Arthur A; Cohen, Lawrence B; Kulkarni, Prasad

    2014-05-01

    This article provides an overview of FDA's regulatory processes for drug development and approval, and the estimated costs associated with the development of a drug, and also examines the issues and challenges facing the FDA in the near future. A literature search was performed using MEDLINE to summarize the current FDA drug approval processes and future directions. MEDLINE was further utilized to search for all cost analysis studies performed to evaluate the pharmaceutical industry R&D productivity and drug development cost estimates. While the drug approval process remains at high risk and spans over multiple years, the FDA drug review and approval process has improved, with the median approval time for new molecular drugs been reduced from 19 months to 10 months. The overall cost to development of a drug remains quite high and has been estimated to range from $868M to $1,241M USD. Several new laws have been enacted, including the FDA Safety and Innovation Act (FDASIA) of 2013, which is designed to improve the drug approval process and enhance access to new medicines. The FDA's improved processes for drug approval and post-market surveillance have achieved the goal of providing patients with timely access to effective drugs while minimizing the risk of drug-related harm. The FDA drug approval process is not without controversy, as a number of well-known gastroenterology drugs have been withdrawn from the US market over the past few years. With the approval of the new FDASIA law, the FDA will continue to improve their processes and, working together with the ACG through the FDA-Related Matters Committee, continue to develop safe and effective drugs for our patients.

  14. Survival benefit of glioblastoma patients after FDA approval of temozolomide concomitant with radiation and bevacizumab: A population-based study.

    PubMed

    Zhu, Ping; Du, Xianglin L; Lu, Guangrong; Zhu, Jay-Jiguang

    2017-07-04

    Few population-based analyses have investigated survival change in glioblastoma multiforme (GBM) patients treated with concomitant radiotherapy-temozolomide (RT-TMZ) and adjuvant temozolomide (TMZ) and then bevacizumab (BEV) after Food and Drug Administration (FDA) approval, respectively. We aimed to explore the effects on survival with RT-TMZ, adjuvant TMZ and BEV in general GBM population based on the Surveillance, Epidemiology, and End Results (SEER) and Texas Cancer Registry (TCR) databases. A total of 28933 GBM patients from SEER (N = 24578) and TCR (N = 4355) between January 2000 and December 2013 were included. Patients were grouped into three calendar periods based on date of diagnosis: pre-RT-TMZ and pre-BEV (1/2000-2/2005, P1), post-RT-TMZ and pre-BEV (3/2005-4/2009, P2), and post-RT-TMZ and post-BEV (5/2009-12/2013, P3). The association between calendar period of diagnosis and survival was analyzed in SEER and TCR, separately, by the Kaplan-Meier method and Cox proportional hazards model. We found a significant increase in median overall survival (OS) across the three periods in both populations. In multivariate models, the risk of death was significantly reduced during P2 and further decreased in P3, which remained unchanged after stratification. Comparison and validation analysis were performed in the combined dataset, and consistent results were observed. We conclude that the OS of GBM patients in a "real-world" setting has been steadily improved from January 2000 to December 2013, which likely resulted from the administrations of TMZ concomitant with RT and adjuvant TMZ for newly diagnosed GBM and then BEV for recurrent GBM after respective FDA approval.

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

    PubMed

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

    2011-10-01

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

  16. Objective Evidence of Reflux Control After Magnetic Sphincter Augmentation: One Year Results From a Post Approval Study.

    PubMed

    Louie, Brian E; Smith, C Daniel; Smith, Christopher C; Bell, Reginald C W; Gillian, George Kevin; Mandel, Jeffrey S; Perry, Kyle A; Birkenhagen, Walter Kurt; Taiganides, Paul A; Dunst, Christy M; McCollister, Howard M; Lipham, John C; Khaitan, Leena K; Tsuda, Shawn T; Jobe, Blair A; Kothari, Shanu N; Gould, Jon C

    2018-04-24

    To report 1-year results from a 5-year mandated study. In 2012, the United States Food and Drug Administration approved magnetic sphincter augmentation (MSA) with the LINX Reflux Management System (Torax Medical, Shoreview, MN), a novel device for the surgical treatment of gastroesophageal reflux disease (GERD). Continued assessment of safety and effectiveness has been monitored in a Post Approval Study. Multicenter, prospective study of patients with pathologic acid reflux confirmed by esophageal pH testing undergoing MSA. Predefined clinical outcomes were assessed at the annual visit including a validated, disease-specific questionnaire, esophagogastricduodenoscopy and esophageal pH monitoring, and use of proton pump inhibitors. A total of 200 patients (102 males, 98 females) with a mean age of 48.5 years (range 19.7-71.6) were treated with MSA between March 2013 and August 2015. At 1 year, the mean total acid exposure time decreased from 10.0% at baseline to 3.6%, and 74.4% of patients had normal esophageal acid exposure time (% time pH<4 ≤5.3%). GERD Health-Related Quality of Life scores improved from a median score of 26.0 at baseline to 4.0 at 1 year, with 84% of patients meeting the predefined success criteria of at least a 50% reduction in total GERD Health-Related Quality of Life score compared with baseline. The device removal rate at 1 year was 2.5%. One erosion and no serious adverse events were reported. Safety and effectiveness of magnetic sphincter augmentation has been demonstrated outside of an investigational setting to further confirm MSA as treatment for GERD.

  17. 48 CFR 752.7028 - Differential and allowances.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... employee is away from his/her post of assignment for purposes of home leave. Short-term employees shall be... approval of the Mission Director, short-term employees may be paid per diem (in lieu of living quarters... time such short-term employees spend at posts of duty in the Cooperating Country under this contract...

  18. 78 FR 42064 - Before Commissioners: Jon Wellinghoff, Chairman; Philip D. Moeller, John R. Norris, Cheryl A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-15

    ... reporting is ``an ex post activity'' that provides only prospective benefits to system reliability.\\14... Section 215, and those obligations that do not, such as administrative record-keeping and ex- post... EOP-004-2 becomes effective. Finally, we approve the proposed violation risk factors and violation...

  19. 13 CFR 123.204 - How much can your business borrow for post-disaster mitigation?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... for post-disaster mitigation? 123.204 Section 123.204 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.204 How much can your business borrow... approved physical disaster business loan to repair or replace your damaged business real estate and other...

  20. Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support).

    PubMed

    Starling, Randall C; Naka, Yoshifumi; Boyle, Andrew J; Gonzalez-Stawinski, Gonzalo; John, Ranjit; Jorde, Ulrich; Russell, Stuart D; Conte, John V; Aaronson, Keith D; McGee, Edwin C; Cotts, William G; DeNofrio, David; Pham, Duc Thinh; Farrar, David J; Pagani, Francis D

    2011-05-10

    The aim of this study was to determine whether results with the HeartMate (HM) II left ventricular assist device (LVAD) (Thoratec Corporation, Pleasanton, California) in a commercial setting are comparable to other available devices for the same indication. After a multicenter pivotal clinical trial conducted from 2005 to 2008, the U.S. Food and Drug Administration approved the HM II LVAD for bridge to transplantation (BTT). A post-approval study was required by the U.S. Food and Drug Administration to determine whether results with the device in a commercial setting are comparable to other available devices for the same indication. The study was a prospective evaluation of the first 169 consecutive HM II patients enrolled in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) who were listed for transplant or likely to be listed. Patients were enrolled from April through August 2008 at 77 U.S. centers and followed for at least 1 year after implant. A comparison group (COMP) included all patients (n = 169 at 27 centers) enrolled in the INTERMACS registry with other types of LVADs (79% HeartMate XVE, 21% Implantable Ventricular Assist Device [Thoratec Corporation]) for the same BTT indication in the same time period. Survival rates, adverse events, and quality of life with the EuroQol EQ-5D visual analog scale were obtained in the INTERMACS registry. Baseline characteristics were similar, but creatinine and blood urea nitrogen were lower in the HM II versus COMP groups, and there were fewer patients in the highest-risk INTERMACS patient profile Number 1 (24% for HM II vs. 39% for COMP). Adverse event rates were similar or lower for HM II versus COMP for all events. Bleeding was the most frequent adverse event for both groups (1.44 vs. 1.79 events/patient-year). Operative 30-day mortality for HM II was 4% versus 11% for COMP. The percentage of patients reaching transplant, cardiac recovery, or ongoing LVAD support by 6 months was 91% for HM II and 80% for COMP, and the Kaplan-Meier survival for patients remaining on support at 1 year was 85% for HM II versus 70% for COMP. Quality of life was significantly improved at 3 months of support and sustained through 12 months in both groups compared with baseline. The results in a post-market approval, actual patient care setting BTT population support the original findings from the pivotal clinical trial regarding the efficacy and risk profile of the HM II LVAD. These data suggest that dissemination of this technology after approval has been associated with continued excellent results. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Synergistic Action of FOXP3 and TSC1 Pathways During Tumor Progression

    DTIC Science & Technology

    2016-10-01

    Tumor progression, Gene therapy, Transcriptional regulation, Post -translational modification ACCOMPLISHMENTS Our preliminary studies provide evidence...Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT

  2. 75 FR 54940 - Agency Information Collection (IC) Activities; Revision of an Approved IC; Accident Recordkeeping...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ... include the Agency name and the docket number for this Notice. Note that DOT posts all comments received... underlying this IC is 49 CFR 390.15, ``Assistance in investigations and special studies.'' It requires motor... Information Technology. [FR Doc. 2010-22456 Filed 9-8-10; 8:45 am] BILLING CODE 4910-EX-P ...

  3. Risk Factors for Post-treatment Complex Regional Pain Syndrome (CRPS): An Analysis of 647 Cases of CRPS from the Danish Patient Compensation Association.

    PubMed

    Petersen, Pelle B; Mikkelsen, Kim L; Lauritzen, Jes B; Krogsgaard, Michael R

    2018-03-01

    Complex regional pain syndrome is a challenging condition that includes a broad spectrum of sensory, autonomic, and motor features predominantly in extremities recovering from a trauma. Few large-scale studies have addressed occurrence of and factors associated with complex regional pain syndrome (CRPS) following orthopedic treatment. The present study aimed to identify factors associated with post-treatment development of CRPS. Using the Danish Patient Compensation Association's database, we identified 647 patients claiming post-treatment CRPS between 1992 and 2015. Age, gender, initial diagnosis, treatment, and amount of compensation were extracted. Multivariate logistic regressions were performed to identify variables associated with approval of the claim. For carpal tunnel syndrome (CTS) patients, we registered whether symptoms were bilateral or unilateral and if neurophysiology prior to treatment was pathologic. The following ratios were found: women:men was 4:1, primary diagnosis to the upper limb:lower limb was 2.5:1, and surgical:nonsurgical treatment was 3:1. Mean age was 47.5 ± 13.7 years, and no intergender difference was detected. Antebrachial fracture (23%) and CTS (9%) were the most common primary conditions. Surgical treatment was associated with approval of the claim (odds ratio 3.5, 95% confidence interval 2.3 to 5.3; P < 0.001). Half of CTS patients had normal neurophysiology prior to surgery; among patients with unilateral symptoms, 71.4% had normal neurophysiology. Female gender, surgical treatment, and treatment to the upper limb were risk factors. Elective surgery accounted for a large number of post-treatment CRPS patients. In CTS patients developing CRPS, normal neurophysiological examination findings were common, and it could be suspected that these patients were suffering from an pre-clinical stage of CRPS, not CTS. © 2017 World Institute of Pain.

  4. Impact of computerized pre-authorization of broad spectrum antibiotics in Pseudomonas aeruginosa at a children's hospital in Japan.

    PubMed

    Horikoshi, Yuho; Higuchi, Hiroshi; Suwa, Junichi; Isogai, Mihoko; Shoji, Takayo; Ito, Kenta

    2016-08-01

    The spread of antimicrobial-resistant organisms is a global concern. To stem this tide, an antimicrobial stewardship program at hospitals is essential to optimize the prescription of broad spectrum antibiotics. In this study we examined the impact of computerized pre-authorization for broad spectrum antibiotics for Pseudomonas aeruginosa at a children's hospital. An antimicrobial stewardship program at Tokyo Metropolitan Children's Medical Center was assessed between March 2010 and March 2015. A paper-based post-prescription audit was switched to computerized pre-authorization for broad antipseudomonal agents in October 2011. The prescriber was required to obtain approval from physicians in the pediatric infectious diseases division before prescribing restricted antimicrobial agents. Approved prescriptions were processed and logged electronically. We evaluated days of therapy per 1000 patient-days, the cost of antibiotics, and the susceptibility of P. aeruginosa to piperacillin, ceftazidime, cefepime, piperacillin/tazobactam, carbapenems, and ciprofloxacin. Also, the average length of admission and infection-related mortality at 30 days were compared pre- and post-intervention. Administration of carbapenems, piperacillin/tazobactam, and ceftazidime decreased significantly after the introduction of computerized pre-authorization. Antibiotic costs were reduced by JPY2.86 million (USD 26,000) annually. None of the antipseudomonal agents showed decreased sensitivity. The average length of admission was shorter in post-intervention. Infection-related mortality at 30 days showed no difference between the pre- and post-intervention periods. An antimicrobial stewardship program using computerized pre-authorization decreased the use and cost of broad spectrum antibiotics without significant difference in infection-related mortality at 30 days, although our study did not improve susceptibilities of P. aeruginosa. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  5. Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

    PubMed

    Uhara, H; Kiyohara, Y; Tsuda, A; Takata, M; Yamazaki, N

    2018-02-01

    Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

  6. A Randomized Effectiveness Trial of a Systems-Level Approach to Stepped Care for War-Related PTSD

    DTIC Science & Technology

    2016-05-01

    period rather than storing the hard copies at their respective posts was approved. Also, an amendment changing the study Initiating PI from COL...care is the de facto mental health system; in Collaborative Medicine Case Studies : Evidence in Prac- tice. Edited by Kessler R, Stafford D. New York...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT During the 6.5 year study period, investigators developed the STEPS UP

  7. 40 CFR Appendix A to Subpart C of... - Alternative Testing Methods Approved for Analyses Under the Safe Drinking Water Act

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Chromatography/Mass Spectrometry (GC/MS) 525.3 24 Carbofuran High-performance liquid chromatography (HPLC) with... (HPLC) with Post-Column Derivatization and Fluorescence Detection 6651 B 6651 B 6651 B-00. Heptachlor... Spectrometry (GC/MS) 525.3 24 Oxamyl High-performance liquid chromatography (HPLC) with post-column...

  8. 78 FR 5292 - Approval and Promulgation of Air Quality Implementation Plans; Massachusetts and New Hampshire...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-25

    ... and New Hampshire. The revised programs in Massachusetts and New Hampshire include a test and repair..., EPA New England Regional Office, Office of Ecosystem Protection, Air Quality Planning Unit, 5 Post... Protection, Air Quality Planning Unit, 5 Post Office Square--Suite 100, (Mail code OEP05-2), Boston, MA 02109...

  9. 77 FR 47472 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-08

    .... During pre and post-market hours, the wider Designated Percentage and Defined Limit associated with the 9... Exchange, the automated quote management functionality (``AQ'') offered by these rules is designed to help Exchange market makers meet the enhanced market maker obligations adopted post May 6, 2010,\\6\\ and avoid...

  10. 13 CFR 123.204 - How much can your business borrow for post-disaster mitigation?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... for post-disaster mitigation? 123.204 Section 123.204 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.204 How much can your business borrow... can request an increase in the approved physical disaster business loan by the lesser of the cost of...

  11. 13 CFR 123.204 - How much can your business borrow for post-disaster mitigation?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... for post-disaster mitigation? 123.204 Section 123.204 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.204 How much can your business borrow... can request an increase in the approved physical disaster business loan by the lesser of the cost of...

  12. 13 CFR 123.204 - How much can your business borrow for post-disaster mitigation?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... for post-disaster mitigation? 123.204 Section 123.204 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.204 How much can your business borrow... can request an increase in the approved physical disaster business loan by the lesser of the cost of...

  13. 13 CFR 123.204 - How much can your business borrow for post-disaster mitigation?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... for post-disaster mitigation? 123.204 Section 123.204 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Physical Disaster Business Loans § 123.204 How much can your business borrow... can request an increase in the approved physical disaster business loan by the lesser of the cost of...

  14. Evaluation of the Impact of Kerojet (trademark) Aquarius Water Scavenger Additive on the Thermal Stability of Jet A Fuels

    DTIC Science & Technology

    2014-12-01

    113 Figure 64 - Elemental Analysis, Typical TMS Post - Test , Post Carbon Burn-off, Hexane rinsed ............ 114 Figure 65 – SEM (20X...Agency’s Wright-Patterson Aerospace Fuels Laboratory AFRL Air Force Research Laboratory AFTSTU Aviation Fuel Thermal Stability Test Unit ARSFSS Advanced...Approved for public release; distribution unlimited. For all ARSFSS testing , SV hysteresis is measure pre- and post - test and is defined by relating

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

    PubMed

    Sato, J

    2001-12-01

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

  16. Update on the everolimus-eluting coronary stent system: results and implications from the SPIRIT clinical trial program

    PubMed Central

    Kirchner, R Michael; Abbott, J Dawn

    2009-01-01

    Drug-eluting stents (DES) have had a major impact in interventional cardiology. Compared to bare metal stents, they significantly reduce restenosis and the need for target vessel revascularization. Four DES are available in the US, the first-generation sirolimus-eluting (Cypher®) and paclitaxel-eluting (Taxus®) stents and later approved second-generation everolimus-eluting (Xience V®) and zotarolimus-eluting (Endeavor®) stents. The Xience V stent was approved on the basis of clinical efficacy and safety data from 3 studies in the SPIRIT clinical trial program. Within this trial series, the Xience V was superior to its bare metal stent counterpart, the Vision® stent, and noninferior to the paclitaxel-eluting stent for target vessel failure at 9 months. This review provides a comprehensive assessment of the data derived from both the pre- and post-approval randomized controlled trials and registry studies of Xience V that comprise the SPIRIT clinical trial program including recently published mid-term outcomes. The implications of the results in terms of interventional practice will be discussed. PMID:20057901

  17. Assessment of the Ability of the Health Care Provider to Detect Manifestations Indicative of TBI Management of care for TBI Through the Utilization of High Fidelity Simulation

    DTIC Science & Technology

    2015-09-01

    position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting...to be tested in the research study were: Hypothesis 1. The study participants will be able to identify the manifestations for patients with traumatic...brain injuries in pre and post evaluation measures. Hypothesis 2. The study participants will have an increased rate of the identification of

  18. 24 CFR 598.425 - Validation of designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... URBAN DEVELOPMENT COMMUNITY FACILITIES URBAN EMPOWERMENT ZONES: ROUND TWO AND THREE DESIGNATIONS Post... of any Empowerment Zone. (b) HUD may approve an Empowerment Zone's request for boundary modification...

  19. Mechanical circulatory support in pediatrics.

    PubMed

    Steffen, Robert J; Miletic, Kyle G; Schraufnagel, Dean P; Vargo, Patrick R; Fukamachi, Kiyotaka; Stewart, Robert D; Moazami, Nader

    2016-05-01

    End-stage heart failure affects thousands of children yearly and mechanical circulatory support is used at many points in their care. Extracorporeal membrane oxygenation supports both the failing heart and lungs, which has led to its use as an adjunct to cardiopulmonary resuscitation as well as in post-operative cardiogenic shock. Continuous-flow ventricular assist devices (VAD) have replaced pulsatile-flow devices in adults and early studies have shown promising results in children. The Berlin paracorporeal pulsatile VAD recently gained U.S. Food and Drug Administration approval and remains the only VAD approved in pediatrics. Failing univentricular hearts and other congenitally corrected lesions are new areas for mechanical support. Finding novel uses, improving durability, and minimizing complications are areas of growth in pediatric mechanical circulatory support.

  20. Safety of the molluscicide Zequanox (R) to nontarget macroinvertebrates Gammarus lacustris (Amphipoda: Gammaridae) and Hexagenia spp. (Ephemeroptera: Ephemeridae)

    USGS Publications Warehouse

    Waller, Diane L.; Luoma, James A.; Erickson, Richard A.

    2016-01-01

    Zequanox® is a commercial formulation of the killed bacterium, Pseudomonas fluorescens (strain CL145A), that was developed to control dreissenid mussels. In 2014, Zequanox became the second product registered by the United States Environmental Protection Agency (USEPA) for use in open water environments as a molluscicide. Previous nontarget studies demonstrated the safety and selectivity of P. fluorescens CL154A, but the database on the toxicity of the formulation (Zequanox) is limited for macroinvertebrate taxa and exposure conditions. We evaluated the safety of Zequanox to the amphipod Gammarus lacustris lacustris, and nymphs of the burrowing mayfly, Hexagenia spp. at the maximum approved concentration (100 mg/L active ingredient, A.I.) and exposure duration (8 h). Survival of animals was assessed after 8 h of exposure and again at 24 and 96 h post-exposure. Histopathology of the digestive tract of control and treated animals was compared at 96 h post-exposure. The results showed no significant effect of Zequanox on survival of either species. Survival of G. lacustris exceeded 85% in all concentrations at all three sampling time points. Survival of Hexagenia spp. ranged from 71% (control) to 91% at 8 h, 89–93% at 24 h post-exposure, and 70–73% at 96 h post-exposure across all treatments. We saw no evidence of pathology in the visceral organs of treated animals. Our results indicate that application of Zequanox at the maximum approved concentration and exposure duration did not cause significant mortality or treatment-related histopathological changes to G. lacustris and Hexagenia spp.

  1. 78 FR 42951 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-18

    ... responses per response (in hours respondent hours) Pre-Test Women's Survey 40 1 23/60 15 Post-Test Women's Survey 40 1 23/60 15 Pre-Test Physician's/Nurses Survey 150 1 5/60 13 Post-Test Physician's/Nurses Survey... initiative to identify and test effective and innovative ways of reducing obesity in lesbian and bisexual...

  2. Developmental TVET Rhetoric In-Action: The White Paper for Post-School Education and Training in South Africa

    ERIC Educational Resources Information Center

    Akoojee, Salim

    2016-01-01

    This paper explores the extent to which latest developments in the Technical and Vocational Education and Training System in South Africa respond to key principles espoused for a developmental, democratic and inclusionary ideal. The White Paper for post school education and training (DHET, 2013) approved by Cabinet in November, 2013 is referred to…

  3. Developmental TVET Rhetoric In-Action: The White Paper for Post-School Education and Training in South Africa

    ERIC Educational Resources Information Center

    Akoojee, Salim

    2016-01-01

    This paper explores the extent to which latest developments in the Technical and Vocational Education and Training System in South Africa respond to key principles espoused for a developmental, democratic and inclusionary ideal. The White Paper for post school education and training approved by Cabinet in November, 2013 is referred to by the…

  4. 13 CFR 123.107 - How much can I borrow for post-disaster mitigation for my home?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...-disaster mitigation for my home? 123.107 Section 123.107 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.107 How much can I borrow for post-disaster... that the approved home disaster loan amount be increased by the lesser of the cost of the mitigation...

  5. 13 CFR 123.107 - How much can I borrow for post-disaster mitigation for my home?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...-disaster mitigation for my home? 123.107 Section 123.107 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.107 How much can I borrow for post-disaster... that the approved home disaster loan amount be increased by the lesser of the cost of the mitigation...

  6. 13 CFR 123.107 - How much can I borrow for post-disaster mitigation for my home?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...-disaster mitigation for my home? 123.107 Section 123.107 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.107 How much can I borrow for post-disaster... that the approved home disaster loan amount be increased by the lesser of the cost of the mitigation...

  7. 13 CFR 123.107 - How much can I borrow for post-disaster mitigation for my home?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...-disaster mitigation for my home? 123.107 Section 123.107 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Home Disaster Loans § 123.107 How much can I borrow for post-disaster... that the approved home disaster loan amount be increased by the lesser of the cost of the mitigation...

  8. Symptoms of dysphagia in children with cleft lip and/or palate pre- and post-surgical correction.

    PubMed

    Freitas, Jordana da Silva; Cardoso, Maria Cristina de Almeida Freitas

    2018-03-05

    Determine the occurrence of dysphagia symptoms in children with cleft lip and/or palate (CLP) pre- and post-surgical correction. Quantitative observational cross-sectional study. Existence of clef lip and/or palate without association with other syndromes was the study inclusion and/or exclusion criterion. Parents and/or legal guardians responded to a recall questionnaire on the identification of occurrence of coughing, choking, vomiting, and nasal escape pre- and postoperatively and whether these symptoms disappeared after surgical correction. The study was approved by the Research Ethics Committee of the aforementioned Institution under protocol no. 1573164. The sample comprised 23 children with mean age of 48 months, mostly male and with unilateral trans-foramen incisor clefts. Statistically significant difference was observed between the pre- and post-surgical periods regarding the presence of dysphagia symptoms. Surgical treatment of patients with cleft lip and/or palate proved to be a resource to prevent the occurrence of dysphagia symptoms when associated with adequate intervention chronology.

  9. Biosimilars in inflammatory bowel disease: A review of post-marketing experience.

    PubMed

    Deiana, Simona; Gabbani, Tommaso; Annese, Vito

    2017-01-14

    Biologic compounds are obtained from living organisms or cell cultures by means of biotechnology methods. A similar biologic drug, commonly called biosimilar, is a product copied by a native approved biologic drug whose license has expired. Biosimilar drugs usually are marketed at a lower price and provide important financial savings for public healthcare systems. Some differences between biosimilars and original biologic drugs might exist but they are acceptable if they fall within defined "boundaries of tolerance": differences in some features between the two molecules are considered important only if clinical relevant. Considering that the efficacy of the innovator biologic drug has already been established, the clinical studies required for approval of a biosimilar could be reduced compared with those required for the approval of the originator. In this review, real life data available in inflammatory bowel disease patients treated with biosimilars are reported, documenting in general satisfactory outcomes, sustained efficacy and no sign of increased immunogenicity, although, further controlled data are awaited.

  10. Pre-clinical evaluation of a nanoparticle-based blood-pool contrast agent for MR imaging of the placenta.

    PubMed

    Ghaghada, Ketan B; Starosolski, Zbigniew A; Bhayana, Saakshi; Stupin, Igor; Patel, Chandreshkumar V; Bhavane, Rohan C; Gao, Haijun; Bednov, Andrey; Yallampalli, Chandrasekhar; Belfort, Michael; George, Verghese; Annapragada, Ananth V

    2017-09-01

    Non-invasive 3D imaging that enables clear visualization of placental margins is of interest in the accurate diagnosis of placental pathologies. This study investigated if contrast-enhanced MRI performed using a liposomal gadolinium blood-pool contrast agent (liposomal-Gd) enables clear visualization of the placental margins and the placental-myometrial interface (retroplacental space). Non-contrast MRI and contrast-enhanced MRI using a clinically approved conventional contrast agent were used as comparators. Studies were performed in pregnant rats under an approved protocol. MRI was performed at 1T using a permanent magnet small animal scanner. Pre-contrast and post-liposomal-Gd contrast images were acquired using T1-weighted and T2-weighted sequences. Dynamic Contrast enhanced MRI (DCE-MRI) was performed using gadoterate meglumine (Gd-DOTA, Dotarem ® ). Visualization of the retroplacental clear space, a marker of normal placentation, was judged by a trained radiologist. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated for both single and averaged acquisitions. Images were reviewed by a radiologist and scored for the visualization of placental features. Contrast-enhanced CT (CE-CT) imaging using a liposomal CT agent was performed for confirmation of the MR findings. Transplacental transport of liposomal-Gd was evaluated by post-mortem elemental analysis of tissues. Ex-vivo studies in perfused human placentae from normal, GDM, and IUGR pregnancies evaluated the transport of liposomal agent across the human placental barrier. Post-contrast T1w images acquired with liposomal-Gd demonstrated significantly higher SNR (p = 0.0002) in the placenta compared to pre-contrast images (28.0 ± 4.7 vs. 6.9 ± 1.8). No significant differences (p = 0.39) were noted between SNR in pre-contrast and post-contrast liposomal-Gd images of the amniotic fluid, indicating absence of transplacental passage of the agent. The placental margins were significantly (p < 0.001) better visualized on post-contrast liposomal-Gd images. DCE-MRI with the conventional Gd agent demonstrated retrograde opacification of the placenta from fetal edge to the myometrium, consistent with the anatomy of the rat placenta. However, no consistent and reproducible visualization of the retroplacental space was demonstrated on the conventional Gd-enhanced images. The retroplacental space was only visualized on post-contrast T1w images acquired using the liposomal agent (SNR = 15.5 ± 3.4) as a sharply defined, hypo-enhanced interface. The retroplacental space was also visible as a similar hypo-enhancing interface on CE-CT images acquired using a liposomal CT contrast agent. Tissue analysis demonstrated undetectably low transplacental permeation of liposomal-Gd, and was confirmed by lack of permeation through a perfused human placental model. Contrast-enhanced T1w-MRI performed using liposomal-Gd enabled clear visualization of placental margins and delineation of the retroplacental space from the rest of the placenta; the space is undetectable on non-contrast imaging and on post-contrast T1w images acquired using a conventional, clinically approved Gd chelate contrast agent. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 30 CFR 15.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... sealed covering and designed to be fired outside the confines of a borehole. Test detonator. An... for use under this part. Post-approval product audit. Examination, testing, or both, by MSHA of...

  12. 30 CFR 15.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... sealed covering and designed to be fired outside the confines of a borehole. Test detonator. An... for use under this part. Post-approval product audit. Examination, testing, or both, by MSHA of...

  13. 30 CFR 15.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... sealed covering and designed to be fired outside the confines of a borehole. Test detonator. An... for use under this part. Post-approval product audit. Examination, testing, or both, by MSHA of...

  14. 30 CFR 15.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... sealed covering and designed to be fired outside the confines of a borehole. Test detonator. An... for use under this part. Post-approval product audit. Examination, testing, or both, by MSHA of...

  15. 7 CFR 1721.109 - OMB control number.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE POST-LOAN POLICIES AND PROCEDURES FOR INSURED ELECTRIC LOANS Extensions of Payments of Principal... approved by the Office of Management and Budget and assigned OMB control number 0572-0123. ...

  16. DDG-1000 Missile Integration: A Case Study

    DTIC Science & Technology

    2014-03-01

    hazards of electromagnetic radiation to ordnance (HERO) from those emitters, are not addressed in the JUWL program because legacy requirements are...UU NSN 7540–01–280–5500 Standard Form 298 (Rev. 2–89) Prescribed by ANSI Std. 239–18 ii THIS PAGE INTENTIONALLY LEFT BLANK iii Approved...weapon link on a xvii new frequency. All other requirements, such as pre- and post-launch interfaces, electromagnetic vulnerability requirements

  17. Comparison of pre/post-operative CT image volumes to preoperative digitization of partial hepatectomies: a feasibility study in surgical validation

    NASA Astrophysics Data System (ADS)

    Dumpuri, Prashanth; Clements, Logan W.; Li, Rui; Waite, Jonathan M.; Stefansic, James D.; Geller, David A.; Miga, Michael I.; Dawant, Benoit M.

    2009-02-01

    Preoperative planning combined with image-guidance has shown promise towards increasing the accuracy of liver resection procedures. The purpose of this study was to validate one such preoperative planning tool for four patients undergoing hepatic resection. Preoperative computed tomography (CT) images acquired before surgery were used to identify tumor margins and to plan the surgical approach for resection of these tumors. Surgery was then performed with intraoperative digitization data acquire by an FDA approved image-guided liver surgery system (Pathfinder Therapeutics, Inc., Nashville, TN). Within 5-7 days after surgery, post-operative CT image volumes were acquired. Registration of data within a common coordinate reference was achieved and preoperative plans were compared to the postoperative volumes. Semi-quantitative comparisons are presented in this work and preliminary results indicate that significant liver regeneration/hypertrophy in the postoperative CT images may be present post-operatively. This could challenge pre/post operative CT volume change comparisons as a means to evaluate the accuracy of preoperative surgical plans.

  18. Intravenous ibuprofen: the first injectable product for the treatment of pain and fever

    PubMed Central

    Bookstaver, P Brandon; Miller, April D; Rudisill, Celeste N; Norris, LeAnn B

    2010-01-01

    This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in a series of post-operative patient populations. Two recent studies have also noted the improvement in fever curves in critically ill and burn patients. These data, along with pharmacokinetic and pharmacologic properties, are explored in this review, which addresses the clinical utility of a parenteral NSAID in a hospitalized patient for post-operative pain management and fever reduction. Further data on intravenous ibuprofen are needed to define long-term utilization, management of acute pain, and use in special populations. PMID:21197311

  19. Advances in the management of multiple sclerosis spasticity: recent clinical trials.

    PubMed

    Fernández, Oscar

    2014-01-01

    Most patients with multiple sclerosis (MS) experience spasticity as the clinical course evolves. Associated symptoms include (often painful) spasms, urinary dysfunction and sleep disturbances. THC:CBD oromucosal spray (Sativex®) is approved for symptom improvement in adult patients with moderate to severe MS-related spasticity who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. In pivotal clinical trials of THC:CBD oromucosal spray, a meaningful proportion of patients with treatment-resistant MS spasticity achieved clinically relevant improvement with active treatment versus placebo. The utility of a 4-week trial of therapy to identify patients who respond to treatment was demonstrated in an enriched-design study. THC:CBD oromucosal spray was well tolerated in these studies, with no evidence of effects typically associated with recreational cannabis use. In a subsequent post approval clinical trial, THC:CBD oromucosal spray had no statistically significant effect on cognition and mood compared with placebo. Moreover, after 50 weeks' treatment, approximately two-thirds of patients, physicians and caregivers reported improvement from baseline in spasticity based on global impressions of change. Key Messages: In phase III clinical trials, approximately one-third of MS patients with treatment-resistant spasticity had a clinically relevant and statistically significant response to THC:CBD oromucosal spray. In addition to a reduction in spasticity, responders experienced meaningful relief from associated symptoms. THC:CBD oromucosal spray was generally well tolerated and efficacy was maintained over the longer term. A post-approval clinical trial indicated no effect of THC:CBD oromucosal spray on cognition or mood after 50 weeks of use. © 2014 S. Karger AG, Basel.

  20. Research Ethics Education in Post-Graduate Medical Curricula in I.R. Iran.

    PubMed

    Nikravanfard, Nazila; Khorasanizadeh, Faezeh; Zendehdel, Kazem

    2017-08-01

    Research ethics training during post-graduate education is necessary to improve ethical standards in the design and conduct of biomedical research. We studied quality and quantity of research ethics training in the curricula of post-graduate programs in the medical science in I.R. Iran. We evaluated curricula of 125 post-graduate programs in medical sciences in I.R. Iran. We qualitatively studied the curricula by education level, including the Master and PhD degrees and analyzed the contents and the amount of teaching allocated for ethics training in each curriculum. We found no research ethics training in 72 (58%) of the programs. Among the 53 (42%) programs that considered research ethics training, only 17 programs had specific courses for research ethics and eight of them had detailed topics on their courses. The research ethics training was optional in 25% and mandatory in 76% of the programs. Post-graduate studies that were approved in the more recent years had more attention to the research ethics training. Research ethics training was neglected in most of the medical post-graduate programs. We suggest including sufficient amount of mandatory research ethics training in Master and PhD programs in I.R. Iran. Further research about quality of research ethics training and implementation of curricula in the biomedical institutions is warranted. © 2016 John Wiley & Sons Ltd.

  1. VA Education Benefits: Actions Taken, but Outreach and Oversight Could Be Improved. Report to the Ranking Member, Subcommittee on Military Personnel, Committee on Armed Services, House of Representatives. GAO-11-256

    ERIC Educational Resources Information Center

    Bertoni, Daniel

    2011-01-01

    The U.S. Department of Veterans Affairs (VA) provided $9 billion in education benefits to service-members and veterans in fiscal year 2010, mostly through the new Post-9/11 GI Bill. In providing education benefits, VA relies on State Approving Agencies (SAA) to approve schools; and on schools to report students' enrollment status. US Government…

  2. Company observational post-marketing studies: drug risk assessment and drug research in special populations--a study-based analysis.

    PubMed

    Hasford, J; Lamprecht, T

    1998-01-01

    Company observational post-marketing studies (COPS) claim to provide essential data about drug risks and effectiveness in special populations not admitted to pre-approval clinical trials. Since COPS are often mainly regarded as a marketing activity, this study-based analysis tries to evaluate the scientific contributions of COPS. Thirty-five COPS were identified by hand-searching through medical journals, writing to pharmaceutical manufacturers and using MEDLINE. Fourteen COPS evaluated cardiovascular drugs, 9 evaluated NSAIDs and 12 evaluated various other indications. Thirty-five COPS listed effectiveness, 31 listed safety and 8 listed patient compliance as principal objectives. Not a single COPS included a control group. Seventeen of 21 evaluable COPS mentioned extensive exclusion criteria similar to those in clinical trials. Median observation time was 8 weeks, too short for chronic diseases and for adverse drug reactions with longer latency periods. One new adverse event was regarded. Global assessments of the outcomes by physicians dominated and were not based on objective clinical findings. None of the studies specified any details concerning the standardisation of observations or quality-control procedures. The current COPS scheme does not contribute significantly to our knowledge of drug safety and the effects in special populations. Despite serious criticism over the past 20 years, the poor quality of COPS compared with dramatic improvements of pre-approval trials - implies a need for detailed guidelines for non-experimental phase IV research, similar to the Good Clinical Practice-Guideline of the European Community.

  3. A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor.

    PubMed

    Licciardello, Marco P; Ringler, Anna; Markt, Patrick; Klepsch, Freya; Lardeau, Charles-Hugues; Sdelci, Sara; Schirghuber, Erika; Müller, André C; Caldera, Michael; Wagner, Anja; Herzog, Rebecca; Penz, Thomas; Schuster, Michael; Boidol, Bernd; Dürnberger, Gerhard; Folkvaljon, Yasin; Stattin, Pär; Ivanov, Vladimir; Colinge, Jacques; Bock, Christoph; Kratochwill, Klaus; Menche, Jörg; Bennett, Keiryn L; Kubicek, Stefan

    2017-07-01

    Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for γ-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.

  4. An Integrated Experimental and Computational Study of Heating due to Surface Catalysis under Hypersonic Conditions

    DTIC Science & Technology

    2012-08-01

    17 1.1.1 Mass production / destruction terms . . . . . . . . . . . . . . . . . . . . 18 1.1.2 Energy exchange terms...that US3D does not cur- rently model electronic energy . If the US3D solution is post-processed to account for electronic energy modes, the computed...nonequilibrium model for electronic energy to the 12 Distribution A: Approved for public release; distribution is unlimited. Figure 9: (left) jet profile solution

  5. Sexual Assaults Under the Uniform Code of Military Justice (UCMJ): Selected Legislative Proposals

    DTIC Science & Technology

    2013-09-06

    review, the Secretary of Defense has directed action to allow victims greater opportunity to participate in post-trial matters.127 Specifically...UCMJ” (Legal Studies Research Paper Series, Working Paper No. 2012-23, University of Pittsburgh School of Law, 2012). 133 Administrative action can...September 6, 2013 Congressional Research Service 7-5700 www.crs.gov R43213 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting

  6. Posturography and locomotor tests of dynamic balance after long-duration spaceflight.

    PubMed

    Cohen, Helen S; Kimball, Kay T; Mulavara, Ajitkumar P; Bloomberg, Jacob J; Paloski, William H

    2012-01-01

    The currently approved objective clinical measure of standing balance in astronauts after space flight is the Sensory Organization Test battery of computerized dynamic posturography. No tests of walking balance are currently approved for standard clinical testing of astronauts. This study determined the sensitivity and specificity of standing and walking balance tests for astronauts before and after long-duration space flight. Astronauts were tested on an obstacle avoidance test known as the Functional Mobility Test (FMT) and on the Sensory Organization Test using sway-referenced support surface motion with eyes closed (SOT 5) before and six months after (n=15) space flight on the International Space Station. They were tested two to seven days after landing. Scores on SOT tests decreased and scores on FMT increased significantly from pre- to post-flight. In other words, post-flight scores were worse than pre-flight scores. SOT and FMT scores were not significantly related. ROC analyses indicated supra-clinical cut-points for SOT 5 and for FMT. The standard clinical cut-point for SOT 5 had low sensitivity to post-flight astronauts. Higher cut-points increased sensitivity to post-flight astronauts but decreased specificity to pre-flight astronauts. Using an FMT cut-point that was moderately highly sensitive and highly specific plus SOT 5 at the standard clinical cut-point was no more sensitive than SOT 5, alone. FMT plus SOT 5 at higher cut-points was more specific and more sensitive. The total correctly classified was highest for FMT, alone, and for FMT plus SOT 5 at the highest cut-point. These findings indicate that standard clinical comparisons are not useful for identifying problems. Testing both standing and walking balance will be more likely to identify balance deficits.

  7. Meta-analysis: pre-operative infliximab treatment and short-term post-operative complications in patients with ulcerative colitis.

    PubMed

    Yang, Z; Wu, Q; Wu, K; Fan, D

    2010-02-15

    Infliximab was approved for use in ulcerative colitis in recent years. It has been debated if infliximab increases the risk of post-operative complications in patients with ulcerative colitis. To perform a meta-analysis that examines the relationship between preoperative infliximab treatment and short-term post-operative complications in patients with ulcerative colitis. We searched the PubMed and MEDLINE databases to identify observational studies on the impact of pre-operative infliximab use on short-term post-operative complications in ulcerative colitis. Infectious complications mainly included wound infection, sepsis and abscess, whereas non-infectious complications included intestinal obstruction, thromboembolism and gastrointestinal haemorrhage. Pooled odds ratios (ORs) were calculated for each relationship. A total of 5 studies and 706 patients were included in our meta-analysis. Overall, we did not find a strong association between pre-operative treatment of infliximab and short-term infectious [OR 2.24, 95% confidence interval (CI) 0.63-7.95] or non-infectious (OR 0.85, 95% CI 0.50-1.45) post-operative complications in ulcerative colitis patients. On the contrary, we discovered that pre-operative infliximab use increased short-term total post-operative complications (OR 1.80, 95% CI 1.12-2.87). Pre-operative infliximab use increased the risk of short-term post-operative complications. Subgroup analysis is underpowered to assess the nature of these complications but shows a trend towards increased post-operative infection.

  8. Portable Low-Volume Therapy for Severe Blood Loss

    DTIC Science & Technology

    2013-06-01

    with Tukey’s post hoc test were performed to find treatment differences within different time points for total hemoglobin (tHb), pH, pressure of...Tukey’s post hoc test were performed to find treatment differences within time points. No correlation was observed for any of the parameters at any...Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB

  9. Enrollment and Monitoring of Women in Post-Approval Studies for Medical Devices Mandated by the Food and Drug Administration

    PubMed Central

    Herz, Naomi; Loyo-Berrios, Nilsa; Tarver, Michelle

    2014-01-01

    Abstract Background: Disease presentation, prevalence, and treatment effects vary by sex, thus it is important to ensure adequate participation of both sexes in medical device post-approval studies (PAS). Methods: The goals of this study were to determine the participation rate of women in PAS mandated by the Food and Drug Administration (FDA) and if participation varied by clinical area. The study also evaluated the frequency in which enrollment by sex is reported by applicant reports and FDA reviews, as well as the frequency in which final study reports analyze whether outcomes differ by sex. Results: Of 89 studies with enrollment completed, data on sex of participants were available in 93% of submitted reports, while data on enrollment by sex was evaluated and noted in 43% of FDA review memos. Study participation varied by clinical area, with female participation ranging from 32% in cardiovascular PAS to 90% in PAS for reconstructive devices. Of 53 completed studies, data on enrollment by sex was provided in 49 of the final reports. Of these 14% included a multivariate analysis that included sex as a covariate and 4% included a subgroup analysis for female participants. Conclusions: Data on sex was not routinely assessed in FDA reviews. Based on these findings, FDA implemented new procedures to ensure participation by sex is evaluated in PAS reviews. FDA will continue working with applicants to develop PAS that enroll and retain proportions of women consistent with the sex-specific prevalence for the disease or condition the device is used to treat. PMID:24405314

  10. Does dexmedetomidine given as a premedication or intraoperatively reduce post-hospitalisation behaviour change in children? A study protocol for a randomised controlled trial in a tertiary paediatric hospital.

    PubMed

    Lee-Archer, Paul; McBride, Craig; Paterson, Rebecca; Reade, Michael; Regli-von Ungern-Sternberg, Britta; Long, Deborah

    2018-04-17

    It has been reported that post-hospitalisation behaviour change (PHBC) occurs in over 50% of children undergoing a general anaesthetic and manifests as behaviours such as sleep and eating disorders, defiance of authority, nightmares, enuresis and temper tantrums. The effect is usually short-lived (2-4 weeks); however, in 5-10% of children, these behaviours can last up to 12 months. The risk factors for developing PHBC include underlying anxiety in the child or parent, a previous bad hospital experience, emergence delirium and preschool age. A recent meta-analysis of alpha-2 agonists (including dexmedetomidine) found that they effectively reduce the incidence of emergence delirium but none of the studies looked at longer term outcomes, such as PHBC. Two-year-old to seven-year-old children requiring general anaesthesia for common day-case procedures will be randomly assigned to one of three groups: a dexmedetomidine pre medication group, an intraoperative dexmedetomidine group and a control group. Baseline anxiety levels of the parent will be recorded and the anxiety of the child during induction of anaesthesia will also be recorded using validated tools. The primary outcome will be negative behaviours after hospitalisation and these will be measured using the Post Hospitalisation Behaviour Questionnaire for Ambulatory Surgery and the Strengths and Difficulties Questionnaire. These questionnaires will be administered by a blinded researcher at days 3, 14 and 28 post surgery. Ethics approval has been granted by the Children's Health Queensland human research ethics committee (HREC/15/QRCH/248) and the University of Queensland human research ethics office (#2016001715). Any amendments to this protocol will be submitted to the ethics committees for approval. ANZCTR:12616000096459; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. First-line treatment disruption among post-menopausal women with HR+/HER2- metastatic breast cancer: a retrospective US claims study.

    PubMed

    Tang, Derek H; Li, Nanxin; Du, Ella X; Peeples, Miranda; Chu, Lihao; Xie, Jipan; Barghout, Victoria

    2017-12-01

    This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post-menopausal women with HR+/HER2- metastatic breast cancer (mBC) in the US. Post-menopausal women with HR+/HER2- mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database. Patients were required to have continuous quarterly activity (defined as ≥1 pharmacy or medical claim) for 12 months prior to and 1 month after the initiation of the index therapy (index date). Treatment disruption was defined as a treatment gap of ≥60 days or adding an agent after the original therapy. Kaplan-Meier analyses were conducted to estimate treatment disruption rates during the 6 months following the index date. Patients without treatment disruption were censored at the end of continuous quarterly activity or end of data. A total of 8,160 and 2,153 eligible patients initiated endocrine therapy or chemotherapy as their first-line mBC treatment, with a median follow-up of 6.7 and 7.6 months, respectively. The three most prevalent metastatic sites were bone (28.1-42.2%), liver (8.8-17.3%), and lung (8.6-9.5%). Overall, 37.7% (n = 3,074) of patients receiving endocrine therapy and 86.1% (n = 1,852) of patients receiving chemotherapy encountered treatment disruption at 6 months (log-rank test p < .05). Treatment disruption rates of first-line therapies were sub-optimal among post-menopausal women with HR+/HER2- mBC, primarily driven by chemotherapy users. New therapies or interventions are needed to reduce treatment disruption in this patient population.

  12. Methodological challenges in monitoring new treatments for rare diseases: lessons from the cryopyrin-associated periodic syndrome registry.

    PubMed

    Tilson, Hugh; Primatesta, Paola; Kim, Dennis; Rauer, Barbara; Hawkins, Philip N; Hoffman, Hal M; Kuemmerle-Deschner, Jasmin; van der Poll, Tom; Walker, Ulrich A

    2013-09-10

    The Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare hereditary autoinflammatory diseases and encompass Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal Onset Multisystem Inflammatory Disease (NOMID). Canakinumab is a monoclonal antibody directed against IL-1 beta and approved for CAPS patients but requires post-approval monitoring due to low and short exposures during the licensing process. Creative approaches to observational methodology are needed, harnessing novel registry strategies to ensure Health Care Provider reporting and patient monitoring. A web-based registry was set up to collect information on long-term safety and effectiveness of canakinumab for CAPS. Starting in November 2009, this registry enrolled 241 patients in 43 centers and 13 countries by December 31, 2012. One-third of the enrolled population was aged < 18; the overall population is evenly divided by gender. Enrolment is ongoing for children. Innovative therapies in orphan diseases require post-approval structures to enable in depth understanding of safety and natural history of disease. The rarity and distribution of such diseases and unpredictability of treatment require innovative methods for enrolment and follow-up. Broad international practice-based recruitment and web-based data collection are practical.

  13. 78 FR 4071 - Approval and Promulgation of State Implementation Plans; State of Utah; Smoke Management...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-18

    ... process for gathering the essential post-burn activity information to support emissions inventory and... considers visibility and is based on the criteria of efficiency, economics, law, emission reduction...

  14. 76 FR 8804 - Agency Information Collection Activities: Revision and Approval of Information Collection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... of external factors on Project expectations. Including an ex post examination of project... consist of a narrative discussion detailing project successes and/or the influence of external factors on...

  15. 7 CFR 319.56-56 - Fresh pomegranates from Chile.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Chile following any post-harvest processing. A biometric sample must be drawn and examined from each... States. (2) A biometric sample of the boxes, crates, or other APHIS-approved packing containers from each...

  16. 7 CFR 319.56-56 - Fresh pomegranates from Chile.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Chile following any post-harvest processing. A biometric sample must be drawn and examined from each... States. (2) A biometric sample of the boxes, crates, or other APHIS-approved packing containers from each...

  17. Defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome following nontransplant-associated chemotherapy: Final results from a post hoc analysis of data from an expanded-access program.

    PubMed

    Kernan, Nancy A; Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Antin, Joseph H; Lehmann, Leslie; Messinger, Yoav; Liang, Wei; Hume, Robin; Tappe, William; Soiffer, Robert J; Grupp, Stephan A

    2018-06-06

    Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) but can occur after nontransplant-associated chemotherapy. Following HSCT, VOD/SOS with multi-organ dysfunction (MOD) may be associated with >80% mortality. Defibrotide is approved to treat severe hepatic VOD/SOS post-HSCT in patients aged >1 month in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Prior to US approval, defibrotide was available to treat VOD/SOS through an expanded-access treatment (T-IND) program. A post hoc analysis of nontransplant-associated VOD/SOS patients treated with defibrotide initiated within 30 days of starting chemotherapy and followed for 70 days is presented. Patients were diagnosed by Baltimore or modified Seattle criteria or biopsy, and received defibrotide 25 mg/kg/day in four divided doses (≥21 days recommended). Of the 1,154 patients in the T-IND, 137 had nontransplant-associated VOD/SOS, 82 of whom developed VOD/SOS within 30 days of starting chemotherapy. Of them, 66 (80.5%) were aged ≤16 years. Across all the 82 patients, Kaplan-Meier estimated day +70 survival was 74.1%, 65.8% in patients with MOD (n = 38), and 81.3% in patients without MOD (n = 44). By age group, Kaplan-Meier estimated day +70 survival was 80.1% in pediatric patients (n = 66) and 50.0% in adults (n = 16). Treatment-related adverse events occurred in 26.8%. In this post hoc analysis of 82 patients initiating defibrotide within 30 days of starting chemotherapy, Kaplan-Meier estimated survival was 74.1% at 70 days after defibrotide initiation. Safety profile was consistent with prior defibrotide studies. © 2018 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

  18. Real-world evidence analysis of palbociclib prescribing patterns for patients with advanced/metastatic breast cancer treated in community oncology practice in the USA one year post approval.

    PubMed

    Kish, J K; Ward, M A; Garofalo, D; Ahmed, H V; McRoy, L; Laney, J; Zanotti, G; Braverman, J; Yu, H; Feinberg, B A

    2018-05-02

    Rapidly evolving understanding of cancer biology has presented novel opportunities to translate that understanding into clinically relevant therapy. Palbociclib, a novel, first-in-class cyclin-dependent kinase (CDK) 4/6 inhibitor was approved in the USA in February 2015 for the treatment of advanced/metastatic breast cancer. We examined real-world evidence in the first year post approval to understand the clinical and demographic characteristics of patients treated with palbociclib in community oncology practices and the dosing, treatment, and complete blood count (CBC) monitoring patterns. This was a retrospective observational study of structured data from a US electronic medical record (EMR) database. Female patients receiving palbociclib after 31 January 2015 were followed through 31 March 2016. Our methodological rules were constructed to aggregate drugs received according to the order in which they are given, i.e., identify the line of therapy as first, second, or third line, etc., using treatment order and course description fields from the EMR. There were 763 patients initiating palbociclib who met the selection criteria. Of those, 612 (80.2%) received palbociclib concomitantly with letrozole. Mean follow up was 6.4 months and mean age at palbociclib initiation was 64 years. Of patients with a known starting dose (n = 417), 79.9% started on palbociclib 125 mg. Dose reductions were observed in 20.1% of patients. Percentages of patients according to line of therapy at initiation of palbociclib were first-line, 39.5%; second-line, 15.7%; third-line, 13.1%; and fourth-line therapy or later, 31.7%. On average, two CBC tests were conducted during the first cycle of palbociclib treatment. Overall, 74.6% of patients had a neutropenic event during follow up including 47.3% and 8.0% of patients with a grade 3 or 4 occurrence, respectively. Real-world palbociclib use one year post US approval demonstrates a more heterogeneous patient population than that studied in the clinical trials with more than half of the patients receiving palbociclib plus letrozole in later lines of therapy. CBC testing rates suggested good provider compliance with monitoring guidelines in the USA prescribing information. The occurrence of grade 3 and 4 neutropenia (based on laboratory results) was consistent with the rates of grade 3 and 4 neutropenia in two phase-III studies (PALOMA-2, 56% and 10%; PALOMA-3, 55% and 11%, respectively). Understanding palbociclib utilization in real-world patients and how drug dosing and monitoring are performed aids in the understanding of safe and effective use of the drug.

  19. Effect of magnesium sulfate nebulization on the incidence of postoperative sore throat.

    PubMed

    Yadav, Monu; Chalumuru, Nitish; Gopinath, Ramachandran

    2016-01-01

    Postoperative sore throat (POST) is a well-recognized complication after general anesthesia (GA). Numerous nonpharmacological and pharmacological measures have been used for attenuating POST with variable success. The present study was conducted to compare the efficiency of preoperative nebulization of normal saline and magnesium sulfate in reducing the incidence of POST following GA. Following institutional ethical committee approval and written informed consent, a prospective randomized double-blinded study was conducted in 100 cases divided into two equal groups. Patients included in the study were of either gender belonging to American Society of Anesthesiologist (ASA) status 1 or 2 undergoing elective surgery of approximately 2 h or more duration requiring tracheal intubation. Patients in Group A are nebulized with 3 ml of normal saline and the patients in Group B are nebulized with 3 ml of 225 mg isotonic nebulized magnesium sulfate for 15 min, 5 min before induction of anesthesia. The incidence of POST at rest and on swallowing and any undue complaints at 0, 2, 4, and 24 h in the postoperative period are evaluated. There is no significant difference in POST at rest during 0(th), 2(nd) and 4(th) h between normal saline and MgSO4. Significant difference is seen at 24(th) h, where MgSO4 lessens POST. There is no significant difference in POST on swallowing during 0(th) and 2(nd) h between normal saline and MgSO4. Significant difference is seen at 4(th) h, where MgSO4 has been shown to lessen POST. MgSO4 significantly reduces the incidence of POST compared to normal saline.

  20. Sample and design considerations in post-disaster mental health needs assessment tracking surveys

    PubMed Central

    Kessler, Ronald C.; Keane, Terence M.; Ursano, Robert J.; Mokdad, Ali; Zaslavsky, Alan M.

    2009-01-01

    Although needs assessment surveys are carried out after many large natural and man-made disasters, synthesis of findings across these surveys and disaster situations about patterns and correlates of need is hampered by inconsistencies in study designs and measures. Recognizing this problem, the US Substance Abuse and Mental Health Services Administration (SAMHSA) assembled a task force in 2004 to develop a model study design and interview schedule for use in post-disaster needs assessment surveys. The US National Institute of Mental Health subsequently approved a plan to establish a center to implement post-disaster mental health needs assessment surveys in the future using an integrated series of measures and designs of the sort proposed by the SAMHSA task force. A wide range of measurement, design, and analysis issues will arise in developing this center. Given that the least widely discussed of these issues concerns study design, the current report focuses on the most important sampling and design issues proposed for this center based on our experiences with the SAMHSA task force, subsequent Katrina surveys, and earlier work in other disaster situations. PMID:19035440

  1. High salinity relay as a post-harvest processing method for reducing Vibrio vulnificus levels in oysters (Crassostrea virginica).

    PubMed

    Audemard, Corinne; Kator, Howard I; Reece, Kimberly S

    2018-08-20

    High salinity relay of Eastern oysters (Crassostrea virginica) was evaluated as a post-harvest processing (PHP) method for reducing Vibrio vulnificus. This approach relies on the exposure of oysters to natural high salinity waters and preserves a live product compared to previously approved PHPs. Although results of prior studies evaluating high salinity relay as a means to decrease V. vulnificus levels were promising, validation of this method as a PHP following approved guidelines is required. This study was designed to provide data for validation of this method following Food and Drug Administration (FDA) PHP validation guidelines. During each of 3 relay experiments, oysters cultured from 3 different Chesapeake Bay sites of contrasting salinities (10-21 psu) were relayed without acclimation to high salinity waters (31-33 psu) for up to 28 days. Densities of V. vulnificus and densities of total and pathogenic Vibrio parahaemolyticus (as tdh positive strains) were measured using an MPN-quantitative PCR approach. Overall, 9 lots of oysters were relayed with 6 exhibiting initial V. vulnificus >10,000/g. As recommended by the FDA PHP validation guidelines, these lots reached both the 3.52 log reduction and the <30 MPN/g densities requirements for V. vulnificus after 14 to 28 days of relay. Densities of total and pathogenic V. parahaemolyticus in relayed oysters were significantly lower than densities at the sites of origin suggesting an additional benefit associated with high salinity relay. While relay did not have a detrimental effect on oyster condition, oyster mortality levels ranged from 2 to 61% after 28 days of relay. Although the identification of the factors implicated in oyster mortality will require further examination, this study strongly supports the validation of high salinity relay as an effective PHP method to reduce levels of V. vulnificus in oysters to endpoint levels approved for human consumption. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Adaptive Pathways: Possible Next Steps for Payers in Preparation for Their Potential Implementation.

    PubMed

    Vella Bonanno, Patricia; Ermisch, Michael; Godman, Brian; Martin, Antony P; Van Den Bergh, Jesper; Bezmelnitsyna, Liudmila; Bucsics, Anna; Arickx, Francis; Bybau, Alexander; Bochenek, Tomasz; van de Casteele, Marc; Diogene, Eduardo; Eriksson, Irene; Fürst, Jurij; Gad, Mohamed; Greičiūtė-Kuprijanov, Ieva; van der Graaff, Martin; Gulbinovic, Jolanta; Jones, Jan; Joppi, Roberta; Kalaba, Marija; Laius, Ott; Langner, Irene; Mardare, Ileana; Markovic-Pekovic, Vanda; Magnusson, Einar; Melien, Oyvind; Meshkov, Dmitry O; Petrova, Guenka I; Selke, Gisbert; Sermet, Catherine; Simoens, Steven; Schuurman, Ad; Ramos, Ricardo; Rodrigues, Jorge; Zara, Corinne; Zebedin-Brandl, Eva; Haycox, Alan

    2017-01-01

    Medicines receiving a conditional marketing authorization through Medicines Adaptive Pathways to Patients (MAPPs) will be a challenge for payers. The "introduction" of MAPPs is already seen by the European Medicines Agency (EMA) as a fait accompli, with payers not consulted or involved. However, once medicines are approved through MAPPs, they will be evaluated for funding by payers through different activities. These include Health Technology Assessment (HTA) with often immature clinical data and high uncertainty, financial considerations, and negotiations through different types of agreements, which can require monitoring post launch. Payers have experience with new medicines approved through conditional approval, and the fact that MAPPs present additional challenges is a concern from their perspective. There may be some activities where payers can collaborate. The final decisions on whether to reimburse a new medicine via MAPPs will have more variation than for medicines licensed via conventional processes. This is due not only to increasing uncertainty associated with medicines authorized through MAPPs but also differences in legal frameworks between member states. Moreover, if the financial and side-effect burden from the period of conditional approval until granting full marketing authorization is shifted to the post-authorization phase, payers may have to bear such burdens. Collection of robust data during routine clinical use is challenging along with high prices for new medicines during data collection. This paper presents the concept of MAPPs and possible challenges. Concerns and potential ways forward are discussed and a number of recommendations are presented from the perspective of payers.

  3. Large-scale prediction of adverse drug reactions using chemical, biological, and phenotypic properties of drugs.

    PubMed

    Liu, Mei; Wu, Yonghui; Chen, Yukun; Sun, Jingchun; Zhao, Zhongming; Chen, Xue-wen; Matheny, Michael Edwin; Xu, Hua

    2012-06-01

    Adverse drug reaction (ADR) is one of the major causes of failure in drug development. Severe ADRs that go undetected until the post-marketing phase of a drug often lead to patient morbidity. Accurate prediction of potential ADRs is required in the entire life cycle of a drug, including early stages of drug design, different phases of clinical trials, and post-marketing surveillance. Many studies have utilized either chemical structures or molecular pathways of the drugs to predict ADRs. Here, the authors propose a machine-learning-based approach for ADR prediction by integrating the phenotypic characteristics of a drug, including indications and other known ADRs, with the drug's chemical structures and biological properties, including protein targets and pathway information. A large-scale study was conducted to predict 1385 known ADRs of 832 approved drugs, and five machine-learning algorithms for this task were compared. This evaluation, based on a fivefold cross-validation, showed that the support vector machine algorithm outperformed the others. Of the three types of information, phenotypic data were the most informative for ADR prediction. When biological and phenotypic features were added to the baseline chemical information, the ADR prediction model achieved significant improvements in area under the curve (from 0.9054 to 0.9524), precision (from 43.37% to 66.17%), and recall (from 49.25% to 63.06%). Most importantly, the proposed model successfully predicted the ADRs associated with withdrawal of rofecoxib and cerivastatin. The results suggest that phenotypic information on drugs is valuable for ADR prediction. Moreover, they demonstrate that different models that combine chemical, biological, or phenotypic information can be built from approved drugs, and they have the potential to detect clinically important ADRs in both preclinical and post-marketing phases.

  4. [HTA-Perspective: Challenges in the early assessment of new oncological drugs].

    PubMed

    Wild, Claudia; Nachtnebel, Anna

    2013-01-01

    Oncologic drug therapies have gained wide attention in the context of health policy priority setting for serious and socially significant diseases with high human and monetary costs. Due to uncertainties and scepticism about the actual therapeutic importance of newly approved oncology products, an early assessment programme was already established in Austria in 2007. The assessment of new oncology products is thereby faced with special challenges, since study populations are frequently not representative or the study design is laid out in such a manner that a definitive assessment of patient-relevant endpoints is not possible (cross-overs after interim assessments, surrogate parameters as primary endpoints, uncontrolled studies or those with unrealistic comparators, invalidated post-hoc identified biomarkers). On account of these major uncertainties, even the European Medicines Agency (EMA) is already contemplating multi-stage, "adaptive" approvals, and national reimbursement institutions are increasingly working with outcome-oriented, conditional reimbursement. (As supplied by publisher). Copyright © 2013. Published by Elsevier GmbH.

  5. NCI ALMANAC Tool for Research on Cancer Drug Combinations

    Cancer.gov

    A Cancer Currents blog post on the NCI ALMANAC, a new resource that provides data showing how well pairs of FDA-approved cancer drugs performed in killing tumor cells from NCI-60 Human Tumor Cell Lines.

  6. 46 CFR 169.849 - Posting placards containing instructions for launching and inflating inflatable liferafts.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... accessible to the ship's company and guests approved placards containing instructions for launching and inflating inflatable liferafts. The number and location of such placards for a particular vessel shall be...

  7. 46 CFR 169.849 - Posting placards containing instructions for launching and inflating inflatable liferafts.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... accessible to the ship's company and guests approved placards containing instructions for launching and inflating inflatable liferafts. The number and location of such placards for a particular vessel shall be...

  8. 46 CFR 169.849 - Posting placards containing instructions for launching and inflating inflatable liferafts.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... accessible to the ship's company and guests approved placards containing instructions for launching and inflating inflatable liferafts. The number and location of such placards for a particular vessel shall be...

  9. 46 CFR 169.849 - Posting placards containing instructions for launching and inflating inflatable liferafts.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... accessible to the ship's company and guests approved placards containing instructions for launching and inflating inflatable liferafts. The number and location of such placards for a particular vessel shall be...

  10. Caterpillar, Inc. — Converter GP-Catalytic Technology (CGP) system

    EPA Pesticide Factsheets

    This EPA memo approves Caterpillar Inc. request for Caterpillar Converter GP-Catalytic Technology (CGP) system for certain wheeled hydraulic excavators in reducing emissions and will be posted on the National Clean Diesel Verified Technologies List.

  11. 76 FR 23850 - Agency Information Collection Activities: Approval of a Revision in Information Collection(s...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-28

    ... successes and/or the influence of external factors on Project expectations. Including an ex post examination... narrative discussion detailing project successes and/or the influence of external factors on project...

  12. "It's Just a Lot of Work": Adolescents' Self-Presentation Norms and Practices on Facebook and Instagram.

    PubMed

    Yau, Joanna C; Reich, Stephanie M

    2018-02-12

    We explored adolescents' (12- to 18-year-olds; n = 51) awareness of their audience and subsequent self-presentation practices on Facebook and Instagram through focus group discussions. Findings suggest that teens, who are developmentally able to perceive a situation from the third-person perspective and who value peer approval, purposefully share content to appear interesting, well liked, and attractive. Some teens invested great effort into posting by these norms, even asking their friends to help; however, this was more common among girls. Older teens especially discussed taking the perspective of their audience when deciding what to post, which is consistent with the finding that perspective taking continues to develop throughout adolescence. These findings suggest that perspective taking skills and need for peer approval influence self-presentation online. © 2018 Society for Research on Adolescence.

  13. Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies

    PubMed Central

    Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

    2017-01-01

    Objectives To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Design Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data sources Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Outcome measures Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. Results The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Conclusions Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress. PMID:29208616

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

    PubMed

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

    2017-01-01

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

  15. [Basic requirements on post-marketing clinical re-evaluation of chinese medicine and phase IV clinical trials].

    PubMed

    Xie, Yanming; Wang, Yanping; Tian, Feng; Wang, Yongyan

    2011-10-01

    As information on safety and effectiveness is not comprehensive, gained from the researches for listing approval of Chinese medicine, it is very necessary to conduct post-marketing clinical re-evaluation of Chinese medicine. Effectiveness, safety and economic evaluation are three main aspects of post-marketing clinical re-evaluation. In this paper, the difference and relations between the post-marketing clinical re-evaluation and the phase IV clinical trials were discussed, and the basic requests and suggestions were proposed, according to the domestic and foreign relevant regulations and experts' suggestions, and discussed the requirements of the phase IV clinical trials on indications, design methods, inclusion and exclusion criteria, sample size, etc.

  16. Lightweight Tactical Client: A Capability-Based Approach to Command Post Computing

    DTIC Science & Technology

    2015-12-01

    bundles these capabilities together is proposed: a lightweight tactical client. In order to avoid miscommunication in the future, it is... solutions and almost definitely rules out most terminal-based thin clients. UNCLASSIFIED Approved for public release

  17. 76 FR 28840 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Approving Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... specifications (updated regarding components and weighting methodology).\\4\\ The only post- proposal difference in... practices, to promote just and equitable principles of trade, to remove impediments to and perfect the...

  18. MedWatch, the FDA Safety Information and Adverse Event Reporting Program

    MedlinePlus

    ... Information and Adverse Event Reporting Program MedWatch: The FDA Safety Information and Adverse Event Reporting Program Share ... use. [Posted 06/01/2018] More What's New FDA Approved Safety Information DailyMed (National Library of Medicine) ...

  19. Time Harmonic Elastography Reveals Sensitivity of Liver Stiffness to Water Ingestion.

    PubMed

    Ipek-Ugay, Selcan; Tzschätzsch, Heiko; Hudert, Christian; Marticorena Garcia, Stephan Rodrigo; Fischer, Thomas; Braun, Jürgen; Althoff, Christian; Sack, Ingolf

    2016-06-01

    The aim of the study was to test the sensitivity of liver stiffness (LS) measured by time harmonic elastography in large tissue windows to water uptake and post-prandial effects. Each subject gave written informed consent to participate in this institutional review board-approved prospective study. LS was measured by time harmonic elastography in 10 healthy volunteers pre- and post-prandially, as well as before, directly after and 2 h after drinking water. The LS-time function during water intake was measured in 14 scans over 3 h in five volunteers. LS increased by 10% (p = 0.0015) post-prandially and by 11% (p = 0.0024) after pure water ingestion, and decreased to normal values after 2 h. LS was lower after overnight fasting than after 2-h fasting (3%, p = 0.04). Over the time course, LS increased to post-water peak values 15 min after drinking 0.25 L water and remained unaffected by further ingestion of water. In conclusion, our study indicates that LS measured by time harmonic elastography represents an effective-medium property sensitive to physiologic changes in vascular load of the liver. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  20. A Comparison of Marginal Fit Between Lithium-Disilicate Press and CAD Fabricated Crowns

    DTIC Science & Technology

    2014-05-27

    CPT Richard Carlile 2. Academic Title: Comprehensive Dentistry Resident, AEGD-2 Hawaii 3. School/Department/Center: Army Post-Graduate Dental School...AEGD-2 Hawaii Schofield Barracks Dental Clinic, HI 4. Phone: 808-433-8838 5. Type of clearance: _Paper _K_Article _Book _Poster_ Presentation...DIRECTOR OR DEPARTMENT HEAD APPROVAL 1. Name: COL Peter H. Guevara 2. School/Dept.: Army Post-Graduate Dental School, AEGD-2 Hawaii 3. Date: 27 May 2014

  1. Factors associated with prescribing restriction on oncology formulary drugs in Malaysia.

    PubMed

    Fatokun, Omotayo; Olawepo, Michael N

    2016-10-01

    Background Drugs listed on formularies are often subjected to a variety of utilization restriction measures. However, the degree of restriction is influenced by multiple factors, including the characteristics and attributes of the listed drugs. Objective To identify the factors that are associated with the levels of prescribing restriction on oncology formulary drugs in Malaysia. Setting Oncology formulary in Malaysia. Method The Malaysia Drug Code assigned to each of the drug products on the Malaysia Ministry of Health (MOH) drug formulary was used to identify oncology drugs belonging to WHO ATC class L (antineoplastic and immunomodulating agents). Main outcome measures Categories of prescribing restrictions, therapeutic class, drug type, administration mode, number of sources and the post-approval use period. Results Oncology drugs having a shorter post-approval use period (p < 0.001), biologic oncology drugs (p = 0.01) and oncology drugs belonging to immunosuppressant therapeutic class (p = 0.03) were all significantly associated with a greater likelihood of being subjected to a higher level of prescribing restriction. Conclusion This study suggests that safety concerns, costs and potentials for inappropriate use were the important considerations influencing a higher level of prescribing restriction placement on oncology drugs in the Malaysia MOH drug formulary.

  2. Blast traumatic brain injury induced cognitive deficits are attenuated by pre- or post-injury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4

    PubMed Central

    Tweedie, David; Rachmany, Lital; Rubovitch, Vardit; Li, Yazhou; Holloway, Harold W.; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G.; Perez, Evelyn; Hoffer, Barry J.; Pick, Chaim G.; Greig, Nigel H.

    2015-01-01

    Background Blast traumatic brain injury (B-TBI) affects military and civilian personnel. Presently there are no approved drugs for blast brain injury. Methods Exendin-4, administered subcutaneously, was evaluated as a pre-treatment (48 hours) and post-injury treatment (2 hours) on neurodegeneration, behaviors and gene expressions in a murine open field model of blast injury. Results B-TBI induced neurodegeneration, changes in cognition and genes expressions linked to dementia disorders. Exendin-4, administered pre- or post-injury ameliorated B-TBI-induced neurodegeneration at 72 hours, memory deficits from days 7–14 and attenuated genes regulated by blast at day 14 post-injury. Conclusions The present data suggest shared pathological processes between concussive and B-TBI, with endpoints amenable to beneficial therapeutic manipulation by exendin-4. B-TBI-induced dementia-related gene pathways and cognitive deficits in mice somewhat parallel epidemiological studies of Barnes and co-workers who identified a greater risk in US military veterans who experienced diverse TBIs, for dementia in later life. PMID:26327236

  3. Interchangeability, Safety and Efficacy of Modified-Release Drug Formulations in the USA: The Case of Opioid and Other Nervous System Drugs.

    PubMed

    Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Hansen, Richard

    2016-04-01

    Modified-release drugs may provide clinical advantages compared to immediate-release forms and improve convenience to the patient and health outcomes. Concerns have been raised regarding interchangeability, efficacy, and safety of modified-release formulations. This study analyses all US Food and Drug Administration (FDA)-approved modified-release formulations and market trends, and illustrates how bioequivalence and safety of generic modified-release products compare to their respective brand name drugs and other generic drugs with different formulation design characteristics. This study also examines major concerns related to modified-release formulations: safety of opioids and bioequivalence of generic bupropion and methylphenidate. Study data were derived from the FDA electronic versions of the FDA's Orange Book (OB) and the FDA safety communications web page. Medicare Part D utilization and expenditures data were extracted from the Centers for Medicare and Medicaid. In May 2015, 276 (11.9 %) of the 2325 active ingredients and fixed-dose combinations listed in the FDA's Orange Book had at least one modified-release form approved by the FDA. The number of approvals increased over time; 52.5 % of modified releases were approved in the period 2000-May 2015. The FDA required a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of extended-release opioids outweighed its risks of overdose and abuse. The REMS involved 16 new drug applications and 25 abbreviated new drug applications. The FDA addressed interchangeability problems with generic modified-release alternatives of bupropion and methylphenidate including lack of bioequivalence, reduced efficacy, and increased incidence of adverse events. Systematic post-marketing surveillance studies are needed to assess differences in safety, interchangeability, and efficacy of drugs with modified- and immediate-release formulations.

  4. [Ten years experience with the first approved biosimilar recombinant human growth hormone drug in normal clinical practice].

    PubMed

    López-Siguero, Juan Pedro; Palla García, Margarida; Martínez Busto, Elena; Rebollo, Francisco José; Pombo, Manuel

    2018-04-01

    Recombinant human growth hormone (rhGH) is the first biosimilar drug approved by the European Medicines Agency in 2006, using the biosimilar registration process. It was authorised for the treatment of growth hormone deficiency, and growth disorders associated with Turner's syndrome, chronic renal failure, Prader-Willi syndrome, and growth disorders in children/adolescents born small for gestational age, and replacement therapy in adults with pronounced growth hormone deficiency. This review is focused on the scientific evidence published about this drug in the last ten years, including the clinical trials on which the approval of the regulatory authority is based, and the most relevant studies evaluating the clinical impact of the drug in clinical practice. The equivalence between biosimilar and original product has been confirmed in the clinical trials published by Romer et al. and López-Siguero et al. Furthermore, studies carried out in real-life conditions confirm its long-term efficacy and safety, as well as the absence of clinical impact by switching treatment from the original to the biosimilar product. The number of patients receiving this medication has continuously increased since its approval. Its equivalence with the original product has been verified. Preliminary data from the post-authorisation PATRO study confirm the efficacy and safety of the biosimilar product in comparison with data from clinical trials. However, final results must be evaluated at the end of the study, which will provide additional information about the long-term efficacy and safety of the biosimilar drug. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. 76 FR 9777 - Recent Postings of Broadly Applicable Alternative Test Methods

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ... Applicable Alternative Test Methods AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of availability. SUMMARY: This notice announces the broadly applicable alternative test method approval decisions... technical questions about individual alternative test method decisions, refer to the contact person...

  6. 75 FR 52053 - Notice of Request To Revise a Currently-Approved Information Collection Request: Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-24

    ... received your comments, please include a self-addressed, stamped envelope or post card or print the... of the registration of a motor carrier, broker, or freight forwarder for willful failure to comply...

  7. 78 FR 25236 - Approval and Promulgation of Implementation Plans; New York; Infrastructure SIP for the 1997 8...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-30

    ... enable the Commissioner to designate air pollution episodes which trigger the action plans. Pursuant to..., posts warnings on the above-referenced Web site and issues press releases to local media outlets if...

  8. Trinity cable safety system.

    DOT National Transportation Integrated Search

    2007-01-31

    Cab1eSafety System (CASS).is being tested by the Oklahoma Department of Transportation (ODOT) along I-35 in McClain County. CASS will be compare with two other system approve by ODOT. Using C-shaped post tensioned cables, CASS is designed to...

  9. 29 CFR 1952.94 - Final approval determination.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... red meat production, or the post-harvest processing of agricultural or horticultural commodities. (c... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... agricultural establishment where employees are engaged in “agricultural employment” within the meaning of the...

  10. 29 CFR 1952.164 - Final approval determination.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... engaged in egg, poultry, or red meat production, or the post-harvest processing of agricultural or... Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION....142, with respect to any agricultural establishment where employees are engaged in “agricultural...

  11. Methodological challenges in monitoring new treatments for rare diseases: lessons from the cryopyrin-associated periodic syndrome registry

    PubMed Central

    2013-01-01

    Background The Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare hereditary autoinflammatory diseases and encompass Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal Onset Multisystem Inflammatory Disease (NOMID). Canakinumab is a monoclonal antibody directed against IL-1 beta and approved for CAPS patients but requires post-approval monitoring due to low and short exposures during the licensing process. Creative approaches to observational methodology are needed, harnessing novel registry strategies to ensure Health Care Provider reporting and patient monitoring. Methods A web-based registry was set up to collect information on long-term safety and effectiveness of canakinumab for CAPS. Results Starting in November 2009, this registry enrolled 241 patients in 43 centers and 13 countries by December 31, 2012. One-third of the enrolled population was aged < 18; the overall population is evenly divided by gender. Enrolment is ongoing for children. Conclusions Innovative therapies in orphan diseases require post-approval structures to enable in depth understanding of safety and natural history of disease. The rarity and distribution of such diseases and unpredictability of treatment require innovative methods for enrolment and follow-up. Broad international practice-based recruitment and web-based data collection are practical. PMID:24016338

  12. A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience.

    PubMed

    Goldkind, Lawrence; Laine, Loren

    2006-04-01

    Drug-induced hepatotoxicity is the leading cause of acute liver failure (ALF) in the US and the most common adverse event causing drug non-approval and drug withdrawal by the U.S. Food and Drug Administration (FDA). Three different nonsteroidal anti-inflammatory drugs (NSAIDs) have been withdrawn in the UK and/or the US due to hepatotoxicity (bromfenac, ibufenac, and benoxaprofen). A systematic review of clinical trials data for these drugs was performed in an effort to identify possible early signals that could have predicted post-marketing serious hepatoxicity. There were very limited published data on benoxaprofen and none on ibufenac or bromfenac. The publicly accessible archives of the FDA provided information on bromfenac. Flu-like symptoms associated with hepatic enzyme elevation and a case of possible drug-related hepatocellular jaundice may in retrospect have been signals for serious hepatotoxicity in the database of 1195 subjects reviewed by the FDA. Following approval, rates of acute liver failure for bromfenac were estimated to be in the range of 1:10 000. In addition, the safety databases of several drugs also accessed through FDA archives have been reviewed (simvastatin, tacrine, troglitazone, and ximelagatran). These data suggest that while ALT elevations alone do not reliably signal serious hepatotoxicity, elevated transaminases in association with symptomatic hepatitis or jaundice may be predictors of an increased risk of ALF. At present, however, pre-approval databases are generally not large enough to rule out low rates of serious hepatotoxicity. Therefore, it remains critical that clinicians report such cases to the FDA through the MEDWATCH system and that active post-marketing monitoring studies be used to identify potential rare cases of hepatotoxicity. Copyright (c) 2006 John Wiley & Sons, Ltd.

  13. Association of the FDA Amendment Act with trial registration, publication, and outcome reporting.

    PubMed

    Phillips, Adam T; Desai, Nihar R; Krumholz, Harlan M; Zou, Constance X; Miller, Jennifer E; Ross, Joseph S

    2017-07-18

    Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry. Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation. Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive. FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

  14. Febuxostat: drug review and update.

    PubMed

    Grewal, Harmanjot K; Martinez, Joseph R; Espinoza, Luis R

    2014-05-01

    Gouty arthritis and hyperuricemia have ailed humans for centuries. Recent advances in understanding of the mechanism(s) of their development have changed our perception of the disease process. Despite these gains, the treatment options available are limited. The FDA approval of febuxostat for the treatment of hyperuricemia in gout has been a significant step forward. Since its approval in 2009, febuxostat has proven to be safe and efficacious although concerns remain regarding its long-term effects and superiority to other uricosuric agents, such as allopurinol. A comprehensive literature review of PubMed and Ovid examining clinical trials and post-marketing studies yielded congruent findings on efficacy and safety in elderly populations and those with mild-to-moderate renal/hepatic impairment. A lack of literature and clinical studies was found with regard to comparison of febuxostat to FDA-approved high-dose allopurinol (> 300 mg), the safety of febuxostat in the treatment of severe renal/hepatic impairment and the benefit in the treatment of secondary cases of hyperuricemia. Febuxostat is effective in the treatment of mild-to-moderate renal/hepatic impairment with dramatic effects on the serum urate level. It can be used safely in patients with hypersensitivity reactions to allopurinol. Further research is needed to determine the long-term benefits and risks.

  15. Adhesive capability of total-etch, self-etch, and self-adhesive systems for fiber post cementation

    NASA Astrophysics Data System (ADS)

    Theodor, Y.; Koesmaningati, H.; Gita, F.

    2017-08-01

    The aim of this study was to analyze whether self-etch and self-adhesive systems are comparable to the total-etch system for fiber post cementation. This experimental laboratory study, which was approved by an ethics committee, was performed using 27 mandibular premolar teeth randomly divided into three groups. Fiber post cementation was done using three different adhesive systems. Specimens were prepared with a thickness of 5 mm, which was measured from the cervical to medial areas of the root, and stored for 24 h in saline solution at room temperature. A push-out test was performed using a universal testing machine (Shimidzu AG-5000E) with a crosshead speed of 0.5 mm/min. The results of one way ANOVA bivariate testing showed that the total-etch and self-etch systems have comparable adhesion capability (p<0.05) and that the self-adhesive system has the lowest adhesion capability (p>0.05). With easier application, the self-etch system has a comparable adhesion capability to the total-etch system.

  16. Adaptive Pathways: Possible Next Steps for Payers in Preparation for Their Potential Implementation

    PubMed Central

    Vella Bonanno, Patricia; Ermisch, Michael; Godman, Brian; Martin, Antony P.; Van Den Bergh, Jesper; Bezmelnitsyna, Liudmila; Bucsics, Anna; Arickx, Francis; Bybau, Alexander; Bochenek, Tomasz; van de Casteele, Marc; Diogene, Eduardo; Eriksson, Irene; Fürst, Jurij; Gad, Mohamed; Greičiūtė-Kuprijanov, Ieva; van der Graaff, Martin; Gulbinovic, Jolanta; Jones, Jan; Joppi, Roberta; Kalaba, Marija; Laius, Ott; Langner, Irene; Mardare, Ileana; Markovic-Pekovic, Vanda; Magnusson, Einar; Melien, Oyvind; Meshkov, Dmitry O.; Petrova, Guenka I.; Selke, Gisbert; Sermet, Catherine; Simoens, Steven; Schuurman, Ad; Ramos, Ricardo; Rodrigues, Jorge; Zara, Corinne; Zebedin-Brandl, Eva; Haycox, Alan

    2017-01-01

    Medicines receiving a conditional marketing authorization through Medicines Adaptive Pathways to Patients (MAPPs) will be a challenge for payers. The “introduction” of MAPPs is already seen by the European Medicines Agency (EMA) as a fait accompli, with payers not consulted or involved. However, once medicines are approved through MAPPs, they will be evaluated for funding by payers through different activities. These include Health Technology Assessment (HTA) with often immature clinical data and high uncertainty, financial considerations, and negotiations through different types of agreements, which can require monitoring post launch. Payers have experience with new medicines approved through conditional approval, and the fact that MAPPs present additional challenges is a concern from their perspective. There may be some activities where payers can collaborate. The final decisions on whether to reimburse a new medicine via MAPPs will have more variation than for medicines licensed via conventional processes. This is due not only to increasing uncertainty associated with medicines authorized through MAPPs but also differences in legal frameworks between member states. Moreover, if the financial and side-effect burden from the period of conditional approval until granting full marketing authorization is shifted to the post-authorization phase, payers may have to bear such burdens. Collection of robust data during routine clinical use is challenging along with high prices for new medicines during data collection. This paper presents the concept of MAPPs and possible challenges. Concerns and potential ways forward are discussed and a number of recommendations are presented from the perspective of payers. PMID:28878667

  17. Addendum to the Closure Report for Corrective Action Unit 271: Areas 25, 26, and 27 Septic Systems Nevada Test Site, Nevada, Revision 0

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

    Lynn Kidman

    This document constitutes an addendum to the August 2004, Closure Report for Corrective Action Unit 271, Areas 25, 26, and 27 Septic Systems as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consistsmore » of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the modification of the UR for CAS 27-05-02, Leachfield. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to modify the UR to an administrative UR. Administrative URs differ from standard URs in that they do not require onsite postings (i.e., signs) or other physical barriers (e.g., fencing, monuments), and they do not require periodic inspections (see Section 6.2 of the Industrial Sites Project Establishment of Final Action Levels [NNSA/NSO, 2006c]). This Administrative UR was based on an “Occasional Use Area” future land use scenario that was used to calculate the FAL. The administrative UR will protect workers from an exposure exceeding that used in the calculation of the FAL (i.e., 400 total work hours). Any proposed activity within this use restricted area that would potentially cause an exposure exceeding this exposure limit would require approval from the Nevada Division of Environmental Protection (NDEP). Requirements for inspecting and maintaining postings at this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

  18. Social desirability bias in dietary self-report may compromise the validity of dietary intake measures.

    PubMed

    Hebert, J R; Clemow, L; Pbert, L; Ockene, I S; Ockene, J K

    1995-04-01

    Self-report of dietary intake could be biased by social desirability or social approval thus affecting risk estimates in epidemiological studies. These constructs produce response set biases, which are evident when testing in domains characterized by easily recognizable correct or desirable responses. Given the social and psychological value ascribed to diet, assessment methodologies used most commonly in epidemiological studies are particularly vulnerable to these biases. Social desirability and social approval biases were tested by comparing nutrient scores derived from multiple 24-hour diet recalls (24HR) on seven randomly assigned days with those from two 7-day diet recalls (7DDR) (similar in some respects to commonly used food frequency questionnaires), one administered at the beginning of the test period (pre) and one at the end (post). Statistical analysis included correlation and multiple linear regression. Cross-sectionally, no relationships between social approval score and the nutritional variables existed. Social desirability score was negatively correlated with most nutritional variables. In linear regression analysis, social desirability score produced a large downward bias in nutrient estimation in the 7DDR relative to the 24HR. For total energy, this bias equalled about 50 kcal/point on the social desirability scale or about 450 kcal over its interquartile range. The bias was approximately twice as large for women as for men and only about half as large in the post measures. Individuals having the highest 24HR-derived fat and total energy intake scores had the largest downward bias due to social desirability. We observed a large downward bias in reporting food intake related to social desirability score. These results are consistent with the theoretical constructs on which the hypothesis is based. The effect of social desirability bias is discussed in terms of its influence on epidemiological estimates of effect. Suggestions are made for future work aimed at improving dietary assessment methodologies and adjusting risk estimates for this bias.

  19. Buprenorphine Treatment for Probationers and Parolees

    PubMed Central

    Gordon, Michael S.; Kinlock, Timothy W.; Schwartz, Robert P.; Couvillion, Kathryn A.; Sudec, Laura J.; O’Grady, Kevin E.; Vocci, Frank J.; Shabazz, Hamin

    2014-01-01

    Background Pharmacotherapy studies involving buprenorphine have rarely been conducted with US community corrections populations. This is one of the first reports of buprenorphine treatment outcomes of adult opioid-dependent probationers and parolees. Methods This longitudinal study examined the 3-month treatment outcomes for a sample of probation and parole clients (N=64) who received community-based buprenorphine treatment. Results Approximately two-thirds of the sample (67%) were still in treatment at three months post-baseline. Furthermore, there was a significant decline in the number of self-reported heroin use days and crime days from baseline to three months post-baseline. While there was not a significant reduction in reincarcerations, there was no evidence that they had increased. Conclusions Given that buprenorphine is approved by the FDA as a safe, effective treatment for opioid use disorders, individuals on parole or probation should have the opportunity to benefit from it through community-based programs. PMID:24701967

  20. Considerations in prophylaxis for tumor-associated epilepsy: prevention of status epilepticus and tolerability of newer generation AEDs.

    PubMed

    Wychowski, Thomas; Wang, Hongyue; Buniak, Liana; Henry, J Craig; Mohile, Nimish

    2013-11-01

    To identify risk factors for the development of tumor-associated epilepsy (TAE) and potential benefit of newer generation AEDs in seizure prevention. We performed an IRB approved retrospective study of newly diagnosed GBM patients at the University of Rochester between 1/1/05 and 5/13/11. Records were reviewed to describe demographics, seizure incidence, occurrence of status epilepticus, and AED use and toxicity. 172 patients with newly diagnosed GBM were included in the study. 53.4% developed TAE. 31.4% had seizure prior to diagnosis. 118 patients were seizure-free at diagnosis: 32.2% developed post-diagnosis TIE (PostTAE) and 60.2% remained seizure-free. 70 seizure-free patients received an AED peri-operatively. 36 were weaned off AEDs and 31 were continued. Incidence of PostTAE and time to first seizure were comparable in AED-treated and untreated patients. 4 PostTAE patients presented with status epilepticus (SE), all were not AED treated. AEDs were withdrawn in 10 patients due to toxicity: 9 from phenytoin and 1 from levetiracetam. There is a high incidence of PostTAE in GBM. Prophylactic AED therapy did not reduce PostTAE but may have prevented SE. Minimal toxicity was observed on 2nd generation AEDs. The high burden of epilepsy in this population and tolerability of newer AEDS suggest that AAN guidelines should be revisited. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Improving readability of informed consents for research at an academic medical institution.

    PubMed

    Hadden, Kristie B; Prince, Latrina Y; Moore, Tina D; James, Laura P; Holland, Jennifer R; Trudeau, Christopher R

    2017-12-01

    The final rule for the protection of human subjects requires that informed consent be "in language understandable to the subject" and mandates that "the informed consent must be organized in such a way that facilitates comprehension." This study assessed the readability of Institutional Review Board-approved informed consent forms at our institution, implemented an intervention to improve the readability of consent forms, and measured the first year impact of the intervention. Readability assessment was conducted on a sample of 217 Institutional Review Board-approved informed consents from 2013 to 2015. A plain language informed consent template was developed and implemented and readability was assessed again after 1 year. The mean readability of the baseline sample was 10th grade. The mean readability of the post-intervention sample (n=82) was seventh grade. Providing investigators with a plain language informed consent template and training can promote improved readability of informed consents for research.

  2. Monitoring Quality of Biotherapeutic Products Using Multivariate Data Analysis.

    PubMed

    Rathore, Anurag S; Pathak, Mili; Jain, Renu; Jadaun, Gaurav Pratap Singh

    2016-07-01

    Monitoring the quality of pharmaceutical products is a global challenge, heightened by the implications of letting subquality drugs come to the market on public safety. Regulatory agencies do their due diligence at the time of approval as per their prescribed regulations. However, product quality needs to be monitored post-approval as well to ensure patient safety throughout the product life cycle. This is particularly complicated for biotechnology-based therapeutics where seemingly minor changes in process and/or raw material attributes have been shown to have a significant effect on clinical safety and efficacy of the product. This article provides a perspective on the topic of monitoring the quality of biotech therapeutics. In the backdrop of challenges faced by the regulatory agencies, the potential use of multivariate data analysis as a tool for effective monitoring has been proposed. Case studies using data from several insulin biosimilars have been used to illustrate the key concepts.

  3. 76 FR 30542 - Adult Signature Services

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-26

    ...[supreg]. USPS[supreg]-approved PC Postage[supreg] (registered end- users only). Permit imprint, if the.... Permit imprint, if the customer electronically submits postage statements and mailing documentation. d... mailpieces (not bearing a permit imprint) with Adult Signature at a Post Office lobby drop, collection box...

  4. 28 CFR 66.32 - Equipment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 66.32... (block or formula funds) shall vest in the criminal justice agency or nonprofit organization that..., subject to the approval of the awarding agency. (d) Management requirements. Procedures for managing...

  5. A new era of prospective real-world safety evaluation primary report of XIENCE V USA (XIENCE V Everolimus Eluting Coronary Stent System condition-of-approval post-market study).

    PubMed

    Krucoff, Mitchell W; Rutledge, David R; Gruberg, Luis; Jonnavithula, Lalitha; Katopodis, John N; Lombardi, William; Mao, Vivian W; Sharma, Samin K; Simonton, Charles A; Tamboli, Hoshedar P; Wang, Jin; Wilburn, Olivia; Zhao, Weiying; Sudhir, Krishnankutty; Hermiller, James B

    2011-12-01

    The XIENCE V USA (XIENCE V Everolimus Eluting Coronary Stent System Condition-of-Approval Post-Market study) sought to: 1) evaluate the safety of everolimus-eluting coronary stent systems (EECSS) in a contemporary cohort of real-world subjects; and 2) prospectively test the quality of event reporting with analysis of matched patients from the randomized SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions) trial. Randomized trials have demonstrated the safety and efficacy of EECSS in selected "standard-risk" patients. The XIENCE V USA trial was a prospective, multicenter, single-arm study in unselected patients. The primary endpoint was Academic Research Consortium (ARC)-defined definite and probable stent thrombosis (ST); the co-primary endpoint was the composite of cardiac death and myocardial infarction at 1 year. Secondary analyses included: 1) stratification by standard-risk and extended-risk cohorts; and 2) late ST after dual antiplatelet therapy interruption. Of 5,054 participants (1,875 standard-risk; 3,179 extended-risk), 4,958 (98.1%) reached 1-year follow-up. The rate of ARC-defined definite and probable ST was 0.84% (95% confidence interval [CI]: 0.60% to 1.14%) in the overall population and 0.33% (95% CI: 0.12% to 10.72%) and 1.14% (95% CI: 0.80% to 11.58%) in the standard-risk and extended-risk cohorts, respectively. No late ST was observed after dual antiplatelet therapy interruption in either cohort after 6 months. The composite rate of cardiac death and ARC-defined myocardial infarction was 6.5% (95% CI: 5.79% to 17.17%) in the overall population, 3.8% (95% CI: 2.98% to 14.78%) in the standard-risk cohort, and 8.0% (95% CI: 7.09% to 19.02%) in the extended-risk cohort. This study comprehensively reports ST rates for EECSS in a contemporary real-world population. The absence of ST after dual antiplatelet therapy interruption beyond 6 months in standard-risk and high-risk patients is notable. Consistent safety outcomes between matched standard-risk cohorts from the XIENCE V USA study and the SPIRIT IV randomized trial suggest that this study affords a reliable benchmark for understanding the safety of EECSS in the context of real-world clinical practice. (XIENCE V Everolimus Eluting Coronary Stent System [EECSS] USA Post-Approval Study; NCT00676520). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. [Importation and transit of products of animal origin at the border inspection post of Hamburg as an example].

    PubMed

    Mielmann, P

    2001-08-01

    The EU conditions for the approval of border inspection posts are explained, just as the modalities of checking (documentary check, identity check, physical examination) and the information and communication systems (ANIMO, Rapid Alerts, EU Internet). The differences in procedure between import, transit and some specials are outlined. An overview is given of the volume, kinds of products, origins and the import figures relating to the transit figures. The results of the checks are commented.

  7. An Unfulfilled Promise: Changes Needed to the Drug Approval Process to Make Personalized Medicine a Reality.

    PubMed

    Riley, Margaret Foster

    2015-01-01

    The widespread availability of drugs for personalized medicine has been an aspiration since before the human genome was sequenced. Recently, there is renewed interest; personalized medicine is much in the news. Legislation has been considered with the goal of smoothing, shortening and incentivizing the approval process for therapeutic products. President Obama mentioned the need for new initiatives to achieve such goals in the State of the Union address. But most of these initiatives do not consider the fundamental changes that personalized medicine demands. It requires a statutory structure designed for the development of products applicable for small subpopulations that is very different from our current model which is designed for the development of products for large populations. The current approval process is purposely not designed to consider individual efficacy. It is designed to incentivize reduced variation in clinical trials rather than embracing variation. In addition, it is based on twentieth-century notions of disease focused on phenotype rather than on pathophysiologic pathways. Current foci on the development of companion diagnostics, orphan drugs and post-approval study are important but insufficient. FDA does not have the authority to require the type of standardization, clinical trial design and extensive data reporting and sharing that. is needed to achieve the goals for personalized medicine. In addition, FDA's current drug approval process is too lengthy and cumbersome to deal with the iterative responses personalized medicine entails. If we are serious about wanting to achieve these goals, we will need to entertain such fundamental changes in authority.

  8. 38 CFR 21.9600 - Overcharges.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approved Programs of Education and Courses § 21...) Overcharges by organizations or entities offering licensing or certification tests may result in disapproval of tests. VA may disapprove an organization or entity offering a licensing or certification test when...

  9. 7 CFR 62.208 - Publication of QSVP assessment status.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... (CONTINUED) LIVESTOCK, MEAT, AND OTHER AGRICULTURAL COMMODITIES (QUALITY SYSTEMS VERIFICATION PROGRAMS) Quality Systems Verification Programs Definitions Service § 62.208 Publication of QSVP assessment status. Approved programs shall be posted for public reference on the ARC Branch Web site: http://www.ams.usda.gov...

  10. 7 CFR 62.208 - Publication of QSVP assessment status.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (CONTINUED) LIVESTOCK, MEAT, AND OTHER AGRICULTURAL COMMODITIES (QUALITY SYSTEMS VERIFICATION PROGRAMS) Quality Systems Verification Programs Definitions Service § 62.208 Publication of QSVP assessment status. Approved programs shall be posted for public reference on the ARC Branch Web site: http://www.ams.usda.gov...

  11. Data Analysis and Reporting of the 150 Chevrolet Volt ARRA Demonstration Fleet

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

    Richard "Barney" Carlson

    This is the final report for the GM Vehicle Demo analysis and reporting. I'd like it to be posted to the AVTA website. It contains no new information than what is in Quarterly reports that were previously approved by GM.

  12. 7 CFR 62.208 - Publication of QSVP assessment status.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... (CONTINUED) LIVESTOCK, MEAT, AND OTHER AGRICULTURAL COMMODITIES (QUALITY SYSTEMS VERIFICATION PROGRAMS) Quality Systems Verification Programs Definitions Service § 62.208 Publication of QSVP assessment status. Approved programs shall be posted for public reference on the ARC Branch Web site: http://www.ams.usda.gov...

  13. 7 CFR 62.208 - Publication of QSVP assessment status.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... (CONTINUED) LIVESTOCK, MEAT, AND OTHER AGRICULTURAL COMMODITIES (QUALITY SYSTEMS VERIFICATION PROGRAMS) Quality Systems Verification Programs Definitions Service § 62.208 Publication of QSVP assessment status. Approved programs shall be posted for public reference on the ARC Branch Web site: http://www.ams.usda.gov...

  14. 7 CFR 62.208 - Publication of QSVP assessment status.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (CONTINUED) LIVESTOCK, MEAT, AND OTHER AGRICULTURAL COMMODITIES (QUALITY SYSTEMS VERIFICATION PROGRAMS) Quality Systems Verification Programs Definitions Service § 62.208 Publication of QSVP assessment status. Approved programs shall be posted for public reference on the ARC Branch Web site: http://www.ams.usda.gov...

  15. 25 CFR 1000.230 - How is a waiver approval documented for the record?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... record? The waiver decision is made part of the AFA by attaching a copy of it to the AFA and by mutually... posted on the Office of Self-Governance web site and all such decisions shall be made available on...

  16. 7 CFR 3016.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Changes. 3016.30 Section 3016.30 Agriculture... GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 3016.30 Changes. (a) General. Grantees... requirements and may make limited program changes to the approved project. However, unless waived by the...

  17. 32 CFR Appendix I to Part 154 - Overseas Investigations

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., the DD Form 1879 and the perceived jurisdictional question should be promptly forwarded to DIS for action and, if appropriate, to the component's headquarters for information. Questions on the... Manual calls for obtaining PIC approval before conducting a Subject interview on a post-adjudicative...

  18. 32 CFR Appendix I to Part 154 - Overseas Investigations

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., the DD Form 1879 and the perceived jurisdictional question should be promptly forwarded to DIS for action and, if appropriate, to the component's headquarters for information. Questions on the... Manual calls for obtaining PIC approval before conducting a Subject interview on a post-adjudicative...

  19. 34 CFR 74.46 - Procurement records.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements... selection; (b) Justification for lack of competition when competitive bids or offers are not obtained; (c) Basis for award cost or price. (Approved by the Office of Management and Budget under control number...

  20. Balancing the benefits and risks of disease-modifying therapy in patients with multiple sclerosis.

    PubMed

    Sørensen, Per Soelberg

    2011-12-01

    Balancing efficacy versus burden of therapy is essential for the choice of disease-modifying therapy in every MS patient. The first-line therapies, interferon-? and glatiramer acetate, have well-established efficacy and present no major safety concerns. Certain second-line therapies, such as natalizumab, offer potentially greater efficacy, but are associated with an increased level of risk. Over the last year, the first two oral treatments of relapsing-remitting multiple sclerosis, cladribine and fingolimod, have been marketed in certain countries, although cladribine was subsequently withdrawn. In the Phase III clinical development programme, both drugs appeared effective and reasonably safe. However, there were cases of serious adverse events (malignancies and fatal infections) whose relationship with treatment was unclear. Specific postmarketing studies will be necessary to assess the risks of these new oral therapies. Indeed, both natalizumab and mitoxantrone are known today to be associated with rare adverse drug reactions (progressive multifocal leukoencephalopathy for natalizumab and treatment-related leukaemia for mitoxantrone), which were not identified before the treatments were approved. The use of therapies carrying potential serious risks is justified in patients who cannot be treated effectively with safe first-line therapies, but probably not in the average relapsing-remitting multiple sclerosis or clinical isolated syndrome patient. Pivotal Phase III clinical trials, on which basis drug approval is generally granted, are designed to demonstrate clinical efficacy and reveal frequently occurring adverse effects of a new drug. However, post-approval trials with extensive patient exposure are needed to generate knowledge of more patient-specific clinical effectiveness and long-term safety, in particular with respect to rare adverse reactions. Other post-approval measures, such as risk management programmes, pharmacovigilance studies, or phased launch of the drug, may be useful to ensure that risks associated with new treatments are identified and minimised. The final evaluation of the benefits to risks balance of a drug should be made in every patient by weighing benefits in disease activity and progression, quality of life and health economy against both commonly occurring mild side-effects and rare potentially life-threatening adverse drug effects. This decision should be shared between the physician and patient, who may not share the same perceptions of acceptable risk. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2017-01-01

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

  2. Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

    PubMed

    Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

    2017-12-05

    To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies' transparency records and recognise exemplary companies may encourage further progress. © 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.

  3. Study on IL-2 and CA 15-3 level as combined biomarkers in monitoring chemotherapeutic response among invasive breast cancer patients

    NASA Astrophysics Data System (ADS)

    Hameed, Ahmed Muthanna Abdul; Hamid, Auni Fatin Abdul; Shahfiza Noor, Nurul; Appalanaido, Gokula Kumar; Bariyah Sahul Hamid, Shahrul

    2017-05-01

    In Malaysia, breast cancer is the most frequent type of disease among women. This study was designed to determine the clinical usefulness of carbohydrate antigen (CA 15-3) and interleukin 2 (IL-2) levels as combined biomarkers in monitoring breast cancer patient’s response to chemotherapy. Ethical approval was obtained to recruit patients with histologically confirmed invasive ductal carcinoma (IDC) attending Oncology Clinic at Advanced Medical and Dental Institute. Whole blood was collected from 10 IDC breast cancer patients’ pre and post primary chemotherapy. Plasma was separated from the whole blood to determine the CA 15-3 level and IL-2 level using enzyme-linked immunosorbent assay (ELISA) pre and post-treatment. In addition, the histological findings, tumour stage and other patients’ data were obtained from the medical record. Findings showed that IL-2 had borderline significant changes between pre- and post-chemotherapy (p = 0.074) whereas for CA 15-3, there was insignificant differences of CA 15-3 level between pre and post-chemotherapy (p > 0.05). It was noted that only CA 15-3 level had significant correlation with tumour size. This study demonstrates that IL-2 level requires further investigation in a larger sample size to correlate its potential use as combined biomarker with CA 15-3 in monitoring response to chemotherapy.

  4. Biomonitoring at the UK Health and Safety Laboratory.

    PubMed

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

    2007-05-01

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

  5. 76 FR 38219 - Submission for OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ... OVERSEAS PRIVATE INVESTMENT CORPORATION [OMB-3420-0011; OPIC-115] Submission for OMB Review AGENCY... OMB review and approval. {Comments were solicited in the 60 day notice, posted on [October 2, 2007..., DC 20527; (202) 336-8563. Summary Form Under Review Type of Request: Revised form. Title: Application...

  6. 77 FR 50071 - Petition for Approval of Alternate Odometer Disclosure Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-20

    ... be better informed and provide a mechanism for tracing odometer tampering and prosecuting violators... background, according to information posted on the Arizona Department of Transportation (ADOT) Web site... explanation for this omission, which could make tracing and prosecuting fraud more difficult.\\38\\ \\38...

  7. 10 CFR 50.82 - Termination of license.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... licensees whose decommissioning plan approval activities have been relegated to notice of opportunity for a... decommissioning activities required in paragraphs (a)(4)(ii) and (a)(5) of this section shall not apply, and any... permanent cessation of operations, the licensee shall submit a post-shutdown decommissioning activities...

  8. 24 CFR 85.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Changes. 85.30 Section 85.30... TRIBAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 85.30 Changes. (a) General... unanticipated requirements and may make limited program changes to the approved project. However, unless waived...

  9. 45 CFR 1174.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Changes. 1174.30 Section 1174.30 Public Welfare... STATE AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 1174.30 Changes... budget to meet unanticipated requirements and may make limited program changes to the approved project...

  10. 49 CFR 18.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Changes. 18.30 Section 18.30 Transportation Office... AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 18.30 Changes. (a) General. Grantees and subgrantees are permitted to rebudget within the approved direct cost...

  11. 36 CFR 1207.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Changes. 1207.30 Section 1207... Post-Award Requirements Changes, Property, and Subawards § 1207.30 Changes. (a) General. Grantees and... requirements and may make limited program changes to the approved project. However, unless waived by the...

  12. 34 CFR 80.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Changes. 80.30 Section 80.30 Education Office of the... TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 80.30 Changes. (a) General. Grantees and subgrantees are permitted to rebudget within the approved direct cost...

  13. 28 CFR 66.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Changes. 66.30 Section 66.30 Judicial... AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 66.30 Changes. (a) General. Grantees and subgrantees are permitted to rebudget within the approved direct cost...

  14. 45 CFR 1183.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Changes. 1183.30 Section 1183.30 Public Welfare... AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 1183.30 Changes. (a) General. Grantees and subgrantees are permitted to rebudget within the approved direct cost...

  15. 44 CFR 13.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Changes. 13.30 Section 13.30... GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 13.30 Changes. (a) General. Grantees... requirements and may make limited program changes to the approved project. However, unless waived by the...

  16. 45 CFR 1157.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Changes. 1157.30 Section 1157.30 Public Welfare... AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 1157.30 Changes. (a... unanticipated requirements and may make limited program changes to the approved project. However, unless waived...

  17. 22 CFR 135.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Changes. 135.30 Section 135.30 Foreign... AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 135.30 Changes. (a) General. Grantees and subgrantees are permitted to rebudget within the approved direct cost...

  18. 48 CFR 32.1007 - Administration and payment of performance-based payments.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Government, post-payment reviews and verifications should normally be arranged as considered appropriate by...-based payment until the specified event or performance criterion has been successfully accomplished in accordance with the contract. If an event is cumulative, the contracting officer shall not approve the...

  19. 48 CFR 32.1007 - Administration and payment of performance-based payments.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Government, post-payment reviews and verifications should normally be arranged as considered appropriate by...-based payment until the specified event or performance criterion has been successfully accomplished in accordance with the contract. If an event is cumulative, the contracting officer shall not approve the...

  20. 48 CFR 32.1007 - Administration and payment of performance-based payments.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Government, post-payment reviews and verifications should normally be arranged as considered appropriate by...-based payment until the specified event or performance criterion has been successfully accomplished in accordance with the contract. If an event is cumulative, the contracting officer shall not approve the...

  1. 75 FR 49457 - Amador County Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ... approval and implementation, and conduct RAC management business. DATES: The meetings will be held on.... SUPPLEMENTARY INFORMATION: The meeting is open to the public. The following business will be conducted: At that... implementation and conduct RAC management buiness. More information will be posted on the Eldorado National...

  2. A fresh perspective on comparing the FDA and the CHMP/EMA: approval of antineoplastic tyrosine kinase inhibitors

    PubMed Central

    Shah, Rashmi R; Roberts, Samantha A; Shah, Devron R

    2013-01-01

    We compared and determined the reasons for any differences in the review and approval times of tyrosine kinase inhibitors (TKIs) by the US Food and Drug Administration (FDA) and the European EMA/CHMP. Applications for these novel cancer drugs were submitted to them within a mean of 31.2 days of each other, providing a fair basis for comparison. The FDA had granted priority review to 12 TKIs but the EMA/CHMP did not grant the equivalent accelerated assessment to any. The FDA granted accelerated approvals to six (38%) and CHMP granted (the equivalent) conditional approvals to four (29%) of these agents. On average, the review and approval times were 205.3 days in the US compared with 409.6 days in the European Union (EU). The active review times, however, were comparable (225.4 days in the EU and 205.3 days in the US). Since oncology drug development lasts about 7 years, the 20 days difference in review times between the two agencies is inconsequential. Clock stops during review and the time required to issue an approval had added the extra 184.2 days to review time in the EU. We suggest possible solutions to expedite the EU review and approval processes. However, post-marketing emergence of adverse efficacy and safety data on gefitinib and lapatinib, respectively, indicate potential risks of expedited approvals. We challenge the widely prevalent myth that early approval translates into early access or beneficial impact on public health. Both the agencies collaborate closely but conduct independent assessments and make decisions based on distinct legislation, procedures, precedents and societal expectations. PMID:23362829

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

    PubMed

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

    2015-11-01

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

  4. Continuing dental education in radiation protection: monitoring the outcomes.

    PubMed

    Absi, Eg; Drage, Na; Thomas, Hs; Newcombe, Rg; Nash, Es

    2009-03-01

    To evaluate an evolving radiation protection dental postgraduate course run in Wales between 2003 and 2007. We compared three standardized course series. Course content was enhanced in 2006 to target areas of weakness. In 2007, a single best answer multiple choice questionnaire instrument superseded a true/false format. Practitioners' performance was studied pre- and immediately post-training. 900 participants completed identical pre- and post-course validated multiple choice questionnaires. 809 (90%) paired morning-afternoon records, including those of 52 dental care professionals (DCPs), were analysed. Mean (standard error) pre- and post-course percentage scores for the three courses were 33.8 (0.9), 35.4 (1.4), 34.6 (1.0) and 63.6 (0.9), 59.0 (1.4), 69.5 (0.9). Pre-training, only 2.4%, 3.1% and 4.9% of participants achieved the pass mark compared to 57.7%, 48.4% and 65.9% post-training, indicating a rather greater pass rate and gain in the most recent series than earlier ones. In recent series, older more experienced candidates scored slightly higher; however, their gain from pre- to post-training was slightly less. Baseline levels of radiation protection knowledge remained very low but attending an approved course improved this considerably. Targeting areas of weaknesses produced higher scores. Current radiation protection courses may not be optimal for DCPs.

  5. Projected 24-hour post-dose ocular itching scores post-treatment with olopatadine 0.7% versus 0.2.

    PubMed

    Fidler, Matthew L; Ogundele, Abayomi; Covert, David; Sarangapani, Ramesh

    2018-04-21

    Olopatadine is an antihistamine and mast cell stabilizer used for treating allergic conjunctivitis. Olopatadine 0.7% has been recently approved for daily dosing in the US, which supersedes the previously approved 0.2% strength. The objective of this analysis was to characterize patients who have better itching relief at 24 h when taking olopatadine 0.7% treatment instead of olopatadine 0.2% (in terms of proportions of responses) and relate this to the severity of baseline itching as an indirect metric of a patient's sensitivity to antihistamines. A differential odds model was developed using data from two conjunctival allergen challenge (CAC) studies to characterize individual-level and population-level response to ocular itching following olopatadine treatment and the data was analyzed retrospectively. This modeling analysis was designed to predict 24 h ocular itching scores and to quantify the differences in 24 h itching relief following treatment with olopatadine 0.2% versus 0.7% in patients with moderate-to-high baseline itching. A one-compartment kinetic-pharmacodynamic E max model was used to determine the effect of olopatadine. Impact of baseline itching severity, vehicle effect and the drug effect on the overall itching scores post-treatment were explicitly incorporated in the model. The model quantified trends observed in the clinical data with regards to both mean scores and the proportions of patients responding to olopatadine treatment. The model predicts a higher proportion of patients in the olopatadine 0.7% versus 0.2% group will experience relief within 24 h. This prediction was confirmed with retrospective clinical data analysis. The number of allergy patients relieved with olopatadine 0.7% increased with higher baseline itching severity scores, when compared to olopatadine 0.2%.

  6. Medicare-approved drug discount cards and renal transplant patients: how much can these cards reduce prescription costs?

    PubMed

    Chisholm, Marie A; Marshall, Josh; Smith, Kimberly E; Garrett, Charlene J; Turner, Jeanie C

    2005-06-01

    Post-transplant prescription medications are expensive, often costing over 12,000 dollars annually. Many solid-organ transplant patients have Medicare coverage and patients enrolled in Medicare-approved drug discount card (MADDC) programs may be able to receive prescription medications at a reduced price. However, many transplant healthcare practitioners are unaware of the utility of MADDCs. The purpose of this study was to determine whether enrolling renal transplant patients (RTPs) into a MADDC produces significant savings in prescription costs. Two Medicare RTPs, with prescription medication profiles representative of an RTP within 3 months post-transplant and an RTP greater than 5 yr post-transplant, were randomly selected from the Medication Access Program's database. Cost benefit analyses were from the patients' perspective and were performed using the: (i) prescription cost from the Medicare website of MADDCs that listed the greatest and least prescription costs compared with the retail cash price of the same prescription without using the MADDCs; and (ii) MADDCs' annual enrollment fee. The potential cost difference of using MADDCs and not using MADDCs to purchase the prescription medications were calculated. RTPs' monthly out-of-pocket cost for prescription medications ranged from 162 dollars to 340 dollars, and MADDCs offered discounts of 20-37% from retail prices; thus outweighing the MADDC enrollment cost. MADDCs, when selected and used appropriately, can reduce prescription medication cost for RTPs. Card selection is of great importance as discount rates vary greatly among cards, and only under restricted circumstances is a patient allowed to switch to another card. It is imperative that practitioners are aware of these programs and utilize cost-effective prescribing practices.

  7. Reprioritizing Research Activity for the Post-Antibiotic Era: Ethical, Legal, and Social Considerations.

    PubMed

    Hey, Spencer Phillips; Kesselheim, Aaron S

    2017-03-01

    Many hold that the so-called golden era of antibiotic discovery has passed, leaving only a limited clinical pipeline for new antibiotics. A logical conclusion of such arguments is that we need to reform the current system of antibiotic drug research-including clinical trials and regulatory requirements-to spur activity in discovery and development. The United States Congress in the past few years has debated a number of bills to address this crisis, including the 2012 Generating Antibiotic Incentives Now Act and the 2016 21st Century Cures Act. Experts have also sought to advance antibiotic development by encouraging greater use of trials with noninferiority hypotheses, which are thought to be easier to conduct. The goal underlying these proposals is to stave off the post-antibiotic era by expanding the pharmaceutical armamentarium as quickly as possible. But although new antibiotic agents are necessary to combat the long-term threat of drug-resistant disease, we argue that these research policies, which effectively lower the bar for antibiotic approval, are ethically problematic. Rather, given broader public health considerations related to the full lifecycle of antibiotic use-including development of resistance-we should reject an overly permissive approach to new antibiotic approval and instead set the bar for regulatory approval at a point that will naturally direct research resources toward the most transformative chemical or social interventions. © 2017 The Hastings Center.

  8. Sodium 4-phenylbutyrate reduces myofiber damage in a mouse model of Duchenne muscular dystrophy.

    PubMed

    Begam, Morium; Abro, Valerie M; Mueller, Amber L; Roche, Joseph A

    2016-10-01

    We performed a placebo-controlled pre-clinical study to determine if sodium 4-phenylbutyrate (4PB) can reduce contraction-induced myofiber damage in the mdx mouse model of Duchenne muscular dystrophy (DMD). At 72 h post-eccentric contractions, 4PB significantly increased contractile torque and reduced myofiber damage and macrophage infiltration. We conclude that 4PB, which is approved by Health Canada (Pheburane) and the United States Food and Drug Administration (Buphenyl) for urea cycle disorders, might modify disease severity in patients with DMD.

  9. Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation.

    PubMed

    Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Kernan, Nancy A; Grupp, Stephan A; Antin, Joseph H; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L; Nejadnik, Bijan; Soiffer, Robert J

    2017-07-01

    Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P < 0·001). These results suggest that initiation of defibrotide should not be delayed after diagnosis of VOD/SOS. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  10. Predicting early post-partum depressive symptoms among older primiparous Japanese mothers.

    PubMed

    Iwata, Hiroko; Mori, Emi; Tsuchiya, Miyako; Sakajo, Akiko; Maehara, Kunie; Ozawa, Harumi; Morita, Akiko; Maekawa, Tomoko; Aoki, Kyoko; Makaya, Miyuki; Tamakoshi, Koji

    2015-10-01

    The number of older primiparas is increasing in Japan. These women have been shown to be more vulnerable to post-partum depression. This study aimed to identify factors for predicting post-partum depressive symptoms during hospitalization after childbirth in Japanese primiparas aged 35 years and over. The present authors used the data of 479 primiparas aged 35 years and over from a prospective cohort study. Data were collected using self-report questionnaires on the day before hospital discharge. The questionnaire consisted of: demographics and background information; depressive symptoms; fatigue; maternal confidence and maternal satisfaction; child-care values; physical symptoms; perceptions of daily life during hospitalization; concerns about child care and daily life; and infant feeding. Additionally, vital records data were obtained from the hospitals. A stepwise logistic regression analysis was performed on the binary outcome variable of depressive symptoms, measured by the Japanese version of the Edinburgh Postnatal Depression Scale. Women who scored 9 or more were considered to be at high risk for post-partum depression. The authors obtained informed consent from all participants and institutional ethics approvals before initiating the study. The following six variables reliably predicted the risk of post-partum depression: emergency cesarean section, lower satisfaction with birth experience, higher physical burden in daily life, long-term complications with the newborn, more concerns about newborn caretaking after discharge, and more concerns about one's own life after discharge. Recognition of women with these factors will help nurses to identify those at risk for developing post-partum depression and to provide appropriate care during hospitalization after childbirth. © 2015 The Authors. Japan Journal of Nursing Science © 2015 Japan Academy of Nursing Science.

  11. A randomized, double-blind, placebo-controlled trial on the role of preemptive analgesia with acetaminophen [paracetamol] in reducing headache following electroconvulsive therapy [ECT].

    PubMed

    Isuru, Amila; Rodrigo, Asiri; Wijesinghe, Chamara; Ediriweera, Dileepa; Premadasa, Shan; Wijesekara, Carmel; Kuruppuarachchi, Lalith

    2017-07-28

    Electroconvulsive therapy (ECT) is a safe and efficient treatment for several severe psychiatric disorders, but its use is limited by side effects. Post-ECT headache is one of the commonest side effects. Preemptive analgesia is effective in post-surgical pain management. The most commonly used analgesic is acetaminophen (paracetamol). However, acetaminophen as a preemptive analgesic for post-ECT headache has not been studied adequately. This study was conducted to compare the incidence and severity of post-ECT headache in patients who were administered acetaminophen pre-ECT with a placebo group. This study was a randomised, double-blind, placebo-controlled trial. Sixty-three patients received 1 g acetaminophen and 63 patients received a placebo identical to acetaminophen. The incidence and severity of headache 2 h before and after ECT were compared between placebo and acetaminophen groups. The severity was measured using a visual analog scale. Generalised linear models were used to evaluate variables associated with post ECT headache. Demographic and clinical variables of placebo and acetaminophen groups were comparable except for the energy level used to induce a seizure. Higher proportion of the placebo group (71.4%) experienced post-ECT headache when compared to the acetaminophen group (p < 0.001). The median pain score for headache was 0 (Inter quartile range: 0-2) in acetaminophen group whereas the score was 2 (IQR: 0-4) in placebo group (P < 0.001). Model fitting showed that the administration of acetaminophen is associated with less post-ECT headache (odds ratio = 0.23, 95% CI: 0.11-0.48, P < 0.001). A significant reduction was seen in both the incidence and severity of post-ECT headache with preemptive analgesia with acetaminophen. Ethical approval was granted by an Ethic review committee, University of Kelaniya, Sri Lanka (P/166/10/2015) and the trial was registered in the Sri Lanka Clinical Trials Registry ( SLCTR/2015/27 ).

  12. Nrf2-ARE activator carnosic acid decreases mitochondrial dysfunction, oxidative damage and neuronal cytoskeletal degradation following traumatic brain injury in mice.

    PubMed

    Miller, Darren M; Singh, Indrapal N; Wang, Juan A; Hall, Edward D

    2015-02-01

    The importance of free radical-induced oxidative damage after traumatic brain injury (TBI) has been well documented. Despite multiple clinical trials with radical-scavenging antioxidants that are neuroprotective in TBI models, none is approved for acute TBI patients. As an alternative antioxidant target, Nrf2 is a transcription factor that activates expression of antioxidant and cytoprotective genes by binding to antioxidant response elements (AREs) within DNA. Previous research has shown that neuronal mitochondria are susceptible to oxidative damage post-TBI, and thus the current study investigates whether Nrf2-ARE activation protects mitochondrial function when activated post-TBI. It was hypothesized that administration of carnosic acid (CA) would reduce oxidative damage biomarkers in the brain tissue and also preserve cortical mitochondrial respiratory function post-TBI. A mouse controlled cortical impact (CCI) model was employed with a 1.0mm cortical deformation injury. Administration of CA at 15 min post-TBI reduced cortical lipid peroxidation, protein nitration, and cytoskeletal breakdown markers in a dose-dependent manner at 48 h post-injury. Moreover, CA preserved mitochondrial respiratory function compared to vehicle animals. This was accompanied by decreased oxidative damage to mitochondrial proteins, suggesting the mechanistic connection of the two effects. Lastly, delaying the initial administration of CA up to 8h post-TBI was still capable of reducing cytoskeletal breakdown, thereby demonstrating a clinically relevant therapeutic window for this approach. This study demonstrates that pharmacological Nrf2-ARE induction is capable of neuroprotective efficacy when administered after TBI. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 34 CFR 74.21 - Standards for financial management systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award... the Federal Government guarantees or insures the repayment of money borrowed by the recipient, the..., as prescribed in 31 CFR Part 223—Surety Companies Doing Business with the United States. (Approved by...

  14. 34 CFR 74.21 - Standards for financial management systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award... the Federal Government guarantees or insures the repayment of money borrowed by the recipient, the..., as prescribed in 31 CFR Part 223—Surety Companies Doing Business with the United States. (Approved by...

  15. 34 CFR 74.21 - Standards for financial management systems.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award... the Federal Government guarantees or insures the repayment of money borrowed by the recipient, the..., as prescribed in 31 CFR Part 223—Surety Companies Doing Business with the United States. (Approved by...

  16. 22 CFR 518.25 - Revision of budget and program plans.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management § 518.25 Revision of budget and program plans. (a) The budget plan is the financial expression of the project or program as approved during the...

  17. Experimental use of flexible guideposts in Oregon : PPM 20-6.3, Category 2 Project : final report.

    DOT National Transportation Integrated Search

    1974-06-25

    During the early months of 1971 the Oregon State Highway Division requested and received FHWA approval to install flexible guideposts in locations where sight post losses from collisions would be expected to be high. The request was to install the fl...

  18. 77 FR 13131 - Proposed Collection: Comment Request Post-Award Reporting Requirements Including New Research...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-05

    ... submitted to the Office of Management and Budget (OMB) for review and approval. Proposed Collection: Title... Administration, Centers for Disease Control and Prevention, and Agency for Healthcare Research and Quality (AHRQ... and principal investigators. The annual reporting burden is as follows: Total Estimated Number of...

  19. 7 CFR 1951.871 - Post award requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... regulations, the loan agreement, the approved work program, security interests, and other conditions which Fm... programs must maintain separate ledgers and segregated accounts for RDLF funds at all times. (d) Reporting... such loan. (f) All loan payments that are due on RDLF loans will be made payable to the Farmers Home...

  20. 76 FR 52931 - Notice of Intent To Request Comments on a Currently Approved Information Collection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ... electronically. Mail: Attention: Phyllis I. Watkins, Agency OMB Clearance Officer, Department of Agriculture....watkins@wdc.usda.gov . All comments received will become a matter of public record and will be posted... INFORMATION CONTACT: Phyllis I. Watkins, Agency OMB Clearance Officer, Department of Agriculture, Natural...

  1. Coast Guard Maritime Commons

    Science.gov Websites

    Center's ballast water management system website The Marine Safety Center recently updated two tools posted to its ballast water management system website to assist industry when completing the ballast water management system type approval process, or when accessing letters of intent. 5/23/2018: Release of Mission

  2. 32 CFR 32.52 - Financial reporting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Financial reporting. 32.52 Section 32.52..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Reports and Records § 32.52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for...

  3. 15 CFR 14.52 - Financial reporting.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Financial reporting. 14.52 Section 14... COMMERCIAL ORGANIZATIONS Post-Award Requirements Reports and Records § 14.52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for obtaining financial...

  4. 45 CFR 2543.52 - Financial reporting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Financial reporting. 2543.52 Section 2543.52... ORGANIZATIONS Post-Award Requirements Property Standards § 2543.52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for obtaining financial information from...

  5. 40 CFR 30.52 - Financial reporting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Financial reporting. 30.52 Section 30..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Reports and Records § 30.52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for...

  6. 38 CFR 49.52 - Financial reporting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Financial reporting. 49..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Reports and Records § 49.52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for...

  7. 25 CFR 535.2 - Assignments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Assignments. 535.2 Section 535.2 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR MANAGEMENT CONTRACT PROVISIONS POST-APPROVAL PROCEDURES... disapprove an assignment applying the standards of, and within the time provided by §§ 535.1(d) and 535.1(e...

  8. 7 CFR 3202.5 - Initial approval process.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .... A standardized application form and instructions are available on the USDA BioPreferred Program Web... post to the USDA BioPreferred Program Web site, and to providing USDA with up-to-date information for... certification. Instructions for submitting the application fee are available on the USDA BioPreferred Program...

  9. 7 CFR 3202.5 - Initial approval process.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... A standardized application form and instructions are available on the USDA BioPreferred Program Web... post to the USDA BioPreferred Program Web site, and to providing USDA with up-to-date information for... certification. Instructions for submitting the application fee are available on the USDA BioPreferred Program...

  10. 7 CFR 3202.5 - Initial approval process.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... A standardized application form and instructions are available on the USDA BioPreferred Program Web... post to the USDA BioPreferred Program Web site, and to providing USDA with up-to-date information for... certification. Instructions for submitting the application fee are available on the USDA BioPreferred Program...

  11. Internet Survey of Nutrition Claim Knowledge

    ERIC Educational Resources Information Center

    Camire, Mary E.; Dougherty, Michael P.

    2005-01-01

    Consumer interest in healthy foods has spurred approval of several health claims for foods and dietary supplements. Although undergraduate and graduate food science curricula address food laws and regulations, nutrition claims may not be fully addressed. We posted a survey on the Internet for 2 mo for food industry professionals and others…

  12. 40 CFR 60.17 - Incorporations by reference.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (C267-01), U.S. EPA, Research Triangle Park, NC or at the National Archives and Records Administration... Testing and Materials (ASTM), 100 Barr Harbor Drive, Post Office Box C700, West Conshohocken, PA 19428...) ASTM D86-96, Standard Test Method for Distillation of Petroleum Products (Approved April 10, 1996), IBR...

  13. 30 CFR 5.10 - Purpose and scope.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., testing, test set up and tear down, consultation on applications and investigator travel, where necessary...) Participation in research conducted by other government agencies or private organizations; (4) Regulatory review... legislation; and (5) Post-approval product audits. [52 FR 17516, May 8, 1987, as amended at 70 FR 46342, Aug...

  14. 30 CFR 5.10 - Purpose and scope.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., testing, test set up and tear down, consultation on applications and investigator travel, where necessary...) Participation in research conducted by other government agencies or private organizations; (4) Regulatory review... legislation; and (5) Post-approval product audits. [52 FR 17516, May 8, 1987, as amended at 70 FR 46342, Aug...

  15. 30 CFR 5.10 - Purpose and scope.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., testing, test set up and tear down, consultation on applications and investigator travel, where necessary...) Participation in research conducted by other government agencies or private organizations; (4) Regulatory review... legislation; and (5) Post-approval product audits. [52 FR 17516, May 8, 1987, as amended at 70 FR 46342, Aug...

  16. 30 CFR 5.10 - Purpose and scope.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., testing, test set up and tear down, consultation on applications and investigator travel, where necessary...) Participation in research conducted by other government agencies or private organizations; (4) Regulatory review... legislation; and (5) Post-approval product audits. [52 FR 17516, May 8, 1987, as amended at 70 FR 46342, Aug...

  17. 30 CFR 5.10 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., testing, test set up and tear down, consultation on applications and investigator travel, where necessary...) Participation in research conducted by other government agencies or private organizations; (4) Regulatory review... legislation; and (5) Post-approval product audits. [52 FR 17516, May 8, 1987, as amended at 70 FR 46342, Aug...

  18. Evaluation of an Audio Cassette Tape Lecture Course

    ERIC Educational Resources Information Center

    Blank, Jerome W.

    1975-01-01

    An audio-cassette continuing education course (Selected Topics in Pharmacology) from Extension Services in Pharmacy at the University of Wisconsin was offered to a selected test market of pharmacists and evaluated using a pre-, post-test design. Results showed significant increase in cognitive knowledge and strong approval of students. (JT)

  19. 77 FR 32703 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-01

    ... organization consents, the Commission shall either approve the proposed rule change, disapprove the proposed...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change Relating to Post-Trade Transparency for Agency Pass...

  20. 21 CFR 1403.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Changes. 1403.30 Section 1403.30 Food and Drugs... AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 1403.30 Changes. (a) General. Grantees and subgrantees are permitted to rebudget within the approved direct cost...

  1. 29 CFR 97.30 - Changes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Changes. 97.30 Section 97.30 Labor Office of the Secretary... GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 97.30 Changes. (a) General. Grantees... requirements and may make limited program changes to the approved project. However, unless waived by the...

  2. 29 CFR 1952.210 - Description of the plan as initially approved.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... recommendations on adoption of at least as effective standards to the Commissioner within 6 months after Federal... issuance and posting of citations; a system of sanctions against employers for violations of standards... under the existing State merit system with the revisions in qualifications as stated in supplements to...

  3. 22 CFR 16.7 - Agency procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... notify the grievant of the time within which to appeal the decision, and identity of the senior official... the decision process and has formally approved the written response of the responsible officer, the... review under § 16.8. (c) Bureau or post review. (1) If the responsible officer's written response does...

  4. 29 CFR 1952.210 - Description of the plan as initially approved.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... promulgation. Maryland also includes in its plan State boiler and elevator standards where applicable. (b)(1... issuance and posting of citations; a system of sanctions against employers for violations of standards... end of three years after the commencement of operations under the plan. Personnel will be employed...

  5. 29 CFR 1952.210 - Description of the plan as initially approved.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... promulgation. Maryland also includes in its plan State boiler and elevator standards where applicable. (b)(1... issuance and posting of citations; a system of sanctions against employers for violations of standards... end of three years after the commencement of operations under the plan. Personnel will be employed...

  6. 29 CFR 1952.210 - Description of the plan as initially approved.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... promulgation. Maryland also includes in its plan State boiler and elevator standards where applicable. (b)(1... issuance and posting of citations; a system of sanctions against employers for violations of standards... end of three years after the commencement of operations under the plan. Personnel will be employed...

  7. 15 CFR 14.52 - Financial reporting.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Financial reporting. 14.52 Section 14... COMMERCIAL ORGANIZATIONS Post-Award Requirements Reports and Records § 14.52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for obtaining financial...

  8. 28 CFR 70.52 - Financial reporting.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Financial reporting. 70.52 Section 70.52...-PROFIT ORGANIZATIONS Post-Award Requirements Reports and Records § 70.52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for obtaining financial...

  9. 45 CFR 2543.52 - Financial reporting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false Financial reporting. 2543.52 Section 2543.52... ORGANIZATIONS Post-Award Requirements Property Standards § 2543.52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for obtaining financial information from...

  10. 40 CFR 30.52 - Financial reporting.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Financial reporting. 30.52 Section 30..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Reports and Records § 30.52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for...

  11. Maintenance of Certification Part 4 Credit and recruitment for practice-based research.

    PubMed

    Gorzkowski, Julie A; Klein, Jonathan D; Harris, Donna L; Kaseeska, Kristen R; Whitmore Shaefer, Regina M; Bocian, Alison B; Davis, James B; Gotlieb, Edward M; Wasserman, Richard C

    2014-10-01

    Competing priorities in pediatric practice have created challenges for practice-based research. To increase recruitment success, researchers must design studies that provide added value to participants. This study evaluates recruitment of pediatricians into a study, before and after the development and addition of a quality improvement (QI) curriculum approved for American Board of Pediatrics Maintenance of Certification (MOC) Part 4 Credit as an enrollment incentive. Researchers implemented multiple outreach methods to enroll pediatric practices over 28 months. Field note review revealed that many physicians declined enrollment, stating that they prioritized MOC Part 4 projects over research studies. A QI curriculum meeting standards for MOC Part 4 Credit was developed and added to the study protocol as an enrollment incentive. Enrollment rates and characteristics of practitioners enrolled pre- and post-MOC were compared. Pre-MOC enrollment contributed 48% of practices in 22 months; post-MOC enrollment contributed 49% of practices in 6 months. An average of 3.5 practices enrolled per month pre-MOC, compared with 13.1 per month post-MOC (P < .001). Clinicians in pre- and post-MOC groups were similar in age, gender, race, and time spent on patient care; practices enrolled post-MOC were more likely to be located in federally designated Medically Underserved Areas than those enrolled pre-MOC (28.6% vs 12%, P = .03). Addition of MOC Part 4 Credit increased recruitment success and increased enrollment of pediatricians working in underserved areas. Including QI initiatives meeting MOC Part 4 criteria in practice-based research protocols may enhance participation and aid in recruiting diverse practice and patient populations. Copyright © 2014 by the American Academy of Pediatrics.

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

    PubMed

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

    2015-05-01

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

  13. Efficacy and Safety of Roflumilast in Korean Patients with COPD

    PubMed Central

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

    2016-01-01

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

  14. Reasons identified for seeking the American Physical Therapy Association-Credentialed Clinical Instructor Program (CCIP) in Florida.

    PubMed

    Musolino, Gina M; van Duijn, Jacqueline; Noonan, Ann C; Eargle, Linda K; Gray, Debra L

    2013-01-01

    The American Physical Therapy Association's (APTA) Strategic Plan strives to increase the number of APTA credentialed clinical instructors. Available to all health care providers, as of 2012, there were 39,851 credentialed clinical instructors. Study purposes were threefold: to determine participants' a. reasons to attend the APTA Credentialed Clinical Instructor Program (CCIP); b. pre-CCIP learning goals; and c. related post-CCIP learning outcomes. This IRB-approved study was completed with informed consent procedures followed. APTA CCIP credentialed trainers (n=5) developed a survey and pilot tested for face and content validity. The instrument included demographics, forced choice and open-ended questions. The pre/post survey was administered to 301 participants of 21 Florida APTA CCIP courses with 5 trainers from 2009-2011. Quantitative survey data were collated, tabulated, and summarized comparing pre/post data. Narrative data was analyzed for codes and themes, synthesized, re-contextualized and triangulated by trainers then cross-compared with APTA CCIP objectives and trainer expertise. The qualitative insights were presented with resulting primary themes and subthemes. Results informed the study purposes with a clear determination of the reasons participants attend the APTA CCIP, the pre-course goals and post learning outcomes. Participants overwhelmingly recommend the APTA CCIP and most receive support from employers with geographic course location being a prime reason for course selection. Precourse learning goals included 5 over-arching themes, with few sub-themes; while post learning outcomes generated 12 specific themes with numerous subthemes. APTA CCIP-credentialed clinical instructors are achieving numerous learning outcomes immediately applicable for clinical education.

  15. Management of Docetaxel Failures in Metastatic Castrate-Resistant Prostate Cancer

    PubMed Central

    Pal, Sumanta K.; Lewis, Brian; Sartor, Oliver

    2013-01-01

    SYNOPSIS The treatment of metastatic castration resistant prostate cancer (mCRPC) has evolved markedly since the approval of docetaxel-based therapy in 2004. Since that time, 3 distinct agents have gained approval for use in the mCRPC setting, namely sipuleucel-T, cabazitaxel and abiraterone. Even more recently, phase III trials have demonstrated a survival benefit in association with the agents MDV-3100 and radium-223, and FDA approval is anticipated for both of these agents. Although these changes undoubtedly represent progress for the patient with mCRPC, for the practicing physician there is the additional challenge of determining the optimal sequencing for each of these agents. This dilemma is particularly relevant to the post-docetaxel setting, where the indication for several of these agents overlap. Herein, we provide the physician with detailed background on the efficacy and safety of these agents so as to provide a framework for their use in the clinic. PMID:23084533

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

    PubMed

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

    2017-11-01

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

  17. Multicenter cohort study on association of genotypes with prospective sports concussion: methods, lessons learned, and recommendations.

    PubMed

    Terrell, Thomas R; Bostick, Roberd; Barth, Jeffrey; Sloane, Richard; Cantu, Robert C; Bennett, Ellen; Galloway, Leslie; Laskowitz, Daniel; Erlanger, Dave; McKeag, Doug; Valentine, Verle; Nichols, Gregory

    2017-01-01

    Approximately 3.8 million sports related TBIs occur per year. Genetic variation may affect both TBI risk and post-TBI clinical outcome. Limited research has focused on genetic risk for concussion among athletes. We describe the design, methods, and baseline characteristics of this prospective cohort study designed to investigate a potential association between genetic polymorphisms of apolipoprotein E gene, APOE promoter G-219T, and Tau gene exon 6 polymorphisms (Ser53 Pro and Hist47Tyr) with: 1) the risk of prospective concussion; 2) concussion severity; and 3) postconcussion neurocognitive recovery. The prospective cohort study included a final population of 2947 college, high school, and professional athletes. Baseline data collection included a concussion/medical history questionnaire, neuropsychological (NP) testing, and genetic sampling for the genetic polymorphisms. Data collection on new concussions experienced utilized post-concussion history/mental status form, Lovell post-concussion symptom score, Standardized Assessment of Concussion (SAC) and/or the Sports Concussion Assessment Tool (SCAT)-1/SCAT-2, and post-concussion NP testing. This paper is focused on discussing the important methodological considerations, organizational challenges and lessons learned in the completion of a multi-center prospective cohort study. A total of 3740 subjects enrolled, with a total of 335 concussions experienced. Of critical importance to the success of a study of this type is to successfully recruit committed institutions with qualified local study personnel, obtain "buy-in" from study sites, and cultivate strong working relationships with study sites. The use of approved incentives may improve study site recruitment, enhance retention, and enhance compliance with study protocols. Future publications will detail the specific findings of this study. Collaborative research is very likely needed given the nature of this study population.

  18. Ethical considerations in design of a study to evaluate a US Food and Drug Administration-approved indication: antivenom versus placebo for copperhead envenomation.

    PubMed

    Gerardo, Charles J; Lavonas, Eric J; McKinney, Ross E

    2014-10-01

    In 2000, the US Food and Drug Administration approved CroFab(®) Crotalidae Polyvalent Immune Fab, ovine (FabAV), which had received orphan drug designation, for use in patients with minimal to moderate North American crotaline envenomations including copperhead snakes. As existing evidence on the effectiveness of FabAV for this indication is limited, wide practice variation in its use exists. In order to provide more definitive clinical evidence as to the role of this treatment, a new randomized, placebo-controlled trial of FabAV specifically for copperhead bites was initiated. In light of the existing US Food and Drug Administration approval, ethical considerations of participation in this trial have been raised. We discuss the ethical principles pertinent to this randomized, placebo-controlled trial with placebo arm. We apply an accepted framework for ethical research to this trial. Due to the evidence gap in the literature, wide-ranging treatment recommendations by medical experts, and broad practice variation, clinical equipoise exists in the treatment of copperhead envenomation with FabAV. The impact of this clinical equipoise on the value and scientific validity of the trial is discussed. The trial's risk-benefit ratio is also considered. Potential risks to the patients are minimized as the protocol includes a plan for rescue therapy in the event that patients progress to severe envenomation symptoms. Overall, risks are further minimized by the inclusion of an interim analysis with stopping rules based on demonstrated efficacy should the therapy clearly prove to be beneficial. Although a post-marketing clinical study of this nature is unusual for an approved indication, this trial adheres to all ethical preconditions found in existing guidelines for clinical research involving human subjects. © The Author(s) 2014.

  19. Fast-track surgery after gynaecological oncological surgery: study protocol for a prospective randomised controlled trial.

    PubMed

    Cui, Ling; Shi, Yu; Zhang, G N

    2016-12-15

    Fast-track surgery (FTS), also known as enhanced recovery after surgery, is a multidisciplinary approach to accelerate recovery, reduce complications, minimise hospital stay without increasing readmission rates, and reduce health care costs, all without compromising patient safety. The advantages of FTS in abdominal surgery most likely extend to gynaecological surgery, but this is an assumption, as FTS in elective gynaecological surgery has not been well studied. No consensus guidelines have been developed for gynaecological oncological surgery although surgeons have attempted to introduce slightly modified FTS programmes for patients undergoing such surgery. To our knowledge, there are no published randomised controlled trials; however, some studies have shown that FTS in gynaecological oncological surgery leads to early hospital discharge with high levels of patient satisfaction. The aim of this study is whether FTS reduces the length of stay in hospital compared to traditional management. The secondary aim is whether FTS is associated with any increase in post-surgical complications compared to traditional management (for both open and laparoscopic surgery). This trial will prospectively compare FTS and traditional management protocols. The primary endpoint is the length of post-operative hospitalisation (days, mean ± standard deviation), defined as the number of days between the date of discharge and the date of surgery. The secondary endpoints are complications in both groups (FTS versus traditional protocol) occurring during the first 3 months post-operatively including infection (wound infection, lung infection, intraperitoneal infection), post-operative nausea and vomiting, ileus, post-operative haemorrhage, post-operative thrombosis, and the Acute Physiology and Chronic Health Enquiry II score. The advantages of FTS most likely extend to gynaecology, although, to our knowledge, there are no randomised controlled trials. The aim of this study is to compare the post-operative length of hospitalisation after major gynaecological or gynaecological oncological surgery and to analyse patients' post-operative complications. This trial may reveal whether FTS leads to early hospital discharge with few complications after gynaecological surgery. NCT02687412 . Approval Number: SCCHEC20160001. Date of registration: registered on 23 February 2016.

  20. Translation into Brazilian Portuguese and validation of the "Quantitative Global Scarring Grading System for Post-acne Scarring" *

    PubMed Central

    Cachafeiro, Thais Hofmann; Escobar, Gabriela Fortes; Maldonado, Gabriela; Cestari, Tania Ferreira

    2014-01-01

    The "Quantitative Global Scarring Grading System for Postacne Scarring" was developed in English for acne scar grading, based on the number and severity of each type of scar. The aims of this study were to translate this scale into Brazilian Portuguese and verify its reliability and validity. The study followed five steps: Translation, Expert Panel, Back Translation, Approval of authors and Validation. The translated scale showed high internal consistency and high test-retest reliability, confirming its reproducibility. Therefore, it has been validated for our population and can be recommended as a reliable instrument to assess acne scarring. PMID:25184939

  1. How familiar are our doctors towards Rabies prophylaxis- A study from coastal south India.

    PubMed

    Holla, Ramesh; Darshan, Bhagawan; Guliani, Astha; Unnikrishnan, Bhaskaran; Thapar, Rekha; Mithra, Prasanna; Kumar, Nithin; Kulkarni, Vaman; Kumar, Avinash; Anwar, Salman

    2017-10-01

    Rabies, a 100% fatal disease claims more than 59,000 human lives every year globally. One human life is lost every 15 minutes due to this deadly preventable disease. Timely initiation of post exposure prophylaxis following an animal exposure can result in 100% preventability of this fatal disease. This facility based study was conducted among clinical fraternities of teaching hospitals. A semi structured questionnaire was used for collection of data. Institutional Ethics Committee approval was sought. The study investigators visited the workplace of the participants and distributed the questionnaire. SPSS Ver 16 (Chicago, IL, USA) was used to analyse the data. Most of the participants knew that veterinary groups and zoo-keepers should be given pre-exposure prophylaxis. Many participants knew about the Intra Muscular schedule of anti-rabies vaccine and its site of administration for pre exposure prophylaxis. It was observed that most participants had knowledge regarding correct intramuscular regimen of anti-rabies vaccine for post-exposure prophylaxis but less than half were able to differentiate between the intramuscular and intradermal regimens. Less than half of participants were aware of the fact that local administration of anti-rabies serum is useful. The knowledge regarding WHO categorisation of animal exposure and recommended post exposure prophylaxis according to type of exposure observed to be minimal among clinical fraternity.

  2. Mandated monitoring of post-project impacts in the Czech EIA

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

    Branis, Martin; Christopoulos, Stamatios

    2005-04-15

    Altogether, 801 documents of consent (50% of all) issued under the EIA Act No. 244/1992 by the competent authorities in the Czech Republic between 1993 and 2001 were studied. The aim of the analysis was to find and characterize conditions prescribing to the developer to perform ex-ante and ex-post monitoring of potential impacts of projects submitted for approval. It was found that each of the studied documents (standpoints) contained on average three to four conditions prescribing to collect data on various environmental factors during the preparation, implementation and/or operation phase of the development in question. The number of monitoring conditionsmore » contained in the standpoints issued by the Ministry of Environment as well as by the District Offices increased during the period studied from about two to five per project indicating a growing interest in and/or need to obtaining such data. Even though there is a good legal background for collecting monitoring data from implementation and operation phase of new developments, the Czech EIA Act (similarly as EIA acts in other countries) does not provide any practical background for this activity. Without relevant institutional, personal and financial support the possibility to impose post-project monitoring to the developer remains rather a challenge to, not advantage of the Czech EIA Act.« less

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

    PubMed

    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.

  4. The effect of online collaborative learning on middle school student science literacy and sense of community

    NASA Astrophysics Data System (ADS)

    Wendt, Jillian Leigh

    This study examines the effects of online collaborative learning on middle school students' science literacy and sense of community. A quantitative, quasi-experimental pretest/posttest control group design was used. Following IRB approval and district superintendent approval, students at a public middle school in central Virginia completed a pretest consisting of the Misconceptions-Oriented Standards-Based Assessment Resources for Teachers (MOSART) Physical Science assessment and the Classroom Community Scale. Students in the control group received in-class assignments that were completed collaboratively in a face-to-face manner. Students in the experimental group received in-class assignments that were completed online collaboratively through the Edmodo educational platform. Both groups were members of intact, traditional face-to-face classrooms. The students were then post tested. Results pertaining to the MOSART assessment were statistically analyzed through ANCOVA analysis while results pertaining to the Classroom Community Scale were analyzed through MANOVA analysis. Results are reported and suggestions for future research are provided.

  5. Recent developments in the understanding and use of anthrax vaccine adsorbed: achieving more with less.

    PubMed

    Schiffer, Jarad M; McNeil, Michael M; Quinn, Conrad P

    2016-09-01

    Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved vaccine for the prevention of anthrax in humans. Recent improvements in pre-exposure prophylaxis (PrEP) use of AVA include intramuscular (IM) administration and simplification of the priming series to three doses over 6 months. Administration IM markedly reduced the frequency, severity and duration of injection site reactions. Refinement of animal models for inhalation anthrax, identification of immune correlates of protection and cross-species modeling have created opportunities for reductions in the PrEP booster schedule and were pivotal in FDA approval of a post-exposure prophylaxis (PEP) indication. Clinical and nonclinical studies of accelerated PEP schedules and divided doses may provide prospects for shortening the PEP antimicrobial treatment period. These data may assist in determining feasibility of expanded coverage in a large-scale emergency when vaccine demand may exceed availability. Enhancements to the AVA formulation may broaden the vaccine's PEP application.

  6. 78 FR 59335 - Notice of Request for Extension of a Previously Approved Information Collection (Industry...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-26

    ... information collection concerning industry responses to noncompliance records. There are no changes to the existing information collection. DATES: Comments on this notice must be received on or before November 25... this docket will be made available for public inspection and posted without change, including any...

  7. 76 FR 15348 - Proposed Extension of the Approval of Information Collection Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-21

    ... property to be used for housing migrant agricultural workers shall not permit such housing to be occupied... conducted the housing safety and health inspection is posted at the site of the facility or real property. The certificate attests that the facility or real property meets applicable safety and health...

  8. 75 FR 54882 - Submission of information collection for approval From the Office of Management and Budget

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ... Floor, 1700 G Street, NW., Washington, DC 20552. We will post all public comments we receive without... site at http://www.fhfa.gov . In addition, copies of all comments received will be available for... supporting documentation, contact Charles McLean, Associate Director, Office of Housing and Community...

  9. Systems Approach to Defeating Maritime Improvised Explosive Devices in U.S. Ports

    DTIC Science & Technology

    2008-12-01

    DETECTION Pfi PROBABILITY OF FALSE IDENTIFICATION PHPK PROBABILITY OF HIT/PROBABILITY OF KILL PMA POST MISSION ANALYSIS PNNL PACIFIC...16 Naval Warfare Publication 27-2(Rev. B), Section 1.8.4.1(unclassified) 42 detection analysis is conducted...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA Approved for public release; distribution is unlimited Prepared

  10. ballast water « Coast Guard Maritime Commons

    Science.gov Websites

    updates to Marine Safety Center's ballast water management system website The Marine Safety Center recently updated two tools posted to its ballast water management system website to assist industry when completing the ballast water management system type approval process, or when accessing letters of intent. 12

  11. Commercial Vessel Compliance « Coast Guard Maritime Commons

    Science.gov Websites

    updates to Marine Safety Center's ballast water management system website The Marine Safety Center recently updated two tools posted to its ballast water management system website to assist industry when completing the ballast water management system type approval process, or when accessing letters of intent. 5

  12. 25 CFR 535.1 - Amendments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... GAMING COMMISSION, DEPARTMENT OF THE INTERIOR MANAGEMENT CONTRACT PROVISIONS POST-APPROVAL PROCEDURES... management contract for the operation of a class II or class III gaming activity. (b) A tribe shall submit an... information required under § 537.1(b)(1) of this chapter for class II gaming contracts or § 537.1(b)(1)(i) of...

  13. 78 FR 36186 - Information Collection(s) Being Submitted for Review and Approval to the Office of Management and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

    ... publish the revised SORN in the Federal Register. In addition, the Commission will post a copy of both the... test systems. However, in this R&O, the Commission declined to authorize remote monitoring of certain... data link land test station, an applicant [[Page 36188

  14. 7 CFR 1955.22 - State supplements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... regulation to provide guidance to FmHA or its successor agency under Public Law 103-354 officials. State supplements will be submitted to the National Office for post approval in accordance with FmHA or its successor agency under Public Law 103-354 Instruction 2006-B (available in any FmHA or its successor agency...

  15. 40 CFR 52.1470 - Identification of plan.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....513 “Fossil fuel” defined 12/4/76 49 FR 11626 (3/27/84) Most recently approved version was submitted... modification or relocation of plants to generate electricity using steam produced by burning of fossil fuels 10... for each source; form of application; issuance or denial; posting 05/04/06 77 FR 59321, 9/27/12...

  16. 76 FR 60048 - Federal Acquisition Regulation; Submission for OMB Review; Trade Agreements Certificate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-28

    ... submitting to the Office of Management and Budget (OMB) a request to review and approve an extension of a... posted without change to http://www.regulations.gov , including any personal and/or business confidential... products. Items having components of unknown origin are considered to have been mined, produced, or...

  17. Expectations, Realizations, and Approval of Tablet Computers in an Educational Setting

    ERIC Educational Resources Information Center

    Hassan, Mamdouh; Geys, Benny

    2016-01-01

    The introduction of new technologies in classrooms is often thought to offer great potential for advancing learning. In this article, we investigate the relationship between such expectations and the post-implementation evaluation of a new technology in an educational setting. Building on psychological research, we argue that (1) high expectations…

  18. 76 FR 10530 - Supplemental Proposed Rule of Source Specific Federal Implementation Plan for Implementing Best...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-25

    ... proposed post-control BART limit of 0.012 lb/MMBtu on Units 1-3. C. Modeling and Demonstrating Reasonable... a different alternative emissions control strategy would achieve more progress than EPA's BART... Background for Proposing To Approve an Alternative Emissions Control Strategy as Achieving Better Progress...

  19. 42 CFR 431.992 - Corrective action plan.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Estimating Improper Payments in Medicaid and CHIP § 431.992 Corrective action plan. (a) The State agency must develop a separate corrective action plan for Medicaid and CHIP, which is not required to be approved by... which the State's Medicaid or CHIP error rates are posted on the CMS contractor's Web site. (d) The...

  20. 42 CFR 431.992 - Corrective action plan.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Estimating Improper Payments in Medicaid and CHIP § 431.992 Corrective action plan. (a) The State agency must develop a separate corrective action plan for Medicaid and CHIP, which is not required to be approved by... which the State's Medicaid or CHIP error rates are posted on the CMS contractor's Web site. (d) The...

  1. 42 CFR 431.992 - Corrective action plan.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Estimating Improper Payments in Medicaid and CHIP § 431.992 Corrective action plan. (a) The State agency must develop a separate corrective action plan for Medicaid and CHIP, which is not required to be approved by... which the State's Medicaid or CHIP error rates are posted on the CMS contractor's Web site. (d) The...

  2. JPRS Report, Proliferation Issues

    DTIC Science & Technology

    1992-06-25

    control of INGTON POST saying: "Secretary of Defense Richard Nuclemon Minero Quimica Ltda. [Nuclebras Monazite and Cheney approved the Pentagon’s plan ... Planned [Alm a-Ata Radio] .................................................................................................. 26 Krasnoyarsk Search for...34 [Article by political staff: "Space plan defended"] He said the aim of the investigation was to determine the market opportunities, risks and

  3. Recalibrating the BC Transfer System: Approved Final Report

    ERIC Educational Resources Information Center

    British Columbia Council on Admissions and Transfer, 2006

    2006-01-01

    In November 2005, the BC Council on Admissions and Transfer launched a consultation entitled Recalibrating the BC Transfer System with the institutional members of the BC Transfer System and other interested parties. This consultation was motivated in large part by significant changes in the BC post-secondary system over the last decade, and…

  4. 34 CFR 674.34 - Deferment of repayment-Federal Perkins loans, NDSLs and Defense loans.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... graduate fellowship program approved by the Secretary; (iii) Engaged in graduate or post-graduate... money, gifts, loans, housing, food, clothes, car, medical and dental care, and payment of college costs. (9) In determining a borrower's Federal education debt burden under paragraphs (e)(4) of this section...

  5. 34 CFR 674.34 - Deferment of repayment-Federal Perkins loans, NDSLs and Defense loans.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... graduate fellowship program approved by the Secretary; (iii) Engaged in graduate or post-graduate... money, gifts, loans, housing, food, clothes, car, medical and dental care, and payment of college costs. (9) In determining a borrower's Federal education debt burden under paragraphs (e)(4) of this section...

  6. 34 CFR 674.34 - Deferment of repayment-Federal Perkins loans, NDSLs and Defense loans.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... graduate fellowship program approved by the Secretary; (iii) Engaged in graduate or post-graduate... money, gifts, loans, housing, food, clothes, car, medical and dental care, and payment of college costs. (9) In determining a borrower's Federal education debt burden under paragraphs (e)(4) of this section...

  7. Evaluation of the 2006-2007 Students' Creative Response to Conflict Program

    ERIC Educational Resources Information Center

    Yungbluth, Stephen C.

    2008-01-01

    A quasi-experimental pre- and post-test design was used to evaluate the Students' Creative Response to Conflict (SCRC) program, which is based on the principles of conflict resolution education and social-emotional learning. It is predicted that SCRC will influence students to reduce their approval of aggression and associated problem behaviors…

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

    PubMed

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

    2017-02-07

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

  9. Addendum to the Closure Report for Corrective Action Unit 326: Areas 6 and 27 Release Sites, Nevada Test Site, Nevada, Revision 1

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

    Grant Evenson

    This document constitutes an addendum to the Closure Report for Corrective Action Unit 326: Areas 6 and 27 Release Sites, Nevada Test Site, Nevada (Revision 1), December 2002 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additional information • Themore » cover, title, and signature pages of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the UR for CAS 06-25-01, CP-1 Heating Oil Release. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was reevaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

  10. Addendum to the Closure Report for Corrective Action Unit 403: Second Gas Station, Tonopah Test Range, Nevada, Revision 0

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

    Grant Evenson

    This document constitutes an addendum to the Closure Report for Corrective Action Unit 403: Second Gas Station, Tonopah Test Range, Nevada, September 1998 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additional information • The cover, title, and signature pagesmore » of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the UR for CAS 03-02-004-0360, Underground Storage Tanks. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was reevaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

  11. Addendum to the Closure Report for Corrective Action Unit 339: Area 12 Fleet Operations Steam Cleaning Discharge Area, Nevada Test Site, Revision 0

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

    Grant Evenson

    This document constitutes an addendum to the Closure Report for CAU 339: Area 12 Fleet Operations Steam Cleaning Discharge Area Nevada Test Site, December 1997 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additional information • The cover, title, andmore » signature pages of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the UR for CAS 12-19-01, A12 Fleet Ops Steam Cleaning Efflu. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was reevaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

  12. Addendum 2 to the Closure Report for Corrective Action Unit 358: Areas 18, 19, 20 Cellars/Mud Pits, Nevada Test Site, Nevada, Revison 0

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

    Grant Evenson

    This document constitutes an addendum to the Closure Report for Corrective Action Unit 358: Areas 18, 19, 20 Cellars/Mud Pits, Nevada Test Site, Nevada, January 2004 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additional information • The cover, title,more » and signature pages of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the UR for CAS 19-09-05, Mud Pit. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was reevaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

  13. EC4 European Syllabus for Post-Graduate Training in Clinical Chemistry and Laboratory Medicine: version 3 - 2005.

    PubMed

    Zerah, Simone; McMurray, Janet; Bousquet, Bernard; Baum, Hannsjorg; Beastall, Graham H; Blaton, Vic; Cals, Marie-Josèphe; Duchassaing, Danielle; Gaudeau-Toussaint, Marie-Françoise; Harmoinen, Aimo; Hoffmann, Hans; Jansen, Rob T; Kenny, Desmond; Kohse, Klaus P; Köller, Ursula; Gobert, Jean-Gérard; Linget, Christine; Lund, Erik; Nubile, Giuseppe; Opp, Matthias; Pazzagli, Mario; Pinon, Georges; Queralto, José M; Reguengo, Henrique; Rizos, Demetrios; Szekeres, Thomas; Vidaud, Michel; Wallinder, Hans

    2006-01-01

    The EC4 Syllabus for Postgraduate Training is the basis for the European Register of Specialists in Clinical Chemistry and Laboratory Medicine. The syllabus: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. The syllabus is not primarily meant to be a training guide, but on the basis of the overview given (common minimal programme), national societies should formulate programmes that indicate where knowledge and experience is needed. The main points of this programme are: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. The aim of this version of the syllabus is to be in accordance with the Directive of Professional Qualifications published on 30 September 2005. To prepare the common platforms planned in this directive, the disciplines are divided into four categories: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. General chemistry, encompassing biochemistry, endocrinology, chemical (humoral), immunology, toxicology, and therapeutic drug monitoring; Haematology, covering cells, transfusion serology, coagulation, and cellular immunology; Microbiology, involving bacteriology, virology, parasitology, and mycology; Genetics and IVF.

  14. High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post-osimertinib progression.

    PubMed

    Ou, Sai-Hong Ignatius; Agarwal, Nikita; Ali, Siraj M

    2016-08-01

    Third-generation EGFR TKI has been approved in the US and EU for the treatment of EGFR mutant T790M+ NSCLC patients that are resistant to first- or second generation EGFR TKIs. Here we report a patient who developed resistance to osimertinib after a confirmed partial response for 9 months. Pre-osimertinib and post-osimertinib tumor biopsy revealed the emergence of high level of MET amplification (30 copies) post osimertinib treatment. Patient was treated with single agent crizotinib, a known MET inhibitor, with transient symptomatic benefit. MET amplification is one potential resistance mechanism to osimertinib and combination of osimertinib and a MET inhibitor should be investigated post-osimertinib progression in EGFR mutant T790M+ NSCLC patients whose harbored acquired MET amplification. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Quality Evaluation Scores are no more Reliable than Gestalt in Evaluating the Quality of Emergency Medicine Blogs: A METRIQ Study.

    PubMed

    Thoma, Brent; Sebok-Syer, Stefanie S; Colmers-Gray, Isabelle; Sherbino, Jonathan; Ankel, Felix; Trueger, N Seth; Grock, Andrew; Siemens, Marshall; Paddock, Michael; Purdy, Eve; Kenneth Milne, William; Chan, Teresa M

    2018-01-30

    Construct: We investigated the quality of emergency medicine (EM) blogs as educational resources. Online medical education resources such as blogs are increasingly used by EM trainees and clinicians. However, quality evaluations of these resources using gestalt are unreliable. We investigated the reliability of two previously derived quality evaluation instruments for blogs. Sixty English-language EM websites that published clinically oriented blog posts between January 1 and February 24, 2016, were identified. A random number generator selected 10 websites, and the 2 most recent clinically oriented blog posts from each site were evaluated using gestalt, the Academic Life in Emergency Medicine (ALiEM) Approved Instructional Resources (AIR) score, and the Medical Education Translational Resources: Impact and Quality (METRIQ-8) score, by a sample of medical students, EM residents, and EM attendings. Each rater evaluated all 20 blog posts with gestalt and 15 of the 20 blog posts with the ALiEM AIR and METRIQ-8 scores. Pearson's correlations were calculated between the average scores for each metric. Single-measure intraclass correlation coefficients (ICCs) evaluated the reliability of each instrument. Our study included 121 medical students, 88 EM residents, and 100 EM attendings who completed ratings. The average gestalt rating of each blog post correlated strongly with the average scores for ALiEM AIR (r = .94) and METRIQ-8 (r = .91). Single-measure ICCs were fair for gestalt (0.37, IQR 0.25-0.56), ALiEM AIR (0.41, IQR 0.29-0.60) and METRIQ-8 (0.40, IQR 0.28-0.59). The average scores of each blog post correlated strongly with gestalt ratings. However, neither ALiEM AIR nor METRIQ-8 showed higher reliability than gestalt. Improved reliability may be possible through rater training and instrument refinement.

  16. Lack of effect of high-protein vs. high-carbohydrate meal intake on stress-related mood and eating behavior

    PubMed Central

    2011-01-01

    Background Consumption of meals with different macronutrients, especially high in carbohydrates, may influence stress-related eating behavior. We aimed to investigate whether consumption of high-protein vs. high-carbohydrate meals influences stress-related mood, food reward, i.e. 'liking' and 'wanting', and post-meal energy intake. Methods Participants (n = 38, 19m/19f, age = 25 ± 9 y, BMI = 25.0 ± 3.3 kg/m2) came to the university four times, fasted, once for a stress session receiving a high-protein meal, once for a rest session receiving a high-protein meal, once for a stress session receiving a high-carbohydrate meal and once for a rest session receiving a high-carbohydrate meal (randomized cross-over design). The high-protein and high-carbohydrate test meals (energy percentage protein/carbohydrate/fat 65/5/30 vs. 6/64/30) matched for energy density (4 kJ/g) and daily energy requirements (30%). Stress was induced using an ego-threatening test. Pre- and post-meal 'liking' and 'wanting' (for bread, filling, drinks, dessert, snacks, stationery (non-food alternative as control)) was measured by means of a computer test. Following the post-meal 'wanting' measurement, participants received and consumed their wanted food items (post-meal energy intake). Appetite profile (visual analogue scales), mood state (Profile Of Mood State and State Trait Anxiety Inventory questionnaires), and post-meal energy intake were measured. Results Participants showed increased feelings of depression and anxiety during stress (P < 0.01). Consumption of the test meal decreased hunger, increased satiety, decreased 'liking' of bread and filling, and increased 'liking' of placebo and drinks (P < 0.0001). Food 'wanting' decreased pre- to post-meal (P < 0.0001). The high-protein vs. high-carbohydrate test meal induced lower subsequent 'wanting' and energy intake (1.7 ± 0.3 MJ vs. 2.5 ± 0.4 MJ) only in individuals characterized by disinhibited eating behavior (factor 2 Three Factor Eating Questionnaire, n = 16), during rest (P ≤ 0.01). This reduction in 'wanting' and energy intake following the high-protein meal disappeared during stress. Conclusions Consumption of a high-protein vs. high-carbohydrate meal appears to have limited impact on stress-related eating behavior. Only participants with high disinhibition showed decreased subsequent 'wanting' and energy intake during rest; this effect disappeared under stress. Acute stress overruled effects of consumption of high-protein foods. Trial registration The study was registered in the Dutch Trial Register (NTR1904). The protocol described here in this study deviates from the trial protocol approved by the Medical Ethical Committee of the Maastricht University as it comprises only a part of the approved trial protocol. PMID:22152216

  17. The Feasibility of Specialized Subcommunities Within the General Unrestricted Line Officer Community.

    DTIC Science & Technology

    1990-09-01

    Navy’s warfighting mission. [Ref. l:p. 12] TL.e GEN URL career path was re- assessed during a 1994 Study on Progress of Women in the Navy [Ref. 2]. As a...L billet in Tour 2 is (0.977)(0.054) = 0.053. All officers in leadership billets in Tour 1, if they continue in thL sistem , must go to non-leadership...required to account for officers with proven subspecialties and/or Navy- approved post -graduate degrees (i.e, officers with C, F, M, Q, R or P subspecialty

  18. Response evaluation of giant-cell tumor of bone treated by denosumab: Histogram and texture analysis of CT images.

    PubMed

    Yi, Jisook; Lee, Young Han; Kim, Sang Kyum; Kim, Seung Hyun; Song, Ho-Taek; Shin, Kyoo-Ho; Suh, Jin-Suck

    2018-05-01

    This study aimed to compare computed tomography (CT) features, including tumor size and textural and histogram measurements, of giant-cell tumors of bone (GCTBs) before and after denosumab treatment and determine their applicability in monitoring GCTB response to denosumab treatment. This retrospective study included eight patients (male, 3; female, 5; mean age, 33.4 years) diagnosed with GCTB, who had received treatment by denosumab and had undergone pre- and post-treatment non-contrast CT between January 2010 and December 2016. This study was approved by the institutional review board. Pre- and post-treatment size, histogram, and textural parameters of GCTBs were compared by the Wilcoxon signed-rank test. Pathological findings of five patients who underwent surgery after denosumab treatment were evaluated for assessment of treatment response. Relative to the baseline values, the tumor size had decreased, while the mean attenuation, standard deviation, entropy (all, P = 0.017), and skewness (P = 0.036) of the GCTBs had significantly increased post-treatment. Although the difference was statistically insignificant, the tumors also exhibited increased kurtosis, contrast, and inverse difference moment (P = 0.123, 0.327, and 0.575, respectively) post-treatment. Histologic findings revealed new bone formation and complete depletion or decrease in the number of osteoclast-like giant cells. The histogram and textural parameters of GCTBs changed significantly after denosumab treatment. Knowledge of the tendency towards increased mean attenuation and heterogeneity but increased local homogeneity in post-treatment CT histogram and textural features of GCTBs might aid in treatment planning and tumor response evaluation during denosumab treatment. Copyright © 2018. Published by Elsevier B.V.

  19. Methodology of AA CRASH: a prospective observational study evaluating the incidence and pathogenesis of adverse post-traumatic sequelae in African-Americans experiencing motor vehicle collision.

    PubMed

    Linnstaedt, Sarah D; Hu, JunMei; Liu, Andrea Y; Soward, April C; Bollen, Kenneth A; Wang, Henry E; Hendry, Phyllis L; Zimny, Erin; Lewandowski, Christopher; Velilla, Marc-Anthony; Damiron, Kathia; Pearson, Claire; Domeier, Robert; Kaushik, Sangeeta; Feldman, James; Rosenberg, Mark; Jones, Jeffrey; Swor, Robert; Rathlev, Niels; McLean, Samuel A

    2016-09-06

    A motor vehicle collision (MVC) is one of the most common life-threatening events experienced by individuals living in the USA. While most individuals recover following MVC, a significant proportion of individuals develop adverse post-traumatic sequelae such as post-traumatic stress disorder or persistent musculoskeletal pain. Adverse post-traumatic sequelae are common, morbid and costly public health problems in the USA and other industrialised countries. The pathogenesis of these disorders following MVC remains poorly understood. In the USA, available data suggest that African-Americans experience an increased burden of adverse post-traumatic sequelae after MVC compared to European Americans, but to date no studies examining the pathogenesis of these disorders among African-Americans experiencing MVC have been performed. The African-American CRASH (AA CRASH) study is an NIH-funded, multicentre, prospective study that enrols African-Americans (n=900) who present to the emergency department (ED) within 24 hours of MVC. Participants are enrolled at 13 ED sites in the USA. Individuals who are admitted to the hospital or who report a fracture or tissue injury are excluded. Participants complete a detailed ED interview that includes an assessment of crash history, current post-traumatic symptoms and health status prior to the MVC. Blood samples are also collected in the ED using PAXgene DNA and PAXgene RNA tubes. Serial mixed-mode assessments 6 weeks, 6 months and 1 year after MVC include an assessment of adverse sequelae, general health status and health service utilisation. The results from this study will provide insights into the incidence and pathogenesis of persistent pain and other post-traumatic sequelae in African-Americans experiencing MVC. AA CRASH has ethics approval in the USA, and the results will be published in a peer-reviewed journal. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. [Consensus Document on post-exposure prophylaxis against HIV, HBV and HCV in adults and children].

    PubMed

    2016-02-01

    This consensus document is an update of occupational and non-occupational prophylaxis guidelines in HIV-patients, promoting appropriate use of them, from the standpoint of care. This document has been approved by expert panel of SPNS, GESIDA, SEMST and different scientific societies related, after reviewing the results of efficacy and safety clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented at conferences and different guidelines. The strength of the recommendation and gradation of their evidence are based on the GRADE system. We have developed recommendations for assessing the risk of transmission in different types of exposure situations in which post-exposure prophylaxis should be recommended, special circumstances to consider, patterns of antiretroviral with the start and duration of early monitoring of tolerance and adherence to treatment, the subsequent monitoring of exposed persons regardless of whether they received post-exposure prophylaxis or not, and the need of psychological support. These new guidelines updated previous recommendations regarding occupational post-exposure prophylaxis and non-occupational, in adults and children. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  1. A decade of safety-related regulatory action in the Netherlands: a retrospective analysis of direct healthcare professional communications from 1999 to 2009.

    PubMed

    Mol, Peter G M; Straus, Sabine M J M; Piening, Sigrid; de Vries, Jonie T N; de Graeff, Pieter A; Haaijer-Ruskamp, Flora M

    2010-06-01

    As pre-approval trials are inherently limited in assessing the complete benefit-risk profile of a new drug, serious safety issues may emerge once a drug gains widespread use after approval. Regulators face the dilemma of balancing timely market access with the need for complete data on risks. This challenge has led to a life-cycle approach but, so far, few data are available on post-approval safety issues requiring regulatory action. The aim of this study is to determine the frequency, timing and nature of safety issues that necessitated safety-related regulatory action in the form of a Direct Healthcare Professional Communication (DHPC) issued by pharmaceutical companies in collaboration with the Dutch Medicines Evaluation Board during the past decade. All DHPCs issued in the Netherlands from 1 January 1999 to 1 January 2009 were retrospectively collected from the national regulatory authorities. Elapsed time between the approval date and the issue of the DHPC was determined. Characteristics of the action including the nature of the safety issue (according to Medical Dictionary for Regulatory Activities [MedDRA] terminology), type of drug and procedural aspects of the regulatory action taken were reviewed. DHPC characteristics were tabulated and explorative non-parametric tests were performed to study the effect of safety issue, drug class, drug type, orphan drug and first-in-class status on elapsed time from approval to the DHPC. 157 DHPCs were issued concerning 112 different active substances, approximately 9% (112/1200) of active substances available in the Netherlands in 2007. The number of DHPCs issued increased by 2.1 (95% CI 1.2, 3.1; p < 0.001) DHPCs per year over the past decade, reaching a total of 25 in 2008. The median time between approval and DHPC was 5.3 years (range 0.13-48 years). No significant trend in elapsed time to DHPC was observed in relation to the studied years (p = 0.06). One-third of all DHPCs were issued in the first 3 years after approval, but 27% (n = 43/157) of the DHPCs were issued 10 or more years after approval. Timing of DHPCs differed depending on safety issue, drug class, drug type and orphan drug status. DHPCs mostly concerned adverse events in the system organ class of 'cardiac disorders' (15%), 'injury, poisoning and procedural complications' (13%) and 'general disorders and administration site conditions' (10%). In ten cases the drug was eventually withdrawn. Withdrawal occurred a median duration of 2.4 years after registration (range of 1.5-48 years) and was most frequently due to cardiac disorders (including QT interval prolongation; four occasions) and hepatobiliary disorders (two occasions). In the past decade, the number of DHPCs has increased over time. This is likely caused by a multitude of factors: increased risk awareness by the public, media, regulators and other stakeholders; the type of drugs approved, such as orphan drugs and biologicals; and the regulatory process, including conditional approvals. The number of DHPCs may in the future increase further with the possibility of screening large epidemiological databases proactively for adverse drug events. Nine percent of all marketed drugs required a safety-related action. Regulatory action is taken shortly (<3 years) after market approval nearly as often as after intermediate (3-10 years) and long-term (>10 years) market exposure. These findings underline the need for risk management during the whole life cycle of a drug.

  2. Effectiveness of inpatient and outpatient strategies in increasing referral and utilization of cardiac rehabilitation: a prospective, multi-site study

    PubMed Central

    2012-01-01

    Background Despite the evidence of benefit, cardiac rehabilitation (CR) remains highly underutilized. The present study examined the effect of two inpatient and one outpatient strategy on CR utilization: allied healthcare provider completion of referral (a policy that had been endorsed and approved by the cardiac program leadership in advance; PRE-APPROVED); CR intake appointment booked before hospital discharge (PRE-BOOKED); and early outpatient education provided at the CR program shortly after inpatient discharge (EARLY ED). In this prospective observational study, 2,635 stable cardiac inpatients from 11 Ontario hospitals completed a sociodemographic survey, and clinical data were extracted from charts. One year later, participants were a mailed survey that assessed CR use. Participating inpatient units and CR programs to which patients were referred were coded to reflect whether each of the strategies was used (yes/no). The effect of each strategy on participants’ CR referral and enrollment was examined using generalized estimating equations. Results A total of 1,809 participants completed the post-test survey. Adjusted analyses revealed that the implementation of one of the inpatient strategies was significantly related to greater referral and enrollment (PRE-APPROVED: OR = 1.96, 95%CI = 1.26 to 3.05, and OR = 2.91, 95%CI = 2.20 to 3.85, respectively). EARLY ED also resulted in significantly greater enrollment (OR = 4.85, 95%CI = 2.96 to 7.95). Conclusions These readily-implementable strategies could significantly increase access to and enrollment in CR for the cardiac population. The impact of these strategies on wait times warrants exploration. PMID:23234558

  3. Space Propulsion Hazards Analysis Manual (SPHAM). Volume 2. Appendices

    DTIC Science & Technology

    1988-10-01

    lb. RESTRICTIVE MARKINGS UNCLASSIFIED 2a. SECURITY CLASSIFICATION AUTHORITY 3 . DISTRIBUTION/AVAILABILITY OF REPORT Approved for public release...Volume I Chapter 2 - Requirementb and the Hazards Analysis Process .... Volume I Chapter 3 - Accident Scenarios...list of the hazardous materials that are discussed; 3 ) description of the failure scenarios; 4) type of post-accident environment that is discussed

  4. 76 FR 63251 - Revisions to Federal Implementation Plans To Reduce Interstate Transport of Fine Particulate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-12

    ... Matter and Ozone AGENCY: Environmental Protection Agency (EPA). ACTION: Announcement of public hearing... Ozone'', which was signed on October 6, 2011 and posted on EPA's website on October 6, 2011. The hearing... Particulate Matter and Ozone and Correction of SIP Approvals). EPA is proposing to amend the assurance penalty...

  5. Mindfulness and the Therapeutic Function of Education

    ERIC Educational Resources Information Center

    Hyland, Terry

    2009-01-01

    Although it has been given qualified approval by a number of philosophers of education, the so-called "therapeutic turn" in education has been the subject of criticism by several commentators on post-compulsory and adult learning over the last few years. A key feature of this alleged development in recent educational policy is said to be the…

  6. 40 CFR 258.62 - Approval of site-specific flexibility requests in Indian country.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) SOLID WASTES CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Closure and Post-Closure Care § 258.62... waste landfill owned and operated by Lake County on the Confederated Salish and Kootenai Tribes... equivalent reduction in infiltration as the infiltration layer specified in § 258.60(a)(1) and (a)(2), and...

  7. 46 CFR 160.135-15 - Production inspections, tests, quality control, and conformance of lifeboats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... materials are as per the plans approved under § 160.135-13(h) of this subpart. (2) Post assembly tests and... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and... Lifeboats (SOLAS) § 160.135-15 Production inspections, tests, quality control, and conformance of lifeboats...

  8. 46 CFR 160.135-15 - Production inspections, tests, quality control, and conformance of lifeboats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... materials are as per the plans approved under § 160.135-13(h) of this subpart. (2) Post assembly tests and... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control, and... Lifeboats (SOLAS) § 160.135-15 Production inspections, tests, quality control, and conformance of lifeboats...

  9. 76 FR 20823 - Agency Information Collection (Veterans Benefits Administration (VBA) Voice of the Veteran (VOV...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... currently somewhere in post-approval, (4) those who have had all their funds disbursed and final accounting is not yet complete, and (5) those who have had all of their funds disbursed and final accounting is... integrated, comprehensive Voice of the Veteran (VOV) measurement program for their lines of business. This...

  10. MASYS: The AKARI Spectroscopic Survey of Symbiotic Stars in the Magellanic Clouds

    NASA Astrophysics Data System (ADS)

    Angeloni, R.; Ciroi, S.; Marigo, P.; Contini, M.; Di Mille, F.; Rafanelli, P.

    2009-12-01

    MASYS is the AKARI spectroscopic survey of Symbiotic Stars in the Magellanic Clouds, and one of the European Open Time Observing Programmes approved for the AKARI (Post-Helium) Phase-3. It is providing the first ever near-IR spectra of extragalactic symbiotic stars. The observations are scheduled to be completed in July 2009.

  11. 40 CFR 63.14 - Incorporations by reference.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (MD-35), U.S. EPA, Research Triangle Park, North Carolina. For information on the availability of this..., Post Office Box C700, West Conshohocken, PA 19428-2959; or ProQuest, 300 North Zeeb Road, Ann Arbor, MI 48106. (1) ASTM D523-89, Standard Test Method for Specular Gloss, IBR approved for § 63.782. (2) ASTM...

  12. 43 CFR 12.925 - Revision of budget and program plans.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Revision of budget and program plans. 12... Organizations Post-Award Requirements § 12.925 Revision of budget and program plans. (a) The budget plan is the...) Recipients are required to report deviations from budget and program plans, and request prior approvals for...

  13. 34 CFR 662.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... fellow shall— (a) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities... DISSERTATION RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 662.41 What are a fellow...

  14. 34 CFR 663.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 663.41 What are a fellow's...) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities during the period of...

  15. 34 CFR 662.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... fellow shall— (a) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities... DISSERTATION RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 662.41 What are a fellow...

  16. 34 CFR 663.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 663.41 What are a fellow's...) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities during the period of...

  17. 34 CFR 662.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... fellow shall— (a) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities... DISSERTATION RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 662.41 What are a fellow...

  18. 34 CFR 663.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 663.41 What are a fellow's...) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities during the period of...

  19. 34 CFR 663.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 663.41 What are a fellow's...) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities during the period of...

  20. 34 CFR 662.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... fellow shall— (a) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities... DISSERTATION RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 662.41 What are a fellow...

  1. 34 CFR 663.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 663.41 What are a fellow's...) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities during the period of...

  2. 34 CFR 662.41 - What are a fellow's responsibilities after the award of a fellowship?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... fellow shall— (a) Maintain satisfactory progress in the conduct of his or her research; (b) Devote full time to research on the approved topic; (c) Not engage in unauthorized income-producing activities... DISSERTATION RESEARCH ABROAD FELLOWSHIP PROGRAM Post-award Requirements for Fellows § 662.41 What are a fellow...

  3. 30 CFR 203.76 - When might MMS withdraw or reduce the approved size of my relief?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... your post-production development report (§ 203.70). Development costs are those expenditures defined in... application (e.g., change from a fixed platform to floating production system, or from an independent development and production system to one with subsea wells tied back to a host production facility, etc.). (b...

  4. Block Transfer: A Private Career College Student's Ladder into the BC Transfer System. Special Report

    ERIC Educational Resources Information Center

    McIvor, Raili

    2010-01-01

    In June 2008 the British Columbia Council on Admissions and Transfer (BCCAT) approved a new policy to publish in the BC Transfer Guide block transfer agreements (BTAs) between BC Transfer System member institutions and private post-secondary institutions accredited by the Private Career Training Institutions Agency (PCTIA). This new policy was…

  5. 76 FR 23637 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... the Event of a Merger Involving One or More Listed Companies April 21, 2011. I. Introduction On... the application of the Exchange's Designated Market Maker (``DMM'') allocation policy in the event of... listed companies merge, the post-merger listed company is assigned to the DMM in the company that is...

  6. 76 FR 23637 - Self-Regulatory Organizations; NYSE Amex LLC; Order Approving a Proposed Rule Change Amending...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... Equities To Modify the Application of the Exchange's Designated Market Maker Allocation Policy in the Event... Maker (``DMM'') allocation policy in the event of a merger involving one or more listed companies. The... Equities Rule 103B provides that when two NYSE Amex listed companies merge, the post- merger listed company...

  7. Brief Report: New Legislation Supports Students with Intellectual Disabilities in Post-Secondary Funding

    ERIC Educational Resources Information Center

    VanBergeijk, Ernst O.; Cavanagh, Paul Kevin

    2012-01-01

    With the passage of the Higher Education Opportunities Act (HEOA) of 2008, students with intellectual disabilities who are enrolled in a federally approved Comprehensive Transition and Postsecondary Program on a college campus will be eligible for some forms of federal student financial aid. This Brief Report discusses the forms of aid available,…

  8. 7 CFR 318.13-26 - Breadfruit, jackfruit, fresh pods of cowpea, dragon fruit, mangosteen, and moringa pods from Hawaii.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and jackfruit from Hawaii must be treated with irradiation in accordance with part 305 of this chapter... before undergoing irradiation treatment in Hawaii at a dose approved to neutralize fruit flies. Fruit.... Post-treatment inspection in Hawaii is not required if the fruit undergoes irradiation treatment at a...

  9. 7 CFR 318.13-26 - Breadfruit, jackfruit, fresh pods of cowpea, dragon fruit, mangosteen, and moringa pods from Hawaii.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... and jackfruit from Hawaii must be treated with irradiation in accordance with part 305 of this chapter... before undergoing irradiation treatment in Hawaii at a dose approved to neutralize fruit flies. Fruit.... Post-treatment inspection in Hawaii is not required if the fruit undergoes irradiation treatment at a...

  10. 7 CFR 318.13-26 - Breadfruit, jackfruit, fresh pods of cowpea, dragon fruit, mangosteen, and moringa pods from Hawaii.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and jackfruit from Hawaii must be treated with irradiation in accordance with part 305 of this chapter... before undergoing irradiation treatment in Hawaii at a dose approved to neutralize fruit flies. Fruit.... Post-treatment inspection in Hawaii is not required if the fruit undergoes irradiation treatment at a...

  11. 76 FR 42677 - Notice of Intent To Seek Approval To Collect Information

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-19

    ... and maintains an on-line recipe database, the Recipe Finder, as a popular feature to the SNAP-Ed Connection Web site. The purpose of the Recipe Finder database is to provide SNAP-Ed providers with low-cost... inclusion in the database. SNAP-Ed staff and providers benefit from collecting and posting feedback on...

  12. TNF-alpha inhibitors in dermatology.

    PubMed

    Cordoro, K M; Feldman, S R

    2007-09-01

    To date, the US FDA has approved three tumor necrosis factor (TNF)-a inhibitors for use in dermatology. Etanercept (Enbrel, Amgen-Wyeth), a fully human fusion protein of TNF receptor II bound to the Fc component of human IgG1, is approved for use in psoriasis (2004) and psoriatic arthritis (2002). Infliximab (Remicade, Centocor) is a chimeric monoclonal antibody that is approved for use in psoriasis (2006) and psoriatic arthritis (2005), and adalimumab (Humira, Abbott Laboratories), a fully human monoclonal antibody, is approved for use in psoriatic arthritis (2005). While data regarding the efficacy and safety of these therapies is abundant, it proves nearly impossible to objectively compare and contrast agents as there are no head-to-head trials. Clinical experience and post-marketing reporting has allowed dermatologists to identify the relative strengths and limitations of each agent. The well-founded enthusiasm for these agents, because of their excellent initial efficacy and safety profile, is reasonably tempered by concerns about declining efficacy over time, the risk of infection, lymphoma and demyelinating disorders, and cost. The distinct and targeted mechanism of action of the TNF inhibitors allows dermatologists to customize therapy to match the individual needs and characteristics of patients who are candidates for systemic or phototherapy.

  13. Discrepancies Between Nomenclature and Indications of Psychotropics.

    PubMed

    Minami, Fusaka; Zohar, Joseph; Suzuki, Takefumi; Koizumi, Teruki; Mimura, Masaru; Yagi, Gohei; Uchida, Hiroyuki

    2018-05-23

    While the current nomenclature of psychotropic drugs is disease-based, their approved indications do not always match their classifications. Information on approved indications of "second-generation antipsychotics" and "newer antidepressants" that are available in the United States (US), the United Kingdom (UK), France, Germany, and Japan were extracted from their packet inserts. A significant proportion of "atypical antipsychotics" were approved for psychiatric conditions other than psychotic disorders (i. e., bipolar disorder, major depressive disorder, and autistic disorder) as follows: 76.9% in the US, 66.7% in the UK, 66.7% in France, 60.0% in Germany, and 44.4% in Japan. Likewise, more than half of "newer antidepressants" had approved indications for psychiatric conditions other than depression (e. g., panic disorder, obsessive compulsive disorder, social anxiety disorder, general anxiety disorder, and post-traumatic stress disorder): 56.3% in the US, 69.2% in the UK, 69.2% in France, 50.0% in Germany, and 62.5% in Japan. Our results raise concerns regarding generic terminologies of "antipsychotics" and "antidepressants" since the conventional indication-based nomenclature does not fit well with the official indication. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Retrospective Analysis of the Post-Operative Changes in Higher Order Aberrations: A Comparison of the WaveLight (registered trademark) EX500 to the Allegretto and Visx (registered trademark) S4 Laser in Refractive Surgery

    DTIC Science & Technology

    2017-06-16

    FROM: 59 MDW/SGVU SUBJECT: Professional Presentation Approval 1. Your paper, entitled Retrospective Analysis of the Post -Operative Changes in Higher...DePl3rtment Defense, or ad State9 Govemme 1- Ions are appro’w’edand dearad for public release TITlE OF RF.’. .\\’E ~. C.•••TE PRE •••• p et spect- e analys...s of the post - ope tive changes in ig e 0 d abe rations: co parison of the av ig tID 500 to t e V @ se in ref act-vesu gery one d Wal r S eiglem n

  15. Challenges in translating endpoints from trials to observational cohort studies in oncology

    PubMed Central

    Ording, Anne Gulbech; Cronin-Fenton, Deirdre; Ehrenstein, Vera; Lash, Timothy L; Acquavella, John; Rørth, Mikael; Sørensen, Henrik Toft

    2016-01-01

    Clinical trials are considered the gold standard for examining drug efficacy and for approval of new drugs. Medical databases and population surveillance registries are valuable resources for post-approval observational research, which are increasingly used in studies of benefits and risk of new cancer drugs. Here, we address the challenges in translating endpoints from oncology trials to observational studies. Registry-based cohort studies can investigate real-world safety issues – including previously unrecognized concerns – by examining rare endpoints or multiple endpoints at once. In contrast to clinical trials, observational cohort studies typically do not exclude real-world patients from clinical practice, such as old and frail patients with comorbidity. The observational cohort study complements the clinical trial by examining the effectiveness of interventions applied in clinical practice and by providing evidence on long-term clinical outcomes, which are often not feasible to study in a clinical trial. Various endpoints can be included in clinical trials, such as hard endpoints, soft endpoints, surrogate endpoints, and patient-reported endpoints. Each endpoint has it strengths and limitations for use in research studies. Endpoints used in oncology trials are often not applicable in observational cohort studies which are limited by the setting of standard clinical practice and by non-standardized endpoint determination. Observational studies can be more helpful moving research forward if they restrict focus to appropriate and valid endpoints. PMID:27354827

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

    PubMed

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

    2018-06-01

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

  17. Introduction of Biosimilar Therapeutics Into Nephrology Practice in the United States: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

    PubMed

    Wish, Jay B; Charytan, Chaim; Chertow, Glenn M; Kalantar-Zadeh, Kamyar; Kliger, Alan S; Rubin, Robert J; Yee, Jerry; Fishbane, Steven

    2016-12-01

    Biosimilars are biologic medicines highly similar to the reference product with no meaningful clinical differences in terms of safety, purity, and potency. All biologic medicines are produced by living cells, resulting in an inherent heterogeneity in their higher order structures and post-translational modifications. In 2010, the US Congress enacted legislation to streamline the approval process for biosimilars of products losing patent protection, with the goal of decreasing costs and improving patient access to therapeutically important but expensive biologic agents. In 2015, the US Food and Drug Administration approved the first biosimilar agent through this pathway. Approval of additional biosimilar agents in the United States, including those used by nephrologists, is anticipated. Given the relative lack of knowledge regarding biosimilars and their approval process and a lack of trust by the nephrology community regarding their safety and efficacy, the National Kidney Foundation conducted a symposium, Introduction of Biosimilar Therapeutics Into Nephrology Practice in the U.S., September 17 to 18, 2015. Issues related to manufacturing, the regulatory approval process, interchangeability, substitution/switching, nomenclature, and clinician and patient awareness and acceptance were examined. This report summarizes the main discussions at the symposium, highlights several controversies, and makes recommendations related to public policy, professional and patient education, and research needs. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. [Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria].

    PubMed

    Igari, Jun; Oguri, Toyoko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

    2002-02-01

    As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the bacteria were also evaluated with the bacterial resistance ratio calculated with the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of Moraxella (Branhamella) catarrhalis (n = 136), Haemophilus influenzae (n = 289), Escherichia coli (n = 276), Klebsiella pneumoniae (n = 192), Klebsiella oxytoca (n = 157), Enterobacter cloacae (n = 189), Enterobacter aerogenes (n = 93), Serratia marcescens (n = 172), Serratia liquefaciens (n = 24), Citrobacter freundii (n = 177), Citrobacter koseri (n = 70), Proteus mirabilis (n = 113), Proteus vulgaris (n = 89), Morganella morganii (n = 116), Providencia spp. (n = 41), Pseudomonas aeruginosa (n = 290), Pseudomonas fluorescens (n = 56), Pseudomonas putida (n = 63), Acinetobacter baumannii (n = 146), Acinetobacter lwoffii (n = 34), Burkholderia cepacia (n = 101), Stenotrophomonas maltophilia (n = 169), Bacteroides fragilis group (n = 196), and Prevotella/Porphyromonas (n = 173). An antibacterial activity of CZOP against E. coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with or more preferable than the study results obtained until the new drug application approval. MIC90 of CZOP against M.(B.) catarrhalis, C. koseri, and P. aeruginosa was not considerably changed and consistent with the study results obtained until the new drug application approval. MIC90 of CZOP against E. cloacae, E. aerogenes, and P. mirabilis increased year by year. The increase in MIC90 of CZOP against E. aerogenes and P. mirabilis, however, was not considered to be an obvious decline in susceptibility. In contract, the susceptibility of E. cloacae to CZOP was suspected to be decreasing because this species showed 20.6% resistance to CZOP. MIC90 of CZOP against C. freundii was variably changed or not one-sidedly, but was higher than the values obtained until the new drug application approval. Additionally, MIC90 of CZOP against H. influenzae was stable during 5 years except being higher in 1999, and, as a whole, was a little higher than the values obtained until the new drug application approval. An antibacterial activity of CZOP against P. fluorescens, P. putida, B. cepacia, S. maltophilia, B. fragilis group, and Prevotella/Porphyromonas was weak like the other cephems. Changes in MIC90 of CZOP against the other bacteria were 2 tubes or more through 5-year study period, but did not tend towards a unilateral direction as meaning a decline in susceptibility.

  19. Mapping by VESGEN of Blood Vessels in the Retinas of Astronauts Pre- and Post-Flight to the ISS

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, P.; Vyas, R. J.; Murray, M. C.; Predovic, M.; Lim, S.; Vizzeri, G.; Taibbi, G.; Mason, S. S.; Zanello, S. B.; Young, M.

    2017-01-01

    Research by NASA [1] established that significant risks for visual and ocular impairments associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. It is well established in physiology and pathology that a fundamental role of the microvasculature is to mediate fluid transfers and remodel actively in response to environmental, immune and other stresses. We therefore hypothesize that remodeling of retinal blood vessels necessarily occurs during accommodation of microgravity-induced fluid shifts prior to subsequent development of visual and ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASA's innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) U.S. crew members before and after ISS missions, and (2) head-down tilt in human subjects before and after 70 days of bed rest. We anticipate that results of the two studies will be complete by the Investigators Workshop (January 22, 2017). METHODS: For the 2013 NASA NRA award, we are concluding the analysis of 30 degree infrared (IR) Heidelberg Spectralis images of retinal blood vessels by VESGEN (patents pending), a mature, automated software developed as a translational and basic vascular research discovery tool, particularly for retinal vascular disease. Subjects of our retrospective study include eight ISS crew members monitored for routine occupational surveillance pre- and post-flight, who provided their study consents to NASAs Lifetime Surveillance of Astronaut Health (LSAH) in coordination with approval of the VESGEN retrospective study protocol by NASAs Institutional Review Board (IRB). The ophthalmic retinal images (average image resolution, approximately 5.6 microns per pixel) are blinded as to pre and post ISS status until the second portion of our study, when VESGEN results will be correlated with other ophthalmic and medical findings for the crew members. Due to image resolution challenges, a novel Matlab tool was developed for aligning pre and post images, and comparing (querying) the two images for differences in the morphology of small vessels. RESULTS: During the past year, LSAH approved the release of all astronaut retinal images to our study for VESGEN analysis. Substantial progress on the initial blinded portion of the study is in place. We anticipate that VESGEN analysis of the 32 Spectralis IR retinal images will be complete for presentation at the 2017 IWS meeting. CONCLUSIONS: Modified retinal vascular patterning may offer early-stage predictions of ocular changes resulting in decreased visual acuity for the VIIP syndrome. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina currently help to guide other NIH- and NASA-supported therapeutic studies of retinal disease and modeling of the VIIP risk. Results of our vascular investigation of the retinas of astronauts pre- and post-flight may help advance the understanding of both healthy and pathological adaptations to fluid shifts in microgravity associated with the VIIP syndrome. Preliminary results indicate that imaging of higher resolution, such as the new OCT angiography (OCT-A) technology, will be required to determine conclusively the role of the smaller retinal and choroidal vessels in VIIP etiology.

  20. Successful support of biventricular heart failure patients by new EXCOR® Adult pumps with bileaflet valves: a prospective study.

    PubMed

    Schmack, Bastian; Weymann, Alexander; Ruschitzka, Frank; Autschbach, Rüdiger; Raake, Philip W; Jurrmann, Nadine; Menon, Ares K; Karck, Matthias; Wilhelm, Markus J; Ruhparwar, Arjang

    2018-05-01

    The Berlin Heart EXCOR ® Adult biventricular assist device (BiVAD) is an approved mechanical circulatory support for patients with end-stage biventricular heart failure. In this prospective post-market clinical follow-up study, we present the first clinical experience of the new EXCOR ® Adult pump with bileaflet (BL) valves in Europe. After CE-mark approval in August 2014, a total of 12 patients were enrolled with a mean age of 44 years ± 11 (range 21-58 years). The majority of patients (n = 11) were in INTERMACS level 1 or 2. Eight patients had a median pre-operative extracorporeal life support (ECLS) of 6 days (range 1-37 days). Primary end point was survival, either to heart transplantation (HTx), recovery or alive at 12 months on device, whichever occurred first. Secondary end point was the number of adverse events throughout EXCOR ® BiVAD support. Median support time up to last follow-up on EXCOR ® BiVAD device was 248 days (range 57-381 days) and patient survival at 1 year was 92%. Half of the EXCOR ® BiVAD patients (n = 6) were transplanted and five patients were still on support at 1 year post-implantation. Complications during EXCOR ® BiVAD support were thoracic bleeding, exit site infection and ischemic cerebrovascular incidents in three cases, respectively. The new EXCOR ® Adult pump with BL provides pulsatile high cardiac output with excellent outcome and successful bridging to HTx, particularly in critically ill patients with INTERMACS level 1 or 2 at the time of implantation.

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