WorldWideScience

Sample records for post approval adverse

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

    Science.gov (United States)

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

    2015-06-01

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

  2. 13 CFR 302.18 - Post-approval requirements.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Post-approval requirements. 302.18 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...

  3. 30 CFR 14.10 - Post-approval product audit.

    Science.gov (United States)

    2010-07-01

    ..., AND APPROVAL OF MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS General Provisions § 14.10 Post-approval product audit. (a) Approved conveyor belts will be subject to... based. MSHA will select an approved conveyor belt to be audited; the selected belt will be...

  4. Do Holocaust survivors show increased vulnerability or resilience to post-Holocaust cumulative adversity?

    Science.gov (United States)

    Shrira, Amit; Palgi, Yuval; Ben-Ezra, Menachem; Shmotkin, Dov

    2010-06-01

    Prior trauma can hinder coping with additional adversity or inoculate against the effect of recurrent adversity. The present study further addressed this issue by examining whether a subsample of Holocaust survivors and comparison groups, drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe, were differentially affected by post-Holocaust cumulative adversity. Post-Holocaust cumulative adversity had a stronger effect on the lifetime depression of Holocaust survivors than on that of comparisons. However, comparisons were more negatively affected by post-Holocaust cumulative adversity when examining markers of physical and cognitive functioning. Our findings suggest that previous trauma can both sensitize and immunize, as Holocaust survivors show general resilience intertwined with specific vulnerability when confronted with additional cumulative adversity.

  5. Adverse Childhood Experiences in a Post-bariatric Surgery Psychiatric Inpatient Sample.

    Science.gov (United States)

    Fink, Kathryn; Ross, Colin A

    2017-12-01

    Sixty-three inpatients in a psychiatric hospital who had previously undergone bariatric surgery were interviewed by the hospital dietitian. The purpose of the study was to determine the frequency of adverse childhood experiences in this population. Participants completed the Adverse Childhood Experiences (ACE) Scale. The average score on the ACE was 5.4 (3.3); 76% of participants reported childhood emotional neglect, 70% childhood verbal abuse, and 64% childhood sexual abuse; only two participants reported no adverse childhood experiences. The participants in the study reported high levels of adverse childhood experiences compared to the general population, which is consistent with prior literature on rates of childhood trauma in post-bariatric surgery patients. The role of adverse childhood experiences in post-bariatric surgery adaptation should be investigated in future research, including in prospective studies.

  6. 30 CFR 71.301 - Respirable dust control plan; approval by District Manager and posting.

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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.

  8. 13 CFR 307.6 - Economic Adjustment Assistance post-approval requirements.

    Science.gov (United States)

    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... § 302.18 of this chapter: (a) Strategy Grants shall comply with the applicable provisions of part 303 of...

  9. Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series.

    Science.gov (United States)

    Martínez-Lavín, Manuel; Amezcua-Guerra, Luis

    2017-10-01

    This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653) [DOSAGE ERROR CORRECTED] . The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

  10. Adverse event reporting patterns of newly approved drugs in the USA in 2006: an analysis of FDA Adverse Event Reporting System data.

    Science.gov (United States)

    Chhabra, Pankdeep; Chen, Xing; Weiss, Sheila R

    2013-11-01

    The Weber effect states that adverse event (AE) reporting tends to increase in the first 2 years after a new drug is placed onto the market, peaks at the end of the second year, and then declines. However, since the Weber effect was originally described, there has been improvement in the communication of safety information and new policies regarding the reporting of AEs by healthcare professionals and consumers, prompting reassessment of the existence of the Weber effect in the current AE reporting scenario. To determine the AE reporting patterns for new molecular entity (NME) drugs and biologics approved in 2006 and to examine these patterns for the existence of the Weber effect. Publicly available FDA Adverse Event Reporting System data were used to assess the AE reporting patterns for a 5-year period from the drug’s approval date. The total number of annual reports from all sources, based on the report date, was plotted against time (in years). In the period from 2006 to 2011, a total of 91,187 AE reports were submitted for 19 NMEs approved in 2006. The highest number of AE reports were submitted for varenicline tartrate (N = 47,158) and the lowest number for anidulafungin (N = 161). Anidulafungin was reported to have the highest proportion of death reports (36 %) and varenicline tartrate the lowest proportion (1.7 %). The classic Weber pattern was not observed for any of the 19 NMEs approved in 2006. While there was no one predominant pattern of AE report volume, we grouped the drugs into four general categories; the majority of drugs had either a continued increase in reports (Category A 31.6 %) or an N-pattern with reporting reaching an initial peak in year 2 or 3, declining and then beginning to climb again (Category B 42.1 %). There have been numerous changes in AE reporting, particularly a huge increase in overall annual report volume, since the Weber effect was first reported. Our results suggest that a Weber-type reporting pattern should not be assumed

  11. Post-operative serious adverse events in a mixed surgical population

    DEFF Research Database (Denmark)

    Hansen, M S; Petersen, E E; Dahl, J B

    2016-01-01

    BACKGROUND: The number of surgical procedures is increasing, and knowledge of surgical risk factors, post-operative mortality and serious adverse events (SAE) is essential. The aim with our study was to determine the risk of a composite outcome of post-operative: death; myocardial infarction...... or gynaecological surgery was conducted retrieving data from The Danish Civil Registration System and the National Patient Register. Total observation time was from January 1, 2012 to June 6, 2013. RESULTS: A total7449 adult patients were included in the final analysis. The risk of the composite outcome during...... of 8.3% (7.8-9.0). The results are applicable in estimations of adequate sample sizes in future clinical trials investigating effects of interventions on SAEs....

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

    Science.gov (United States)

    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.

  13. 20 CFR 617.22 - Approval of training.

    Science.gov (United States)

    2010-04-01

    .... Perkins Vocational and Applied Technology Education Act, and employers). (i) This means that training is...) Conditions for approval. Training shall be approved for an adversely affected worker if the State agency...) available for an adversely affected worker. (i) This means that for the worker for whom approval of training...

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

    Science.gov (United States)

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

    OpenAIRE

    Lee, Bruce Y.; Burke, Donald S.

    2009-01-01

    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 deve...

  16. 24 CFR 886.107 - Approval of applications.

    Science.gov (United States)

    2010-04-01

    ...) The Owner's Affirmative Fair Housing Marketing Plan is approvable. (b) The HUD-approved unit rents are... climatic or geological conditions or local codes are examples which may justify such variations. (d) A... neighborhood in a substantially adverse manner. Examples of such adverse effects are (1) substantial move-outs...

  17. Post-marketing withdrawal of analgesic medications because of adverse drug reactions: a systematic review.

    Science.gov (United States)

    Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

    2018-01-01

    Many analgesics have been withdrawn from the market because of adverse drug reactions. Controversy still surrounds the use of some approved analgesics for pain management. However, the trends and reasons for withdrawal of analgesics when harms are attributed to their use have not been systematically assessed. Areas covered: We conducted searches in PubMed; Embase; Google Scholar; clinicaltrials.gov; WHO databases of withdrawn products; websites of the European Medicines Agency, the US Food and Drug Administration, the UK Medicines and Healthcare products Regulatory Agency; Meyler's Side Effects of Drugs; Stephens' Detection of New Adverse Drug Reactions; the Pharmaceutical Manufacturing Encyclopedia; and the Merck Index. We included licensed analgesics that were withdrawn after marketing because of adverse reactions between 1950 and March 2017. We excluded herbal products, non-human medicines, and non-prescription medicines. We used the Oxford Centre for Evidence Based Medicine criteria to document the levels of evidence, and chi-squared tests to compare withdrawal patterns across geographical regions. Expert opinion: Pharmacovigilance systems in low-resource settings should be strengthened. Greater co-ordination across regulatory authorities in assessing and interpreting the benefit-harm balance of new analgesics should be encouraged. Future reporting of harms in clinical trials of analgesics should follow standardized guidelines.

  18. The applicability of animal health surveillance systems for post-market monitoring of potential adverse effects of genetically modified (GM) feed.

    Science.gov (United States)

    Vince, L; Kleter, G A; Kostov, K; Pfeiffer, D U; Guitian, J

    2018-04-20

    A facultative post market monitoring of potential health impacts of genetically modified (GM) feedstuffs on livestock consuming these feeds after pre-market risk assessment is under ongoing consideration. Within the IPAFEED database, scientific studies on health effects beyond performance in livestock and the results of a systematic search for evidence of outcome effects due to GM feed are consolidated. These outcomes were reviewed and checked for consistency in order to identify plausible syndromes suitable for conducting surveillance. The 24 selected studies showed no consistent changes in any health parameter. There were no repeated studies in any species by GM crop type and animal species. As such, there is insufficient evidence to inform the design of surveillance systems for detecting known adverse effects. Animal health surveillance systems have been proposed for the post market monitoring of potential adverse effects in animals. Such systems were evaluated for their applicability to the detection of hypothetical adverse effects and their strengths and weaknesses to detect syndromes of concern are presented. For known adverse effects, applied controlled post-market studies may yield conclusive and high-quality evidence. For detecting unknown adverse effects, the use of existing surveillance systems may still be of interest. A simulation tool developed within the project can be adapted and applied to existing surveillance systems to explore their applicability to the detection of potential adverse effects of GM feed. Copyright © 2018. Published by Elsevier Ltd.

  19. Financial impact of inaccurate Adverse Event recording post Hip Fracture surgery: Addendum to 'Adverse event recording post hip fracture surgery'.

    Science.gov (United States)

    Lee, Matthew J; Doody, Kevin; Mohamed, Khalid M S; Butler, Audrey; Street, John; Lenehan, Brian

    2018-02-15

    A study in 2011 by (Doody et al. Ir Med J 106(10):300-302, 2013) looked at comparing inpatient adverse events recorded prospectively at the point of care, with adverse events recorded by the national Hospital In-Patient Enquiry (HIPE) System. In the study, a single-centre University Hospital in Ireland treating acute hip fractures in an orthopaedic unit recorded 39 patients over a 2-month (August-September 2011) period, with 55 adverse events recorded prospectively in contrast to the HIPE record of 13 (23.6%) adverse events. With the recent change in the Irish hospital funding model from block grant to an 'activity-based funding' on the basis of case load and case complexity, the hospital financial allocation is dependent on accurate case complexity coding. A retrospective assessment of the financial implications of the two methods of adverse incident recording was carried out. A total of €39,899 in 'missed funding' for 2 months was calculated when the ward-based, prospectively collected data was compared to the national HIPE data. Accurate data collection is paramount in facilitating activity-based funding, to improve patient care and ensure the appropriate allocation of resources.

  20. Becoming a "second victim" in health care: Pathway of recovery after adverse event.

    Science.gov (United States)

    Rinaldi, C; Leigheb, F; Vanhaecht, K; Donnarumma, C; Panella, M

    2016-07-01

    The healthcare worker involved in an unanticipated adverse patient event can become second victim. These workers suffer physically and psycho-socially and try to overcome the post-event emotional stress by obtaining emotional support in a variety of ways. The goal of this research was to study second victims among health care providers in Italy. This contribution contains the results of 33 interviews of nurses, physicians and other healthcare workers. After institutional approval, the semi-structured interview, composed of 25 questions, was translated from English into Italian. The audio-interviews were transcribed on paper verbatim by the interviewer. It was then verified if the interviewees experienced the six post-event stages of second victim recovery previously described within the literature. The interviewees described the post-event recovery stages described by literature but stages were not detailed in the exact succession order as the American study. All participants clearly remembered the adverse event and referred the physical and psycho-social symptoms. The psychological support obtained by second victims was described as poor and inefficient. The post-event recovery pathway is predictable but not always clearly respected as defined within this Italian sample. Future study of the second-victim phenomenon and desired supportive interventions is necessary to understand the experience and interventions to mitigate harm of future clinicians. Every day healthcare workers become second victims and, considering that human resources are the most important heritage of healthcare infrastructures, after an adverse event it is very important to execute valid interventional programs to support and train these workers. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. How do Singapore patients view post-anaesthesia adverse outcomes? A single-centre willingness-to-pay study.

    Science.gov (United States)

    Look, Xinqi; Mok, May Un Sam; Tay, Yan Sheng; Abdullah, Hairil Rizal

    2018-05-01

    Knowing how patients value the quality of anaesthesia helps anaesthesiologists to customise their service. However, generalising findings from Western population-based willingness-to-pay studies across different cultures and societies might result in the oversight of some contextualised perspectives of the anaesthesia experience. This study aimed to capture the Singapore perspective of undesired post-anaesthesia outcomes. 132 patients recruited in a pre-anaesthetic evaluation clinic were given questionnaires describing ten possible post-anaesthetic outcomes. Outcomes were ranked for undesirability and assigned relative value through the hypothetical proportioning of SGD 100 to avoid their occurrence. Data was analysed with reference to patients' background and anaesthetic history. A response rate of 69.1% (n = 132/191) was achieved. Outcomes from the most to least undesirable were pain; vomiting; nausea; shivering; orodental trauma; sore throat; abrasions; somnolence; and thirst. Relative values allocated, in descending order, were pain; vomiting; nausea; orodental trauma; abrasions; sore throat; shivering; somnolence; and thirst. Similar to previous studies in Western populations, pain, vomiting and nausea were the top three adverse outcomes that Singapore patients wished to avoid. However, discrepancies with Western patients were seen in spending attitudes, possibly accounted for by differences in healthcare socioeconomics. This study provided a better understanding of Singapore patients' perspectives on post-anaesthesia adverse outcomes and could help to improve treatment strategy and resource management. Copyright: © Singapore Medical Association.

  2. A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER Database and Association Analysis.

    Directory of Open Access Journals (Sweden)

    Masakazu Fujiwara

    Full Text Available Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender has not been proposed.We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA. We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male.Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions

  3. Post-donation telephonic interview of blood donors providing an insight into delayed adverse reactions: First attempt in India.

    Science.gov (United States)

    Tiwari, Aseem K; Aggarwal, Geet; Dara, Ravi C; Arora, Dinesh; Srivastava, Khushboo; Raina, Vimarsh

    2017-04-01

    Blood donor experiences both immediate adverse reactions (IAR) and delayed adverse reactions (DAR). With limited published data available on the incidence of DAR, a study was conducted to estimate incidence and profile of DAR through telephonic interview. Study was conducted over a 45-day period for consecutive volunteer whole blood donations at tertiary care hospital. Donors were divided into first-time, repeat and regular and were monitored for IAR. They were given written copy of post-donation advice. Donors were contacted telephonically three weeks post-donation and enquired about general wellbeing and specific DAR in accordance with a standard n international (International Society of Blood Transfusion) standard format. Donors participated in the study of which 1.6% donors experienced an IAR. Much larger number reported DAR (10.3% vs.1.6% pdonors (age donors (>50 years). First time (12.3%) and repeat donors (13.5%) had similar frequency of DAR but were lower among regular donors (6.7%). DARs are more common than IAR and are of different profile. Post-donation interview has provided an insight into donor experiences and can be used as a valuable tool in donor hemovigilance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Differential roles of childhood adversities and stressful war experiences in the development of mental health symptoms in post-war adolescents in northern Uganda.

    Science.gov (United States)

    Okello, James; De Schryver, Maarten; Musisi, Seggane; Broekaert, Eric; Derluyn, Ilse

    2014-09-09

    Previous studies have shown a relationship between stressful war experiences and mental health symptoms in children and adolescents. To date, no comprehensive studies on the role of childhood adversities have been conducted with war-exposed adolescents living in post-war, low-resource settings in Sub-Saharan Africa. A cross-sectional study of 551 school-going adolescents aged 13-21 years old was undertaken four years post-war in northern Uganda. Participants completed self-administered questionnaires assessing demographics, stressful war experiences, childhood adversities, posttraumatic stress disorder (PTSD), depression, and anxiety symptoms. Our analyses revealed a main effect of gender on all mental health outcomes except avoidance symptoms, with girls reporting higher scores than boys. Stressful war experiences were associated with all mental health symptoms, after adjusting for potential confounders. Childhood adversity was independently associated with depression symptoms but not PTSD, anxiety, and PTSD cluster symptoms. However, in situations of high childhood adversity, our analyses showed that stressful war experiences were less associated with vulnerability to avoidance symptoms than in situations of low childhood adversity. Both stressful war experiences and childhood adversities are risk factors for mental health symptoms among war-affected adolescents. Adolescents with histories of high childhood adversities may be less likely to develop avoidance symptoms in situations of high stressful war experiences. Further exploration of the differential roles of childhood adversities and stressful war experiences is needed.

  5. 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.

    Science.gov (United States)

    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.

  6. Assessing long-term and rare adverse effects of medicines

    NARCIS (Netherlands)

    Duijnhoven, R.G.|info:eu-repo/dai/nl/357218574

    2016-01-01

    Clinical studies in the development of new medicines are primarily designed to investigate efficacy. Knowledge of adverse effects is therefore limited at the time of approval of new medicines. In this thesis several studies were conducted to investigate long-term and rare adverse effects of

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    ... Reporting Program MedWatch: The FDA Safety Information and Adverse Event Reporting Program Share Tweet Linkedin Pin it ... approved information that can help patients avoid serious adverse events. Potential Signals of Serious Risks/New Safety ...

  9. 29 CFR 37.64 - What procedures must the Director follow when CRC has completed a post-approval compliance review?

    Science.gov (United States)

    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...

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

    OpenAIRE

    Ahmad, Syed Rizwanuddin

    2003-01-01

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

  11. Adverse or acceptable: negotiating access to a post-apartheid health care contract.

    Science.gov (United States)

    Harris, Bronwyn; Eyles, John; Penn-Kekana, Loveday; Thomas, Liz; Goudge, Jane

    2014-05-15

    As in many fragile and post-conflict countries, South Africa's social contract has formally changed from authoritarianism to democracy, yet access to services, including health care, remains inequitable and contested. We examine access barriers to quality health services and draw on social contract theory to explore ways in which a post-apartheid health care contract is narrated, practiced and negotiated by patients and providers. We consider implications for conceptualizing and promoting more inclusive, equitable health services in a post-conflict setting. Using in-depth interviews with 45 patients and 67 providers, and field observations from twelve health facilities in one rural and two urban sub-districts, we explore access narratives of those seeking and delivering - negotiating - maternal health, tuberculosis and antiretroviral services in South Africa. Although South Africa's right to access to health care is constitutionally guaranteed, in practice, a post-apartheid health care contract is not automatically or unconditionally inclusive. Access barriers, including poverty, an under-resourced, hierarchical health system, the nature of illness and treatment, and negative attitudes and actions, create conditions for insecure or adverse incorporation into this contract, or even exclusion (sometimes temporary) from health care services. Such barriers are exacerbated by differences in the expectations that patients and providers have of each other and the contract, leading to differing, potentially conflicting, identities of inclusion and exclusion: defaulting versus suffering patients, uncaring versus overstretched providers. Conversely, caring, respectful communication, individual acts of kindness, and institutional flexibility and leadership may mitigate key access barriers and limit threats to the contract, fostering more positive forms of inclusion and facilitating easier access to health care. Building health in fragile and post-conflict societies requires

  12. 50 CFR 37.22 - Approval of exploration plan.

    Science.gov (United States)

    2010-10-01

    ... § 37.21(b), the Regional Director shall promptly publish notice of the application and text of the plan... exploration plan shall be approved by the Regional Director if he determines that it satisfies the....11(b), or minimize adverse impacts on subsistence uses, the Regional Director may approve or...

  13. Data-mining for detecting signals of adverse drug reactions of fluoxetine using the Korea Adverse Event Reporting System (KAERS) database.

    Science.gov (United States)

    Kim, Seonji; Park, Kyounghoon; Kim, Mi-Sook; Yang, Bo Ram; Choi, Hyun Jin; Park, Byung-Joo

    2017-10-01

    Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database. We defined signals in this study by the reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) indices. The KAERS database included 860,224 AE reports, among which 866 reports contained fluoxetine. We compared the labels of fluoxetine among the United States, UK, Germany, France, China, and Korea. Some of the signals, including emotional lability, myositis, spinal stenosis, paradoxical drug reaction, drug dependence, extrapyramidal disorder, adrenal insufficiency, and intracranial hemorrhage, were not labeled in the six countries. In conclusion, we identified new signals that were not known at the time of market approval. However, certain factors should be required for signal evaluation, such as clinical significance, preventability, and causality of the detected signals. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Adverse events and adherence to HIV post-exposure prophylaxis: a cohort study at the Korle-Bu Teaching Hospital in Accra, Ghana.

    Science.gov (United States)

    Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Nortey, Priscilla A; Dodoo, Alexander N O

    2015-06-20

    There is strong evidence that post-exposure prophylaxis (PEP) with antiretroviral drugs in the timely management of occupational exposures sustained by healthcare workers decreases the risk of HIV infection and PEP is now widely used. Antiretroviral drugs have well documented toxicities and produce adverse events in patients living with HIV/AIDS. In the era of "highly active antiretroviral therapy", non-adherence to treatment has been closely linked to the occurrence of adverse events in HIV patients and this ultimately influences treatment success but the influence of adverse events on adherence during PEP is less well studied. Following the introduction of a HIV post-exposure prophylaxis program in the Korle-Bu Teaching Hospital in January 2005, the incidence of adverse events and adherence were documented in occupationally-exposed healthcare workers (HCWs) and healthcare students (HCSs). Cohort event monitoring was used in following-up on exposed HCWs/HCSs for the two study outcomes; adverse events and adherence. All adverse events reported were grouped by MedDRA system organ classification and then by preferred term according to prophylaxis regimen. Adherence was determined by the completion of prophylaxis schedule. Cox proportional regression analysis was applied to determine the factors associated with the cohort study outcomes. Differences in frequencies were tested using the Chi square test and p < 0.05 was considered statistically significant. A total of 228 exposed HCWs/HCSs were followed up during the study, made up of 101 exposed HCWs/HCSs administered lamivudine/zidovudine (3TC/AZT) for 3 days; 75 exposed HCWs/HCSs administered lamivudine/zidovudine (3TC/AZT) for 28 days; and 52 exposed HCWs/HCSs administered lamivudine/zidovudine/lopinavir-ritonavir (3TC/AZT/LPV-RTV) for 28 days. The frequency of adverse events was 28% (n = 28) in exposed HCWs/HCSs administered 3TC/AZT for 3 days, 91% (n = 68) in exposed HCWs/HCSs administered 3TC/AZT for

  15. Review of adverse reactions to injections of Chinese materia medica.

    Science.gov (United States)

    Bian, Zhaoxiang; Shang, Hongcai; Cheng, Chungwah; Wu, Taixiang; Li, Youping; Zhang, Boli

    2010-05-01

    Using Chinese Materia Medica (CM) as injections is an innovation that is proving effective in extensive clinical use in Mainland China. However, recent reports have focused on adverse reactions, ignoring the considerable successes of these preparations. In order to achieve balance in the media and in the minds of the public, we suggest the first step is to clarify the concepts of and differences between adverse drug reactions (ADR) and adverse events (AE) for all concerned-the public, medical practitioners, government officials, and lawmakers. Second, the State Food and Drug Administration should raise the requirements for Chinese Materia Medica Injection (CMI) registration and license approval and emphasize the importance of evidence-based CMI development and evidence-based CMI license approval. Thirdly, drug companies and institutions should reinforce basic research about the quality control of herbs and CMI-drug interactions. Fourth, the Government should clarify the legal responsibilities for CMI approval agencies, CMI developers, medical doctors, and patients. Fifth, the medical association and Government should enhance training for health care professionals concerning the usage of CMIs. And finally sixth, State Food and Drug Administration should monitor the content and quality of the directions for use of CMI. © 2010 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

  16. Immunotherapy Combination Approved for Advanced Kidney Cancer

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Strech Daniel

    2012-07-01

    Full Text Available Abstract 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.

  18. Adverse respiratory events in a post-anesthesia care unit.

    Science.gov (United States)

    Xará, Daniela; Santos, Alice; Abelha, Fernando

    2015-02-01

    Adverse respiratory events (ARE) are a leading causes of postoperative morbidity and mortality. This study investigated the incidence and determinants of postoperative ARE. This observational prospective study was conducted in a post anesthesia care unit (PACU). A total of 340 adult subjects were admitted consecutively, and AREs were measured after elective surgery. Population demographics, perioperative parameters, ARE occurrence, and length of stay in the postoperative PACU and in hospital were recorded. Data were analyzed descriptively using the Mann-Whitney U-test and the Chi-square or Fisher's exact test. Multivariate analyses were carried outusing logistic binary regression, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Postoperative AREs occurred in 67 subjects (19.7%). AREs were more frequent after high-risk procedures (42% vs 24%; P=.003), in patients undergoing major surgery (37% vs 25%; P=.041), those receiving general anesthesia (85% vs 67%; P=.004), and in patients administered intraoperative muscle relaxants (79% vs 55%; P<.001) and neostigmine (69% vs 49%; P=.002). Hypoactive emergence (13% vs 5%; P=.015) and residual neuromuscular blockade (46% versus 11%; P<.001) were more frequent in subjects with postoperative ARE. On multivariate analyses, residual neuromuscular blockade was an independent risk factor for ARE in the PACU (OR 6.4; CI 3.0-13.4; P<.001). ARE is an important and common postoperative complication. Residual neuromuscular blockade was an independent risk factor for ARE in the PACU. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  19. Adverse Event Reporting System (AERS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Adverse Event Reporting System (AERS) is a computerized information database designed to support the FDA's post-marketing safety surveillance program for all...

  20. ADVERSE EVENTS POST-DTAP AND DTwP VACCINATION IN THAI CHILDREN.

    Science.gov (United States)

    Fortuna, Librada; Sirivichayakul, Chukiat; Watanaveeradej, Veerachai; Soonthornworasiri, Ngamphol; Sitcharungsi, Raweerat

    2015-07-01

    We conducted a prospective study to compare the development of fever (axillary T ≥ 37.9 °C) within 4 hours of vaccination, determine the proportion of children who develop high fever (T ≥ 39°C) and evaluate parental days missed from work due to their children's vaccination with either the diphtheria-tetanus-whole cell pertussis (DTwP) or diphtheria-tetanus-acellular pertussis (DTaP) vaccine. The results of this study can help physicians and parents decide whether to have their child vaccinated with the DTwP or more expensive DTaP vaccine. We studied 140 healthy Thai children aged 2 months to 6 years from December 2011 to March 2012 who presented for vaccination. Parents recorded their child's temperature, local and systemic adverse reactions and missed days from work due to these adverse events on a diary card. Of the 140 participants, 72 received the DTwP vaccine and 68 received the DTaP vaccine. The median (IQR) age was 4 (2-6) months and the median weight was 7.1 (5.6-8.7) kg. Twenty children developed fever (axillary T ≥ 37.9°C) within 4 hours following vaccination, 17 (23.6%) had received the DTwP vaccine and 3 (4.4%) had received the DTaP vaccine (p = 0.040). One child (1.4%) who had received the DTwP vaccine and none who received the DTaP vaccine developed high fever (T ≥ 39°C) within 4 hours of vaccination (p = 0.329). Parents of two children who received the DTwP vaccine and one child who received the DTaP vaccine missed work following vaccination (p = 0.059). In conclusion, children who received the DTwP vaccines were more likely to have early post-vaccination fever and higher fever but there was no significant difference between the two groups in parental days lost from work.

  1. 75 FR 57019 - Pesticide Product Registrations; Conditional Approval

    Science.gov (United States)

    2010-09-17

    ..., the Agency was able to make basic health and safety determinations which show that use of flutriafol... unreasonable adverse effects to man and the environment. III. Conditional Approval Form EPA issued a notice...

  2. Excess dietary cholesterol may have an adverse effect on growth performance of early post-larval Litopenaeus vannamei

    Science.gov (United States)

    2012-01-01

    One experiment was conducted to determine the nutritive value of cholesterol for post-larval shrimp, Litopenaeus vannamei. Four isoenergetic and isonitrogenous diets supplemented with four levels of cholesterol (D1, D2, D3 and D4 with 0, 0.5%, 1% and 2% cholesterol, respectively) were fed to triplicate groups of L. vannamei shrimp (mean initial wet weight 0.8 mg) for 27 days. After the trial, shrimp fed the D1 diet had the best growth performance (final body weights: FBW; weight gain: WG; specific growth rate: SGR), while there was no significant difference between diet treatments with respect to survival. The whole body crude protein level in the shrimp decreased with the increase in dietary cholesterol levels, while the whole body crude lipid level in shrimps in the D4 diet treatment was significantly higher (P vannamei; excess dietary cholesterol may thus lead to adverse effects on the growth performance of post-larval shrimp. PMID:22958647

  3. Excess dietary cholesterol may have an adverse effect on growth performance of early post-larval Litopenaeus vannamei

    Directory of Open Access Journals (Sweden)

    Niu Jin

    2012-06-01

    Full Text Available Abstract One experiment was conducted to determine the nutritive value of cholesterol for post-larval shrimp, Litopenaeus vannamei. Four isoenergetic and isonitrogenous diets supplemented with four levels of cholesterol (D1, D2, D3 and D4 with 0, 0.5%, 1% and 2% cholesterol, respectively were fed to triplicate groups of L. vannamei shrimp (mean initial wet weight 0.8 mg for 27 days. After the trial, shrimp fed the D1 diet had the best growth performance (final body weights: FBW; weight gain: WG; specific growth rate: SGR, while there was no significant difference between diet treatments with respect to survival. The whole body crude protein level in the shrimp decreased with the increase in dietary cholesterol levels, while the whole body crude lipid level in shrimps in the D4 diet treatment was significantly higher (P L. vannamei; excess dietary cholesterol may thus lead to adverse effects on the growth performance of post-larval shrimp.

  4. Benefits and adverse effects of post-operative radiation therapy after radical cystectomy for patients with advanced bladder cancer

    International Nuclear Information System (INIS)

    Yabusaki, Noboru; Komatsu, Hideki; Tanabe, Nobuaki; Tago, Kiichiro; Ueno, Akira

    1995-01-01

    The benefits and adverse effects of post-operative irradiation for advanced bladder cancer patients were investigated. Ten patients with pT3b, pT4 or pN+ bladder cancer who underwent radical cystectomy at Yamanashi Medical University Hospital during 7 years and 3 months from October 1983 to December 1991 received adjuvant chemotherapy and radiotherapy (Group 1). During the same period, six patients with recurrent tumor after radical cystectomy were treated by radiotherapy (Group II). Stages of the primary tumors were PT2 in 1, pT3a in 2, pT3b in 6 and pT4 in 7 cases. In addition, 10 of 16 patients (63%) had positive nodes. During the follow-up period, seven patients died of cancer, and one died of other cause. As a result eight patients (5 in Group I, 3 in Group II) are alive. The cumulative 5-year survival rate is 50%. However, nine of the 16 patients (56%) suffered from the small bowel obstruction as an adverse effect of irradiation. Six patients required resection of the small bowel or bypass surgery. Radiation after radical cystectomy seemed to be effective for the local control of the tumor, but the adverse effect to the digestive system was very severe and common. (author)

  5. Dabrafenib Plus Trametinib Approved for Melanoma, Thyroid Cancer

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2017-12-01

    Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at

  7. 29 CFR 1952.10 - Requirements for approval of State posters.

    Science.gov (United States)

    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...

  8. The effect of prophylactic antipyretic administration on post-vaccination adverse reactions and antibody response in children: a systematic review.

    Directory of Open Access Journals (Sweden)

    Rashmi Ranjan Das

    Full Text Available Prophylactic antipyretic administration decreases the post-vaccination adverse reactions. Recent study finds that they may also decrease the antibody responses to several vaccine antigens. This systematic review aimed to assess the evidence for a relationship between prophylactic antipyretic administration, post-vaccination adverse events, and antibody response in children.A systematic search of major databases including MEDLINE and EMBASE was carried out till March 2014. Randomized controlled trials (RCTs comparing prophylactic antipyretic treatment versus placebo post-vaccination in children ≤ 6 years of age were included. Two reviewers independently applied eligibility criteria, assessed the studies for methodological quality, and extracted data [PROSPERO registration: CRD42014009717].Of 2579 citations retrieved, a total of 13 RCTs including 5077 children were included in the review. Prophylactic antipyretic administration significantly reduced the febrile reactions (≥ 38.0 °C after primary and booster vaccinations. Though there were statistically significant differences in the antibody responses between the two groups, the prophylactic PCM group had what would be considered protective levels of antibodies to all of the antigens given after the primary and booster vaccinations. No significant difference in the nasopharyngeal carriage rates (short-term and long-term of H. influenzae or S. pneumoniae serotypes was found between the prophylactic and no prophylactic PCM group. There was a significant reduction in the local and systemic symptoms after primary, but not booster vaccinations.Though prophylactic antipyretic administration leads to relief of the local and systemic symptoms after primary vaccinations, there is a reduction in antibody responses to some vaccine antigens without any effect on the nasopharyngeal carriage rates of S. pneumoniae & H. influenza serotypes. Future trials and surveillance programs should also aim at

  9. Automatically Recognizing Medication and Adverse Event Information From Food and Drug Administration's Adverse Event Reporting System Narratives.

    Science.gov (United States)

    Polepalli Ramesh, Balaji; Belknap, Steven M; Li, Zuofeng; Frid, Nadya; West, Dennis P; Yu, Hong

    2014-06-27

    The Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) is a repository of spontaneously-reported adverse drug events (ADEs) for FDA-approved prescription drugs. FAERS reports include both structured reports and unstructured narratives. The narratives often include essential information for evaluation of the severity, causality, and description of ADEs that are not present in the structured data. The timely identification of unknown toxicities of prescription drugs is an important, unsolved problem. The objective of this study was to develop an annotated corpus of FAERS narratives and biomedical named entity tagger to automatically identify ADE related information in the FAERS narratives. We developed an annotation guideline and annotate medication information and adverse event related entities on 122 FAERS narratives comprising approximately 23,000 word tokens. A named entity tagger using supervised machine learning approaches was built for detecting medication information and adverse event entities using various categories of features. The annotated corpus had an agreement of over .9 Cohen's kappa for medication and adverse event entities. The best performing tagger achieves an overall performance of 0.73 F1 score for detection of medication, adverse event and other named entities. In this study, we developed an annotated corpus of FAERS narratives and machine learning based models for automatically extracting medication and adverse event information from the FAERS narratives. Our study is an important step towards enriching the FAERS data for postmarketing pharmacovigilance.

  10. Serious adverse events with infliximab: analysis of spontaneously reported adverse events.

    Science.gov (United States)

    Hansen, Richard A; Gartlehner, Gerald; Powell, Gregory E; Sandler, Robert S

    2007-06-01

    Serious adverse events such as bowel obstruction, heart failure, infection, lymphoma, and neuropathy have been reported with infliximab. The aims of this study were to explore adverse event signals with infliximab by using a long period of post-marketing experience, stratifying by indication. The relative reporting of infliximab adverse events to the U.S. Food and Drug Administration (FDA) was assessed with the public release version of the adverse event reporting system (AERS) database from 1968 to third quarter 2005. On the basis of a systematic review of adverse events, Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to predefined categories of adverse events, including death, heart failure, hepatitis, infection, infusion reaction, lymphoma, myelosuppression, neuropathy, and obstruction. Disproportionality analysis was used to calculate the empiric Bayes geometric mean (EBGM) and corresponding 90% confidence intervals (EB05, EB95) for adverse event categories. Infliximab was identified as the suspect medication in 18,220 reports in the FDA AERS database. We identified a signal for lymphoma (EB05 = 6.9), neuropathy (EB05 = 3.8), infection (EB05 = 2.9), and bowel obstruction (EB05 = 2.8). The signal for granulomatous infections was stronger than the signal for non-granulomatous infections (EB05 = 12.6 and 2.4, respectively). The signals for bowel obstruction and infusion reaction were specific to patients with IBD; this suggests potential confounding by indication, especially for bowel obstruction. In light of this additional evidence of risk of lymphoma, neuropathy, and granulomatous infections, clinicians should stress this risk in the shared decision-making process.

  11. Adverse events in children and adolescents treated with quetiapine: an analysis of adverse drug reaction reports from the Danish Medicines Agency database

    DEFF Research Database (Denmark)

    Jakobsen, Klaus D.; Wallach-Kildemoes, Helle; Bruhn, Christina H.

    2017-01-01

    Quetiapine is a low-affinity dopamine D2 receptor antagonist, approved for the treatment of bipolar disorder and schizophrenia in children and adolescents by the Food and Drug Administration, but not by European Medicine Agency. Although knowledge of adverse drug reactions in children...... and adolescents is scarce, quetiapine is increasingly being used for youth in Denmark. The aim of this case study is to discuss adverse drug events (ADEs) spontaneously reported to the Danish Medicines Agency on quetiapine used in the pediatric population in relation to adversive drug reactions (ADRs) reported......, hallucinations. As some of the reported ADEs are life threatening and not listed as ADRs in the SPCs, off-label use of quetiapine in children and adolescents gives rise to safety concerns....

  12. 38 CFR 21.9765 - Program of education approval.

    Science.gov (United States)

    2010-07-01

    ... education offered by an institution of higher learning if that program of education is approved under 38 U.S... 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...

  13. Adverse drug events in the oral cavity.

    Science.gov (United States)

    Yuan, Anna; Woo, Sook-Bin

    2015-01-01

    Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and the new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. Some examples include osteonecrosis, seen with not only bisphosphonates but also antiangiogenic agents, and the distinctive ulcers caused by mammalian target of rapamycin inhibitors. As newer therapeutic agents are approved, it is likely that more adverse drug events will be encountered. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely, xerostomia, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, white lesions, dysesthesia, osteonecrosis, infection, angioedema, and malignancy. Oral health care providers should be familiar with such events, as they will encounter them in their practice. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Care-seeking behavior of Japanese gynecological cancer survivors suffering from adverse effects

    Directory of Open Access Journals (Sweden)

    Oshima Sumiko

    2013-01-01

    Full Text Available Abstract Background Post-treatment follow-up visits for gynecological cancer survivors should provide opportunities for management of adverse physical/psychological effects of therapy and early recurrence detection. However, the adequacy of such visits in Japan is poorly documented. We qualitatively explored care-seeking experiences of Japanese gynecological cancer survivors and deduced factors influencing care-seeking behaviors and treatment access. Methods We conducted 4 semi-structured focus groups comprising altogether 28 Japanese gynecological cancer survivors to collect a variety of participants’ post-treatment care-seeking behaviors through active interaction with participants. Factors influencing access to treatment for adverse effects were analyzed qualitatively. Results Survivors sought care through specialty clinic visits when regular post-treatment gynecological follow-ups were inadequate or when symptoms seemed to be non-treatment related. Information provided by hospital staff during initial treatment influenced patients’ understanding and response to adverse effects. Lack of knowledge and inaccurate symptom interpretation delayed help-seeking, exacerbating symptoms. Gynecologists’ attitudes during follow-ups frequently led survivors to cope with symptoms on their own. Information from mass media, Internet, and support groups helped patients understand symptoms and facilitated care seeking. Conclusions Post-treatment adverse effects are often untreated during follow-up visits. Awareness of possible post-treatment adverse effects is important for gynecological cancer survivors in order to obtain appropriate care if the need arises. Consultation during the follow-up visit is essential for continuity in care.

  15. Pharmacovigilance of biologicals : dynamics in post-approval safety learning

    NARCIS (Netherlands)

    Vermeer, N.S.

    2015-01-01

    Regulatory decisions to allow new drugs on the market by definition have to accept a certain level of uncertainty about the full benefit-risk balance. Pre-approval studies typically provide information on a limited number of patients over a relative short follow-up period, and handle strict

  16. High-Performance Signal Detection for Adverse Drug Events using MapReduce Paradigm.

    Science.gov (United States)

    Fan, Kai; Sun, Xingzhi; Tao, Ying; Xu, Linhao; Wang, Chen; Mao, Xianling; Peng, Bo; Pan, Yue

    2010-11-13

    Post-marketing pharmacovigilance is important for public health, as many Adverse Drug Events (ADEs) are unknown when those drugs were approved for marketing. However, due to the large number of reported drugs and drug combinations, detecting ADE signals by mining these reports is becoming a challenging task in terms of computational complexity. Recently, a parallel programming model, MapReduce has been introduced by Google to support large-scale data intensive applications. In this study, we proposed a MapReduce-based algorithm, for common ADE detection approach, Proportional Reporting Ratio (PRR), and tested it in mining spontaneous ADE reports from FDA. The purpose is to investigate the possibility of using MapReduce principle to speed up biomedical data mining tasks using this pharmacovigilance case as one specific example. The results demonstrated that MapReduce programming model could improve the performance of common signal detection algorithm for pharmacovigilance in a distributed computation environment at approximately liner speedup rates.

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

    Science.gov (United States)

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

    2017-01-01

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

  18. 75 FR 5698 - Approval and Promulgation of Implementation Plans; Albuquerque-Bernalillo County, NM; Excess...

    Science.gov (United States)

    2010-02-04

    ... adverse comments by March 8, 2010. If adverse comments are received, EPA will publish a timely withdrawal... also included proposed revisions to NMAC 20.11.69--Pathological Waste Destructors. NMAC 20.11.69-- Pathological Waste Destructors is not currently in the EPA-approved SIP for Albuquerque-Bernalillo County. We...

  19. 12 CFR 225.12 - Transactions not requiring Board approval.

    Science.gov (United States)

    2010-01-01

    ... Merger Act. The merger or consolidation of a subsidiary bank of a bank holding company with another bank... application under this subpart if it determines that the merger or consolidation would have a significant adverse impact on the financial condition of the bank holding company, or otherwise requires approval...

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

    Directory of Open Access Journals (Sweden)

    Uwe Rudolf Max Reuter

    2018-04-01

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

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

    Science.gov (United States)

    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.

  2. Proarrhythmic potential of dronedarone: emerging evidence from spontaneous adverse event reporting.

    Science.gov (United States)

    Kao, David P; Hiatt, William R; Krantz, Mori J

    2012-08-01

    To characterize the frequency and type of cardiac events, including torsade de pointes, associated with dronedarone and its structural analog, amiodarone, outside of the clinical trial setting. Retrospective analysis. Spontaneous reports in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database generated between July 1, 2009, and June 30, 2011. All reports of adverse events during the study period were reviewed to identify cardiac events associated with any approved drug in the United States. The type and number of cardiac events associated with dronedarone and amiodarone were determined. Active ingredients were identified using the Drugs@FDA database, and the Medical Dictionary for Regulatory Activities (MedDRA) was used to aggregate related adverse events. To avoid redundant reporting, all statistics were generated in reference to unique case identifiers. Dronedarone was associated with more adverse cardiovascular event reports than amiodarone (810 vs 493 reports) during the study period. Dronedarone was also associated with the most reports of torsade de pointes of any approved drug in the United States (37 reports), followed by amiodarone (29 reports). Reports of ventricular arrhythmias and cardiac arrest (138 vs 113 reports) as well as heart failure (179 vs 126 reports) were more common with dronedarone than amiodarone. Dronedarone was associated with reports of ventricular arrhythmia, cardiac arrest, and torsade de pointes in clinical practice. Whether this observation accounts for the increased risk of fatal arrhythmia observed in a recent prospective trial requires further investigation. © 2012 Pharmacotherapy Publications, Inc. All rights reserved.

  3. Surgical adverse outcomes and patients' evaluation of quality of care: inherent risk or reduced quality of care?

    Science.gov (United States)

    Marang-van de Mheen, Perla J; van Duijn-Bakker, Nanny; Kievit, Job

    2007-12-01

    Previous research has shown that sicker patients are less satisfied with their healthcare, but specific effects of adverse health outcomes have not been investigated. The present study aimed to assess whether patients who experience adverse outcomes, in hospital or after discharge, differ in their evaluation of quality of care compared with patients without adverse outcomes. In hospital adverse outcomes were prospectively recorded by surgeons and surgical residents as part of routine care. Four weeks after discharge, patients were interviewed by telephone about the occurrence of post-discharge adverse outcomes, and their overall evaluation of quality of hospital care and specific suggestions for improvements in the healthcare provided. Of 2145 surgical patients admitted to the Leiden University Medical Center in 2003, 1876 (88%) agreed to be interviewed. Overall evaluation was less favourable by patients who experienced post-discharge adverse outcomes only (average 19% lower). These patients were also more often dissatisfied (OR 2.02, 95% CI 1.24 to 3.31) than patients without adverse outcomes, and they more often suggested that improvements were needed in medical care (OR 2.07, 1.45 to 2.95) and that patients were discharged too early (OR 3.26, 1.72 to 6.20). The effect of in hospital adverse outcomes alone was not statistically significant. Patients with both in hospital and post-discharge adverse outcomes also found the quality of care to be lower (on average 33% lower) than patients without adverse outcomes. Post-discharge adverse outcomes negatively influence patients' overall evaluation of quality of care and are perceived as being discharged too early, suggesting that patients need better information at discharge.

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

    Science.gov (United States)

    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.

  5. Adversity and Resilience Are Associated with Outcome after Mild Traumatic Brain Injury in Military Service Members.

    Science.gov (United States)

    Reid, Matthew W; Cooper, Douglas B; Lu, Lisa H; Iverson, Grant L; Kennedy, Jan E

    2018-05-15

    The objective of this study was to assess the associations between resilience, adversity, post-concussion symptoms, and post-traumatic stress symptom reporting after mild traumatic brain injury (mTBI). We hypothesized that resilience would be associated with less symptom reporting, and adversity would be associated with greater symptom reporting. This was a cross-sectional study of retrospective data collected for an ongoing TBI repository. United States military service members who screened positive for mTBI during a primary care visit completed the Trauma History Screen (THS), Connor-Davidson Resilience Scale (CD-RISC), Neurobehavioral Symptom Inventory (NSI), and post-traumatic stress disorder (PTSD) Checklist-Civilian Version (PCL-C). Data collected from February 2015 to August 2016 were used for the present study. Only participants with complete data for the above measures were included, yielding a sample size of 165 participants. Adversity (THS) and resilience (CD-RISC) scores were each correlated significantly with post-concussion (NSI) and traumatic stress (PCL-C) total and subscale scores in the hypothesized direction. Interactions between adversity and resilience were absent for all measures except the NSI sensory subscale. Four traumatic event types were significantly associated positively with most NSI and PCL-C total and subscale scores, but the age at which traumatic events were first experienced showed few and mixed significant associations. In conclusion, resilience and adversity were significantly associated with symptom endorsement after mTBI. Screening for cumulative adversity may identify individuals at greater risk of developing persistent post-concussion symptoms and/or PTSD, and interventions that increase resilience may reduce symptom severity.

  6. Spontaneously Reported Adverse Reactions for Herbal Medicinal Products and Natural Remedies in Sweden 2007-15: Report from the Medical Products Agency.

    Science.gov (United States)

    Svedlund, Erika; Larsson, Maria; Hägerkvist, Robert

    2017-06-01

    In relation to the extensive use of herbal medicinal products in self-care, the safety information is limited and there is a need for improvement. This study describes spontaneously reported adverse reactions related to herbal medicinal products and natural remedies in Sweden. To evaluate the characteristics and frequency of adverse events recorded by the Swedish Medical Products Agency, where herbal medicinal products and natural remedies were suspected as causative agents. Adverse drug reactions reported to the Swedish Medical Product Agency during 2007-15 related to approved herbal medicinal products or natural remedies were included and analysed in the retrospective study. Reports had been assessed for causality when they were lodged and only reports that had been assessed as at least possible were included in the study. In total, 116 reports (concerning 259 adverse reactions) related to herbal medicinal products or natural remedies were found in the Swedish national pharmacovigilance database. The active ingredients most frequently suspected during the study period were black cohosh rhizome (15 reports), purple coneflower herb (14 reports) and a combination of extracts of pollen (13 reports). Adverse reactions related to skin and subcutaneous tissue were the most commonly reported reactions. No previously unknown safety problems have been discovered in the present study. This finding could be explained by a thorough pre-approval assessment of medicinal products and the fact that most herbal preparations in medicinal products have been in clinical use for many years (for traditional herbal medicinal products, the requirements are ≥30 years), i.e. adverse reactions are acknowledged and assessed before approval.

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

    Science.gov (United States)

    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

  8. Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009-2015.

    Science.gov (United States)

    Arana, Jorge E; Harrington, Theresa; Cano, Maria; Lewis, Paige; Mba-Jonas, Adamma; Rongxia, Li; Stewart, Brock; Markowitz, Lauri E; Shimabukuro, Tom T

    2018-03-20

    The Food and Drug Administration (FDA) approved quadrivalent human papillomavirus vaccine (4vHPV) for use in females and males aged 9-26 years, since 2006 and 2009 respectively. We characterized reports to the Vaccine Adverse Event Reporting System (VAERS), a US spontaneous reporting system, in females and males who received 4vHPV vaccination. We searched VAERS for US reports of adverse events (AEs) following 4vHPV from January 2009 through December 2015. Signs and symptoms were coded using Medical Dictionary for Regulatory Activities (MedDRA). We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reports. Clinicians reviewed available information, including medical records, and reports of selected pre-specified conditions. VAERS received 19,760 reports following 4vHPV; 60.2% in females, 17.2% in males, and in 22.6% sex was missing. Overall, 94.2% of reports were non-serious; dizziness, syncope and injection site reactions were commonly reported in both males and females. Headache, fatigue and nausea were commonly reported serious AEs. More than 60 million 4vHPV doses were distributed during the study period. Crude AE reporting rates were 327 reports per million 4vHPV doses distributed for all reports, and 19 per million for serious reports. Among 29 verified reports of death, there was no pattern of clustering of deaths by diagnosis, co-morbidities, age, or interval from vaccination to death. No new or unexpected safety concerns or reporting patterns of 4vHPV with clinically important AEs were detected. Safety profile of 4vHPV is consistent with data from pre-licensure trials and postmarketing safety data. Published by Elsevier Ltd.

  9. Machine driving of wooden and steel highway guardrail posts under adverse conditions

    Science.gov (United States)

    Charles J. Gatchell; Edwin L. Lucas; Edwin L. Lucas

    1971-01-01

    In an exploratory study, we drove 32 wooden posts and 26 steel posts into a rock-filled base that was topped with limestone gravel and shale. We found that, though both post materials perform well, wood is superior to steel in resisting damage below the groundline.

  10. Childhood adversity and insomnia in adolescence.

    Science.gov (United States)

    Wang, Yan; Raffeld, Miriam R; Slopen, Natalie; Hale, Lauren; Dunn, Erin C

    2016-05-01

    The study aims to evaluate the association between exposure to childhood adversity and insomnia, with an emphasis on the role of adversity type, timing, and accumulation (i.e., the number of specific types of adversities the child reported being exposed to). Our analytic sample comprised 9582 adolescents from the National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a nationally representative population-based sample. We examined the association between 18 different types of retrospectively reported adversities (capturing interpersonal violence, accidents and injuries, social network or witnessing events, and other adverse events) and risk of self-reported past-year insomnia. We also examined whether the age at first exposure to adversity was associated with the risk of insomnia, and whether exposure to a greater number of different types of adversities (ie, accumulation) conferred an elevated risk of insomnia. In addition, we performed a sensitivity analysis excluding adolescents with a past-year diagnosis of major depression, dysthymia, post-traumatic stress disorder (PTSD), or generalized anxiety disorder. Almost one-third of adolescents reported insomnia, with a higher prevalence among girls and those from racial/ethnic minority groups. Adolescents exposed to at least one childhood adversity of any type (59.41%) were more likely than their nonexposed peers to experience insomnia (across adversities, prevalence ratios (PRs) ranged from 1.31 to 1.89). Risk of insomnia differed based on the age at first exposure to adversity as well as the type of adversity. Adolescents exposed to a greater number of different types of adversities had a higher risk of insomnia compared to those experiencing fewer adversities. These results were similar, by and large, to those obtained after excluding adolescents with at least one of the four past-year psychiatric disorders. Exposure to adversity confers an elevated risk of insomnia. This association varied by type

  11. Identifying Adverse Drug Events by Relational Learning.

    Science.gov (United States)

    Page, David; Costa, Vítor Santos; Natarajan, Sriraam; Barnard, Aubrey; Peissig, Peggy; Caldwell, Michael

    2012-07-01

    The pharmaceutical industry, consumer protection groups, users of medications and government oversight agencies are all strongly interested in identifying adverse reactions to drugs. While a clinical trial of a drug may use only a thousand patients, once a drug is released on the market it may be taken by millions of patients. As a result, in many cases adverse drug events (ADEs) are observed in the broader population that were not identified during clinical trials. Therefore, there is a need for continued, post-marketing surveillance of drugs to identify previously-unanticipated ADEs. This paper casts this problem as a reverse machine learning task , related to relational subgroup discovery and provides an initial evaluation of this approach based on experiments with an actual EMR/EHR and known adverse drug events.

  12. Medical marijuana patient counseling points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs.

    Science.gov (United States)

    Parmar, Jayesh R; Forrest, Benjamin D; Freeman, Robert A

    2016-01-01

    The purpose of this report is to present a review of the medical uses, efficacy, and adverse effects of the three approved cannabis-based medications and ingested marijuana. A literature review was conducted utilizing key search terms: dronabinol, nabilone, nabiximols, cannabis, marijuana, smoke, efficacy, toxicity, cancer, multiple sclerosis, nausea, vomiting, appetite, pain, glaucoma, and side effects. Abstracts of the included literature were reviewed, analyzed, and organized to identify the strength of evidence in medical use, efficacy, and adverse effects of the approved cannabis-based medications and medical marijuana. A total of 68 abstracts were included for review. Dronabinol's (Marinol) most common medical uses include weight gain, chemotherapy-induced nausea and vomiting (CINV), and neuropathic pain. Nabiximol's (Sativex) most common medical uses include spasticity in multiple sclerosis (MS) and neuropathic pain. Nabilone's (Cesamet) most common medical uses include CINV and neuropathic pain. Smoked marijuana's most common medical uses include neuropathic pain and glaucoma. Orally ingested marijuana's most common medical uses include improving sleep, reducing neuropathic pain, and seizure control in MS. In general, all of these agents share similar medical uses. The reported adverse effects of the three cannabis-based medications and marijuana show a major trend in central nervous system (CNS)-related adverse effects along with cardiovascular and respiratory related adverse effects. Marijuana shares similar medical uses with the approved cannabis-based medications dronabinol (Marinol), nabiximols (Sativex), and nabilone (Cesamet), but the efficacy of marijuana for these medical uses has not been fully determined due to limited and conflicting literature. Medical marijuana also has similar adverse effects as the FDA-approved cannabis-based medications mainly consisting of CNS related adverse effects but also including cardiovascular and respiratory

  13. Adverse effects during the oral glucose tolerance test in post-bariatric surgery patients

    OpenAIRE

    Andrade,Heliana Fernanda de Albuquerque; Pedrosa,William; Diniz,Maria de Fátima Haueisen Sander; Passos,Valéria Maria Azeredo

    2016-01-01

    ABSTRACT Objective The oral glucose tolerance test (OGTT) is used in the screening of gestational diabetes, in diagnosis of type 2 diabetes in conjunction with fasting blood glucose and glycated hemoglobin. The aim of this study was to examine the incidence and risk factors of adverse effects of OGTT in patients who underwent bariatric surgery, in addition to proposing standardization for ordering the OGTT in these patients. Subjects and methods This study assessed the incidence of adverse ...

  14. Adverse Effects of Nutraceuticals and Dietary Supplements.

    Science.gov (United States)

    Ronis, Martin J J; Pedersen, Kim B; Watt, James

    2018-01-06

    Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions.

  15. Mining adverse drug reactions from online healthcare forums using hidden Markov model.

    Science.gov (United States)

    Sampathkumar, Hariprasad; Chen, Xue-wen; Luo, Bo

    2014-10-23

    Adverse Drug Reactions are one of the leading causes of injury or death among patients undergoing medical treatments. Not all Adverse Drug Reactions are identified before a drug is made available in the market. Current post-marketing drug surveillance methods, which are based purely on voluntary spontaneous reports, are unable to provide the early indications necessary to prevent the occurrence of such injuries or fatalities. The objective of this research is to extract reports of adverse drug side-effects from messages in online healthcare forums and use them as early indicators to assist in post-marketing drug surveillance. We treat the task of extracting adverse side-effects of drugs from healthcare forum messages as a sequence labeling problem and present a Hidden Markov Model(HMM) based Text Mining system that can be used to classify a message as containing drug side-effect information and then extract the adverse side-effect mentions from it. A manually annotated dataset from http://www.medications.com is used in the training and validation of the HMM based Text Mining system. A 10-fold cross-validation on the manually annotated dataset yielded on average an F-Score of 0.76 from the HMM Classifier, in comparison to 0.575 from the Baseline classifier. Without the Plain Text Filter component as a part of the Text Processing module, the F-Score of the HMM Classifier was reduced to 0.378 on average, while absence of the HTML Filter component was found to have no impact. Reducing the Drug names dictionary size by half, on average reduced the F-Score of the HMM Classifier to 0.359, while a similar reduction to the side-effects dictionary yielded an F-Score of 0.651 on average. Adverse side-effects mined from http://www.medications.com and http://www.steadyhealth.com were found to match the Adverse Drug Reactions on the Drug Package Labels of several drugs. In addition, some novel adverse side-effects, which can be potential Adverse Drug Reactions, were also

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

    Science.gov (United States)

    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.

  17. Nursing students' post-traumatic growth, emotional intelligence and psychological resilience.

    Science.gov (United States)

    Li, Y; Cao, F; Cao, D; Liu, J

    2015-06-01

    Nursing students in the present sample who have experienced childhood adversity have a certain level of post-traumatic growth. If introduced into nursing curricula, emotional intelligence interventions may increase emotional coping resources and enhance social skills for nurses, which may benefit their long-term occupational health. As researchers consider personal resilience a strategy for responding to workplace adversity in nurses, resilience building should be incorporated into nursing education. This is a preliminary study that may guide future investigations of the curvilinear relationship rather than linear relationship between post-traumatic growth and positive factors in the special sample of nursing students. Resilience, emotional intelligence and post-traumatic growth may benefit nursing students' careers and personal well-being in clinical work. Developing both their emotional intelligence and resilience may assist their individual post-traumatic growth and enhance their ability to cope with clinical stress. To investigate the relationships among post-traumatic growth, emotional intelligence and psychological resilience in vocational school nursing students who have experienced childhood adversities, a cross-sectional research design with anonymous questionnaires was conducted and self-report data were analysed. The Childhood Adversities Checklist (Chinese version), Posttraumatic Growth Inventory, Emotional Intelligence Scale and the 10-item Connor-Davidson Resilience Scale were used. Survey data were collected from 202 Chinese vocational school nursing students during 2011. Post-traumatic growth was associated with emotional intelligence and psychological resilience. Results indicated a curvilinear relationship between emotional intelligence and post-traumatic growth, and between psychological resilience and post-traumatic growth. Moderate-level emotional intelligence and psychological resilience were most associated with the greatest levels of growth

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

    Science.gov (United States)

    Zippel, Claus; Bohnet-Joschko, Sabine

    2017-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Balassy, Csilla [Medical University of Vienna, Vienna General Hospital, Department of Radiology, Division of General and Pediatric Radiology, Vienna (Austria); Roberts, Donna [Medical University of South Carolina, Department of Radiology, Charleston, SC (United States); Miller, Stephen F. [LeBonheur Children' s Hospital, Department of Radiology, Memphis, TN (United States)

    2015-11-15

    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. (orig.)

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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. (orig.)

  2. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    Science.gov (United States)

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications. © 2013 Pharmacotherapy Publications, Inc.

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

    Science.gov (United States)

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

    2011-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Ross JS

    2015-05-01

    Full Text Available Joseph S Ross, Katrina L Blount, Jessica D Ritchie, Beth Hodshon, Harlan M Krumholz Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA 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. Keywords: FDA, PMA pathway, post-market surveillance

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

    Science.gov (United States)

    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.

  6. Managing adverse effects of immunotherapy.

    Science.gov (United States)

    Gerson, James N; Ramamurthy, Chethan; Borghaei, Hossein

    2018-05-01

    Remarkable efficacy has been achieved in a variety of cancer types by targeting immune checkpoints. The cytotoxic T-lymphocyte-associated antigen 4 inhibitor ipilimumab, the programmed death 1 inhibitors nivolumab and pembrolizumab, and the programmed death ligand 1 inhibitors atezolizumab, avelumab, and durvalumab are the agents currently approved by the US Food and Drug Administration for the treatment of certain advanced malignancies. These agents mark a departure from both standard cytotoxic chemotherapy and targeted therapy. However, they are associated with a unique set of immune-related adverse events (irAEs), which can manifest as a wide range of autoimmune phenomena. The irAEs can affect any system in the body and in rare cases are life-threatening. It is critical for the practicing medical oncologist to recognize and promptly treat any irAEs that may develop.

  7. The Ontology of Vaccine Adverse Events (OVAE) and its usage in representing and analyzing adverse events associated with US-licensed human vaccines.

    Science.gov (United States)

    Marcos, Erica; Zhao, Bin; He, Yongqun

    2013-11-26

    Licensed human vaccines can induce various adverse events (AE) in vaccinated patients. Due to the involvement of the whole immune system and complex immunological reactions after vaccination, it is difficult to identify the relations among vaccines, adverse events, and human populations in different age groups. Many known vaccine adverse events (VAEs) have been recorded in the package inserts of US-licensed commercial vaccine products. To better represent and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology (VO). Like OAE and VO, OVAE is aligned with the Basic Formal Ontology (BFO). The commercial vaccines and adverse events in OVAE are imported from VO and OAE, respectively. A new population term 'human vaccinee population' is generated and used to define VAE occurrence. An OVAE design pattern is developed to link vaccine, adverse event, vaccinee population, age range, and VAE occurrence. OVAE has been used to represent and classify the adverse events recorded in package insert documents of commercial vaccines licensed by the USA Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms, including 87 distinct types of VAEs associated with 63 human vaccines licensed in the USA. For each vaccine, occurrence rates for every VAE in different age groups have been logically represented in OVAE. SPARQL scripts were developed to query and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs most frequently observed among vaccines were identified and analyzed. Asserted and inferred ontology hierarchies classify VAEs in different levels of AE groups. Different VAE occurrences in different age groups were also analyzed. The ontology-based data representation and integration using the FDA-approved information from the vaccine package insert documents

  8. Number of patients studied prior to approval of new medicines

    DEFF Research Database (Denmark)

    Duijnhoven, Ruben G; Straus, Sabine M J M; Raine, June M

    2013-01-01

    length of time), whereas 67 (79.8%) of the medicines met the criteria for 12-mo patient exposure (at least 100 participants studied for 12 mo). CONCLUSIONS: For medicines intended for chronic use, the number of patients studied before marketing is insufficient to evaluate safety and long-term efficacy....... Both safety and efficacy require continued study after approval. New epidemiologic tools and legislative actions necessitate a review of the requirements for the number of patients studied prior to approval, particularly for chronic use, and adequate use of post-marketing studies. Please see later...

  9. Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

    International Nuclear Information System (INIS)

    Herrera, Higmar; Yanez, Elvia; Deras, Diana C.; Reyes, Francianella

    2010-01-01

    This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55±13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

  10. Coding of adverse events of suicidality in clinical study reports of duloxetine for the treatment of major depressive disorder

    DEFF Research Database (Denmark)

    Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn

    2014-01-01

    OBJECTIVE: To assess the effects of coding and coding conventions on summaries and tabulations of adverse events data on suicidality within clinical study reports. DESIGN: Systematic electronic search for adverse events of suicidality in tables, narratives, and listings of adverse events...... identification number, we attempted to reconcile data on the same event between the different formats for presenting data on adverse events within the clinical study report. SETTING: 9 randomised placebo controlled trials of duloxetine for major depressive disorder submitted to the European Medicines Agency...... for marketing approval. DATA SOURCES: Clinical study reports obtained from the EMA in 2011. RESULTS: Six trials used the medical coding dictionary COSTART (Coding Symbols for a Thesaurus of Adverse Reaction Terms) and three used MedDRA (Medical Dictionary for Regulatory Activities). Suicides were clearly...

  11. Adverse Events Involving Radiation Oncology Medical Devices: Comprehensive Analysis of US Food and Drug Administration Data, 1991 to 2015

    International Nuclear Information System (INIS)

    Connor, Michael J.; Marshall, Deborah C.; Moiseenko, Vitali; Moore, Kevin; Cervino, Laura; Atwood, Todd; Sanghvi, Parag; Mundt, Arno J.; Pawlicki, Todd; Recht, Abram; Hattangadi-Gluth, Jona A.

    2017-01-01

    Purpose: Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administration's postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non–radiation oncology devices. Methods and Materials: MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact). Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ"2 test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. Results: There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). Conclusions: Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance, improved

  12. Adverse Events Involving Radiation Oncology Medical Devices: Comprehensive Analysis of US Food and Drug Administration Data, 1991 to 2015

    Energy Technology Data Exchange (ETDEWEB)

    Connor, Michael J. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Radiation Oncology, University of California Irvine School of Medicine, Irvine, California (United States); Marshall, Deborah C.; Moiseenko, Vitali; Moore, Kevin; Cervino, Laura; Atwood, Todd; Sanghvi, Parag; Mundt, Arno J.; Pawlicki, Todd [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2017-01-01

    Purpose: Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administration's postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non–radiation oncology devices. Methods and Materials: MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact). Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ{sup 2} test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. Results: There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). Conclusions: Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance

  13. Acute disseminated encephalomyelitis onset: evaluation based on vaccine adverse events reporting systems.

    Directory of Open Access Journals (Sweden)

    Paolo Pellegrino

    Full Text Available OBJECTIVE: To evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM by considering data from different pharmacovigilance surveillance systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS database and the EudraVigilance post-authorisation module (EVPM were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed. RESULTS: We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40±21.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines. CONCLUSIONS: This study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely not [corrected] due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reaction.

  14. Metabolites as Biomarkers of Adverse Reactions Following Vaccination: A Pilot Study using Nuclear Magnetic Resonance Metabolomics

    Science.gov (United States)

    McClenathan, Bruce M.; Stewart, Delisha A.; Spooner, Christina E.; Pathmasiri, Wimal W.; Burgess, Jason P.; McRitchie, Susan L.; Choi, Y. Sammy; Sumner, Susan C.J.

    2017-01-01

    An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers. PMID:28169076

  15. Adverse events following immunisation with a meningococcal serogroup B vaccine: report from post-marketing surveillance, Germany, 2013 to 2016.

    Science.gov (United States)

    Mentzer, Dirk; Oberle, Doris; Keller-Stanislawski, Brigitte

    2018-04-01

    Background and aimIn January 2013, a novel vaccine against Neisseria meningitidis serogroup B, the multicomponent meningococcal serogroup B vaccine (4CMenB), was approved by the European Medicines Agency. We aimed to evaluate the safety profile of this vaccine. Methods: All adverse events following immunisation (AEFI) reported from Germany since the vaccine's launch in Germany in November 2013 through December 2016 were reviewed and analysed. Results: Through December 2016, a total of 664 individual case safety reports (ICSR) notifying 1,960 AEFI were received. A majority of vaccinees for whom AEFI were reported were children 2 to 11 years of age (n = 280; 42.2%) followed by infants and toddlers aged 28 days to 23 months (n = 170; 25.6%). General disorders and administration site conditions was the System Organ Class (SOC) with the majority of AEFI (n = 977; 49.8%), followed by nervous system disorders (n = 249; 12.7%), and skin and subcutaneous tissue disorders (n = 191; 9.7%). Screening of patient records for immune-mediated and neurological diseases did not raise any safety signal in terms of an increased proportional reporting ratio (PRR). Conclusions: The safety profile described in the Summary of Product Characteristics, in general, is confirmed by data from spontaneous reporting. No safety concerns were identified.

  16. Systematic review of reporting rates of adverse events following immunization: an international comparison of post-marketing surveillance programs with reference to China.

    Science.gov (United States)

    Guo, Biao; Page, Andrew; Wang, Huaqing; Taylor, Richard; McIntyre, Peter

    2013-01-11

    China is the most populous country in the world, with an annual birth cohort of approximately 16 million, requiring an average of 500 million vaccine doses administered annually. In China, over 30 domestic and less than 10 overseas vaccine manufacturers supply over 60 licensed vaccine products, representing a growing vaccine market mainly due to recent additions to the national immunization schedule, but data on post-marketing surveillance for adverse events following immunization (AEFI) are sparse. To compare reporting rates for various categories of AEFI from China with other routine post-marketing surveillance programs internationally. Systematic review of published studies reporting rates of AEFI by vaccine, category of reaction and age from post-marketing surveillance systems in English and Chinese languages. Overall AEFI reporting rates (all vaccines, all ages) in Chinese studies were consistent with those from similar international studies elsewhere, but there was substantial heterogeneity in regional reporting rates in China (range 2.3-37.8/100,000 doses). The highest AEFI reporting rates were for diphtheria-tetanus-pertussis whole-cell (DTwP) and acellular (DTaP) vaccines (range 3.3-181.1/100,000 doses for DTwP; range 3.5-92.6/100,000 doses for DTaP), with higher median rates for DTwP than DTaP, and higher than expected rates for DTaP vaccine. Similar higher rates for DTwP and DTaP containing vaccines, and relatively lower rates for vaccines against hepatitis B virus, poliovirus, and Japanese encephalitis virus were found in China and elsewhere in the world. Overall AEFI reporting rates in China were consistent with similar post-marketing surveillance systems in other countries. Sources of regional heterogeneity in AEFI reporting rates, and their relationships to differing vaccine manufacturers versus differing surveillance practices, require further exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. [Management of adverse drug effects].

    Science.gov (United States)

    Schlienger, R G

    2000-09-01

    Adverse drug reactions (ADRs) are still considered one of the main problems of drug therapy. ADRs are associated with considerable morbidity, mortality, decreased compliance and therapeutic success as well as high direct and indirect medical costs. Several considerations have to come into play when managing a potential ADR. It is critical to establish an accurate clinical diagnosis of the adverse event. Combining information about drug exposure together with considering other possible causes of the reaction is crucial to establish a causal relationship between the reaction and the suspected drug. Identification of the underlying pathogenesis of an ADR together with the severity of the reaction will have profound implications on continuation of drug therapy after an ADR. Since spontaneous reports about ADRs are a key stone of a functioning post-marketing surveillance system and therefore play a key role in improving drug safety, health care professionals are highly encouraged to report ADRs to a local or national organization. However, because the majority of ADRs is dose-dependent and therefore preventable, individualization of pharmacotherapy may have a major impact on reducing such events.

  18. Analysis of spontaneous inquiries about suspected adverse drug reactions posted by the general public on the electronic Japanese bulletin board “Yahoo! Japan Chiebukuro”

    Directory of Open Access Journals (Sweden)

    Dobashi A

    2016-04-01

    Full Text Available Akira Dobashi,1 Kaori Kurata,1 Mitsuhiro Okazaki,2,3 Mari Nishizawa4 1Education and Research Institute of Information Science, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 2Faculty of Health Sciences, Health Innovation and Technology Center, Hokkaido University, Hokkaido, 3Cross Care Field Co., Ltd., 4Yakuju Corporation, Tokyo, Japan Purpose: Spontaneous inquiries about the development of adverse drug reactions (ADRs to medicines can be extracted based on the questions posted by the general public on the electronic Japanese bulletin board “Yahoo! Japan Chiebukuro”. Our aim was to clarify the characteristics related to people’s descriptions of suspected ADRs and determine the reasons for submitting a spontaneous inquiry. Methods: Fifty brand names of medicines used for inquiry extraction were chosen by selecting 35 pharmaceutical products, based on the generic names that had the highest sales in Japan. Questions containing both the brand name of one of these medicines and the term “Fukusayō” (ADR in Japanese that were posted from July 2004 to June 2009 were extracted from the site. Results: Among 1,419 questions extracted, 614 questions had at least one identifiable brand name of a suspected medicine, an ADR description, and the extent to which the ADR appeared to be caused by the suspected medicine(s. Among these 614 questions, 589 described in detail the symptoms/signs that the inquirers themselves or their families had experienced as ADRs. The highest number of questions was found for Paxil (525. Posts asking whether the symptoms being experienced were due to an ADR accounted for the highest number of questions. In most cases, the inquirer suspected that a single medicine led to an ADR and was seeking advice from others taking the same medicine. Conclusion: Our examination of spontaneous inquiries showed that people have sufficient knowledge to adequately report potential ADRs in terms of their symptoms

  19. Rethinking childhood adversity in chronic fatigue syndrome.

    Science.gov (United States)

    Clark, James E; Davidson, Sean L; Maclachlan, Laura; Newton, Julia L; Watson, Stuart

    2018-01-01

    Background: Previous studies have consistently shown increased rates of childhood adversity in chronic fatigue syndrome (CFS). However, such aetiopathogenic studies of CFS are potentially confounded by co-morbidity and misdiagnosis particularly with depression. Purpose: We examined the relationship between rates of childhood adversity using two complimentary approaches (1) a sample of CFS patients who had no lifetime history of depression and (2) a modelling approach. Methods: Childhood trauma questionnaire (CTQ) administered to a sample of 52 participants with chronic fatigue syndrome and 19 controls who did not meet criteria for a psychiatric disorder (confirmed using the Structured Clinical Interview for DSM-IV). Subsequently, Mediation Analysis (Baye's Rules) was used to establish the risk childhood adversity poses for CFS with and without depression. Results: In a cohort of CFS patients with depression comprehensively excluded, CTQ scores were markedly lower than in all previous studies and, in contrast to these previous studies, not increased compared with healthy controls. Post-hoc analysis showed that CTQ scores correlated with the number of depressive symptoms during the lifetime worst period of low mood. The probability of developing CFS given a history of childhood trauma is 4%, a two-fold increased risk compared to the general population. However, much of this risk is mediated by the concomitant development of major depression. Conclusions: The data suggests that previous studies showing a relationship between childhood adversity and CFS may be attributable to the confounding effects of co-morbid or misdiagnosed depressive disorder. Abbreviations: CFS: Chronic fatigue syndrome; CTQ: Childhood trauma questionnaire; MDD: Major depressive disorder; CA: Childhood adversity; P : Probability.

  20. The European Medicines Agency's approval of new medicines for type 2 diabetes.

    Science.gov (United States)

    Blind, Eberhard; Janssen, Heidi; Dunder, Kristina; de Graeff, Pieter A

    2018-05-08

    Since 2005, more than 40 new medicines for the treatment of type 2 diabetes have been introduced on the market. These consist of 15 new active substances establishing three new classes of non-insulin products, and several new or modified insulin products and combinations. The approval of these products in Europe is regulated via the centralized procedure at the European Medicines Agency. Demonstration of benefit with regard to improved glucose control remains the principal outcome required from confirmatory studies to demonstrate efficacy. For the majority of these new medicines approved since 2005, cardiovascular outcome trials have now been completed, and have invariably supported the cardiovascular safety of these products. In some of these trials additional important benefits have been observed, for instance, a reduction in major adverse cardiovascular events and improvement of renal outcome. The existing regulatory framework and the continuous adaption of regulatory requirements to emerging developments will continue to guide the approval of new products in the future. © 2018 John Wiley & Sons Ltd.

  1. Intravenous iron vs blood for acute post-partum anaemia (IIBAPPA): a prospective randomised trial.

    Science.gov (United States)

    Chua, Seng; Gupta, Sarika; Curnow, Jennifer; Gidaszewski, Beata; Khajehei, Marjan; Diplock, Hayley

    2017-12-19

    Acute post-partum anaemia can be associated with significant morbidity including a predisposition for postnatal depression. Lack of clear practice guidelines means a number of women are treated with multiple blood transfusions. Intravenous iron has the potential to limit the need for multiple blood transfusions but its role in the post-partum setting is unclear. IIBAPPA is a multi-centre randomised non-inferiority trial. Women with a primary post-partum haemorrhage (PPH) >1000 mL and resultant haemoglobin (Hb) 5.5-8.0 g/dL after resuscitation with ongoing symptomatic anaemia who are otherwise stable (no active bleeding) are eligible to participate. Patients with sepsis or conditions necessitating rapid Hb restoration are excluded. Eligible participants are randomised to receive a blood transfusion or a single dose of intravenous iron polymaltose calculated using the Ganzoni formula. Primary outcome measures include Hb, Ferritin and C-Reactive Protein levels on Day 7. Secondary outcomes evaluate (i) Hb, Ferritin and CRP levels on Day 14, 28, (ii) anaemia symptoms on Day 0, 7, 14 and 28 using structured health related quality of life questionnaires, (iii) treatment safety by assessing adverse reactions and infection endpoints and (iv) the quantitative impact of anaemia on breast feeding quality using a hospital designed questionnaire. If equivalence in Hb and ferritin levels, symptom scores and safety endpoints is demonstrated, intravenous iron may become the preferred treatment for women with acute post-partum anaemia to minimise transfusion reactions and costs. Australian and New Zealand Clinical Trials Registry: ACTRN12615001370594 on 16th December, 2015 (prospective approval).

  2. Augmentation therapy with alpha1-antitrypsin: patterns of use and adverse events.

    Science.gov (United States)

    Stoller, James K; Fallat, Robert; Schluchter, Mark D; O'Brien, Ralph G; Connor, Jason T; Gross, Nicholas; O'Neil, Kevin; Sandhaus, Robert; Crystal, Ronald G

    2003-05-01

    To describe patterns of prescribing augmentation therapy, and types and rates of adverse events in the National Heart, Lung, and Blood Institute Registry for Individuals with Severe Deficiency of Alpha(1)-Antitrypsin. Observational cohort study with follow-up visits every 6 to 12 months for up to 7 years. The rate and dosing frequency with which Registry participants were prescribed to receive augmentation therapy by their managing physicians, and the type and frequency of adverse events, classified in two ways: severity of self-reported symptoms, and actions taken as a consequence of the symptom. Over the course of Registry follow-up, 66% (n = 747) of the participants received augmentation therapy at some time. In keeping with recommendations made in the 1989 American Thoracic Society (ATS) statement, 75% of participants with airflow obstruction at first visit (defined as FEV(1) or = 80% predicted (14%) also received augmentation therapy. Among those with COPD for whom augmentation therapy was not prescribed, financial constraints were the reported cause in 30%. Observed patterns also varied from approved practice, in that dosing frequencies other than the US Food and Drug Administration-approved, once-weekly regimen were frequently prescribed. The overall rate of reported adverse events was 0.02 per patient-month, with 83% of participants reporting no events. This overall rate was composed of 16% considered mild events, 76% moderate events, and 9% severe events. We conclude that augmentation therapy was generally well tolerated and, consistent with ATS guidelines, physicians generally did not prescribe augmentation therapy for subjects with FEV(1) > or = 80% predicted. However, the large percentage of subjects with FEV(1) <80% predicted not receiving augmentation therapy and the frequent use of 2- to 3-week or monthly dosing reflects variation of practice from suggested treatment guidelines.

  3. iADRs: towards online adverse drug reaction analysis.

    Science.gov (United States)

    Lin, Wen-Yang; Li, He-Yi; Du, Jhih-Wei; Feng, Wen-Yu; Lo, Chiao-Feng; Soo, Von-Wun

    2012-12-01

    Adverse Drug Reaction (ADR) is one of the most important issues in the assessment of drug safety. In fact, many adverse drug reactions are not discovered during limited pre-marketing clinical trials; instead, they are only observed after long term post-marketing surveillance of drug usage. In light of this, the detection of adverse drug reactions, as early as possible, is an important topic of research for the pharmaceutical industry. Recently, large numbers of adverse events and the development of data mining technology have motivated the development of statistical and data mining methods for the detection of ADRs. These stand-alone methods, with no integration into knowledge discovery systems, are tedious and inconvenient for users and the processes for exploration are time-consuming. This paper proposes an interactive system platform for the detection of ADRs. By integrating an ADR data warehouse and innovative data mining techniques, the proposed system not only supports OLAP style multidimensional analysis of ADRs, but also allows the interactive discovery of associations between drugs and symptoms, called a drug-ADR association rule, which can be further developed using other factors of interest to the user, such as demographic information. The experiments indicate that interesting and valuable drug-ADR association rules can be efficiently mined.

  4. [Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].

    Science.gov (United States)

    Uesawa, Yoshihiro

    2018-01-01

     Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

  5. Dermal Coverage of Traumatic War Wounds

    Science.gov (United States)

    2015-11-01

    visit by the  Food  and Drug Administration  (FDA), Office for  Human  Research Protections, or other government agency concerning this research;  the... hematology  Other Treatment-related adverse events requiring surgical intervention prior to 12 weeks post-treatment and serious adverse event (SAE...966- 72. 16 APPENDICES:  FDA IDE Final Approval  HRPO Amendment Approval 2015-01-21 15:38 caER 71-5221 3015951304 » 4128642673 P 1/4 FOOD AND DRUG

  6. Post-term surveillance and birth outcomes in South Asian-born compared with Australian-born women.

    Science.gov (United States)

    Yim, C; Wong, L; Cabalag, C; Wallace, E M; Davies-Tuck, M

    2017-02-01

    To determine if apparently healthy post-term South Asian-born (SA) women were more likely to have abnormal post-term fetal surveillance than Australian- and New Zealand-born (AUS/NZ) women, whether those abnormalities were associated with increased rates of obstetric intervention and adverse perinatal outcomes, and whether SA women and their babies were at higher risk of adverse outcomes in the post-term period irrespective of their post-term surveillance outcomes. Post-term surveillance and perinatal outcomes of 145 SA and 272 AUS/NZ nulliparous women with a singleton post-term pregnancy were compared in a retrospective multicentre cohort analysis. Post-term SA women were not significantly more likely to have a low amniotic fluid index (AFI) than AUS/NZ women. However, they were nearly four times more likely (odds ratio 3.75; 95% CI 1.49-9.44) to have an abnormal CTG (P=0.005). Irrespective of maternal region of birth having an abnormal cardiotocography (CTG) or AFI was not associated with adverse intrapartum or perinatal outcomes. However, post-term SA women were significantly more likely than AUS/NZ women to have intrapartum fetal compromise (P=0.03) and an intrapartum cesarean section (P=0.002). Babies of SA women were more also significantly likely to be admitted to the Special Care Nursery or Neonatal Intensive Care Unit (P=0.02). Post-term SA women experience higher rates of fetal compromise (antenatal and intrapartum) and obstetric intervention than AUS/NZ women. Irrespective of maternal region of birth an abnormal CTG or AFI was not predictive of adverse outcomes.

  7. Adverse Renal Effects of Novel Molecular Oncologic Targeted Therapies: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Kenar D. Jhaveri

    2017-01-01

    Full Text Available Novel targeted anti-cancer therapies have resulted in improvement in patient survival compared to standard chemotherapy. Renal toxicities of targeted agents are increasingly being recognized. The incidence, severity, and pattern of renal toxicities may vary according to the respective target of the drug. Here we review the adverse renal effects associated with a selection of currently approved targeted cancer therapies, directed to EGFR, HER2, BRAF, MEK, ALK, PD1/PDL1, CTLA-4, and novel agents targeted to VEGF/R and TKIs. In summary, electrolyte disorders, renal impairment and hypertension are the most commonly reported events. Of the novel targeted agents, ipilumumab and cetuximab have the most nephrotoxic events reported. The early diagnosis and prompt recognition of these renal adverse events are essential for the general nephrologist taking care of these patients.

  8. Growth and development in internationally adopted children: extent and timing of recovery after early adversity.

    Science.gov (United States)

    Palacios, Jesús; Román, Maite; Camacho, Carlos

    2011-03-01

    Following initial adversity, internationally adopted children arrive with significant growth and developmental delays. Post-placement recovery has been widely documented, but little has been known about its extent and timing several years after placement and in children with diverse pre-adoptive experiences. A total of 289 children adopted from six countries into Spanish families were studied. Growth and psychological development were considered on arrival and after an average of over 3 years. Growth and developmental initial delays affected a substantial percentage of the children. Post-adoption recovery seemed quicker and more complete in weight and height than in head circumference and psychological development. Initial and later values were correlated, but growth-development relation on arrival subsequently lost significance. Most of the catch-up happened in the first three post-adoption years. Adoption offers an impressive opportunity for recovery after previous adversity, although continuity between past and present persists. The improvement is more marked in some areas than in others and more substantial in the first post-adoption years. © 2010 Blackwell Publishing Ltd.

  9. Relative lack of depressive cognitions in post-myocardial infarction depression

    DEFF Research Database (Denmark)

    Martens, Elisabeth J; Denollet, Johan; Pedersen, Susanne S.

    2006-01-01

    Depression has been associated with adverse clinical events in myocardial infarction (MI) patients, but many questions about the nature of post-MI depression remain unanswered. We examined whether depressive cognitions characteristic of depression in psychiatric patients are also present in post-...

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

    Science.gov (United States)

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

    2014-08-01

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

  11. Seven-year cost-effectiveness of ProDisc-C total disc replacement: results from investigational device exemption and post-approval studies.

    Science.gov (United States)

    Radcliff, Kris; Lerner, Jason; Yang, Chao; Bernard, Thierry; Zigler, Jack E

    2016-05-01

    OBJECTIVE The purpose of this study was to evaluate the 7-year cost-effectiveness of cervical total disc replacement (CTDR) versus anterior cervical discectomy and fusion (ACDF) for the treatment of patients with single-level symptomatic degenerative disc disease. A change in the spending trajectory for spine care is to be achieved, in part, through the selection of interventions that have been proven effective yet cost less than other options. This analysis complements and builds upon findings from other cost-effectiveness evaluations of CTDR through the use of long-term, patient-level data from a randomized study. METHODS This was a 7-year health economic evaluation comparing CTDR versus ACDF from the US commercial payer perspective. Prospectively collected health care resource utilization and treatment effects (quality-adjusted life years [QALYs]) were obtained from individual patient-level adverse event reports and SF-36 data, respectively, from the randomized, multicenter ProDisc-C total disc replacement investigational device exemption (IDE) study and post-approval study. Statistical distributions for unit costs were derived from a commercial claims database and applied using Monte Carlo simulation. Patient-level costs and effects were modeled via multivariate probabilistic analysis. Confidence intervals for 7-year costs, effects, and net monetary benefit (NMB) were obtained using the nonparametric percentile method from results of 10,000 bootstrap simulations. The robustness of results was assessed through scenario analysis and within a parametric regression model controlling for baseline variables. RESULTS Seven-year follow-up data were available for more than 70% of the 209 randomized patients. In the base-case analysis, CTDR resulted in mean per-patient cost savings of $12,789 (95% CI $5362-$20,856) and per-patient QALY gains of 0.16 (95% CI -0.073 to 0.39) compared with ACDF over 7 years. CTDR was more effective and less costly in 90.8% of probabilistic

  12. 7 CFR 4274.332 - Post award requirements.

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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

  14. Hospitalization due to Adverse Drug Reactions and Drug Interactions before and after HAART

    Directory of Open Access Journals (Sweden)

    Michelle M Foisy

    2000-01-01

    Full Text Available OBJECTIVE: To characterize and compare the rates of adverse drug reactions (ADRs and interactions on admission in two, one-year periods: pre-highly active antiretroviral therapy (HAART (phase 1 and post-HAART (phase 2.

  15. High rate of adverse events following circumcision of young male ...

    African Journals Online (AJOL)

    (94) refusing circumcision by the TK technique; 34 men were randomised to the FG group and 35 to the TK group, and 32 and 24 patients were circumcised by the FG and TK methods respectively, of whom 29 and 19 respectively attended the post-circumcision visit. All 12 adverse event sheets corresponded to the TK group ...

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

    Science.gov (United States)

    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

  17. Evaluating imbalances of adverse events during biosimilar development

    Science.gov (United States)

    Vana, Alicia M.; Freyman, Amy W.; Reich, Steven D.; Yin, Donghua; Li, Ruifeng; Anderson, Scott; Jacobs, Ira A.; Zacharchuk, Charles M.; Ewesuedo, Reginald

    2016-01-01

    ABSTRACT Biosimilars are designed to be highly similar to approved or licensed (reference) biologics and are evaluated based on the totality of evidence from extensive analytical, nonclinical and clinical studies. As part of the stepwise approach recommended by regulatory agencies, the first step in the clinical evaluation of biosimilarity is to conduct a pharmacokinetics similarity study in which the potential biosimilar is compared with the reference product. In the context of biosimilar development, a pharmacokinetics similarity study is not necessarily designed for a comparative assessment of safety. Development of PF-05280014, a potential biosimilar to trastuzumab, illustrates how a numerical imbalance in an adverse event in a small pharmacokinetics study can raise questions on safety that may require additional clinical trials. PMID:27050730

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

    Science.gov (United States)

    Tamura, Kazuo; Hashimoto, Kazue; Nishikawa, Kiyohiro

    2018-05-01

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

  19. Late post-operative hypoxaemia and organ dysfunction

    DEFF Research Database (Denmark)

    Kehlet, H; Rosenberg, J

    1995-01-01

    an adverse effect of tissue hypoxia on wound healing and on resistance to bacterial wound infections. Finally, mental confusion and surgical delirium may be related to inadequate arterial oxygenation during the late post-operative period. Late post-operative constant and episodic hypoxaemia may therefore......Constant and episodic hypoxaemia are common after major operations in the late post-operative period in the surgical ward. Recent studies have shown that hypoxaemia may be related to the development of myocardial ischaemia and cardiac arrhythmias. Experimental and clinical studies have demonstrated...

  20. A dataset of 200 structured product labels annotated for adverse drug reactions.

    Science.gov (United States)

    Demner-Fushman, Dina; Shooshan, Sonya E; Rodriguez, Laritza; Aronson, Alan R; Lang, Francois; Rogers, Willie; Roberts, Kirk; Tonning, Joseph

    2018-01-30

    Adverse drug reactions (ADRs), unintended and sometimes dangerous effects that a drug may have, are one of the leading causes of morbidity and mortality during medical care. To date, there is no structured machine-readable authoritative source of known ADRs. The United States Food and Drug Administration (FDA) partnered with the National Library of Medicine to create a pilot dataset containing standardised information about known adverse reactions for 200 FDA-approved drugs. The Structured Product Labels (SPLs), the documents FDA uses to exchange information about drugs and other products, were manually annotated for adverse reactions at the mention level to facilitate development and evaluation of text mining tools for extraction of ADRs from all SPLs. The ADRs were then normalised to the Unified Medical Language System (UMLS) and to the Medical Dictionary for Regulatory Activities (MedDRA). We present the curation process and the structure of the publicly available database SPL-ADR-200db containing 5,098 distinct ADRs. The database is available at https://bionlp.nlm.nih.gov/tac2017adversereactions/; the code for preparing and validating the data is available at https://github.com/lhncbc/fda-ars.

  1. Suspected adverse reactions to contrast media in Campania Region (Italy): results from 14 years of post-marketing surveillance.

    Science.gov (United States)

    Sessa, Maurizio; Rossi, Claudia; Mascolo, Annamaria; Grassi, Enrico; Fiorentino, Sonia; Scavone, Cristina; Reginelli, Alfonso; Rotondo, Antonio; Sportiello, Liberata

    2015-01-01

    During the last years in Italy, contrast media (CM) use increased. An increase of monitoring activities on CM-induced adverse drug reaction (ADR) is necessary, also in our regional territory. The main aim of this study was to give a preliminary evaluation of all Spontaneous Reports of ADRs (SRA) attributed to CM sent to Campania Pharmacovigilance Regional Center (CRFVC) from 01 January 2001 to 31 October 2014. For each SRA we evaluated: frequency and source, ADRs onset (time to event, seriousness and outcome), socio-demographic characteristics and risk factors of cases, the most reported CM (checking for pharmacodynamic and pharmacokinetic interactions). A total of 111 SRA were sent to CRFVC; specialist in radiology was the main source of reports. Ninety-seven SRA (87.3%) were referable to hypersensitivity reactions. Thirty-four SRA (30.6%) reported serious ADRs. The most reported CM were iopamidol, gadobenic acid and gadoteric acid. We identified two SRA induced by pharmacokinetic and/or pharmacodynamic interactions. During 14 years of post-marketing surveillance, only few SRA concerning CM-induced ADRs were sent to CRFVC probably due to underreporting. We aim to improve monitoring activity on CM-induced ADRs especially in hospitals. Most reported ADR and CM were in line with current body of literature.

  2. 30 CFR 285.803 - How must I conduct my approved activities to protect essential fish habitats identified and...

    Science.gov (United States)

    2010-07-01

    ... protect essential fish habitats identified and described under the Magnuson-Stevens Fishery Conservation... Act? (a) If, during the conduct of your approved activities, MMS finds that essential fish habitat or... adverse affects on Essential Fish Habitat will be incorporated as terms and conditions in the lease and...

  3. Vaccine Adverse Events

    Science.gov (United States)

    ... for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More sharing ... in the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA ( ...

  4. 77 FR 26034 - Information Collection Request Sent to the Office of Management and Budget (OMB) for Approval...

    Science.gov (United States)

    2012-05-02

    ... the ESA will certainly meet both the monetary bar and the adverse impacts bar. Response: The burden... cannot use economic impacts as part of our listing determination. Commenter 1 stated that the PECE policy... Collection Request Sent to the Office of Management and Budget (OMB) for Approval; Policy for Evaluation of...

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

    Science.gov (United States)

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

    2012-11-01

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

  6. Vigilância de eventos adversos pós-vacinação e segurança de programas de imunização Vigilancia de eventos adversos post vacunación y seguridad de programas de inmunización Surveillance of adverse effects following vaccination and safety of immunization programs

    Directory of Open Access Journals (Sweden)

    Eliseu Alves Waldman

    2011-02-01

    Full Text Available O objetivo da revisão foi analisar aspectos conceituais e operacionais de sistemas de vigilância de eventos adversos pós-vacina. Foram incluídos artigos disponíveis em formato eletrônico, publicados entre 1985 e 2009, selecionados nas bases Medline/PubMed, com as palavras-chave: "adverse events following vaccine", "adverse events following vaccine surveillance", "post-marketing surveillance" e "safety vaccine" e "Phase IV clinical trials", e excluídos aqueles com foco em tipos específicos desses eventos. Foram apontados os principais aspectos que justificam a importância dos eventos adversos pós-vacina em saúde pública, os instrumentos que garantem a segurança das vacinas e as finalidades, atributos, tipos, interpretações de dados, limitações e novos desafios da vigilância de eventos adversos pós-vacina, bem como estratégias para aumentar sua sensibilidade. A revisão é concluída com desafios para os próximos anos, visando à segurança e confiabilidade dos programas de vacinação.El objetivo de la revisión fue analizar aspectos conceptuales y operacionales de sistemas de vigilancia de eventos adversos post vacuna. Fueron incluidos artículos disponibles en formato electrónico, publicados entre 1985 y 2009, seleccionados en las bases PubMed/Medline, con las palabras clave: "vigilancia de eventos adversos post vacuna", "vigilancia post comercialización", "seguridad de vacunas" y "estudios de Fase IV", y excluidos aquellos con foco en tipos específicos de tales eventos. Se señalaron los principales aspectos que justifican la importancia de los eventos adversos post vacuna en salud pública, los instrumentos que garantizan la seguridad de las vacunas y las finalidades, atributos, tipos, interpretaciones de datos, limitaciones y nuevos desafíos de la vigilancia de eventos adversos post vacuna, así como estrategias para aumentar su sensibilidad. Se concluye con desafíos para los próximos años, buscando seguridad y

  7. The role of donor characteristics and post-granulocyte colony-stimulating factor white blood cell counts in predicting the adverse events and yields of stem cell mobilization.

    Science.gov (United States)

    Chen, Shu-Huey; Yang, Shang-Hsien; Chu, Sung-Chao; Su, Yu-Chieh; Chang, Chu-Yu; Chiu, Ya-Wen; Kao, Ruey-Ho; Li, Dian-Kun; Yang, Kuo-Liang; Wang, Tso-Fu

    2011-05-01

    Granulocyte colony-stimulating factor (G-CSF) is now widely used for stem cell mobilization. We evaluated the role of post-G-CSF white blood cell (WBC) counts and donor factors in predicting adverse events and yields associated with mobilization. WBC counts were determined at baseline, after the third and the fifth dose of G-CSF in 476 healthy donors. Donors with WBC ≥ 50 × 10(3)/μL post the third dose of G-CSF experienced more fatigue, myalgia/arthralgia, and chills, but final post-G-CSF CD34(+) cell counts were similar. Although the final CD34(+) cell count was higher in donors with WBC ≥ 50 × 10(3)/μL post the fifth G-CSF, the incidence of side effects was similar. Females more frequently experienced headache, nausea/anorexia, vomiting, fever, and lower final CD34(+) cell count than did males. Donors with body mass index (BMI) ≥ 25 showed higher incidences of sweat and insomnia as well as higher final CD34(+) cell counts. Donor receiving G-CSF ≥ 10 μg/kg tended to experience bone pain, headache and chills more frequently. Multivariate analysis indicated that female gender is an independent factor predictive of the occurrence of most side effects, except for ECOG > 1 and chills. Higher BMI was also an independent predictor for fatigue, myalgia/arthralgia, and sweat. Higher G-CSF dose was associated with bone pain, while the WBC count post the third G-CSF was associated with fatigue only. In addition, one donor in the study period did not complete the mobilization due to suspected anaphylactoid reaction. Observation for 1 h after the first injection of G-CSF is required to prevent complications from unpredictable side effects.

  8. 40 CFR 265.118 - Post-closure plan; amendment of plan.

    Science.gov (United States)

    2010-07-01

    ... mail. In addition, for facilities without approved post-closure plans, it must also be provided during... requirements. At the end of the specified period of suspension, the Regional Ad-min-is-tra-tor would then...

  9. 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.

    Science.gov (United States)

    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.

  10. Post-traumatic stress disorder in the perinatal period: A concept analysis.

    Science.gov (United States)

    Vignato, Julie; Georges, Jane M; Bush, Ruth A; Connelly, Cynthia D

    2017-12-01

    To report an analysis of the concept of perinatal post-traumatic stress disorder. Prevalence of perinatal post-traumatic stress disorder is rising in the USA, with 9% of the U.S. perinatal population diagnosed with the disorder and an additional 18% being at risk for the condition. Left untreated, adverse maternal-child outcomes result in increased morbidity, mortality and healthcare costs. Concept analysis via Walker and Avant's approach. The databases Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline, Academic Search Premier and PsychINFO were searched for articles, written in English, published between 2006-2015, containing the terms perinatal and post-traumatic stress disorder. Perinatal post-traumatic stress disorder owns unique attributes, antecedents and outcomes when compared to post-traumatic stress disorder in other contexts, and may be defined as a disorder arising after a traumatic experience, diagnosed any time from conception to 6 months postpartum, lasting longer than 1 month, leading to specific negative maternal symptoms and poor maternal-infant outcomes. Attributes include a diagnostic time frame (conception to 6 months postpartum), harmful prior or current trauma and specific diagnostic symptomatology defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. Antecedents were identified as trauma (perinatal complications and abuse), postpartum depression and previous psychiatric history. Consequences comprised adverse maternal-infant outcomes. Further research on perinatal post-traumatic stress disorder antecedents, attributes and outcomes in ethnically diverse populations may provide clinicians a more comprehensive framework for identifying and treating perinatal post-traumatic stress disorder. Nurses are encouraged to increase their awareness of perinatal post-traumatic stress disorder for early assessment and intervention, and prevention of adverse maternal-infant outcomes. © 2017 John Wiley

  11. Frequency of adverse events in plateletpheresis donors in regional transfusion centre in North India.

    Science.gov (United States)

    Patidar, Gopal Kumar; Sharma, Ratti Ram; Marwaha, Neelam

    2013-10-01

    Although automated cell separators have undergone a lot of technical refinements, attention has been focused on the quality of platelet concentrates than on donor safety. We planned this prospective study to look into donor safety aspect by studying adverse events in normal healthy plateletpheresis donors. The study included 500 healthy, first-time (n=301) and repeat (n=199) plateletpheresis donors after informed consent. The plateletpheresis procedures were performed on Trima Accel (5.1 version, GAMBRO BCT) and Amicus (3.2 version FENWAL) cell separators. The adverse events during procedure were recorded and classified according to their nature. The pre and post procedure hematological and biochemical profiles of these donors were also assessed with the help of automated cell counter and analyser respectively. A total of 18% (n=90) adverse events were recorded in 500 plateletpheresis donors, of which 9% of were hypocalcaemia in nature followed by hematoma (7.4%), vasovagal reaction (0.8%) and kit related adverse events in (0.8%). There was significant post procedure drop in Hb, Hct, platelet count of the donors (padverse events in Trima Accel (5.1 version, GAMBRO BCT) and Amicus (3.2 version FENWAL) cell separators. Donor reactions can adversely affect the voluntary donor recruitment strategies to increase the public awareness regarding constant need for blood and blood products. Commonly observed adverse events in plateletpheresis donors were hypocalcemia, hematoma formation and vasovagal reactions which can be prevented by pre-donation education of the donors and change of machine configuration. Nevertheless, more prospective studies on this aspect are required in order to establish guidelines for donor safety in apheresis and also to help in assessing donor suitability, especially given the present trend of double product apheresis collections. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Vitex agnus castus: a systematic review of adverse events.

    Science.gov (United States)

    Daniele, Claudia; Thompson Coon, Joanna; Pittler, Max H; Ernst, Edzard

    2005-01-01

    Vitex agnus castus L. (VAC) [Verbenaceae] is a deciduous shrub that is native to Mediterranean Europe and Central Asia. Traditionally, VAC fruit extract has been used in the treatment of many female conditions, including menstrual disorders (amenorrhoea, dysmenorrhoea), premenstrual syndrome (PMS), corpus luteum insufficiency, hyperprolactinaemia, infertility, acne, menopause and disrupted lactation. The German Commission E has approved the use of VAC for irregularities of the menstrual cycle, premenstrual disturbances and mastodynia. Clinical reviews are available for the efficacy of VAC in PMS, cycle disorders, hyperprolactinaemia and mastalgia, but so far no systematic review has been published on adverse events or drug interactions associated with VAC. Therefore, this review was conducted to evaluate all the available human safety data of VAC monopreparations. Literature searches were conducted in six electronic databases, in references lists of all identified papers and in departmental files. Data from spontaneous reporting schemes of the WHO and national drug safety bodies were also included. Twelve manufacturers of VAC-containing preparations and five herbalist organisations were contacted for additional information. No language restrictions were imposed. Combination preparations including VAC or homeopathic preparations of VAC were excluded. Data extraction of key data from all articles reporting adverse events or interactions was performed independently by at least two reviewers, regardless of study design. Data from clinical trials, postmarketing surveillance studies, surveys, spontaneous reporting schemes, manufacturers and herbalist organisations indicate that the adverse events following VAC treatment are mild and reversible. The most frequent adverse events are nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, pruritus and erythematous rash. No drug interactions were reported. Use of VAC should be avoided during pregnancy or

  13. Objective evaluation of acute adverse events and image quality of gadolinium-based contrast agents (gadobutrol and gadobenate dimeglumine) by blinded evaluation. Pilot study.

    Science.gov (United States)

    Semelka, Richard C; Hernandes, Mateus de A; Stallings, Clifton G; Castillo, Mauricio

    2013-01-01

    The purpose was to objectively evaluate a recently FDA-approved gadolinium-based contrast agent (GBCA) in comparison to our standard GBCA for acute adverse events and image quality by blinded evaluation. Evaluation was made of a recently FDA-approved GBCA, gadobutrol (Gadavist; Bayer), in comparison to our standard GBCA, gadobenate dimeglumine (MultiHance; Bracco), in an IRB- and HIPAA-compliant study. Both the imaging technologist and patient were not aware of the brand of the GBCA used. A total of 59 magnetic resonance studies were evaluated (59 patients, 31 men, 28 women, age range of 5-85 years, mean age of 52 years). Twenty-nine studies were performed with gadobutrol (22 abdominal and 7 brain studies), and 30 studies were performed with gadobenate dimeglumine (22 abdominal and 8 brain studies). Assessment was made of acute adverse events focusing on objective observations of vomiting, hives, and moderate and severe reactions. Adequacy of enhancement was rated as poor, fair and good by one of two experienced radiologists who were blinded to the type of agent evaluated. No patient experienced acute adverse events with either agent. The target minor adverse events of vomiting or hives, and moderate and severe reactions were not observed in any patient. Adequacy of enhancement was rated as good for both agents in all patients. Objective, blinded evaluation is feasible and readily performable for the evaluation of GBCAs. This proof-of-concept study showed that both GBCAs evaluated exhibited consistent good image quality and no noteworthy adverse events. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arres

    DEFF Research Database (Denmark)

    Bro-Jeppesen, John; Hassager, Christian; Wanscher, Michael

    2013-01-01

    Post-cardiac arrest fever has been associated with adverse outcome before implementation of therapeutic hypothermia (TH), however the prognostic implications of post-hypothermia fever (PHF) in the era of modern post-resuscitation care including TH has not been thoroughly investigated. The aim...

  15. Post-Traumatic Growth in Mothers of Children with Autism: A Phenomenological Study

    Science.gov (United States)

    Zhang, Wei; Yan, Ting Ting; Barriball, K. Louise; While, Alison E.; Liu, Xiao Hong

    2015-01-01

    While the adverse effects of raising a child with autism are well demonstrated, there have been few reports of the post-traumatic growth of mothers of children with autism. The purpose of this research was to explore dimensions of post-traumatic growth in this population in Mainland China and identify the factors facilitating post-traumatic…

  16. A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Fu-Shun Hsu

    2017-01-01

    Full Text Available Few effective treatment options are available for patients with advanced or metastatic urothelial carcinoma (UC after unsuccessful first-line platinum-based chemotherapy. To date, immune checkpoint inhibitors are novel therapeutic agents for UC treatment. From May 2016 to May 2017, five anti-PD-1/PD-L1 monoclonal antibodies received accelerated or regular approval from the US Food and Drug Administration (FDA for the treatment of patients with locally advanced or metastatic UC. The present comprehensive review presents the background information of these five US FDA-approved anticancer agents to provide a basic but concise understanding of these agents for advanced studies. We summarize their immune checkpoint mechanisms, clinical efficacy, recommended usage protocols, adverse events, and the limitations of the PD-L1 biomarker assays.

  17. The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

    Science.gov (United States)

    Kennedy, Ann

    human trials necessary to demonstrate "efficacy" for a beneficial effect on the long term adverse health effects of radiation, such as the development of cancer, cataracts, etc., is expected to take particularly long periods of time. To avoid the long time delay in the development of new drugs as countermeasures for radiation induced adverse health effects, the NSBRI Center for Acute Radiation Research (CARR) is currently focused on the use of drugs that have already been approved for human use by the FDA. Currently there are no approved countermeasures for external radiation exposure by the US Army or by NASA. The appropriate medications for symptoms of the Acute Radiation Syndrome (ARS) due to exposure to solar particle event (SPE) radiation are unknown, but there are medications appropriate for ARS symptoms caused by exposure to conventional ra-diation. The Armed Forces Radiobiology Research Institute (AFRRI) has medical guidelines for ARS medications (http://www.afrri.usuhs.mil/outreach/guidance.htm#policies), as does the US Dept. of Health and Human Services (the REMM (Radiation Event Medical Manage-ment) site (http://www.remm.nlm.gov). Supportive care when ARS symptoms develop include the administration of antimicrobial agents (which can include systemic antibiotics [especially those directed at gram-negative bacteria]), antiemetic agents, antidiarrheal agents, fluids, elec-trolytes, analgesic agents and topical burn creams (Waselenko, J.K. et al. Ann. Intern. Med. 140: 1037, 2004). For nausea and vomiting, serotonin receptor antagonists (5HT3 receptor antagonists) are very effective prophylaxis. There are two drugs that have been approved by the FDA (Zofran and Kytril) for radiation induced nausea and vomiting. Kytril (granisetron) is preferred by the US Army and is currently maintained in the US National Stockpile. Both of these drugs are known to stop retching and vomiting when given either before or after irradi-ation, even when vomiting and/or retching are

  18. Quality indicators of preventable adverse drug events in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Thomsen, Linda Aagaard

    associated with HbA1c monitoring and treatment was determined using logistic regression. The fourth step in the model was a health economic evaluation of the cost-effectiveness of shifting patients from inadequate to adequate medical treatment. The database used for the AMI indicator study formed...... the database for this study. Five post AMI treatment scenarios were analysed, and incremental cost-effectiveness ratios calculated. Results: The systematic literature review (Article 1) revealed that preventable adverse drug The systematic literature review (Article 1) revealed that preventable adverse drug......, that from a public health care systems' point of view, providing intensive cardioprotective treatment according to already accepted guidelines to type 2 diabetes patients is cost-effective. The HbA1c study demonstrated how diabetes-related hospital admissions are frequent, and how preventable adverse drug...

  19. Individual differences in early adolescents' latent trait cortisol: Interaction of early adversity and 5-HTTLPR.

    Science.gov (United States)

    Chen, Frances R; Stroud, Catherine B; Vrshek-Schallhorn, Suzanne; Doane, Leah D; Granger, Douglas A

    2017-10-01

    The present study aimed to examine the interaction of 5-HTTLPR and early adversity on trait-like levels of cortisol. A community sample of 117 early adolescent girls (M age=12.39years) provided DNA samples for 5-HTTLPR genotyping, and saliva samples for assessing cortisol 3 times a day (waking, 30min post-waking, and bedtime) over a three-day period. Latent trait cortisol (LTC) was modeled using the first 2 samples of each day. Early adversity was assessed with objective contextual stress interviews with adolescents and their mothers. A significant 5-HTTLPR×early adversity interaction indicated that greater early adversity was associated with lower LTC levels, but only among individuals with either L/L or S/L genotype. Findings suggest that serotonergic genetic variation may influence the impact of early adversity on individual differences in HPA-axis regulation. Future research should explore whether this interaction contributes to the development of psychopathology through HPA axis functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. FDA Approval: Alectinib for the Treatment of Metastatic, ALK-Positive Non-Small Cell Lung Cancer Following Crizotinib.

    Science.gov (United States)

    Larkins, Erin; Blumenthal, Gideon M; Chen, Huanyu; He, Kun; Agarwal, Rajiv; Gieser, Gerlie; Stephens, Olen; Zahalka, Eias; Ringgold, Kimberly; Helms, Whitney; Shord, Stacy; Yu, Jingyu; Zhao, Hong; Davis, Gina; McKee, Amy E; Keegan, Patricia; Pazdur, Richard

    2016-11-01

    On December 11, 2015, the FDA granted accelerated approval to alectinib (Alecensa; Genentech) for the treatment of patients with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This approval was based on two single-arm trials including 225 patients treated with alectinib 600 mg orally twice daily. The objective response rates (ORR) by an independent review committee in these studies were 38% [95% confidence interval (CI), 28-49] and 44% (95% CI, 36-53); the median durations of response (DOR) were 7.5 months and 11.2 months. In a pooled analysis of 51 patients with measurable disease in the central nervous system (CNS) at baseline, the CNS ORR was 61% (95% CI, 46-74); the CNS DOR was 9.1 months. The primary safety analysis population included 253 patients. The most common adverse reactions were fatigue (41%), constipation (34%), edema (30%), and myalgia (29%). The most common laboratory abnormalities were anemia (56%), increased aspartate aminotransferase (51%), increased alkaline phosphatase (47%), increased creatine phosphokinase (43%), hyperbilirubinemia (39%), hyperglycemia (36%), increased alanine aminotransferase (34%), and hypocalcemia (32%). Dose reductions due to adverse reactions occurred in 12% of patients, whereas 27% of patients had alectinib dosing interrupted for adverse reactions. Permanent discontinuation of alectinib due to adverse reactions occurred in only 6% of patients. With the clinically meaningful ORR and DOR as well as the safety profile observed in these trials, alectinib was determined to have a favorable benefit-risk profile for the treatment of the indicated population. Clin Cancer Res; 22(21); 5171-6. ©2016 AACR. ©2016 American Association for Cancer Research.

  1. Military service and military vocational training effects on post-service earnings

    OpenAIRE

    Bolin, Phil Warren

    1980-01-01

    Approved for public release; distribution is unlimited. The influence of military service and military vocational training on post-service earnings was analyzed using the National Longitudinal Survey of young men (14-24 years of age in 1966) . When individuals were classified by their propensity to use training neither military service nor military vocational training was a significant determinant of post-service earnings. A disaggregation of the sample IQ revealed that m...

  2. Association of nutritional status-related indices and chemotherapy-induced adverse events in gastric cancer patients.

    Science.gov (United States)

    Seo, Seung Hee; Kim, Sung-Eun; Kang, Yoon-Koo; Ryoo, Baek-Yeol; Ryu, Min-Hee; Jeong, Jae Ho; Kang, Shin Sook; Yang, Mihi; Lee, Jung Eun; Sung, Mi-Kyung

    2016-11-18

    Malnutrition in gastrectomized patients receiving chemotherapy is associated with the susceptibility to chemotherapy-related adverse events. This study evaluated pre-operative nutritional status-related indices associated with adverse events in post-operation gastric cancer patients receiving chemotherapy. Medical records of 234 gastrectomized patients under adjuvant tegafur/gimeracil/oteracil chemotherapy with extended lymph node dissection were analyzed. Nutritional status assessment included Patient-Generated Subjective Global Assessment (PG-SGA), body weight, body mass index, serum albumin concentration, and Nutrition Risk Index (NRI). Chemotherapy-originated adverse events were determined using Common Terminology Criteria for Adverse Events. PG-SGA indicated 59% of the patients were malnourished, and 27.8% of the patients revealed serious malnutrition with PG-SGA score of ≥9. Fifteen % of patients lost ≥10% of the initial body weight, 14.5% of the patients had hypoalbuminemia (cancer patients.

  3. Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

    Science.gov (United States)

    Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

    2016-07-01

    We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

  4. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial.

    Science.gov (United States)

    Kanes, Stephen; Colquhoun, Helen; Gunduz-Bruce, Handan; Raines, Shane; Arnold, Ryan; Schacterle, Amy; Doherty, James; Epperson, C Neill; Deligiannidis, Kristina M; Riesenberg, Robert; Hoffmann, Ethan; Rubinow, David; Jonas, Jeffrey; Paul, Steven; Meltzer-Brody, Samantha

    2017-07-29

    Post-partum depression is a serious mood disorder in women that might be triggered by peripartum fluctuations in reproductive hormones. This phase 2 study investigated brexanolone (USAN; formerly SAGE-547 injection), an intravenous formulation of allopregnanolone, a positive allosteric modulator of γ-aminobutyric acid (GABA A ) receptors, for the treatment of post-partum depression. For this double-blind, randomised, placebo-controlled trial, we enrolled self-referred or physician-referred female inpatients (≤6 months post partum) with severe post-partum depression (Hamilton Rating Scale for Depression [HAM-D] total score ≥26) in four hospitals in the USA. Eligible women were randomly assigned (1:1), via a computer-generated randomisation program, to receive either a single, continuous intravenous dose of brexanolone or placebo for 60 h. Patients and investigators were masked to treatment assignments. The primary efficacy endpoint was the change from baseline in the 17-item HAM-D total score at 60 h, assessed in all randomised patients who started infusion of study drug or placebo and who had a completed baseline HAM-D assessment and at least one post-baseline HAM-D assessment. Patients were followed up until day 30. This trial is registered with ClinicalTrials.gov, number NCT02614547. This trial was done between Dec 15, 2015 (first enrolment), and May 19, 2016 (final visit of the last enrolled patient). 21 women were randomly assigned to the brexanolone (n=10) and placebo (n=11) groups. At 60 h, mean reduction in HAM-D total score from baseline was 21·0 points (SE 2·9) in the brexanolone group compared with 8·8 points (SE 2·8) in the placebo group (difference -12·2, 95% CI -20·77 to -3·67; p=0·0075; effect size 1·2). No deaths, serious adverse events, or discontinuations because of adverse events were reported in either group. Four of ten patients in the brexanolone group had adverse events compared with eight of 11 in the placebo group. The most

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

    Science.gov (United States)

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

    2011-10-01

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

  6. Detection of systemic hypersensitivity to drugs using standard guinea pig assays.

    Science.gov (United States)

    Weaver, James L; Staten, David; Swann, Joslyn; Armstrong, George; Bates, Melissa; Hastings, Kenneth L

    2003-12-01

    The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals.

  7. A post-marketing study of gadodiamide hydrate in patients with cerebral infarction

    International Nuclear Information System (INIS)

    Ono, Yuko; Aoki, Shigeki

    2003-01-01

    We evaluated the efficacy and safety of gadodiamide hydrate (GH: Omuniscan) in patients with cerebral infarction in a multicenter post-marketing study. A total of 122 patients enrolled in this study at 16 institutions in throughout Japan. We administrated GH to patients intravenously at 0.2 mL/kg, an approved usage and dosage for head MRI. Efficacy was evaluated by comparing contrast intensity and diagnostic improvement on T1WI before and after the administration of GH and diagnostic significance was investigated. Moreover, clinical data thus obtained were compared with those of phase III studies of GH and other contrast agents with respect to general evaluation of diagnostic improvement. The effects of contrast enhancement on the detection and extent of lesions as well as image quality were judged in terms of improving general evaluation and diagnosis, which was observed in 93.3% of the patients. No serious adverse event were associated with GH administration. The efficacy of GH in this clinical trial was higher, than historical data, with respect to general evaluation and diagnostic improvement. Contrast enhanced MRI with GH in cerebral infarction was confirmed to be of diagnostic value. (author)

  8. Intravenous analgesics for pain management in post- operative ...

    African Journals Online (AJOL)

    Intravenous analgesics for pain management in post- operative patients: a comparative study of their efficacy and adverse ... patient anxiety, stress, and dissatisfaction. Adequate ... genders who were scheduled to undergo abdominal surgery (hemicolectomy, exploratory ... analysis (n = 48) and separated into three groups.

  9. An analysis of legal warnings after drug approval in Thailand.

    Science.gov (United States)

    Sriphiromya, Pakawadee; Theeraroungchaisri, Anuchai

    2015-02-01

    Drug risk management has many tools for minimizing risk and black-boxed warnings (BBWs) are one of those tools. Some serious adverse drug reactions (ADRs) emerge only after a drug is marketed and used in a larger population. In Thailand, additional legal warnings after drug approval, in the form of black-boxed warnings, may be applied. Review of their characteristics can assist in the development of effective risk mitigation. This study was a cross sectional review of all legal warnings imposed in Thailand after drug approval (2003-2012). Any boxed warnings for biological products and revised warnings which were not related to safety were excluded. Nine legal warnings were evaluated. Seven related to drugs classes and two to individual drugs. The warnings involved four main types of predictable ADRs: drug-disease interactions, side effects, overdose and drug-drug interactions. The average time from first ADRs reported to legal warnings implementation was 12 years. The triggers were from both safety signals in Thailand and regulatory measures in other countries outside Thailand. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials

    Directory of Open Access Journals (Sweden)

    Str

    2015-05-01

    Full Text Available Vibeke Strand,1 Louis F McIntyre,2 William R Beach,3 Larry E Miller,4,5 Jon E Block5 1Stanford University School of Medicine, Palo Alto, CA, USA; 2New York University Medical Center, White Plains, NY, USA; 3Tuckahoe Orthopaedics, Richmond, VA, USA; 4Miller Scientific Consulting, Inc., Asheville, NC, USA; 5The Jon Block Group, San Francisco, CA, USA Background: Intra-articular injection of hyaluronic acid is a common, yet controversial, therapeutic option for patients with knee osteoarthritis (OA. The purpose of this research was to determine the safety and efficacy of US-approved viscosupplements for symptomatic knee OA. Methods: We searched MedLine and EMBase for randomized, sham-controlled trials evaluating safety and/or clinical efficacy of US-approved viscosupplements in patients with symptomatic knee OA. Knee pain severity and knee joint function were assessed at 4 to 13 weeks and 14 to 26 weeks. Safety outcomes included serious adverse events, treatment-related serious adverse events, patient withdrawal, and adverse event-related patient withdrawal occurring at any time during follow-up. Results: A total of 29 studies representing 4,866 unique patients (active: 2,673, control: 2,193 were included. All sham-controlled trials used saline injections as a control. Viscosupplementation resulted in very large treatment effects between 4 and 26 weeks for knee pain and function compared to preinjection values, with standardized mean difference values ranging from 1.07 to 1.37 (all P<0.001. Compared to controls, standardized mean difference with viscosupplementation ranged from 0.38 to 0.43 for knee pain and 0.32 to 0.34 for knee function (all P<0.001. There were no statistically significant differences between viscosupplementation and controls for any safety outcome, with absolute risk differences of 0.7% (95% confidence interval [CI]: –0.2 to 1.5% for serious adverse events, 0% (95% CI: –0.4 to 0.4% for treatment-related serious adverse

  11. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects.

    Directory of Open Access Journals (Sweden)

    Viswanathan Rajagopalan

    Full Text Available A large body of evidence suggests that thyroid hormones (THs are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3 treatment in myocardial infarction (MI rats increased left ventricular (LV contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day was available in drinking water ad libitum immediately following MI and continuing for 2 month(s (mo. Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.

  12. 39 CFR 111.4 - Approval of the Director of the Federal Register.

    Science.gov (United States)

    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...) and 1 CFR part 51 on June 4, 2010. (5 U.S.C. 552(a); 39 U.S.C. 401, 404, 407, 408, 3001-3011, 3201...

  13. Stimulated reporting: the impact of US food and drug administration-issued alerts on the adverse event reporting system (FAERS).

    Science.gov (United States)

    Hoffman, Keith B; Demakas, Andrea R; Dimbil, Mo; Tatonetti, Nicholas P; Erdman, Colin B

    2014-11-01

    The US Food and Drug Administration (FDA) uses the Adverse Event Reporting System (FAERS) to support post-marketing safety surveillance programs. Currently, almost one million case reports are submitted to FAERS each year, making it a vast repository of drug safety information. Sometimes cited as a limitation of FAERS, however, is the assumption that "stimulated reporting" of adverse events (AEs) occurs in response to warnings, alerts, and label changes that are issued by the FDA. To determine the extent of "stimulated reporting" in the modern-day FAERS database. One hundred drugs approved by the FDA between 2001 and 2010 were included in this analysis. FDA alerts were obtained by a comprehensive search of the FDA's MedWatch and main websites. Publicly available FAERS data were used to assess the "primary suspect" AE reporting pattern for up to four quarters before, and after, the issuance of an FDA alert. A few drugs did demonstrate "stimulated reporting" trends. A majority of the drugs, however, showed little evidence for significant reporting changes associated with the issuance of alerts. When we compared the percentage changes in reporting after an FDA alert with those after a sham "control alert", the overall reporting trends appeared to be quite similar. Of 100 drugs analyzed for short-term reporting trends, 21 real alerts and 25 sham alerts demonstrated an increase (greater than or equal to 1 %) in reporting. The long-term analysis of 91 drugs showed that 24 real alerts and 28 sham alerts demonstrated a greater than or equal to 1 % increase. Our results suggest that most of modern day FAERS reporting is not significantly affected by the issuance of FDA alerts.

  14. Design and analysis of post-marketing research.

    Science.gov (United States)

    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.

  15. 38 CFR 17.65 - Approvals and provisional approvals of community residential care facilities.

    Science.gov (United States)

    2010-07-01

    ... approvals of community residential care facilities. 17.65 Section 17.65 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Community Residential Care § 17.65 Approvals and provisional approvals of community residential care facilities. (a) An approval of a facility meeting all of...

  16. Post-traumatic stress disorder in U.S. soldiers with post-traumatic headache.

    Science.gov (United States)

    Rosenthal, Jacqueline F; Erickson, Jay C

    2013-01-01

    To determine the impact of post-traumatic stress disorder (PTSD) on headache characteristics and headache prognosis in U.S. soldiers with post-traumatic headache. PTSD and post-concussive headache are common conditions among U.S. Army personnel returning from deployment. The impact of comorbid PTSD on the characteristics and outcomes of post-traumatic headache has not been determined in U.S. Army soldiers. A retrospective cohort study was conducted among 270 consecutive U.S. Army soldiers diagnosed with post-traumatic headache at a single Army neurology clinic. All subjects were screened for PTSD at baseline using the PTSD symptom checklist. Headache frequency and characteristics were determined for post-traumatic headache subjects with and without PTSD at baseline. Headache measures were reassessed 3 months after the baseline visit, and were compared between groups with and without PTSD. Of 270 soldiers with post-traumatic headache, 105 (39%) met screening criteria for PTSD. There was no significant difference between subjects with PTSD and those without PTSD with regard to headache frequency (17.2 vs 15.7 headache days per month; P = .15) or chronic daily headache (58.1% vs 52.1%; P = .34). Comorbid PTSD was associated with higher headache-related disability as measured by the Migraine Disability Assessment Score. Three months after the baseline neurology clinic visit, the number of subjects with at least 50% reduction in headache frequency was similar among post-traumatic headache cases with and without PTSD (25.9% vs 26.8%). PTSD is prevalent among U.S. Army soldiers with post-traumatic headache. Comorbid PTSD is not associated with more frequent headaches or chronic daily headache in soldiers evaluated at a military neurology clinic for chronic post-traumatic headache. Comorbid PTSD does not adversely affect short-term headache outcomes, although prospective controlled trials are needed to better assess this relationship. © 2013 American Headache

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

    Science.gov (United States)

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

    2017-11-01

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

  18. Perampanel with concomitant levetiracetam and topiramate: Post hoc analysis of adverse events related to hostility and aggression.

    Science.gov (United States)

    Chung, Steve; Williams, Betsy; Dobrinsky, Cindy; Patten, Anna; Yang, Haichen; Laurenza, Antonio

    2017-10-01

    In 4 Phase III registration trials (3 in patients with partial seizures, N=1480; 1 in patients with PGTCS, N=163), perampanel administered to patients already receiving 1-3 concomitant antiepileptic drugs (AEDs) demonstrated statistically superior efficacy compared to placebo in reducing seizure frequency. However, use of perampanel in these studies was associated with a risk of psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. The present study is a post hoc analysis of pooled data from these 4 trials to determine if concomitant treatment with levetiracetam and/or topiramate increased the risk of hostility- and aggression-related AEs. Treatment-emergent AEs (TEAEs) were determined using a "Narrow & Broad" search based on the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA query (SMQ) for hostility- and aggression-related events. The rate of hostility- and aggression-related TEAEs was observed to be similar among perampanel-treated patients: a) receiving levetiracetam (N=340) compared to those not receiving levetiracetam (N=779); b) receiving topiramate (N=223) compared to those not receiving topiramate (N=896); and c) receiving both levetiracetam and topiramate (N=47) compared to those not receiving levetiracetam and topiramate (N=1072). Severe and serious TEAEs related to hostility and aggression were rare and occurred at a similar rate regardless of concomitant levetiracetam and/or topiramate therapy. Taken together, these results suggest that concomitant treatment with levetiracetam and/or topiramate has no appreciable effect on the occurrence of hostility- or aggression-related TEAEs in patients receiving perampanel. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Vaxtracker: Active on-line surveillance for adverse events following inactivated influenza vaccine in children.

    Science.gov (United States)

    Cashman, Patrick; Moberley, Sarah; Dalton, Craig; Stephenson, Jody; Elvidge, Elissa; Butler, Michelle; Durrheim, David N

    2014-09-22

    Vaxtracker is a web based survey for active post marketing surveillance of Adverse Events Following Immunisation. It is designed to efficiently monitor vaccine safety of new vaccines by early signal detection of serious adverse events. The Vaxtracker system automates contact with the parents or carers of immunised children by email and/or sms message to their smart phone. A hyperlink on the email and text messages links to a web based survey exploring adverse events following the immunisation. The Vaxtracker concept was developed during 2011 (n=21), and piloted during the 2012 (n=200) and 2013 (n=477) influenza seasons for children receiving inactivated influenza vaccine (IIV) in the Hunter New England Local Health District, New South Wales, Australia. Survey results were reviewed by surveillance staff to detect any safety signals and compare adverse event frequencies among the different influenza vaccines administered. In 2012, 57% (n=113) of the 200 participants responded to the online survey and 61% (290/477) in 2013. Vaxtracker appears to be an effective method for actively monitoring adverse events following influenza vaccination in children. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  20. BCG and Adverse Events in the Context of Leprosy

    Directory of Open Access Journals (Sweden)

    Renate Richardus

    2018-04-01

    Full Text Available BackgroundNotwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (revaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations.MethodsWithin a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae antigens in overnight whole-blood assays (WBA. M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination.ResultsOut of the 14,828 contacts who received BCG vaccination, 50 (0.34% presented with adverse events, mainly (80% consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60% had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1 in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin.ConclusionSkin complications after BCG vaccination present surrogate markers for protective

  1. 77 FR 16805 - Notice of Request for Extension and Revision of a Currently Approved Information Collection...

    Science.gov (United States)

    2012-03-22

    ... Monitoring System and the Food Safety Mobile Questionnaire) AGENCY: Food Safety and Inspection Service, USDA... Safety Mobile questionnaire. The approval for this information collection is due to expire. FSIS is... post their personal contact information--mailing address, email address, and telephone number-- on the...

  2. Intimate partner violence among Egyptian pregnant women: incidence, risk factors, and adverse maternal and fetal outcomes.

    Science.gov (United States)

    Ibrahim, Z M; Sayed Ahmed, W A; El-Hamid, S A; Hagras, A M

    2015-01-01

    To assess incidence and risk factors of intimate partner violence (IPV) during pregnancy among a sample of women from Egypt and to evaluate its impact on maternal and fetal adverse health outcomes. After obtaining ethical approval, a total of 1,857 women aged 18 - 43 years completed the study and were investigated using an interview questionnaire. The questionnaire contains five main items: demographic characteristics of women, intimate partner characteristics, assessment of IPV during current pregnancy, and assessment of maternal as well as fetal/neonatal adverse outcomes. Women were also examined to detect signs of violence and identify injuries. Exposure to IPV during pregnancy was reported among 44.1% of the studied women. Emotional violence was the most common form. Women exposed to violence were of younger age, higher parity, and lower educational level. Their partners were older, less educated, and more likely to be addicted to drugs and alcohol. Women were also found to have significantly higher incidence of adverse pregnancy outcomes (miscarriage, preterm labor, and premature rupture of membrane), and fetal/neonatal adverse outcomes (fetal distress, fetal death, and low birth weight). A total of 297 cases had been exposed to physical violence (15.9%) vs 32.6% and 10% exposed to emotional and sexual violence, respectively. The most common form of physical violence was kicking. Violence during pregnancy is prevalent among Egyptian women. Exposure to violence was a significant risk factor for multiple adverse maternal and fetal health outcomes.

  3. 19 CFR 115.41 - Certificate of approval for containers approved after manufacture.

    Science.gov (United States)

    2010-04-01

    ... after manufacture. 115.41 Section 115.41 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT... PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS Procedures for Approval of Containers After Manufacture § 115.41 Certificate of approval for containers approved after manufacture. The Certifying Authority shall...

  4. Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials.

    Science.gov (United States)

    Federer, Callie; Yoo, Minjae; Tan, Aik Choon

    2016-12-01

    Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov ( https://clinicaltrials.gov/ ), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov . Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs.

  5. EVAR using the Nellix Sac-anchoring endoprosthesis: treatment of favourable and adverse anatomy.

    Science.gov (United States)

    Krievins, D K; Holden, A; Savlovskis, J; Calderas, C; Donayre, C E; Moll, F L; Katzen, B; Zarins, C K

    2011-07-01

    The study aimed to review the results of endovascular aneurysm repair (EVAR) using a novel sac-anchoring endoprosthesis in patients with favourable and adverse anatomy. This is a prospective, multicentre, clinical trial. The Nellix endoprosthesis consists of dual, balloon-expandable endoframes, surrounded by polymer-filled endobags, which obliterate the aneurysm sac and maintain endograft position. The study reviewed worldwide clinical experience and Core Lab evaluation of computed tomography (CT) scans. From 2008 to 2010, 34 patients (age 71 ± 8 years, abdominal aortic aneurysm (AAA) diameter 5.8 ± 0.8 cm) were treated at four clinical sites. Seventeen patients (50%) met the inclusion criteria for Food and Drug Administration (FDA)-approved endografts (favourable anatomy); 17 (50%) had one or more adverse anatomic feature: neck length 60° (9%) and iliac diameter >23 mm (38%). Device deployment was successful in all patients; iliac aneurysm treatment preserved hypogastric patency. Perioperative mortality was 1/34 (2.9%); one patient died at 10 months of congestive heart failure (CHF); one patient had a secondary procedure at 15 months. During 15 ± 6 months follow-up, there were no differences in outcome between favourable and adverse anatomy patients. Follow-up CT extending up to 2 years revealed no change in aneurysm size or endograft position and no new endoleaks. Favourable and adverse anatomy patients can be successfully treated using the Nellix sac-anchoring endoprosthesis. Early results are promising but longer-term studies are needed. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  6. Adverse Weather Evokes Nostalgia.

    Science.gov (United States)

    van Tilburg, Wijnand A P; Sedikides, Constantine; Wildschut, Tim

    2018-03-01

    Four studies examined the link between adverse weather and the palliative role of nostalgia. We proposed and tested that (a) adverse weather evokes nostalgia (Hypothesis 1); (b) adverse weather causes distress, which predicts elevated nostalgia (Hypothesis 2); (c) preventing nostalgia exacerbates weather-induced distress (Hypothesis 3); and (d) weather-evoked nostalgia confers psychological benefits (Hypothesis 4). In Study 1, participants listened to recordings of wind, thunder, rain, and neutral sounds. Adverse weather evoked nostalgia. In Study 2, participants kept a 10-day diary recording weather conditions, distress, and nostalgia. We also obtained meteorological data. Adverse weather perceptions were positively correlated with distress, which predicted higher nostalgia. Also, adverse natural weather was associated with corresponding weather perceptions, which predicted elevated nostalgia. (Results were mixed for rain.) In Study 3, preventing nostalgia (via cognitive load) increased weather-evoked distress. In Study 4, weather-evoked nostalgia was positively associated with psychological benefits. The findings pioneer the relevance of nostalgia as source of comfort in adverse weather.

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

    Science.gov (United States)

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

    2008-03-01

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

  8. Life adverse experiences in relation with obesity and binge eating disorder: A systematic review

    Science.gov (United States)

    Palmisano, Giovanni Luca; Innamorati, Marco; Vanderlinden, Johan

    2016-01-01

    Background and aims Several studies report a positive association between adverse life experiences and adult obesity. Despite the high comorbidity between binge eating disorder (BED) and obesity, few authors have studied the link between trauma and BED. In this review the association between exposure to adverse life experiences and a risk for the development of obesity and BED in adulthood is explored. Methods Based on a scientific literature review in Medline, PubMed and PsycInfo databases, the results of 70 studies (N = 306,583 participants) were evaluated including 53 studies on relationship between adverse life experiences and obesity, 7 studies on post-traumatic stress disorder (PTSD) symptoms in relation to obesity, and 10 studies on the association between adverse life experiences and BED. In addition, mediating factors between the association of adverse life experiences, obesity and BED were examined. Results The majority of studies (87%) report that adverse life experiences are a risk factor for developing obesity and BED. More precisely a positive association between traumatic experiences and obesity and PTSD and obesity were found, respectively, in 85% and 86% of studies. Finally, the great majority of studies (90%) between trauma and the development of BED in adulthood strongly support this association. Meanwhile, different factors mediating between the trauma and obesity link were identified. Discussion and conclusions Although research data show a strong association between life adverse experiences and the development of obesity and BED, more research is needed to explain this association. PMID:28092189

  9. Evaluation of risk profiles for gastrointestinal and cardiovascular adverse effects in nonselective NSAID and COX-2 inhibitor users - A cohort study using pharmacy dispensing data in the Netherlands

    NARCIS (Netherlands)

    Layton, Deborah; Souverein, Patrick C.; Heerdink, Eibert R.; Shakir, Saad A. W.; Egberts, Antoine C. G.

    2008-01-01

    Background: Newly approved drugs, in comparison with older drugs, are more often prescribed to patients who have not responded satisfactorily to established related drugs or as first-line therapy to patients with a high baseline risk for adverse outcomes (i.e. channelling). However, these patients

  10. 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.

    Science.gov (United States)

    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

  11. Epigenomic mechanisms of early adversity and HPA dysfunction: Considerations for PTSD research

    Directory of Open Access Journals (Sweden)

    Patrick O McGowan

    2013-09-01

    Full Text Available Childhood adversity can have life-long consequences for the response to stressful events later in life. Abuse or severe neglect are well known risk factors for post-traumatic stress disorder (PTSD, at least in part via changes in neural systems mediating the endocrine response to stress. Determining the biological signatures of risk for stress-related mental disorders such as PTSD is important for identifying homogenous subgroups and improving treatment options. This review will focus on epigenetic regulation in early life by adversity and parental care – prime mediators of offspring neurodevelopment - in order to address several questions: (1 what have studies of humans and analogous animal models taught us about molecular mechanisms underlying changes in stress-sensitive physiological systems in response to early life trauma? (2 What are the considerations for studies relating early adversity and PTSD risk, going forward? I will summarize studies in animals and humans that address the epigenetic response to early adversity in the brain and in peripheral tissues. In so doing, I will describe work on the Glucocorticoid Receptor (GR and other well-characterized genes within the stress response pathway and then turn to genomic studies to illustrate the use of increasingly powerful high-throughput approaches to the study of epigenomic mechanisms.

  12. Adverse events following quadrivalent meningococcal CRM-conjugate vaccine (Menveo®) reported to the Vaccine Adverse Event Reporting system (VAERS), 2010-2015.

    Science.gov (United States)

    Myers, Tanya R; McNeil, Michael M; Ng, Carmen S; Li, Rongxia; Lewis, Paige W; Cano, Maria V

    2017-03-27

    Limited data are available describing the post-licensure safety of meningococcal vaccines, including Menveo®. We reviewed reports of adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS) to assess safety in all age groups. VAERS is a national spontaneous vaccine safety surveillance system co-administered by the Centers for Disease Control and Prevention and the US Food and Drug Administration. We searched the VAERS database for US reports of adverse events in persons who received Menveo from 1 January 2010 through 31 December 2015. We clinically reviewed reports and available medical records for serious AEs, selected pre-specified outcomes, and vaccination during pregnancy. We used empirical Bayesian data mining to identify AEs that were disproportionately reported after receipt of Menveo. During the study period, VAERS received 2614 US reports after receipt of Menveo. Of these, 67 were classified as serious, including 1 report of death. Adolescents (aged 11-18years) accounted for 74% of reports. Most of the reported AEs were non-serious and described AEs consistent with data from pre-licensure studies. Anaphylaxis and syncope were the two most common events in the serious reports. We did not identify any new safety concerns after review of AEs that exceeded the data mining threshold, although we did observe disproportionate reporting for terms that were not associated with an adverse event (e.g., "incorrect drug dosage form administered", "wrong technique in drug usage process"). Although reports were limited, we did not find any evidence for concern regarding the use of Menveo during pregnancy. In our review of VAERS reports, findings of AEs were consistent with the data from pre-licensure studies. Vaccine providers should continue to emphasize and adhere to proper administration of the vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. 46 CFR 169.849 - Posting placards containing instructions for launching and inflating inflatable liferafts.

    Science.gov (United States)

    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. ...

  14. 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.

    Science.gov (United States)

    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.

  15. Post-Closure Inspection Report for Corrective Action Unit 453: Area 9 UXO Landfill Tonopah Test Range, Nevada, Calendar Year 2000; TOPICAL

    International Nuclear Information System (INIS)

    K. B. Campbell

    2001-01-01

    Post-closure monitoring requirements for the Area 9 Unexploded Ordnance Landfill (Corrective Action Unit[CAU] 453) (Figure 1) are described in Closure Report for Corrective Action Unit 453: Area 9 UXO Landfill, Tonopah Test Range, Nevada, report number DOE/NV-284. The Closure Report (CR) was submitted to the Nevada Division of Environmental Protection (NDEP) on August 5,1999. The CR (containing the Post-Closure Monitoring Plan) was approved by the NDEP on September 10,1999. Post-closure monitoring at CAU 453 consists of the following: (1) Site inspections done twice a year to evaluate the condition of the unit; (2) Verification that the site is secure; (3) Notice of any subsidence or deficiencies that may compromise the integrity of the unit; (4) Remedy of any deficiencies within 90 days of discovery; and (5) Preparation and submittal of an annual report. Site inspections were conducted on June 20, 2000 and November 21, 2000. Both site inspections were conducted after NDEP approval of the CR, and in accordance with the Post-Closure Monitoring Plan in the NDEP-approved CR. This report includes copies of the inspection checklists, photographs, recommendations, and conclusions. The Post-Closure Inspection Checklists are found in Attachment A, a copy of the field notes is found in Attachment B, and inspection photographs are found in Attachment C

  16. Coding of adverse events of suicidality in clinical study reports of duloxetine for the treatment of major depressive disorder

    DEFF Research Database (Denmark)

    Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn

    2014-01-01

    in individual patients within clinical study reports. Where possible, for each event we extracted the original term reported by the investigator, the term as coded by the medical coding dictionary, medical coding dictionary used, and the patient's trial identification number. Using the patient's trial...... for marketing approval. DATA SOURCES: Clinical study reports obtained from the EMA in 2011. RESULTS: Six trials used the medical coding dictionary COSTART (Coding Symbols for a Thesaurus of Adverse Reaction Terms) and three used MedDRA (Medical Dictionary for Regulatory Activities). Suicides were clearly...... identifiable in all formats of adverse event data in clinical study reports. Suicide attempts presented in tables included both definitive and provisional diagnoses. Suicidal ideation and preparatory behaviour were obscured in some tables owing to the lack of specificity of the medical coding dictionary...

  17. Redfield Energy Approval

    Science.gov (United States)

    This September 19, 2016 letter from EPA approves the petition from Poet Biorefining-Lake Crystal, regarding non-This October 27, 2016 letter from EPA approves the petition from Redfield Energy, LLC, regarding non-grandfathered ethanol produced

  18. Adverse Effects of Bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...

  19. Adverse effects of bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...

  20. Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011

    Science.gov (United States)

    Nordanger, Dag Ø.; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

    2014-01-01

    Background Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. Objective To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. Method We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. Results All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents’ proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Conclusions Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care. PMID:24872862

  1. Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011.

    Science.gov (United States)

    Nordanger, Dag Ø; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

    2014-01-01

    Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents' proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care.

  2. Innovating by developing new uses of already-approved drugs: trends in the marketing approval of supplemental indications.

    Science.gov (United States)

    DiMasi, Joseph A

    2013-06-01

    Much of the literature on trends and factors affecting biopharmaceutical innovation has focused overwhelmingly on the development and approval of never-before approved drugs and biologics. Little attention has been paid to new uses for already-approved compounds, which can be an important form of innovation. This paper aimed to determine and analyze recent trends in the number and type of new or modified US indication approvals for drugs and biologics. We also examine regulatory approval-phase times for new-use efficacy supplements and compare them to approval-phase times for original-use approvals over the same period. We developed a data set of efficacy supplements approved by the US Food and Drug Administration (FDA) from 1998 to 2011 that includes information on the type, approval-phase time (time from submission to the FDA of an application for marketing approval to approval of the application), and FDA therapeutic-significance rating for the approved application, which we obtained from an FDA Web site. This data set was merged with a Tufts Center for the Study of Drug Development (CSDD) data set of US new drug and biologics approvals. We developed descriptive statistics on trends in the number and type of new-use efficacy supplements, on US regulatory approval-phase times for the supplements, and on original new drug and biologics approvals over the study period and for the time from original- to new-use approval. The total number of new-use efficacy-supplement approvals did not exhibit a marked trend, but the number of new pediatric-indication approvals increased substantially. Approval-phase times for new-use supplements varied by therapeutic class and FDA therapeutic-significance rating. Mean approval-phase times were highest for central nervous system compounds (13.8 months) and lowest for antineoplastics (8.9 months). The mean time from original to supplement approval was substantially longer for new pediatric indications than for other new uses. Mean

  3. Medicaid program; Medicaid Management Information Systems; conditions of approval and reapproval and procedures for reduction of federal financial participation--Health Care Financing Administration. Proposed rule.

    Science.gov (United States)

    1983-03-03

    This proposal adds to regulations new conditions and procedures for initial approval and for reapproval of Medicaid Management Information Systems (MMIS) to update the regulations to reflect additional requirements added by section 901 of the Mental Health Systems Act of 1980 (Pub. L. 96-398). The proposal specifies procedures for reducing the level of Federal financial participation in a State's administrative expenditures when a State fails to meet the conditions for initial operation, initial approval or reapproval of an MMIS. It also proposes procedures with respect to waivers of the conditions of approval and reapproval and to appeals of adverse decisions. These provisions are intended to improve States' MMIS, and to ensure efficient system operations, and to detect cases of fraud, waste, and abuse effectively.

  4. Analysis of economic and social costs of adverse events associated with blood transfusions in Spain.

    Science.gov (United States)

    Ribed-Sánchez, Borja; González-Gaya, Cristina; Varea-Díaz, Sara; Corbacho-Fabregat, Carlos; Bule-Farto, Isabel; Pérez de-Oteyza, Jaime

    2018-02-16

    To calculate, for the first time, the direct and social costs of transfusion-related adverse events in order to include them in the National Healthcare System's budget, calculation and studies. In Spain more than 1,500 patients yearly are diagnosed with such adverse events. Blood transfusion-related adverse events recorded yearly in Spanish haemovigilance reports were studied retrospectively (2010-2015). The adverse events were coded according to the classification of Diagnosis-Related Groups. The direct healthcare costs were obtained from public information sources. The productivity loss (social cost) associated with adverse events was calculated using the human capital and hedonic salary methodologies. In 2015, 1,588 patients had adverse events that resulted in direct health care costs (4,568,914€) and social costs due to hospitalization (200,724€). Three adverse reactions resulted in patient death (at a social cost of 1,364,805€). In total, the cost of blood transfusion-related adverse events was 6,134,443€ in Spain. For the period 2010-2015: the trends show a reduction in the total amount of transfusions (2 vs. 1.91M€; -4.4%). The number of adverse events increased (822 vs. 1,588; +93%), as well as their related direct healthcare cost (3.22 vs. 4.57M€; +42%) and the social cost of hospitalization (110 vs 200M€; +83%). Mortality costs decreased (2.65 vs. 1.36M€; -48%). This is the first time that the costs of post-transfusion adverse events have been calculated in Spain. These new figures and trends should be taken into consideration in any cost-effectiveness study or trial of new surgical techniques or sanitary policies that influence blood transfusion activities. Copyright © 2018 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Radiological Medical Device Innovation: Approvals via the Premarket Approval Pathway From 2000 to 2015.

    Science.gov (United States)

    Ghobadi, Comeron W; Hayman, Emily L; Finkle, Joshua H; Walter, Jessica R; Xu, Shuai

    2017-01-01

    The aim of this study was to critically assess the clinical evidence leading to radiologic medical device approvals via the premarket approval pathway from 2000 to 2015. This study used the publically available FDA premarket database for radiologic device approvals over the past 15 years (September 1, 2000, to August 31, 2015). Approval characteristics were collected for each device, and statistical analysis was performed on the data for each pivotal trial. Additionally, methodological quality of the pivotal trial was determined using the Quality Assessment of Diagnostic Accuracy Studies tool. Twenty-three class III radiologic device approvals were identified, with breast imaging accounting for 16 (70%) and computer-aided detection software accounting for 9 (39%) approvals. The median premarket approval time was 475 days (range, 180-1,116). Twenty-one devices were approved on the basis of multireader, multicenter studies, one on the basis of a randomized controlled trial, and one on the basis of a preclinical technical equivalence trial. The median number of patients per pivotal trial was 201 (range, 25-3,946). Twenty-six of the 34 pivotal trials (76%) had at least one methodologic bias. Breast imaging devices had a greater number of patients per pivotal trial (P = .009) and more prospective studies. With regard to all modalities, increased time to device approval correlated with weaker trial quality (r = 0.600, P assessing diagnostic technologies. Given that radiologic devices play a key role in modern medicine, further efforts should be made to increase transparency of clinical data leading to approval. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  6. Systematic review on the prevalence, frequency and comparative value of adverse events data in social media

    Science.gov (United States)

    Golder, Su; Norman, Gill; Loke, Yoon K

    2015-01-01

    Aim The aim of this review was to summarize the prevalence, frequency and comparative value of information on the adverse events of healthcare interventions from user comments and videos in social media. Methods A systematic review of assessments of the prevalence or type of information on adverse events in social media was undertaken. Sixteen databases and two internet search engines were searched in addition to handsearching, reference checking and contacting experts. The results were sifted independently by two researchers. Data extraction and quality assessment were carried out by one researcher and checked by a second. The quality assessment tool was devised in-house and a narrative synthesis of the results followed. Results From 3064 records, 51 studies met the inclusion criteria. The studies assessed over 174 social media sites with discussion forums (71%) being the most popular. The overall prevalence of adverse events reports in social media varied from 0.2% to 8% of posts. Twenty-nine studies compared the results from searching social media with using other data sources to identify adverse events. There was general agreement that a higher frequency of adverse events was found in social media and that this was particularly true for ‘symptom’ related and ‘mild’ adverse events. Those adverse events that were under-represented in social media were laboratory-based and serious adverse events. Conclusions Reports of adverse events are identifiable within social media. However, there is considerable heterogeneity in the frequency and type of events reported, and the reliability or validity of the data has not been thoroughly evaluated. PMID:26271492

  7. Adverse Event extraction from Structured Product Labels using the Event-based Text-mining of Health Electronic Records (ETHER)system.

    Science.gov (United States)

    Pandey, Abhishek; Kreimeyer, Kory; Foster, Matthew; Botsis, Taxiarchis; Dang, Oanh; Ly, Thomas; Wang, Wei; Forshee, Richard

    2018-01-01

    Structured Product Labels follow an XML-based document markup standard approved by the Health Level Seven organization and adopted by the US Food and Drug Administration as a mechanism for exchanging medical products information. Their current organization makes their secondary use rather challenging. We used the Side Effect Resource database and DailyMed to generate a comparison dataset of 1159 Structured Product Labels. We processed the Adverse Reaction section of these Structured Product Labels with the Event-based Text-mining of Health Electronic Records system and evaluated its ability to extract and encode Adverse Event terms to Medical Dictionary for Regulatory Activities Preferred Terms. A small sample of 100 labels was then selected for further analysis. Of the 100 labels, Event-based Text-mining of Health Electronic Records achieved a precision and recall of 81 percent and 92 percent, respectively. This study demonstrated Event-based Text-mining of Health Electronic Record's ability to extract and encode Adverse Event terms from Structured Product Labels which may potentially support multiple pharmacoepidemiological tasks.

  8. 30 CFR 18.95 - Approval of machines constructed of components approved, accepted or certified under Bureau of...

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approval of machines constructed of components... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.95 Approval of machines constructed of components approved...

  9. Evaluation of adverse events and imaging quality in contrast-enhanced abdominal CT using generic CT contrast developed in South Korea: A multicenter prospective observational study

    International Nuclear Information System (INIS)

    Kim, You Sung; Jung, Seung Eun; Park, Micheal Yong; Rha, Sung Eun; Lee, Soo Rim; Hwang, Seong Su; Lim, Yeon Soo; Park, Jeong Mi

    2017-01-01

    The purpose of this study is to evaluate the clinical safety and usefulness of the Prosure®300 in contrast-enhanced abdominal CT. This prospective study was approved by our center's Institutional Review Board. This study included 727 patients in four hospitals who underwent contrast-enhanced abdominal CT using Prosure®300 from December 2010 to June 2011. Adverse events were classified into minor and major adverse events. Logistic regression analysis was used to evaluate the relationship between adverse events and patient gender, age, underlying disease, and amount of injected contrast agent. Two radiologists independently evaluated imaging quality as poor, insufficient, sufficient, good, or very good. One hundred seventy-six out of 727 patients complained of adverse events, but most of them were minor adverse events. Five patients complained of dyspnea and one patient had hoarseness, but recovered without treatment. The rate of adverse events was significantly higher in men (p = 0.011), and a greater amount of injected contrast agent was related to a higher rate of adverse events (p = 0.000). Imaging quality was evaluated as 'good' or 'very good' in all cases. Prosure®300, a generic CT contrast agent developed in South Korea, can be used in contrast-enhanced abdominal CT

  10. Evaluation of adverse events and imaging quality in contrast-enhanced abdominal CT using generic CT contrast developed in South Korea: A multicenter prospective observational study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, You Sung [Dept. of Radiology, Ilsan Paik Hospital, College of Medicine, Inje University, Goyang (Korea, Republic of); Jung, Seung Eun; Park, Micheal Yong; Rha, Sung Eun [Dept. of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Lee, Soo Rim [Dept. of Radiology, Uijeongbu St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu (Korea, Republic of); Hwang, Seong Su [Dept. of Radiology, St. Vincent Hospital, College of Medicine, The Catholic University of Korea, Suwon (Korea, Republic of); Lim, Yeon Soo [Dept. of Radiology, Bucheon St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Bucheon (Korea, Republic of); Park, Jeong Mi [Dept. of Radiology, Yeouido St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2017-02-15

    The purpose of this study is to evaluate the clinical safety and usefulness of the Prosure®300 in contrast-enhanced abdominal CT. This prospective study was approved by our center's Institutional Review Board. This study included 727 patients in four hospitals who underwent contrast-enhanced abdominal CT using Prosure®300 from December 2010 to June 2011. Adverse events were classified into minor and major adverse events. Logistic regression analysis was used to evaluate the relationship between adverse events and patient gender, age, underlying disease, and amount of injected contrast agent. Two radiologists independently evaluated imaging quality as poor, insufficient, sufficient, good, or very good. One hundred seventy-six out of 727 patients complained of adverse events, but most of them were minor adverse events. Five patients complained of dyspnea and one patient had hoarseness, but recovered without treatment. The rate of adverse events was significantly higher in men (p = 0.011), and a greater amount of injected contrast agent was related to a higher rate of adverse events (p = 0.000). Imaging quality was evaluated as 'good' or 'very good' in all cases. Prosure®300, a generic CT contrast agent developed in South Korea, can be used in contrast-enhanced abdominal CT.

  11. Adverse perinatal outcomes for advanced maternal age: a cross-sectional study of Brazilian births

    Directory of Open Access Journals (Sweden)

    Núbia Karla O. Almeida

    2015-10-01

    Full Text Available ABSTRACT OBJECTIVES: To investigate the risk of adverse perinatal outcomes in women aged ≥41 years relatively to those aged 21-34. METHODS: Approximately 8.5 million records of singleton births in Brazilian hospitals in the period 2004-2009 were investigated. Odds ratios were estimated for preterm and post-term births, for low Apgar scores at 1 min and at 5 min, for asphyxia, for low birth weight, and for macrosomia. RESULTS: For pregnant women ≥41, increased risks were identified for preterm births, for post-term births (except for primiparous women with schooling ≥12 years, and for low birth weight. When comparing older vs. younger women, higher educational levels ensure similar risks of low Apgar score at 1 min (for primiparous mothers and term births, of low Apgar score at 5 min (for term births, of macrosomia (for non-primiparous women, and of asphyxia. CONCLUSION: As a rule, older mothers are at higher risk of adverse perinatal outcomes, which, however, may be mitigated or eliminated, depending on gestational age, parity, and, especially, on the education level of the pregnant woman.

  12. Effects of post-fire logging on California spotted owl occupancy

    Directory of Open Access Journals (Sweden)

    Chad T. Hanson

    2018-01-01

    Full Text Available In fire-adapted forest ecosystems around the world, there has been growing concern about adverse impacts of post-fire logging on native biodiversity and ecological processes. This is also true in conifer forests of California, U.S.A. which are home to a rare and declining owl subspecies, the California spotted owl (Strix occidentalis occidentalis. While there has been recent concern about the California spotted owl occupancy in large fire areas where some territories have substantial high-severity fire effects, the influence of post-fire logging on the California spotted owl occupancy has been investigated very little, leading to some uncertainty about interpretation of conflicting results in different large fires. Research has found these owls preferentially select high-severity fire areas, characterised by high levels of snags and native shrubs, for foraging in forests that were not logged after fire, suggesting that removal of this foraging habitat might impact occupancy. The authors assessed the effect of post-fire logging and high-severity fire, on occupancy of this subspecies in eight large fire areas, within spotted owl sites with two different levels of high-severity fire effects. They found a significant adverse effect of such logging and no effect of high-severity fire alone. These results indicate it is post-fire logging, not large fires themselves, that poses a conservation threat to this imperilled species.

  13. Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

    DEFF Research Database (Denmark)

    Mathiesen, O; Wetterslev, Jørn; Kontinen, V K

    2014-01-01

    with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects...... of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality...

  14. Finasteride Side Effects and Post-Finasteride Syndrome in Male Androgenic Alopecia

    Directory of Open Access Journals (Sweden)

    Manea Mirela

    2015-10-01

    Full Text Available Finasteride is in present a relatively frequent prescribed drug for male androgenic alopecia. The adverse effects reported by some patients seem to be notable, consisting of various (physical, mental/ neurological, sexual, etc. manifestations which are encountered both during Finasteride administration and after treatment cessation (in the form of `post-Finasteride syndrome`. The pharmacological action and the corresponding adverse effects related to Finasteride administration were investigated and published in literature through several and successive studies. In respect to psychiatric disorders, the most notable concern is related to depressive symptoms and suicidal thoughts among former users of finasteride with persistent adverse effects. Regarding genito-urinary symptoms, these are usually represented by gynecomastia, decreased interest in sexual intercourse/ low level of sexual desire and erectile dysfunction. Finally, we viewed Finasteride side effects and post-Finasteride syndrome as distinct physiopathologic entities, thus requiring possible distinct therapeutic approaches. Additional studies will be necessary, in order to further investigate the cerebral neuromodulation of the two relational (cognitive and sexual functions, both of which may be interfered by administration of hormones or by the corresponding compounds such as Finasteride.

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

    Science.gov (United States)

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

    2017-10-01

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

  16. Drugs Approved for Breast Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Breast Cancer This page lists cancer drugs approved by the ... are not listed here. Drugs Approved to Prevent Breast Cancer Evista (Raloxifene Hydrochloride) Raloxifene Hydrochloride Tamoxifen Citrate Drugs ...

  17. Post-Closure Inspection Report for Corrective Action Unit 427: Septic Waste Systems 2 and 6 Tonopah Test Range, Nevada Calendar Year 2000; TOPICAL

    International Nuclear Information System (INIS)

    K. B. Campbell

    2001-01-01

    Post-closure inspection requirements for the Area 3 Septic Waste Systems 2 and 6 (Corrective Action Unit[CAU] 427) (Figure 1) are described in Closure Report for Corrective Action Unit 427. Area 3 Septic Waste Systems 2 and 6. Tonopah Test Range, Nevada, report number DOE/NV-561. The Closure Report (CR) was submitted to the Nevada Division of Environmental Protection (NDEP) on August 16, 1999. The CR (containing the Post-Closure Inspection Plan) was approved by the NDEP on August 27, 1999. The annual post-closure inspection at CAU 427 consists of the following: Verification of the presence of all leachfield and septic tank below-grade markers; Verification that the warning signs are in-place, intact, and readable; and Visual observation of the soil and asphalt cover for indications of subsidence, erosion, and unauthorized use. The site inspections were conducted on June 20, 2000, and November 21, 2000. All inspections were made after NDEP approval of the CR and were conducted in accordance with the Post-Closure Inspection Plan in the NDEP-approved CR. No maintenance or repairs were conducted at the site. This report includes copies of inspection checklists, photographs, recommendations, and conclusions. Copies of the Post-Closure Inspection Checklists are found in Attachment A, a copy of the field notes is found in Attachment B, and a copy of the inspection photographs is found in Attachments C

  18. Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011

    Directory of Open Access Journals (Sweden)

    Dag Ø. Nordanger

    2014-05-01

    Full Text Available Background: Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. Objective: To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. Method: We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. Results: All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents’ proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Conclusions: Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care.

  19. A survey of the FDA's AERS database regarding muscle and tendon adverse events linked to the statin drug class.

    Directory of Open Access Journals (Sweden)

    Keith B Hoffman

    Full Text Available BACKGROUND: Cholesterol management drugs known as statins are widely used and often well tolerated; however, a variety of muscle-related side effects can arise. These adverse events (AEs can have serious impact, and form a significant barrier to therapy adherence. Surveillance of post-marketing AEs is of vital importance to understand real-world AEs and reporting differences between individual statin drugs. We conducted a review of post-approval muscle and tendon AE reports in association with statin use, to assess differences within the drug class. METHODS: We analyzed all case reports from the FDA AE Reporting System (AERS database linking muscle-related AEs to statin use (07/01/2005-03/31/2011. Drugs examined were: atorvastatin, simvastatin, lovastatin, pravastatin, rosuvastatin, and fluvastatin. RESULTS: Relative risk rates for rosuvastatin were consistently higher than other statins. Atorvastatin and simvastatin showed intermediate risks, while pravastatin and lovastatin appeared to have the lowest risk rates. Relative risk of muscle-related AEs, therefore, approximately tracked with per milligram LDL-lowering potency, with fluvastatin an apparent exception. Incorporating all muscle categories, rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55%, 26%, 17%, and 7.5% as high, as rosuvastatin, approximately tracking per milligram potency (Rosuvastatin>Atorvastatin>Simvastatin>Pravastatin ≈ Lovastatin and comporting with findings of other studies. Relative potency, therefore, appears to be a fundamental predictor of muscle-related AE risk, with fluvastatin, the least potent statin, an apparent exception (risk 74% vs rosuvastatin. INTERPRETATION: AE reporting rates differed strikingly for drugs within the statin class, with relative reporting aligning substantially with potency. The data presented in this report offer important reference points for the selection of statins for cholesterol management in

  20. Classification of nervous system withdrawn and approved drugs with ToxPrint features via machine learning strategies.

    Science.gov (United States)

    Onay, Aytun; Onay, Melih; Abul, Osman

    2017-04-01

    Early-phase virtual screening of candidate drug molecules plays a key role in pharmaceutical industry from data mining and machine learning to prevent adverse effects of the drugs. Computational classification methods can distinguish approved drugs from withdrawn ones. We focused on 6 data sets including maximum 110 approved and 110 withdrawn drugs for all and nervous system diseases to distinguish approved drugs from withdrawn ones. In this study, we used support vector machines (SVMs) and ensemble methods (EMs) such as boosted and bagged trees to classify drugs into approved and withdrawn categories. Also, we used CORINA Symphony program to identify Toxprint chemotypes including over 700 predefined chemotypes for determination of risk and safety assesment of candidate drug molecules. In addition, we studied nervous system withdrawn drugs to determine the key fragments with The ParMol package including gSpan algorithm. According to our results, the descriptors named as the number of total chemotypes and bond CN_amine_aliphatic_generic were more significant descriptors. The developed Medium Gaussian SVM model reached 78% prediction accuracy on test set for drug data set including all disease. Here, bagged tree and linear SVM models showed 89% of accuracies for phycholeptics and psychoanaleptics drugs. A set of discriminative fragments in nervous system withdrawn drug (NSWD) data sets was obtained. These fragments responsible for the drugs removed from market were benzene, toluene, N,N-dimethylethylamine, crotylamine, 5-methyl-2,4-heptadiene, octatriene and carbonyl group. This paper covers the development of computational classification methods to distinguish approved drugs from withdrawn ones. In addition, the results of this study indicated the identification of discriminative fragments is of significance to design a new nervous system approved drugs with interpretation of the structures of the NSWDs. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Drugs Approved for Thyroid Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) Doxorubicin ...

  2. [Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

    Science.gov (United States)

    Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

    2011-01-01

    Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

  3. [Adverse effects of oxcarbazepine].

    Science.gov (United States)

    Fang, Shu; Gong, Zhi-Cheng

    2015-04-01

    Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.

  4. Filtering big data from social media--Building an early warning system for adverse drug reactions.

    Science.gov (United States)

    Yang, Ming; Kiang, Melody; Shang, Wei

    2015-04-01

    Adverse drug reactions (ADRs) are believed to be a leading cause of death in the world. Pharmacovigilance systems are aimed at early detection of ADRs. With the popularity of social media, Web forums and discussion boards become important sources of data for consumers to share their drug use experience, as a result may provide useful information on drugs and their adverse reactions. In this study, we propose an automated ADR related posts filtering mechanism using text classification methods. In real-life settings, ADR related messages are highly distributed in social media, while non-ADR related messages are unspecific and topically diverse. It is expensive to manually label a large amount of ADR related messages (positive examples) and non-ADR related messages (negative examples) to train classification systems. To mitigate this challenge, we examine the use of a partially supervised learning classification method to automate the process. We propose a novel pharmacovigilance system leveraging a Latent Dirichlet Allocation modeling module and a partially supervised classification approach. We select drugs with more than 500 threads of discussion, and collect all the original posts and comments of these drugs using an automatic Web spidering program as the text corpus. Various classifiers were trained by varying the number of positive examples and the number of topics. The trained classifiers were applied to 3000 posts published over 60 days. Top-ranked posts from each classifier were pooled and the resulting set of 300 posts was reviewed by a domain expert to evaluate the classifiers. Compare to the alternative approaches using supervised learning methods and three general purpose partially supervised learning methods, our approach performs significantly better in terms of precision, recall, and the F measure (the harmonic mean of precision and recall), based on a computational experiment using online discussion threads from Medhelp. Our design provides

  5. FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    de Claro, R Angelo; McGinn, Karen M; Verdun, Nicole; Lee, Shwu-Luan; Chiu, Haw-Jyh; Saber, Haleh; Brower, Margaret E; Chang, C J George; Pfuma, Elimika; Habtemariam, Bahru; Bullock, Julie; Wang, Yun; Nie, Lei; Chen, Xiao-Hong; Lu, Donghao Robert; Al-Hakim, Ali; Kane, Robert C; Kaminskas, Edvardas; Justice, Robert; Farrell, Ann T; Pazdur, Richard

    2015-08-15

    On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥ 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea. ©2015 American Association for Cancer Research.

  6. Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus.

    Science.gov (United States)

    Patel, Neal; Bichoupan, Kian; Ku, Lawrence; Yalamanchili, Rachana; Harty, Alyson; Gardenier, Donald; Ng, Michel; Motamed, David; Khaitova, Viktoriya; Bach, Nancy; Chang, Charissa; Grewal, Priya; Bansal, Meena; Agarwal, Ritu; Liu, Lawrence; Im, Gene; Leong, Jennifer; Kim-Schluger, Leona; Odin, Joseph; Ahmad, Jawad; Friedman, Scott; Dieterich, Douglas; Schiano, Thomas; Perumalswami, Ponni; Branch, Andrea

    2016-03-07

    To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV infection. Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events (SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIV-infected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome. Median age of the 42 patients was 60 years [Interquartile Range (IQR): 56-65 years], 33% (14/42) were female, 21% (9/42) were Hispanic, and 9% (4/42) were Black. The median time from transplant to treatment initiation was 5.4 years (IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62% (8/13) patients, while 54% (7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31% (95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin (OR = 0.61 per g/dL, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate (OR = 0.95 per mL/min per 1.73 m(2), 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin (OR = 2.43 per mg/dL, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases. Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

  7. Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions.

    Science.gov (United States)

    Ryu, JiHyeon; Lee, HeeYoung; Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

    2015-01-01

    We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary's teaching hospital, Daejeon, Korea) from 2010-2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton's preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization-Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p contrast media-induced adverse reactions. The World Health Organization-Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results.

  8. Quality assurance of approved out of programme psychiatry training and research over the past 5 years

    Science.gov (United States)

    Osman-Hicks, Victoria; Graham, Hannah; Leadbetter, Peter; Brittlebank, Andrew

    2015-01-01

    Aims and method This paper intends to analyse the number of applications, trainee demographic and approval rate of those applying for out of programme training (OOPT) or out of programme research (OOPR) between January 2008 and April 2013 using the committee’s anonymised database. We also describe the process of application and approval by the Quality Assurance Committee. Results There were 90 applications, including 10 resubmissions during the 64-month period. Most applicants (77%) were higher trainees; 53% of applicants were from the London deanery; 60% of applications were for research posts and higher degrees (OOPR). Overall, 64% were approved by the committee: 70% for OOPRs and 53% for OOPTs. Clinical implications This paper shows with transparency the breakdown of applications to the Quality Assurance Committee. Around two-thirds of applications to the committee are supported (64%). Relatively few psychiatry trainees (2.5%) have applied for an OOPT or an OOPR over the past 5 years. PMID:26191450

  9. Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

    Science.gov (United States)

    Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B

    2017-05-01

    Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.

  10. Menstrual cyclicity post OC withdrawal in PCOS: Use of non-hormonal options.

    Science.gov (United States)

    Kulshreshtha, Bindu; Arora, Arpita; Pahuja, Isha; Sharma, Neera; Pant, Shubhi

    2016-08-01

    There is no data on menstrual cyclicity post oral contraceptive (OC) withdrawal with nonhormonal options in PCOS patients. OC could affect obesity, insulin and gonadotropins factors integral to pathogenesis of PCOS, thereby adversely affecting the HPG axis. Menstrual cycles of PCOS patients were retrospectively studied post OCP. Patients developing regular versus irregular cycles post OC were compared. Forty-eight PCOS patients were followed for an average of 1.9 years post OC. Thirty-six (75%) achieved regular cycles over a period of one year with other nonhormonal options like spironolactone and metformin. Seven patients required no treatment. Patients who continued to have irregular cycles had a longer pre OC cycle length (p PCOS may not require any treatment post OC.

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

    Science.gov (United States)

    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. Shared consultant physician posts.

    LENUS (Irish Health Repository)

    Cooke, J

    2012-01-31

    Our aim was to assess the acceptability and cost-efficiency of shared consultancy posts. Two consultant physicians worked alternate fortnights for a period of twelve months. Questionnaires were distributed to general practitioners, nurses, consultants and junior doctors affected by the arrangement. Patients or their next of kin were contacted by telephone. 1\\/17 of consultants described the experience as negative. 14\\/19 junior doctors reported a positive experience. 11 felt that training had been improved while 2 felt that it had been adversely affected. 17\\/17 GPs were satisfied with the arrangement. 1\\/86 nurses surveyed reported a negative experience. 1\\/48 patients were unhappy with the arrangement. An extra 2.2 (p<0.001) patients were seen per clinic. Length of stay was shortened by 2.49 days (p<0.001). A saving of 69,212 was made due to decreased locum requirements. We present data suggesting structured shared consultancy posts can be broadly acceptable and cost efficient in Ireland.

  13. Suspected post-vaccinal acute polyradiculoneuritis in a puppy : short communication

    Directory of Open Access Journals (Sweden)

    R. Gehring

    2001-07-01

    Full Text Available A 4-month-old German shepherd puppy developed hindquarter weakness after vaccination with a multivalent vaccine. This is suggestive of post-vaccinal polyradiculoneuritis. To date, only 1 similar case has been reported, which may be due to the under-reporting of suspected adverse drug reactions.

  14. Systematic Review: FDA-Approved Prescription Medications for Adults With Constipation

    Science.gov (United States)

    Lacy, Brian E.

    2006-01-01

    Constipation is a common, often chronic, gastrointestinal disorder that can negatively impact the lives of those it affects and can be difficult to treat satisfactorily. The objective of this systematic review is to identify and analyze the available published literature on US Food and Drug Administration–approved prescription therapies for adults with constipation (episodic and chronic) and to assess their place in therapy, based on the methodologic strength and results of identified clinical trials. Ovid MEDLINE, PubMed, and EMBASE databases were used to search the published literature. Studies were included if they were randomized and prospective, conducted in adults (age ≥18), published as full-length manuscripts in English, and compared the test agent with placebo or a comparator(s). Studies were excluded if they involved patients with constipation attributed to secondary causes. Because fully published manuscripts from phase III efficacy trials involving the recently approved medication lubiprostone were not available, a manual search was performed of abstracts from the two annual major gastroenterology meetings (American College of Gastroenterology and Digestive Disease Week) from the past 4 years. Data on study design; number, age, and sex of patients; duration of treatment period; primary efficacy variable; secondary efficacy variables; adverse events; and discontinuations because of adverse events were abstracted from eligible articles. Eligible studies were assessed using well-established recommendations and a preformatted standardized form. A scoring system, with scores ranging from 1 to 15, was used to individually and separately assess the methodologic quality of the studies. Results of this analysis indicate a general lack of methodologically high-quality clinical trials supporting the use of lactulose and PEG 3350 to treat patients with chronic constipation, but data support their use in acute, episodic constipation. Conversely, high

  15. Review by a local medical research ethics committee of the conduct of approved research projects, by examination of patients' case notes, consent forms, and research records and by interview.

    Science.gov (United States)

    Smith, T; Moore, E J; Tunstall-Pedoe, H

    1997-05-31

    To monitor the conduct of medical research projects that have already been approved by the local medical research ethics committee. Follow up study of ethically approved studies (randomly selected from all the studies approved in the previous year) by examination of patients' case notes, consent forms, and research records and by interview of the researchers at their workplace. Tayside, Scotland (mixed rural and urban population). 30 research projects approved by Tayside local medical research ethics committee. Adherence to the agreed protocol, particularly for recruitment (obtaining and recording informed consent) and for specific requirements of the ethics committee, including notification of changes to the protocol and of adverse events. In one project only oral consent had been obtained, and in a quarter of the studies one or more consent forms were incorrectly completed. Inadequate filing of case notes in five studies and of consent forms in six made them unavailable for scrutiny. Adverse events were reported, but there was a general failure to report the abandoning or non-starting of projects in two studies the investigators failed to notify a change in the responsible researcher. Monitoring of medical research by local medical research ethics committees promotes and preserves ethical standards, protects subjects and researchers, discourages fraud, and has the support of investigators. We recommend that 10% of projects should undergo on-site review, with all others monitored by questionnaire. This would require about six person hours of time and a salary bill of 120 pounds per study monitored.

  16. Childhood Adversity and Pain Sensitization.

    Science.gov (United States)

    You, Dokyoung Sophia; Meagher, Mary W

    Childhood adversity is a vulnerability factor for chronic pain. However, the underlying pain mechanisms influenced by childhood adversity remain unknown. The aim of the current study was to evaluate the impact of childhood adversity on dynamic pain sensitivity in young adults. After screening for childhood adverse events and health status, healthy individuals reporting low (below median; n = 75) or high levels of adversity (the top 5%; n = 51) were invited for pain testing. Both groups underwent heat pain threshold and temporal summation of second pain (TSSP) testing after reporting depressive symptoms. TSSP refers to a progressive increase in pain intensity with repetition of identical noxious stimuli and is attributed to central sensitization. Changes in pain ratings over time (slope) were computed for TSSP sensitization and decay of subsequent aftersensations. The high-adversity group showed greater TSSP sensitization (meanslope, 0.75; SDpositive slope, 1.78), and a trend toward a slower decay (meanslope, -11.9; SD, 3.4), whereas the low-adversity group showed minimal sensitization (meanslope, 0.07; SDnear-zero slope, 1.77), F(1,123) = 5.84, p = .017 and faster decay (meanslope, -13.1; SD, 3.4), F(1,123) = 3.79, p = .054. This group difference remained significant even after adjusting for adult depressive symptoms (p = .033). No group difference was found in heat pain threshold (p = .85). Lastly, the high-adversity group showed blunted cardiac and skin conductance responses. These findings suggest that enhancement of central sensitization may provide a mechanism underlying the pain hypersensitivity and chronicity linked to childhood adversity.

  17. Post-traumatic stress disorder: medicine and politics.

    Science.gov (United States)

    Stein, Dan J; Seedat, Soraya; Iversen, Amy; Wessely, Simon

    2007-01-13

    Regrettably, exposure to trauma is common worldwide, and can have serious adverse psychological results. The introduction of the notion of post-traumatic stress disorder has led to increasing medicalisation of the problem. This awareness has helped popular acceptance of the reality of post-traumatic psychiatric sequelae, which has boosted research into the pathogenesis of the disorder, leading to improved pharmacological and psychological management. The subjective experience of trauma and subsequent expression of symptoms vary considerably over space and time, and we emphasise that not all psychological distress or psychiatric disorders after trauma should be termed post-traumatic stress disorder. There are limits to the medicalisation of distress and there is value in focusing on adaptive coping during and after traumas. Striking a balance between a focus on heroism and resilience versus victimhood and pathological change is a crucial and constant issue after trauma for both clinicians and society. In this Review we discuss the advantages and disadvantages of medicalising trauma response, using examples from South Africa, the Armed Services, and post-disaster, to draw attention to our argument.

  18. Lymphoma Therapy and Adverse Events: Nursing Strategies for Thinking Critically and Acting Decisively.

    Science.gov (United States)

    Goodrich, Amy; Wagner-Johnston, Nina; Delibovi, Dana

    2017-02-01

    Multiple treatment options, combined with disease heterogeneity, have created nursing challenges in the management of adverse events (AEs) during antilymphoma therapy. Testing has revealed that less than half of participating nurses correctly graded peripheral neuropathy and neutropenia related to antilymphoma regimens. This article identifies nursing challenges in the management of AEs associated with therapy for lymphomas and describes how strategies in critical thinking can help meet those challenges. A comprehensive literature search in oncology nursing, nursing education, and critical thinking was conducted; participant responses to pre- and post-tests at nursing education programs were evaluated; and a roundtable meeting of authors was convened. Oncology nurses can cultivate critical thinking skills, practice thinking critically in relation to team members and patients, leverage information from the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events, and manage workflow to allow more opportunity for critical thinking.

  19. Is peri-operative cortisol secretion related to post-operative cognitive dysfunction?

    NARCIS (Netherlands)

    Rasmussen, L.S.; O'Brien, J.T.; Silverstein, J.H.; Johnson, T.; Siersma, V.D.; Canet, J.; Jolles, J.; Hanning, C.D.; Kuipers, H.M.; Abildstrom, H.; Papaioannou, A.; Raeder, J.; Yli-Hankala, A.; Sneyd, J.R.; Munoz, L.; Moller, J.T.

    2005-01-01

    Background: The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post-operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in

  20. Coding of adverse events of suicidality in clinical study reports of duloxetine for the treatment of major depressive disorder: descriptive study.

    Science.gov (United States)

    Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn; Lundh, Andreas; Gøtzsche, Peter C

    2014-06-04

    To assess the effects of coding and coding conventions on summaries and tabulations of adverse events data on suicidality within clinical study reports. Systematic electronic search for adverse events of suicidality in tables, narratives, and listings of adverse events in individual patients within clinical study reports. Where possible, for each event we extracted the original term reported by the investigator, the term as coded by the medical coding dictionary, medical coding dictionary used, and the patient's trial identification number. Using the patient's trial identification number, we attempted to reconcile data on the same event between the different formats for presenting data on adverse events within the clinical study report. 9 randomised placebo controlled trials of duloxetine for major depressive disorder submitted to the European Medicines Agency for marketing approval. Clinical study reports obtained from the EMA in 2011. Six trials used the medical coding dictionary COSTART (Coding Symbols for a Thesaurus of Adverse Reaction Terms) and three used MedDRA (Medical Dictionary for Regulatory Activities). Suicides were clearly identifiable in all formats of adverse event data in clinical study reports. Suicide attempts presented in tables included both definitive and provisional diagnoses. Suicidal ideation and preparatory behaviour were obscured in some tables owing to the lack of specificity of the medical coding dictionary, especially COSTART. Furthermore, we found one event of suicidal ideation described in narrative text that was absent from tables and adverse event listings of individual patients. The reason for this is unclear, but may be due to the coding conventions used. Data on adverse events in tables in clinical study reports may not accurately represent the underlying patient data because of the medical dictionaries and coding conventions used. In clinical study reports, the listings of adverse events for individual patients and narratives

  1. New therapies versus first-generation biologic drugs in psoriasis: a review of adverse events and their management.

    Science.gov (United States)

    Carrascosa, J M; Del-Alcazar, E

    2018-04-01

    Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy. Expert commentary: More than a decade after the first approval of biologic drugs for use in psoriasis, the good safety profile of these drugs is one of the main justifications and incentives for their long-term use. The emergence of new pharmacological groups has made it possible to avoid some of the class effects of first-generation biologic agents and the new therapies appear to pose less risk of reactivation of latent infections, such as hepatitis B virus and tuberculosis. However, they are associated with new adverse effects related to their mechanism of action, including candidiasis and the risk of exacerbation or onset of inflammatory bowel disease.

  2. Comparison of the Adverse Event Profile of TheraSphere® with SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review.

    Science.gov (United States)

    Kallini, Joseph Ralph; Gabr, Ahmed; Thorlund, Kristian; Balijepalli, Chakrapani; Ayres, Dieter; Kanters, Steve; Ebrahim, Shanil; Mills, Edward; Lewandowski, Robert J; Salem, Riad

    2017-07-01

    To compare the safety profiles of TheraSphere ® (glass) and SIR-Spheres ® (resin) Y90 microspheres for the treatment of hepatocellular carcinoma. A systematic review was conducted using the databases MEDLINE, Embase, and Cochrane Trials Register to identify all relevant studies. Baseline characteristics and adverse events of all grades related to gastrointestinal, hepatobiliary, and respiratory systems were collected along with commonly reported outcomes related to post-embolization syndrome. For all outcomes, data from each study were tabulated for each intervention. Adverse events and patients were summed across studies on TheraSphere ® and SIR-Spheres ® , respectively, and the resulting proportion of patients experiencing an outcome for both interventions was calculated. Thirty-one observational studies were included in the review. In the adverse events of all grades, more patients treated with resin microspheres reported gastric ulcers, hepatic encephalopathy, cholecystitis, hepatic failure, and pleural effusion. Patients treated with resin microspheres also had more hepatobiliary adverse events of grade 3 or higher. In the events related to post-embolization syndrome, glass microspheres exhibited a similar safety profile compared to resin microspheres. Ascites and nausea grade 3 or higher were recorded more frequently with glass microsphere treatment. Based on this review of the published literature, glass microspheres exhibit a safety profile with fewer gastrointestinal and pulmonary adverse events compared to resin microspheres in the treatment of hepatocellular carcinoma.

  3. The two sides of adversity: the effect of distant versus recent adversity on updating emotional content in working memory.

    Science.gov (United States)

    Levens, Sara M; Armstrong, Laura Marie; Orejuela-Dávila, Ana I; Alverio, Tabitha

    2017-09-01

    Previous research suggests that adversity can have both adaptive and maladaptive effects, yet the emotional and working memory processes that contribute to more or less adaptive outcomes are unclear. The present study sought to investigate how updating emotional content differs in adolescents who have experienced past, recent, or no adversity. Participants who had experienced distant adversity (N = 53), no adversity (N = 58), or recent adversity only (N = 20) performed an emotion n-back task with emotional facial expressions. Results revealed that the distant adversity group exhibited significantly faster reaction times (RTs) than the no adversity and recent adversity only groups. In contrast, the recent adversity only group exhibited significantly slower RTs and more errors than the distant adversity and no adversity groups. These results suggest an emotion and executive control pathway by which both the benefits and negative effects of adversity may be conferred. Results also highlight the importance of time in assessing the impact of adversity.

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

    Science.gov (United States)

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

    2014-09-01

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

  5. OAE: The Ontology of Adverse Events.

    Science.gov (United States)

    He, Yongqun; Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Guo, Abra; Zhang, Shelley; Jagannathan, Desikan; Toldo, Luca; Tao, Cui; Smith, Barry

    2014-01-01

    A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term 'adverse event' denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e

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

    Science.gov (United States)

    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

  7. Childhood adversity and adult personality.

    Science.gov (United States)

    Rosenman, Stephen; Rodgers, Bryan

    2006-05-01

    To explore how recalled childhood adversity affects trait measures of personality in three age cohorts of an Australian adult population and to examine the effects of particular adversities on adult personality traits. A total of 7485 randomly selected subjects in the age bands of 20-24, 40-44 and 60-64 years were interviewed at the outset of a longitudinal community study of psychological health in the Canberra region of Australia. In the initial interview, subjects answered 17 questions about domestic adversity and three questions on positive aspects of upbringing to age 16 years. Personality traits were measured by Eysenck Personality Questionnaire, Behavioural Activation and Inhibition Scales, Positive and Negative Affect Scales and a measure of dissocial behaviours. Higher levels of childhood adversity substantially increase the risk of high neuroticism (OR = 2.6) and negative affect (OR = 2.6), less for behavioural inhibition (OR = 1.7) and for dissocial behaviour (OR = 1.7). No significant effect is seen for extraversion, psychoticism or behavioural activation. Age and gender had little effect on the pattern of risk. Maternal depression has significant and substantial independent effects on measures of neuroticism and negative affect as well as most other measures of personality. Childhood domestic adversity has substantial associations with clinically important aspects of personality: neuroticism and negative affect. Only small effects are seen on behavioural inhibition and dissocial behaviour, and no significant effect on extraversion and behavioural activation. These unexpected findings contradict clinical belief. Maternal psychological ill-health is pre-eminent among adversities predicting later disadvantageous traits, even for those traits that had only the slightest association with childhood adversity. Consequences of childhood adversity prevail throughout the lifespan in men and women equally. The study underlines the importance of childhood domestic

  8. Biosimilars approval process.

    Science.gov (United States)

    Zuñiga, Leyre; Calvo, Begoña

    2010-04-01

    For similar biological medicinal products, the so-called biosimilars, clinical trials are required rather than just the bioequivalence studies required to support the registration of a generic small molecule drug product. The EU Directive 2001/83/EC, as amended, stated that where a biological medicinal product which is similar to a reference biological product, does not meet the conditions in the definition of generic medicinal products the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided. The challenge is to determine the exact nature of the non-clinical and clinical programme required to gain regulatory approval. The applicant is encouraged to provide a detailed description of the strategy used to demonstrate the biosimilar and the reference product have similar profiles in terms of quality, safety and efficacy. The extent to which comparability can be proven will have quite an impact on how many non-clinical and clinical studies the biosimilar applicant will be required to conduct. The dossier submitted by the applicant to the EMEA should cover all aspects of the comparability assessment and must include data on possible unwanted immune reactions to the therapeutic protein. Post-marketing pharmacovigilance plans are also expected to be included in the biosimilar dossier. Copyright 2009 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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

  10. A Pilot Health Information Technology-Based Effort to Increase the Quality of Transitions From Skilled Nursing Facility to Home: Compelling Evidence of High Rate of Adverse Outcomes.

    Science.gov (United States)

    Donovan, Jennifer L; Kanaan, Abir O; Gurwitz, Jerry H; Tjia, Jennifer; Cutrona, Sarah L; Garber, Lawrence; Preusse, Peggy; Field, Terry S

    2016-04-01

    Older adults are often transferred from hospitals to skilled nursing facilities (SNFs) for post-acute care. Patients may be at risk for adverse outcomes after SNF discharges, but little research has focused on this period. Assessment of the feasibility of a transitional care intervention based on a combination of manual information transmission and health information technology to provide automated alert messages to primary care physicians and staff; pre-post analysis to assess potential impact. A multispecialty group practice. Adults aged 65 and older, discharged from SNFs to home; comparison group drawn from SNF discharges during the previous 1.5 years, matched on facility, patient age, and sex. For the pre-post analysis, we tracked rehospitalization within 30 days after discharge and adverse drug events within 45 days. The intervention was developed and implemented with manual transmission of information between 8 SNFs and the group practice followed by entry into the electronic health record. The process required a 5-day delay during which a large portion of the adverse events occurred. Over a 1-year period, automated alert messages were delivered to physicians and staff for the 313 eligible patients discharged from the 8 SNFs to home. We compared outcomes to those of individually matched discharges from the previous 1.5 years and found similar percentages with 30-day rehospitalizations (31% vs 30%, adjusted HR 1.06, 95% CI 0.80-1.4). Within the adverse drug event (ADE) study, 30% of the discharges during the intervention period and 30% of matched discharges had ADEs within 45 days. Older adults discharged from SNFs are at high risk of adverse outcomes immediately following discharge. Simply providing alerts to outpatient physicians, especially if delivered multiple days after discharge, is unlikely to have any impact on reducing these rates. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All

  11. Anti-infective medicine quality: analysis of basic product quality by approval status and country of manufacture

    Directory of Open Access Journals (Sweden)

    Bate R

    2012-07-01

    failure rates among WHO-approved products suggest there may be some weakness in post-marketing surveillance of these products, especially of Chinese-made WHO-approved products. The discrepancy between the failure rate of WHO-approved products from India (2.39% and China (17.65% is cause for concern. It is possible that more of the failures originating in China are counterfeit products, but this cannot be ascertained without greater help from the manufacturers themselves.Keywords: stringent regulatory authority, World Health Organization prequalification program, product approval, counterfeit, India, China

  12. Prevalence and impact of childhood adversities and post-traumatic stress disorder in women with fibromyalgia and chronic widespread pain.

    Science.gov (United States)

    Coppens, E; Van Wambeke, P; Morlion, B; Weltens, N; Giao Ly, H; Tack, J; Luyten, P; Van Oudenhove, L

    2017-10-01

    This study investigates the prevalence of different types of childhood adversities (CA) and posttraumatic stress disorder (PTSD) in female patients with Fibromyalgia or Chronic Widespread Pain (FM/CWP) compared to patients with Functional Dyspepsia (FD) and achalasia. In FM/CWP, we also investigated the association between CA and PTSD on the one hand and pain severity on the other. Patient samples consisted of 154 female FM/CWP, 83 female FD and 53 female achalasia patients consecutively recruited from a tertiary care hospital. Well-validated self-report questionnaires were used to investigate CA and PTSD. Forty-nine per cent of FM/CWP patients reported at least 1 type of CA, compared to 39.7% of FD patients and 23.4% of achalasia patients (p PTSD than both FD (p PTSD comorbidity, but not CA, was associated with self-reported pain severity and PTSD severity mediated the relationship between CA and pain severity. In summary, the prevalence of CA is higher in FM/CWP compared to achalasia, but similar to FD. However, PTSD is more prevalent in FM/CWP compared to FD and associated with higher pain intensity in FM/CWP. As expected and has been shown in other functional disorders, we found elevated levels of childhood adversity in FM/CWP patients. Results of this study however suggest that the impact of childhood adversity (i.e. whether such events have led to the development of PTSD symptoms), rather than the mere presence of such adversity, is of crucial importance in FM/CWP patients. Screening for PTSD symptoms should be an essential part of the assessment process in patients suffering from FM/CWP, and both prevention and intervention efforts should take into account PTSD symptoms and their impact on pain severity and general functioning. © 2017 European Pain Federation - EFIC®.

  13. The association between cumulative adversity and mental health: considering dose and primary focus of adversity.

    Science.gov (United States)

    Keinan, Giora; Shrira, Amit; Shmotkin, Dov

    2012-09-01

    The study addressed the dose-response model in the association of cumulative adversity with mental health. Data of 1,725 participants aged 50+ were drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe. Measures included an inventory of potentially traumatic events, distress (lifetime depression, depressive symptoms), and well-being (quality of life, optimism/hope). The maximal effect of cumulative trauma emerged in the contrast between 0-2 and 3+ events, where the higher number of events related to higher distress but also to higher well-being. While self-oriented adversity revealed no, or negative, association with well-being, other-oriented adversity revealed a positive association. The study suggests an experiential dose of cumulative adversity leading to a co-activation of distress and well-being. The source of this co-activation seems to be other-oriented adversity.

  14. A research framework for pharmacovigilance in health social media: Identification and evaluation of patient adverse drug event reports.

    Science.gov (United States)

    Liu, Xiao; Chen, Hsinchun

    2015-12-01

    Social media offer insights of patients' medical problems such as drug side effects and treatment failures. Patient reports of adverse drug events from social media have great potential to improve current practice of pharmacovigilance. However, extracting patient adverse drug event reports from social media continues to be an important challenge for health informatics research. In this study, we develop a research framework with advanced natural language processing techniques for integrated and high-performance patient reported adverse drug event extraction. The framework consists of medical entity extraction for recognizing patient discussions of drug and events, adverse drug event extraction with shortest dependency path kernel based statistical learning method and semantic filtering with information from medical knowledge bases, and report source classification to tease out noise. To evaluate the proposed framework, a series of experiments were conducted on a test bed encompassing about postings from major diabetes and heart disease forums in the United States. The results reveal that each component of the framework significantly contributes to its overall effectiveness. Our framework significantly outperforms prior work. Published by Elsevier Inc.

  15. Methodological Considerations for Comparison of Brand Versus Generic Versus Authorized Generic Adverse Event Reports in the US Food and Drug Administration Adverse Event Reporting System (FAERS).

    Science.gov (United States)

    Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Peissig, Peggy L; Berg, Richard L; Page, David C; Hansen, Richard A

    2017-12-01

    The US Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing safety database, can be used to differentiate brand versus generic safety signals. To explore the methods for identifying and analyzing brand versus generic adverse event (AE) reports. Public release FAERS data from January 2004 to March 2015 were analyzed using alendronate and carbamazepine as examples. Reports were classified as brand, generic, and authorized generic (AG). Disproportionality analyses compared reporting odds ratios (RORs) of selected known labeled serious adverse events stratifying by brand, generic, and AG. The homogeneity of these RORs was compared using the Breslow-Day test. The AG versus generic was the primary focus since the AG is identical to brand but marketed as a generic, therefore minimizing generic perception bias. Sensitivity analyses explored how methodological approach influenced results. Based on 17,521 US event reports involving alendronate and 3733 US event reports involving carbamazepine (immediate and extended release), no consistently significant differences were observed across RORs for the AGs versus generics. Similar results were obtained when comparing reporting patterns over all time and just after generic entry. The most restrictive approach for classifying AE reports yielded smaller report counts but similar results. Differentiation of FAERS reports as brand versus generic requires careful attention to risk of product misclassification, but the relative stability of findings across varying assumptions supports the utility of these approaches for potential signal detection.

  16. Electronic Approval of Invoices (AEF)

    CERN Document Server

    2004-01-01

    With a view to the simplification of administrative procedures, AS and FI Departments have completed the second phase of the new procedure for the electronic approval of invoices via the EDH application. The aim of this new procedure is to rationalise the invoice approval process, notably by eliminating paper copies from the approval circuit. This will simplify the processing of invoices and facilitate their timely settlement, while at the same time maintaining a high level of security. Phase II includes handling the electronic approval process of invoices whose amounts do not correspond exactly to those of the associated orders. In such cases, budgetary approval is required for the entire invoiced amount. Further information can be obtained at : http://ais.cern.ch/projs/AEF/help/F_help.htm Phase II of the procedure will be introduced gradually with effect from April 2004. Finance Department, Accounts Payable Section Tel: 72295 Organisation and Procedures Tel: 75885 Information Technologies Department,...

  17. Adverse reactions to contrast media: an analysis of spontaneous reports in the database of the pharmacovigilance programme of India.

    Science.gov (United States)

    Kalaiselvan, Vivekanandan; Sharma, Surbhi; Singh, Gyanendra Nath

    2014-09-01

    Contrast media are used widely to improve medical imaging. Like all other pharmaceuticals, these agents are not completely devoid of risk, and continuous monitoring of adverse reactions with these agents is important. Spontaneous reporting is the simplest method for understanding the safety profile of pharmaceutical products after their approval. Our objective was to identify the pattern and characteristics of adverse reactions attributed to contrast media in the Indian population reported to the National Coordination Centre for the Pharmacovigilance Programme of India (NCC-PvPI). Individual case safety reports (ICSRs) attributed to contrast media submitted spontaneously to the NCC-PvPI were extracted from the database for July 2010 to September 2013. We analysed these reports for information related to reporter's professional category, patient's age and sex, reporter's diagnosis of the reaction, seriousness of the reaction, type of contrast media exposure, system organ class (SOC) affected (as described in World Health Organization Adverse Reaction Terminology [WHO-ART]) and outcome. Of the total 59,915 ICSRs in the database, 415 (0.7%) were suspected adverse reactions to contrast media; 44 reports were serious, including three fatal cases. The most affected SOCs were skin and appendage disorders, body as a whole-general disorders, gastrointestinal system disorders and respiratory system disorders. Hypersensitivity reactions were reported in the majority of ICSRs. The contrast media with the highest number of reports were iohexol (40.7%), iomeprol (17.8%), iopamidol (12%) and diatrizoate (12%). Most of the reactions to contrast media were allergic-like, and no previously unrecognised adverse reactions were observed in the Indian population. Further data and increased awareness among healthcare professionals is required to signal and prevent the consequences of adverse reactions attributed to contrast media.

  18. Adverse Events With Sustained-Release Donepezil in Alzheimer Disease: Relation to Body Mass Index.

    Science.gov (United States)

    Lee, Chunsoo; Lee, Kyungsang; Yu, Hyewon; Ryu, Seung-Ho; Moon, Seok Woo; Han, Changsu; Lee, Jun-Young; Lee, Young Min; Kim, Shin-Gyeom; Kim, Ki Woong; Lee, Dong Woo; Kim, Seong Yoon; Lee, Sang-Yeol; Bae, Jae Nam; Jung, Young-Eun; Kim, Jeong Lan; Kim, Byung-Soo; Shin, Il-Seon; Kim, Young Hoon; Kim, Bong Jo; Kang, Hyo Shin; Myung, Woojae; Carroll, Bernard J; Kim, Doh Kwan

    2017-08-01

    Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population. To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months. After screening, we analyzed a final cohort of 166 patients who received donepezil 23 mg/d for 24 weeks to compare the occurrence of treatment-emergent adverse events (TEAEs) between patients with high versus low body mass index (BMI) based on the World Health Organization overweight criteria for Asian populations (23 kg/m). Treatment-emergent adverse events were reported by 79.45% of patients in the lower BMI group and 58.06% of patients in the higher BMI group (odds ratio, 2.79; 95% confidence interval, 1.39-5.63; χ = 7.58, P = 0.006). In a multivariable survival analysis, the group with lower BMI showed a higher occurrence of TEAEs (hazard ratio, 1.83; 95% confidence interval, 1.25-2.68; P = 0.002). In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.

  19. Outcomes of Endovascular Aneurysm Repair using the Ovation Stent Graft System in Adverse Anatomy.

    Science.gov (United States)

    Greaves, Nicholas S; Moore, Aiden; Seriki, Dare; Ghosh, Jonathan

    2018-04-01

    The aim was the evaluation of mid-term efficacy and safety outcome measures for the Ovation (Endologix, Santa Rosa, CA, USA) stent graft system in the management of infrarenal abdominal aortic aneurysms (iAAA) with adverse anatomy. A retrospective observational study of all patients undergoing elective iAAA repair was carried out from 2012 to 2017 using Ovation Prime or iX stent grafts with a minimum of 3 months follow-up at a single UK vascular centre. Post-operative surveillance involved computed tomography scans at 3 months and 1 year, with duplex ultrasound yearly thereafter. Outcome measures were established with retrospective analysis of pre- and post-operative imaging, and included peri-operative mortality, major adverse events, limb complications, aneurysm diameter change, and endoleak rates. All patients were within Ovation instructions for use (IFU), and assessment was made to determine whether aneurysms had anatomical features considered adverse for other commonly used stent graft platforms. Ovation stent grafts were implanted in 52 patients (79% male, mean age 75.7 years) with a mean aneurysm diameter of 62.5 mm (range 55-107 mm). There was 100% technical deployment success. The 30 day mortality was 0% and there was no aneurysm related mortality during follow-up (median 24 months, range 3-48 months). There were no type I or III endoleaks, but 19% developed type II endoleaks with one patient requiring re-intervention. No iliac limb occlusions were identified but one case required relining for limb kinking. All 52 cases were within the IFU for Ovation but only 12% met the IFU criteria for the Cook and Medtronic devices. The mid-term experience with Ovation demonstrates safe, durable treatment of iAAAs, including those with unfavourable anatomy, frequently off IFU for other commonly used devices. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

  20. Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

    Science.gov (United States)

    Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

    2010-01-01

    Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal

  1. Human trafficking and U.S. government responses post- 9/11

    OpenAIRE

    DeCeoursty, Kevin D.

    2016-01-01

    Approved for public release; distribution is unlimited The thesis examines the effectiveness of U.S. government anti-human trafficking efforts in the post- 9/11 environment. The body of human trafficking literature has revealed four common themes: human agency, labor rights, the sex industry, and crime control. The thesis examines five federal departments that were selected based on their relative experience, expertise, and operational mandates. Open source statistical data and other infor...

  2. Marketing Approval of Ethical Kampo Medicines.

    Science.gov (United States)

    Hakamatsuka, Takashi

    2017-01-01

    Kampo medicine is an original traditional medicine in Japan. Currently, 148 ethical Kampo formulations (Kampo prescription drugs) are registered in the National Health Insurance Price List. Kampo medicines can be prescribed under the national insurance system, which shows that they are part of conventional medicine in Japan. Japan has a unified drug approval system that does not distinguish between Western and Kampo medicines, and both are subject to the same regulations. The application for the market approval of ethical Kampo medicines is based on the general notification for drugs, i.e., "Handling of Ethical Combination Drugs" in "Precautions Necessary When Applying for Drug Marketing Approval" (Yakushokushinsa Notification No. 1121-12 of November 21, 2014). Furthermore, applications for the market approval of ethical Kampo medicines should follow the Kampo-specific notification of "Handling of Ethical Kampo Medicines" (Yakushin Notification No. 804 of June 25, 1980). Data from comparative studies with standard decoctions must be submitted with approval applications according to Yakushin 2 Notification No. 120 of May 31, 1985. The safety, efficacy, and quality of Kampo medicines are comprehensively assured by the Japanese Pharmacopoeia, Good Manufacturing Practice, Good Agricultural and Collection Practices, marketing approval certificate, approval standard, and pharmacovigilance. I believe that the basic framework for the market approval of ethical Kampo medicines has been established as described above. The key factors for the practical application of superior manufacturing technology and research achievements and the promotion of drug development are the specific guidelines for the approval of drugs of herbal origin.

  3. 40 CFR 145.31 - Approval process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Approval process. 145.31 Section 145.31 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE UIC PROGRAM REQUIREMENTS Program Approval, Revision and Withdrawal § 145.31 Approval process. (a...

  4. 40 CFR 52.2122 - Approval status.

    Science.gov (United States)

    2010-07-01

    ... sources covered by CTGs issued by the previous January. (b) EPA disapproved South Carolina's generic...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Carolina § 52.2122 Approval status. (a) With the exceptions set forth in this subpart, the Administrator approves South Carolina's plans for...

  5. 75 FR 48302 - Notice of Request for Extension of Approval of an Information Collection; Credit Account Approval...

    Science.gov (United States)

    2010-08-10

    ....gov ). FOR FURTHER INFORMATION CONTACT: For information on credit account approval for reimbursable..., at (301) 851-2908. SUPPLEMENTARY INFORMATION: Title: Credit Account Approval for Reimbursable... Inspection Service [Docket No. APHIS-2010-0071] Notice of Request for Extension of Approval of an Information...

  6. 78 FR 54617 - Notice of Request for Extension of Approval of an Information Collection; Credit Account Approval...

    Science.gov (United States)

    2013-09-05

    ...] Notice of Request for Extension of Approval of an Information Collection; Credit Account Approval for... (202) 799-7039 before coming. FOR FURTHER INFORMATION CONTACT: For information on credit account... Coordinator, at (301) 851-2908. SUPPLEMENTARY INFORMATION: Title: Credit Account Approval for Reimbursable...

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

    Science.gov (United States)

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

    2017-12-01

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

  8. 40 CFR 52.1772 - Approval status.

    Science.gov (United States)

    2010-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) North Carolina § 52.1772 Approval status. (a) With the exceptions set forth in this subpart, the Administrator approves North Carolina's plans for... CTGs issued by the previous January. (b) New Source review permits issued pursuant to section 173 of...

  9. CTCAE v.3.0 in evaluation the radiation adverse events in cancer patients after pelvic irradiation (Contemporary mechanisms of radiation and comprehensive damage after cancer treatment)

    International Nuclear Information System (INIS)

    Encheva, E.; Zahariev, Z.; Sultanov, B.; Hadjieva, T.

    2010-01-01

    The authors present the first report of applying the NCI CTCAE v.3.0 for evaluation of radiation adverse events in Bulgaria. The adverse events are observed in early stage cervical and endometrial cancer patients receiving external beam radiotherapy after radical surgery during the radiotherapy and 3 months after it ended. The paper discusses the contemporary concepts of the normal tissue morbidity, the issue early-late adverse events, comprehensive factors and causes, except irradiation, involved in their occurrence. The possibility to define the single method contribution of the comprehensive cancer treatment for development of post-treatment adverse events in cancer survivors in effort to improve their quality of life is discussed. (authors)

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

    Science.gov (United States)

    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

  11. 9 CFR 147.52 - Approved tests.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Approved tests. 147.52 Section 147.52 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Approved Tests § 147.52 Approved tests. (a) The procedures for the bacteriological examination of poultry...

  12. Ontology-Based Vaccine Adverse Event Representation and Analysis.

    Science.gov (United States)

    Xie, Jiangan; He, Yongqun

    2017-01-01

    Vaccine is the one of the greatest inventions of modern medicine that has contributed most to the relief of human misery and the exciting increase in life expectancy. In 1796, an English country physician, Edward Jenner, discovered that inoculating mankind with cowpox can protect them from smallpox (Riedel S, Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center) 18(1):21, 2005). Based on the vaccination worldwide, we finally succeeded in the eradication of smallpox in 1977 (Henderson, Vaccine 29:D7-D9, 2011). Other disabling and lethal diseases, like poliomyelitis and measles, are targeted for eradication (Bonanni, Vaccine 17:S120-S125, 1999).Although vaccine development and administration are tremendously successful and cost-effective practices to human health, no vaccine is 100% safe for everyone because each person reacts to vaccinations differently given different genetic background and health conditions. Although all licensed vaccines are generally safe for the majority of people, vaccinees may still suffer adverse events (AEs) in reaction to various vaccines, some of which can be serious or even fatal (Haber et al., Drug Saf 32(4):309-323, 2009). Hence, the double-edged sword of vaccination remains a concern.To support integrative AE data collection and analysis, it is critical to adopt an AE normalization strategy. In the past decades, different controlled terminologies, including the Medical Dictionary for Regulatory Activities (MedDRA) (Brown EG, Wood L, Wood S, et al., Drug Saf 20(2):109-117, 1999), the Common Terminology Criteria for Adverse Events (CTCAE) (NCI, The Common Terminology Criteria for Adverse Events (CTCAE). Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html . Access on 7 Oct 2015), and the World Health Organization (WHO) Adverse Reactions Terminology (WHO-ART) (WHO, The WHO Adverse Reaction Terminology - WHO-ART. Available from: https://www.umc-products.com/graphics/28010.pdf

  13. 7 CFR 1710.406 - Loan approval.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Loan approval. 1710.406 Section 1710.406 Agriculture... GENERAL AND PRE-LOAN POLICIES AND PROCEDURES COMMON TO ELECTRIC LOANS AND GUARANTEES Application Requirements and Procedures for Loans § 1710.406 Loan approval. (a) A loan is approved when the Administrator...

  14. 40 CFR 123.61 - Approval process.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Approval process. 123.61 Section 123... REQUIREMENTS Program Approval, Revision, and Withdrawal § 123.61 Approval process. (a) After determining that a...; and (6) Briefly outline the fundamental aspects of the State's proposed program, and the process for...

  15. Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse RemodelingCLINICAL PERSPECTIVE

    Energy Technology Data Exchange (ETDEWEB)

    Kali, Avinash; Cokic, Ivan; Tang, Richard; Dohnalkova, Alice; Kovarik, Libor; Yang, Hsin-Jung; Kumar, Andreas; Prato, Frank S.; Wood, John C.; Underhill, David; Marban, Eduardo; Dharmakumar, Rohan

    2016-11-01

    Emerging evidence now supports the notion that persistent microvascular obstruction (PMO) may be more predictive of major adverse cardiovascular events than MI size itself. But, how PMO, a phenomenon limited to the acute/sub-acute period of MI, imparts adverse remodeling throughout the post MI period, particularly after its resolution, is incompletely understood. We hypothesized that PMOs resolve into chronic iron crystals within MI territories and actively impart a proinflammatory burden and adverse remodeling of infarction and LV in the chronic phase of MI. Canine models reperfused (n=20) and non-reperfused (n=20) with and without PMO were studied with serial cardiac MRI to characterize the spatiotemporal relationships between PMO, iron deposition, and infarct and LV remodeling indices between acute (day 7, post MI) and chronic (week 8, post MI). Histopathology and immunohistochemistry were used to validate the iron deposition, microscopically map and quantify the relationship between iron-rich chronic MI regions against pro-inflammatory macrophages, proinflammatory cytokines and matrix metalloproteinase. Atomic resolution transmission electron microscopy (TEM) was used to determine the crystallinity of iron and assess the physical effects of iron on lysosomes within macrophages, and energy-dispersive X-ray spectroscopy (EDS) to identify the chemical composition of the iron composite. Results showed that PMOs lead to iron deposition within chronic MI and that the extent of chronic iron deposition is strongly related to PMO Volume (r>0.6, p<0.001). TEM and EDS analysis showed that iron within chronic MI is found within macrophages as aggregates of nanocrystals of ~2.5 nm diameter in ferric state. Correlative histological studies showed that iron content, proinflammatory burden and collagen degrading enzyme were highly correlated (r >0.7, p<0.001). Iron within chronic MI was significantly associated with infarct resorption (r>0.5, p<0.001) and adverse structural (r

  16. Thallium imaging in management of post-revascularization patients

    International Nuclear Information System (INIS)

    Alazraki, N.; Krawczynska, E.

    1996-01-01

    The role of myocardial perfusion imaging in the evaluation of post revascularization patients has not been well defined. Published data with special emphasis on the results from the Emory Angioplasty versus Surgery Trial (EAST) indicate that the frequency of adverse cardiac events (death, MI, repeat revascularization) following PTCA or CABG is equal in symptomatic and asymptomatic patients with ischemic thallium defects. Current American Heart Association Guidelines recommend radionuclide studies only in symptomatic patients. Recently reported data support the need for non invasive testing in asymptomatic as well as symptomatic patients at 1 year postrevascularization. Prognostic variables including transient and permanent left ventricular dilatation and thallium lung uptake in addition to stress perfusion defect reversibility on myocardial thallium SPECT scans are important prognostic indicators in post revascularization patients

  17. [Trends in drug-induced liver injury based on reports of adverse reactions to PMDA in Japan].

    Science.gov (United States)

    Sudo, Chie; Maekawa, Keiko; Segawa, Katsunori; Hanatani, Tadaaki; Sai, Kimie; Saito, Yoshiro

    2012-01-01

    Reports on drug-related adverse reactions from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated under the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety measures. Although association between the medicine and the adverse event has not been clearly evaluated, and an incidence may be redundantly reported, this information would be useful to roughly grasp the current status of drug-related adverse reactions. In the present study, we analyzed the incidence of drug-induced liver injury by screening the open-source data publicized by the homepage of Pharmaceutical and Medical Devices Agency from 2005 to 2011 fiscal years. Major drug-classes suspected to cause general drug-induced liver injury were antineoplastics, anti-inflammatory agents/common cold drugs, chemotherapeutics including antituberculous drugs, antidiabetics, antiulcers and antiepileptics. In addition, reported cases for fulminant hepatitis were also summarized. We found that antituberculous isoniazid and antineoplastic tegafur-uracil were the top two suspected drugs. These results might deepen understanding of current situations for the drug-induced liver injury in Japan.

  18. Patient stratification and identification of adverse event correlations in the space of 1190 drug related adverse events

    DEFF Research Database (Denmark)

    Roitmann, Eva; Eriksson, Robert; Brunak, Søren

    2014-01-01

    New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse...

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

    Directory of Open Access Journals (Sweden)

    Gattis Katherine G

    2009-08-01

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

  20. Adulthood Personality Correlates of Childhood Adversity

    Directory of Open Access Journals (Sweden)

    Charles S. Carver

    2014-11-01

    Full Text Available Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, which we termed Anger/Aggression, Extrinsic focus, Agreeableness, and Engagement. Results: Controlling for concurrent depressive symptoms and gender, higher levels of reported childhood adversity related to lower Agreeableness and to higher Anger/Aggression and Extrinsic focus. Conclusions: Findings suggest that early adversity is linked to personality variables relevant to the building of social connection.

  1. Periodontal treatment during pregnancy decreases the rate of adverse pregnancy outcome: a controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Adriana Campos Passanezi Sant'Ana

    2011-04-01

    Full Text Available OBJECTIVES: The aim of this study was to evaluate the effects of non-surgical treatment of periodontal disease during the second trimester of gestation on adverse pregnancy outcomes. MATERIAL AND METHODS: Pregnant patients during the 1st and 2nd trimesters at antenatal care in a Public Health Center were divided into 2 groups: NIG - "no intervention" (n=17 or IG- "intervention" (n=16. IG patients were submitted to a non-surgical periodontal treatment performed by a single periodontist consisting of scaling and root planning (SRP, professional prophylaxis (PROPH and oral hygiene instruction (OHI. NIG received PROPH and OHI during pregnancy and were referred for treatment after delivery. Periodontal evaluation was performed by a single trained examiner, blinded to periodontal treatment, according to probing depth (PD, clinical attachment level (CAL, plaque index (PI and sulcular bleeding index (SBI at baseline and 35 gestational weeks-28 days post-partum. Primary adverse pregnancy outcomes were preterm birth (0.05 at IG and worsening of all periodontal parameters at NIG (p<0.0001, except for PI. Signifcant differences in periodontal conditions of IG and NIG were observed at 2nd examination (p<0.001. The rate of adverse pregnancy outcomes was 47.05% in NIG and 6.25% in IG. Periodontal treatment during pregnancy was associated to a decreased risk of developing adverse pregnancy outcomes [OR=13.50; CI: 1.47-123.45; p=0.02]. CONCLUSIONS: Periodontal treatment during the second trimester of gestation contributes to decrease adverse pregnancy outcomes.

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

    Directory of Open Access Journals (Sweden)

    Ying-Ying Yan

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

  3. Childhood adversities: Social support, premorbid functioning and social outcome in first-episode psychosis and a matched case-control group.

    Science.gov (United States)

    Trauelsen, Anne Marie; Bendall, Sarah; Jansen, Jens E; Nielsen, Hanne-Grethe L; Pedersen, Marlene B; Trier, Christopher H; Haahr, Ulrik H; Simonsen, Erik

    2016-08-01

    The establishment of childhood adversities as risk factors for non-affective psychosis has derived a need to consider alternative interpretations of several psychosis-related factors. This paper sought to examine premorbid adjustment trajectories and social outcome factors in relation to childhood adversities. Perceived support has been found to decrease the risk of post-traumatic stress disorder, and we wished to compare perceived support in people with first-episode psychosis to non-clinical control persons and explore its relation to childhood adversities. Every individual presenting with a non-affective first-episode psychosis (F20-29, except F21) in Region Zealand over a 2-year period was approached for participation and the 101 consenting participants were matched to 101 people with no psychiatric disorders. Comprehensive demographic data were collected. Assessment instruments included the Premorbid Assessment Scale, the Global Assessment of Functioning scale and the Childhood Trauma Questionnaire. The latter represented the childhood adversities in addition to parental separation and institutionalization. There were no associations between number of childhood adversities and different social or academic premorbid trajectories. Those with more adversities had lower global functioning the year prior to treatment start and reported lower rates of perceived support during childhood along with less current face-to-face contact with family members. Lack of peer support remained a significant predictor of psychosis when adversities were adjusted for; peer support diminished the risk of psychosis caused by childhood adversities by 10%. Childhood adversities may not predict specific premorbid trajectories, but have an effect on global functioning when the psychosis has begun. Perceived support, especially from peers, may be important in the development of psychosis, and those with more adversities may represent a vulnerable subgroup who need more assistance to

  4. 40 CFR 52.1323 - Approval status.

    Science.gov (United States)

    2010-07-01

    ... on January 16, 1979 (44 FR 3274) are met. (b) The Administrator approves Rule 10 CSR 10-2.290 as.... (c) The Administrator approves Rule 10 CSR 10-2.230 as identified under § 52.1320, paragraph (c)(70... SIP would be the emission limits stated in the rule. (d) The Administrator approves Rule 10 CSR 10-5...

  5. Mentality of nuclear energy and industry experts from post-socialist and post-capitalist countries and a problem of cooperation

    International Nuclear Information System (INIS)

    Gavrilov, S.D.; Kremnev, V.A.

    1996-01-01

    The disintegration of the Socialist Community and thereafter Yugoslavia, the Soviet Union and Czechoslovakia has led to the establishment of more than 20 post-socialist states. Their economies differ widely, and yet a mentality of the overwhelming majority of various strata of the population, including scientists and engineers, is almost invariable so far. The processes have had an effect on the mentality of nuclear experts, especially those who deal with nuclear weapon. The superposition of general crises of post-socialist countries and an availability of nuclear facilities and installations and nuclear technologies have already had an adverse effect on the specialists' mentality. On the other hand, experts from the post-capitalist countries have other mentalities and their socioeconomic position is cardinally distinguished. Thus, at most they may barely perceive the post-socialist specialists' envelope of mentality. It doesn't only prevent individuals' collaboration and organizations' cooperation by the lack of socio-culture-psychological misunderstanding,. In some instances it has already resulted in the interruption or cancellation of joint projects at the early stages of their implementation. The report is devoted to the problem of mutually beneficial interaction between experts and organizations from recently antagonistic systems, promoting better understanding, and a different rank specialists mentality convergence. The mentality and economic situation for experts from both the post-socialist countries and the Western industrial economies are discussed

  6. Decision support methods for the detection of adverse events in post-marketing data.

    Science.gov (United States)

    Hauben, M; Bate, A

    2009-04-01

    Spontaneous reporting is a crucial component of post-marketing drug safety surveillance despite its significant limitations. The size and complexity of some spontaneous reporting system databases represent a challenge for drug safety professionals who traditionally have relied heavily on the scientific and clinical acumen of the prepared mind. Computer algorithms that calculate statistical measures of reporting frequency for huge numbers of drug-event combinations are increasingly used to support pharamcovigilance analysts screening large spontaneous reporting system databases. After an overview of pharmacovigilance and spontaneous reporting systems, we discuss the theory and application of contemporary computer algorithms in regular use, those under development, and the practical considerations involved in the implementation of computer algorithms within a comprehensive and holistic drug safety signal detection program.

  7. Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Anuj Sharma

    2018-01-01

    Full Text Available Background: Chikungunya virus (CHIKV is a re-emerging pathogen that has caused widespread outbreaks affecting millions of people around the globe. Currently, there is no specific therapeutic drug against CHIKV, with symptomatic treatment only to manage the disease. Pi3-akt signaling has been implicated in infection of several viruses including that of CHIKV. Effect of Pi3-akt signaling inhibitors on CHIKV replication was evaluated in this study. Methods: Human primary dermal fibroblast cells were treated with inhibitors of the Pi3-akt signaling pathway. Suppression of CHIKV replication was evaluated as reduction in virus titer in cell supernatants. Effect of miltefosine (MF on CHIKV replication was evaluated in pre and post treatment regimen. Inhibition of virus replication was determined by cell growth, virus titer and western blot. Results: Inhibition of Akt-phosphorylation significantly inhibited CHIKV replication. No effect on CHIKV replication was observed after treatment with Pi3-kinase and mTOR activation inhibitors. Further, MF, an FDA-approved Akt-inhibitor, inhibited CHIKV replication in pre- and post-infection treatment regimens. Conclusion: Data suggests that Akt-phosphorylation can be an amenable target of therapy against CHIKV infection. This is the first study to show inhibition of CHIKV replication by MF, and presents a case for further development of MF as an anti-CHIKV drug.

  8. Towards standardized measurement of adverse events in spine surgery: conceptual model and pilot evaluation

    Directory of Open Access Journals (Sweden)

    Deyo Richard A

    2006-06-01

    kappa = 0.44. Adverse occurrence severity rating had fair agreement (mean weighted kappa = 0.33 when using a scale based on the JCAHO Sentinel Event Policy, but agreement was substantial for severity ratings on a new 11-point numerical severity scale (ICC = 0.74. There was excellent inter-rater agreement for a lumbar degenerative disease severity score (ICC = 0.98 and an index of surgery invasiveness (ICC = 0.99. Conclusion Composite measures of disease severity and surgery invasiveness may allow development of risk-adjusted predictive models for adverse events in spine surgery. Standard measures of adverse events and risk adjustment may also facilitate post-marketing surveillance of spinal devices, effectiveness research, and quality improvement.

  9. 30 CFR 14.7 - Approval marking and distribution records.

    Science.gov (United States)

    2010-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS General Provisions § 14.7 Approval marking and distribution records. (a) An approved conveyor belt must be marketed only under the name specified in the approval. (b) Approved conveyor belt must be legibly and...

  10. Hospital deaths and adverse events in Brazil

    Directory of Open Access Journals (Sweden)

    Pavão Ana Luiza B

    2011-09-01

    Full Text Available Abstract Background Adverse events are considered a major international problem related to the performance of health systems. Evaluating the occurrence of adverse events involves, as any other outcome measure, determining the extent to which the observed differences can be attributed to the patient's risk factors or to variations in the treatment process, and this in turn highlights the importance of measuring differences in the severity of the cases. The current study aims to evaluate the association between deaths and adverse events, adjusted according to patient risk factors. Methods The study is based on a random sample of 1103 patient charts from hospitalizations in the year 2003 in 3 teaching hospitals in the state of Rio de Janeiro, Brazil. The methodology involved a retrospective review of patient charts in two stages - screening phase and evaluation phase. Logistic regression was used to evaluate the relationship between hospital deaths and adverse events. Results The overall mortality rate was 8.5%, while the rate related to the occurrence of an adverse event was 2.9% (32/1103 and that related to preventable adverse events was 2.3% (25/1103. Among the 94 deaths analyzed, 34% were related to cases involving adverse events, and 26.6% of deaths occurred in cases whose adverse events were considered preventable. The models tested showed good discriminatory capacity. The unadjusted odds ratio (OR 11.43 and the odds ratio adjusted for patient risk factors (OR 8.23 between death and preventable adverse event were high. Conclusions Despite discussions in the literature regarding the limitations of evaluating preventable adverse events based on peer review, the results presented here emphasize that adverse events are not only prevalent, but are associated with serious harm and even death. These results also highlight the importance of risk adjustment and multivariate models in the study of adverse events.

  11. Premarket safety and efficacy studies for ADHD medications in children.

    Directory of Open Access Journals (Sweden)

    Florence T Bourgeois

    Full Text Available Attention-deficit hyperactivity disorder (ADHD is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated prior to their market authorization. We aimed to quantify the number of participants studied and their length of exposure in ADHD drug trials prior to marketing.We identified all ADHD medications approved by the Food and Drug Administration (FDA and extracted data on clinical trials performed by the sponsor and used by the FDA to evaluate the drug's clinical efficacy and safety. For each ADHD medication, we measured the total number of participants studied and the length of participant exposure and identified any FDA requests for post-marketing trials.A total of 32 clinical trials were conducted for the approval of 20 ADHD drugs. The median number of participants studied per drug was 75 (IQR 0, 419. Eleven drugs (55% were approved after <100 participants were studied and 14 (70% after <300 participants. The median trial length prior to approval was 4 weeks (IQR 2, 9, with 5 (38% drugs approved after participants were studied <4 weeks and 10 (77% after <6 months. Six drugs were approved with requests for specific additional post-marketing trials, of which 2 were performed.Clinical trials conducted for the approval of many ADHD drugs have not been designed to assess rare adverse events or long-term safety and efficacy. While post-marketing studies can fill in some of the gaps, better assurance is needed that the proper trials are conducted either before or after a new medication is approved.

  12. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

  13. Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: The CHAMACOS cohort.

    Science.gov (United States)

    Stein, Lauren J; Gunier, Robert B; Harley, Kim; Kogut, Katherine; Bradman, Asa; Eskenazi, Brenda

    2016-09-01

    Previous studies have observed an adverse association between prenatal exposure to organophosphate pesticide (OPs) and child cognition, but few studies consider the potential role of social stressors in modifying this relationship. We seek to explore the potential role of early social adversities in modifying the relationship between OPs and child IQ in an agricultural Mexican American population. Participants from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a prospective longitudinal pre-birth cohort study, include 329 singleton infants and their mothers followed from pregnancy through age 7. Dialkyl phosphate metabolite concentrations (DAPs), a biomarker of organophosphate pesticide exposure, were measured in maternal urine collected twice during pregnancy and averaged. Child cognitive ability was assessed at 7 years using the Wechsler Intelligence Scale for Children - Fourth Edition. Demographic characteristics and adversity information were collected during interviews and home visits at numerous time points from pregnancy until age 7. Among low-income Latina mothers and their children in the Salinas Valley, total adversity and specific domains of adversity including poor learning environment and adverse parent-child relationships were negatively associated with child cognition. Adverse associations between DAP concentrations and IQ were stronger in children experiencing greater adversity; these associations varied by child sex. For example, the association between prenatal OP exposure and Full-Scale IQ is potentiated among boys who experienced high adversity in the learning environment (β=-13.3; p-value child IQ differently among male and female children. These findings emphasize the need to consider plausible interactive pathways between social adversities and environmental exposures. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Trial endpoints for drug approval in oncology: Chemoprevention.

    Science.gov (United States)

    Beitz, J

    2001-04-01

    As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

  15. Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text.

    Science.gov (United States)

    Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

    2013-01-01

    Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives.

  16. Pathophysiological links between traumatic brain injury and post-traumatic headaches [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Robert L. Ruff

    2016-08-01

    Full Text Available This article reviews possible ways that traumatic brain injury (TBI can induce migraine-type post-traumatic headaches (PTHs in children, adults, civilians, and military personnel. Several cerebral alterations resulting from TBI can foster the development of PTH, including neuroinflammation that can activate neural systems associated with migraine. TBI can also compromise the intrinsic pain modulation system and this would increase the level of perceived pain associated with PTH. Depression and anxiety disorders, especially post-traumatic stress disorder (PTSD, are associated with TBI and these psychological conditions can directly intensify PTH. Additionally, depression and PTSD alter sleep and this will increase headache severity and foster the genesis of PTH. This article also reviews the anatomic loci of injury associated with TBI and notes the overlap between areas of injury associated with TBI and PTSD.

  17. The Relationship between Gender, Cumulative Adversities and ...

    African Journals Online (AJOL)

    The Relationship between Gender, Cumulative Adversities and Mental Health of Employees in ... CAs were measured in three forms (family adversities (CAFam), personal adversities ... Age of employees ranged between 18-65 years.

  18. Future Directions in Childhood Adversity and Youth Psychopathology.

    Science.gov (United States)

    McLaughlin, Katie A

    2016-01-01

    Despite long-standing interest in the influence of adverse early experiences on mental health, systematic scientific inquiry into childhood adversity and developmental outcomes has emerged only recently. Existing research has amply demonstrated that exposure to childhood adversity is associated with elevated risk for multiple forms of youth psychopathology. In contrast, knowledge of developmental mechanisms linking childhood adversity to the onset of psychopathology-and whether those mechanisms are general or specific to particular kinds of adversity-remains cursory. Greater understanding of these pathways and identification of protective factors that buffer children from developmental disruptions following exposure to adversity is essential to guide the development of interventions to prevent the onset of psychopathology following adverse childhood experiences. This article provides recommendations for future research in this area. In particular, use of a consistent definition of childhood adversity, integration of studies of typical development with those focused on childhood adversity, and identification of distinct dimensions of environmental experience that differentially influence development are required to uncover mechanisms that explain how childhood adversity is associated with numerous psychopathology outcomes (i.e., multifinality) and identify moderators that shape divergent trajectories following adverse childhood experiences. A transdiagnostic model that highlights disruptions in emotional processing and poor executive functioning as key mechanisms linking childhood adversity with multiple forms of psychopathology is presented as a starting point in this endeavour. Distinguishing between general and specific mechanisms linking childhood adversity with psychopathology is needed to generate empirically informed interventions to prevent the long-term consequences of adverse early environments on children's development.

  19. Evaluation of the adverse effects of subcutaneous carprofen over six days in healthy cats.

    Science.gov (United States)

    Steagall, P V M; Moutinho, F Q; Mantovani, F B; Passarelli, D; Thomassian, A

    2009-02-01

    This study evaluated the adverse effects of carprofen in seven healthy cats. Values for CBC, biochemical profiles and platelet aggregation were measured before and at seven days after SID treatment with subcutaneous carprofen: 4 mg/kg (day 1), 2mg/kg (day 2 and 3) and 1mg/kg (day 4 and 6) (CG) or 0.35 ml of saline (SG) for six days in a randomized, blinded, cross-over study with a four-week washout period. No treatment was given on day 5. Endoscopy of the GI tract was performed pre-treatment and on day 7 post-treatment. There were no significant changes in hematological profiles, biochemical profiles and endoscopy grading scores within nor between groups, except for lower albumin values at baseline than on day 7 (CG), and globulin and ALP values were higher at baseline than on day 7 in CG and SG. SC administration of carprofen over six days did not cause any adverse effects on gastrointestinal, hematological, or serum biochemical variables.

  20. Trends in global approvals of biotech crops (1992-2014).

    Science.gov (United States)

    Aldemita, Rhodora R; Reaño, Ian Mari E; Solis, Renando O; Hautea, Randy A

    2015-01-01

    With the increasing number of genetically modified (GM) events, traits, and crops that are developed to benefit the global population, approval of these technologies for food, feed, cultivation and import in each country may vary depending on needs, demand and trade interest. ISAAA established a GMO Approval Database to document global approvals of biotech crops. GM event name, crops, traits, developer, year of approval for cultivation, food/feed, import, and relevant dossiers were sourced from credible government regulatory websites and biosafety clearinghouses. This paper investigates the trends in GM approvals for food, feed and cultivation based on the number of approving countries, GM crops, events, and traits in the last 23 y (1992-2014), rationale for approval, factors influencing approvals, and their implications in GM crop adoption. Results show that in 2014, there was an accumulative increase in the number of countries granting approvals at 29 (79% developing countries) for commercial cultivation and 31 (70% developing countries) for food and 19 (80% developing developing) for feed; 2012 had the highest number of approving countries and cultivation approvals; 2011 had the highest number of country approvals for feed, and 2014 for food approvals. Herbicide tolerance trait had the highest events approved, followed by insect tolerance traits. Approvals for food product quality increased in the second decade. Maize had the highest number of events approved (single and stacked traits), and stacked traits product gradually increased which is already 30% of the total trait approvals. These results may indicate understanding and acceptance of countries to enhance regulatory capability to be able to benefit from GM crop commercialization. Hence, the paper provided information on the trends on the growth of the GM crop industry in the last 23 y which may be vital in predicting future GM crops and traits.

  1. Adversity, time, and well-being: A longitudinal analysis of time perspective in adulthood.

    Science.gov (United States)

    Holman, E Alison; Silver, Roxane Cohen; Mogle, Jacqueline A; Scott, Stacey B

    2016-09-01

    Despite the prominence of time in influential aging theories and the ubiquity of stress across the life span, research addressing how time perspective (TP) and adversity are associated with well-being across adulthood is rare. Examining the role of TP in coping with life events over the life span would be best accomplished after large-scale population-based exposure to a specific event, with repeated assessments to examine within- and between-person differences over time. A national sample aged 18-91 years (N = 722, M = 49.4 years) was followed for 3 years after the September 11, 2001 (9/11) terrorist attacks. Respondents completed assessments of 9/11-related television (TV) exposure 9-21 days after the attacks, temporal disintegration 2 months post-9/11, and TP, ongoing stress, and well-being at 12, 24, and 36 months post-9/11. Results provided support for measurement invariance of TP across time and across age. Early 9/11-related TV exposure was significantly associated with greater temporal disintegration. Temporal disintegration and ongoing stress, in turn, were associated with between- and within-person variation in past TP. This effect was qualified by an age interaction that indicated a stronger relationship between ongoing stress and past TP for younger compared with older adults. Past and future TP were significantly and independently related to individual differences and within-person variation in psychological well-being, regardless of age. Future work should incorporate adversity as an important correlate of TP across adulthood. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  2. 40 CFR 52.2352 - Change to approved plan.

    Science.gov (United States)

    2010-07-01

    ... Utah's approved State Implementation Plan (SIP). This rule language pertains to State Sales Tax... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Change to approved plan. 52.2352... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Utah § 52.2352 Change to approved...

  3. Post Fukushima safety enhancements in Indian PHWRS

    International Nuclear Information System (INIS)

    Ramasomayajulu, M.; Khot, Pankaj; Chauhan, Ashok

    2016-01-01

    Fukushima event was reviewed in Nuclear Power Corporation of India (NPCIL) and based on these reviews, safety enhancements were identified for Indian PHWRs. Safety enhancements such as additional emergency power sources, enhanced onsite water inventories, external water injection arrangements (Hook up points), measures related to hydrogen management, containment venting provision, seismic trip, mobile pumps, onsite emergency support Centre. These safety enhancements were reviewed by the regulatory body (Atomic Energy Regulatory Board, AERB) and were approved for implementation. Most of these are either implemented or in the advance stage of implementation. The paper elaborates above safety enhancements implemented post Fukushima accident; and preparedness to use these provisions. (author)

  4. Post-Closure Inspection Report for Corrective Action Unit 404: Roller Coaster Sewage Lagoons and North Disposal Trench Tonopah Test Range, Nevada, Calendar Year 2000

    Energy Technology Data Exchange (ETDEWEB)

    K. B. Campbell

    2001-06-01

    Post-closure monitoring requirements for the Roller Coaster Sewage Lagoons and North Disposal Trench (Corrective Action Unit [CAW 404]) (Figure 1) are described in Closure Report for Corrective Action Unit 404, Roller Coaster Sewage Lagoons and North Disposal Trench, Tonopah Test Range, Nevada, report number DOE/NV--187. The Closure Report (CR) was submitted to the Nevada Division of Environmental Protection (NDEP) on September 11, 1998. Permeability results of soils adjacent to the engineered cover and a request for closure of CAU 404 were transmitted to the NDEP on April 29, 1999. The CR (containing the Post-Closure Monitoring Plan) was approved by the NDEP on May 18, 1999. Post-closure monitoring at CAU 404 consists of the following: (1) Site inspections done twice a year to evaluate the condition of the unit; (2) Verification that the site is secure; (3) Notice of any subsidence or deficiencies that may compromise the integrity of the unit; (4) Remedy of any deficiencies within 90 days of discovery; and (5) Preparation and submittal of an annual report. Site inspections were conducted on June 19, 2000, and November 21, 2000. The site inspections were conducted after completion of the revegetation activities (October 30, 1997) and NDEP approval of the CR (May 18, 1999). All site inspections were conducted in accordance with the Post-Closure Monitoring Plan in the NDEP-approved CR. This report includes copies of inspection checklists, photographs, recommendations, and conclusions. The Post-Closure Inspection Checklists are found in Attachment A, a copy of the field notes is found in Attachment B, and copies of the inspection photographs are found in Attachment C.

  5. Active surveillance for influenza vaccine adverse events: the integrated vaccine surveillance system.

    Science.gov (United States)

    Newes-Adeyi, Gabriella; Greece, Jacey; Bozeman, Sam; Walker, Deborah Klein; Lewis, Faith; Gidudu, Jane

    2012-02-01

    We conducted a pilot study of the Integrated Vaccine Surveillance System (IVSS), a novel active surveillance system for monitoring influenza vaccine adverse events that could be used in mass vaccination settings. We recruited 605 adult vaccinees from a convenience sample of 12 influenza vaccine clinics conducted by public health departments of two U.S. metropolitan regions. Vaccinees provided daily reports on adverse reactions following immunization (AEFI) using an interactive voice response system (IVR) or the internet for 14 consecutive days following immunization. Followup with nonrespondents was conducted through computer-assisted telephone interviewing (CATI). Data on vaccinee reports were available real-time through a dedicated secure website. 90% (545) of vaccinees made at least one daily report and 49% (299) reported consecutively for the full 14-day period. 58% (315) used internet, 20% (110) IVR, 6% (31) CATI, and 16% (89) used a combination for daily reports. Of the 545 reporters, 339 (62%) reported one or more AEFI, for a total of 594 AEFIs reported. The majority (505 or 85%) of these AEFIs were mild symptoms. It is feasible to develop a system to obtain real-time data on vaccine adverse events. Vaccinees are willing to provide daily reports for a considerable time post vaccination. Offering multiple modes of reporting encourages high response rates. Study findings on AEFIs showed that the IVSS was able to exhibit the emerging safety profile of the 2008 seasonal influenza vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. DebrisLV Hypervelocity Impact Post-Shot Physical Results Summary

    Science.gov (United States)

    2015-02-27

    simulaFng  a  solar-­‐panel   •  15  MJoules  energy   •  6061-T6 Frame •  Nylon Body •  Hollow Center for Electronics BODY...model  results  to  predict   plasm  jet  formaOon  in  relaOvely  simple  structures.    More  modeling  needs  to...Post-­‐Shot  Materials  Physics  Results,”   TOR-­‐2014-­‐03192   Approved Electronically by: Technical Peer Review Performed by

  7. The Evolution of Approval Services.

    Science.gov (United States)

    Warzala, Martin

    1994-01-01

    Describes major developments in book approval plans used by academic libraries for acquisition and for information dissemination and document distribution services based on approval-like concepts. Topics addressed include publishers; marketing; the impact of library automation; value-added services; the economic climate; the influence of…

  8. Approval plans issues and innovations

    CERN Document Server

    Katz, Linda S

    2013-01-01

    How can you, as an acquisition librarians, keep current on the output of hundreds of publishers? The answer, of course, is that you cannot. For over 30 years, approval plans have been used by librarians to acquire current titles, save staff time, and build core collections. Even today, these reasons seem appropriate, as libraries try to maintain up-to-date collections and control personnel and operating budgets. However, as shown in Approval Plans: Issues and Innovations, the use of approval plans is not so simple and straightforward; their use is subject to complex procedures and policies--an

  9. Biomarkers of adverse drug reactions.

    Science.gov (United States)

    Carr, Daniel F; Pirmohamed, Munir

    2018-02-01

    Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

  10. 48 CFR 750.7105 - Approving authorities.

    Science.gov (United States)

    2010-10-01

    ... CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS Extraordinary Contractual Actions To Protect Foreign Policy Interests of the United States 750.7105 Approving authorities. All authority to approve actions...

  11. Adulthood personality correlates of childhood adversity

    OpenAIRE

    Carver, Charles S.; Johnson, Sheri L.; McCullough, Michael E.; Forster, Daniel E.; Joormann, Jutta

    2014-01-01

    Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, whic...

  12. Periodontal treatment during pregnancy decreases the rate of adverse pregnancy outcome: a controlled clinical trial.

    Science.gov (United States)

    Sant'Ana, Adriana Campos Passanezi; Campos, Marinele R de; Passanezi, Selma Campos; Rezende, Maria Lúcia Rubo de; Greghi, Sebastião Luiz Aguiar; Passanezi, Euloir

    2011-04-01

    The aim of this study was to evaluate the effects of non-surgical treatment of periodontal disease during the second trimester of gestation on adverse pregnancy outcomes. Pregnant patients during the 1st and 2nd trimesters at antenatal care in a Public Health Center were divided into 2 groups: NIG--"no intervention" (n=17) or IG--"intervention" (n=16). IG patients were submitted to a non-surgical periodontal treatment performed by a single periodontist consisting of scaling and root planning (SRP), professional prophylaxis (PROPH) and oral hygiene instruction (OHI). NIG received PROPH and OHI during pregnancy and were referred for treatment after delivery. Periodontal evaluation was performed by a single trained examiner, blinded to periodontal treatment, according to probing depth (PD), clinical attachment level (CAL), plaque index (PI) and sulcular bleeding index (SBI) at baseline and 35 gestational weeks-28 days post-partum. Primary adverse pregnancy outcomes were preterm birth (Periodontal treatment resulted in stabilization of CAL and PI (p>0.05) at IG and worsening of all periodontal parameters at NIG (pperiodontal conditions of IG and NIG were observed at 2nd examination (ppregnancy outcomes was 47.05% in NIG and 6.25% in IG. Periodontal treatment during pregnancy was associated to a decreased risk of developing adverse pregnancy outcomes [OR=13.50; CI: 1.47-123.45; p=0.02]. Periodontal treatment during the second trimester of gestation contributes to decrease adverse pregnancy outcomes.

  13. Adverse environments and children's creativity development: transforming the notion of "success in adversity" in China.

    Science.gov (United States)

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications for China's future as it brings together one of China's core cultural values-"success in adversity"-the importance of creativity, and very real social and economic needs. "Success in adversity" reflects the strongly held belief that individuals who suffer adverse environments can rise to excellence and success through persistence, effort, and creativity. In this article, we briefly explore the historical sources of this belief and how it is closely related to the Chinese conception of creativity. We then present some studies on the creativity of some of China's migrant children. Findings show that while migrant children as a group may not generally exhibit higher creativity than their urban peers as hypothesized, indications of resilience and creative potential suggest that the notion of success in adversity may contribute to the positive development of China's migrant children more substantially when it is informed by research and augmented by research-supported policy. © 2015 Wiley Periodicals, Inc.

  14. Vedolizumab: first global approval.

    Science.gov (United States)

    Poole, Raewyn M

    2014-07-01

    Vedolizumab [Entyvio(®) (US, Europe)], a humanized monoclonal antibody α4β7 integrin receptor antagonist, has been developed by Millennium Pharmaceuticals (d/b/a Takeda Pharmaceuticals International) for the treatment of ulcerative colitis and Crohn's disease. Vedolizumab has received its first global approval for the treatment of ulcerative colitis and Crohn's disease in the US, for use in adult patients with moderate-to-severe disease who have had an inadequate response, loss of response or intolerance to one or more standard therapies (corticosteroids, immunomodulators or tumour necrosis factor-α inhibitor) or demonstrated dependence on corticosteroids. Vedolizumab has since been approved for ulcerative colitis and Crohn's disease in the EU, Norway, Iceland and Liechtenstein. This article summarizes the milestones in the development of vedolizumab leading to its first approval for the treatment of ulcerative colitis and Crohn's disease.

  15. Transient post-operative atrial fibrillation predicts short and long term adverse events following CABG

    Science.gov (United States)

    Becker, Matthew; Galla, John; Blackstone, Eugene; Kapadia, Samir R.

    2014-01-01

    Objective To assess the relationship between the development of transient post-operative atrial fibrillation (TPOAF) following coronary artery bypass graft (CABG) surgery and risk of long-term mortality. Background Atrial fibrillation (AF) following CABG is common and associated with increased morbidity and mortality in the perioperative period. However the impact of TPOAF and its management on long-term morbidity and mortality in patients undergoing first time, isolated CABG surgery remains unclear. Methods The Cleveland Clinic Cardiovascular Information Registry was used to identify 5,205 consecutive patients who underwent CABG between January 1993 and December 2005. Patients with TPOAF (n=1,490) were compared to those without post-operative AF (n=3,645) for the endpoints of death, myocardial infarction (MI), or stroke at 1 year. Results Overall rates of 1-year mortality, MI and stroke were 3.7%, 0.8%, and 2.6%, respectively. Patients with TPOAF had an increased risk of death at 1 year as compared to patients without POAF (6.4% vs. 2.7%; P<0.001), but there was not an increased risk of stroke or MI. Multivariate analysis identified TPOAF as an independent predictor of death at 1 year (HR 1.89, 95% CI, 1.42-2.53; P<0.001). After propensity matching, patients who developed TPOAF experienced a significantly increased risk of death compared with those without TPOAF (HR 1.96, 95% CI, 1.34-2.86; P<0.001). Conclusions In patients undergoing first time, isolated CABG, the presence of TPOAF identifies a subgroup of patients at increased risk for all-cause mortality. Future prospective studies to determine potential beneficial interventions in this large population are warranted. PMID:25414823

  16. Adulthood Personality Correlates of Childhood Adversity

    OpenAIRE

    Charles S. Carver; Charles S. Carver; Sheri L Johnson; Sheri L Johnson; Michael E McCullough; Daniel E Forster; Jutta eJoormann

    2014-01-01

    Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, which w...

  17. 19 CFR 115.55 - Termination of approval.

    Science.gov (United States)

    2010-04-01

    ... vehicle by a major repair or alteration of any of the essential features required in § 115.51. Repairs by... TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS Procedures for Approval of Individual Road Vehicles § 115.55 Termination of approval. Approval of a road...

  18. An adverse drug event manager facilitates spontaneous reporting of adverse drug reactions

    DEFF Research Database (Denmark)

    Vinther, Siri; Klarskov, Pia; Borgeskov, Hanne

    2017-01-01

    INTRODUCTION: Spontaneous reporting of adverse drug reactions (ADRs) is used for continuous risk-benefit evaluation of marketed pharmaceutical products and for signal detection. The Adverse Drug Event Manager (ADEM) is a service offered to clinicians employed at hospitals in the Capital Region......%). The drugs most frequently reported were lisdexamphetamine (n = 40), rivaroxaban (n = 16) and warfarin (n = 15) (vaccines excluded). In 13 out of 484 reports, the ADR was associated with a fatal outcome. CONCLUSION: The findings of this study indicate that an ADEM promotes and facilitates spontaneous ADR...

  19. Post-Closure Inspection Report for Corrective Action Unit 404: Roller Coaster Sewage Lagoons and North Disposal Trench Tonopah Test Range, Nevada, Calendar Year 2000; TOPICAL

    International Nuclear Information System (INIS)

    K. B. Campbell

    2001-01-01

    Post-closure monitoring requirements for the Roller Coaster Sewage Lagoons and North Disposal Trench (Corrective Action Unit[CAW 404]) (Figure 1) are described in Closure Report for Corrective Action Unit 404, Roller Coaster Sewage Lagoons and North Disposal Trench, Tonopah Test Range, Nevada, report number DOE/NV-187. The Closure Report (CR) was submitted to the Nevada Division of Environmental Protection (NDEP) on September 11, 1998. Permeability results of soils adjacent to the engineered cover and a request for closure of CAU 404 were transmitted to the NDEP on April 29, 1999. The CR (containing the Post-Closure Monitoring Plan) was approved by the NDEP on May 18, 1999. Post-closure monitoring at CAU 404 consists of the following: (1) Site inspections done twice a year to evaluate the condition of the unit; (2) Verification that the site is secure; (3) Notice of any subsidence or deficiencies that may compromise the integrity of the unit; (4) Remedy of any deficiencies within 90 days of discovery; and (5) Preparation and submittal of an annual report. Site inspections were conducted on June 19, 2000, and November 21, 2000. The site inspections were conducted after completion of the revegetation activities (October 30, 1997) and NDEP approval of the CR (May 18, 1999). All site inspections were conducted in accordance with the Post-Closure Monitoring Plan in the NDEP-approved CR. This report includes copies of inspection checklists, photographs, recommendations, and conclusions. The Post-Closure Inspection Checklists are found in Attachment A, a copy of the field notes is found in Attachment B, and copies of the inspection photographs are found in Attachment C

  20. 30 CFR 75.1108 - Approved conveyor belts.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approved conveyor belts. 75.1108 Section 75... Fire-Resistant Hydraulic Fluids on Underground Equipment § 75.1108 Approved conveyor belts. (a) Until December 31, 2009 conveyor belts placed in service in underground coal mines shall be: (1) Approved under...

  1. 45 CFR 1340.13 - Approval of applications.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Approval of applications. 1340.13 Section 1340.13... NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Grants to States § 1340.13 Approval of applications. (a) The Commissioner shall approve an application for an award for...

  2. Leukocytes and transfusion related adverse events: the effects of leuko-reduction process in the prevention of adverse reactions resulted from the transfusion of blood components: review article

    Directory of Open Access Journals (Sweden)

    Ehteramolsadat Hosseini

    2017-05-01

    Full Text Available Blood transfusion is commonly implemented to manage life and health-threatening conditions on a rapid and short-term basis. Over the years, ongoing technical advances have dramatically improved transfusion medicine to provide more safety and effectiveness. However, transfusion is still complicated with different adverse events that mainly induced by the presence of allogeneic leukocytes in the blood products. Several lines of evidence have shown that leukocytes in blood components are involved in the induction of febrile nonhemolytic transfusion reactions (FNHTRs, HLA alloimmunization and platelet refractoriness as well as the increased risk of the infectious diseases transmitted by leukotropic viruses including cytomegalovirus (CMV, human T-lymphotropic virus (HTLV-I/II and Epstein-Barr virus (EBV. During current decades, introducing various leuko-reduction techniques have shown to be associated with less transfusion related adverse events and improved clinical outcomes. The lower incidence and severity of febrile transfusion reactions; reduced risk of transfusion related transmission of CMV or other leukocyte-associated infections, lowered incidence of alloimmune platelet refractoriness in addition to reducing risk of mortality and morbidity in patients are considered as clinical benefits of leuko-reduced products. Currently, by the use of 3rd and 4th generation of filters, the highest levels of leukoreduction in blood components have been achieved. Filtration techniques have also the advantages of being performed shortly after preparation of components (pre-storage or post-storage even at the patient’s bedside. However, it seems that pre-storage depletion of leukocytes provides better protection than post-storage techniques due to the elimination of leukocyte-derived cytokines effects which are increasingly released during storage. Particularly in platelet products, the earlier depletion of leukocyte also favors less platelet

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

    Science.gov (United States)

    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

  4. A prospective study on paediatric traffic injuries : health-related quality of life and post-traumatic stress

    NARCIS (Netherlands)

    Sturms, LM; van der Sluis, CK; Stewart, RE; Groothoff, JW; ten Duis, HJ; Eisma, WH

    Objectives: To examine children's reports of their health- related quality of life ( HRQoL) following paediatric traffic injury, to explore child and parental post- traumatic stress, and to identify children and parents with adverse outcomes. Design: Prospective cohort study. Assessments: shortly

  5. A review of low-level air pollution and adverse effects on human health: implications for epidemiological studies and public policy

    Science.gov (United States)

    Olmo, Neide Regina Simões; do Nascimento Saldiva, Paulo Hilário; Braga, Alfésio Luís Ferreira; Lin, Chin An; de Paula Santos, Ubiratan; Pereira, Luiz Alberto Amador

    2011-01-01

    The aim of this study was to review original scientific articles describing the relationship between atmospheric pollution and damage to human health. We also aimed to determine which of these studies mentioned public policy issues. Original articles relating to atmospheric pollution and human health published between 1995 and 2009 were retrieved from the PubMed database and analyzed. This study included only articles dealing with atmospheric pollutants resulting primarily from vehicle emissions. Three researchers were involved in the final selection of the studies, and the chosen articles were approved by at least two of the three researchers. Of the 84 non-Brazilian studies analyzed, 80 showed an association between atmospheric pollution and adverse effects on human health. Moreover, 66 showed evidence of adverse effects on human health, even at levels below the permitted emission standards. Three studies mentioned public policies aimed at changing emission standards. Similarly, the 29 selected Brazilian studies reported adverse associations with human health, and 27 showed evidence of adverse effects even at levels below the legally permitted emission standards. Of these studies, 16 mentioned public policies aimed at changing emission standards. Based on the Brazilian and non-Brazilian scientific studies that have been conducted, it can be concluded that, even under conditions that are compliant with Brazilian air quality standards, the concentration of atmospheric pollutants in Brazil can negatively affect human health. However, as little discussion of this topic has been generated, this finding demonstrates the need to incorporate epidemiological evidence into decisions regarding legal regulations and to discuss the public policy implications in epidemiological studies. PMID:21655765

  6. 27 CFR 5.55 - Certificates of label approval.

    Science.gov (United States)

    2010-04-01

    ..., DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Requirements for Approval of... certificates of label approval and certificates of exemption from label approval, as well as appeal procedures...

  7. 46 CFR 188.10-3 - Approved container.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Approved container. 188.10-3 Section 188.10-3 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-3 Approved container. This term means a container which is properly labeled, marked and approved by DOT for the commodity which it contains. [CGFR...

  8. 7 CFR 1900.55 - Adverse action procedures.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Adverse action procedures. 1900.55 Section 1900.55 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... REGULATIONS GENERAL Adverse Decisions and Administrative Appeals § 1900.55 Adverse action procedures. (a) If...

  9. The effects of early life adversity on the immune system.

    Science.gov (United States)

    Elwenspoek, Martha M C; Kuehn, Annette; Muller, Claude P; Turner, Jonathan D

    2017-08-01

    Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the 'ELA immune phenotype', characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study – PRIME study

    Directory of Open Access Journals (Sweden)

    Shah K

    2017-05-01

    Full Text Available Kshitij Shah,1 Omvijay B Chaudhari,2 Palash Gupta,3 R Hom Chaudhuri,4 Ranjan Kamilya,5 Shreedhar S Kulkarni,6 S Subbaiah,7 Zubair H Sorathia,8 Gauri Billa9 1MS Orthopedic, Prime Hospital, Andheri (West, 2Vatsalya Nursing Home, Kalyan (West, Mumbai, 3Dr. Palash Gupta Clinic, Rohini, New Delhi, 4Homchaudhuri’s Clinic, 5Apollo Gleneagles Hospital, Kolkata, West Bengal, 6Amrit Clinic, Matunga, Mumbai, 7Subbaiah’s Clinic, West Mambalam, Chennai, 8Medicare Hospital, Marol, Andheri East, 9Medical Services, Abbott Healthcare Pvt. Ltd, Mulund (West, Mumbai, Maharashtra, India Objective: To assess the effectiveness, overall tolerability, and gastrointestinal (GI tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg] in symptomatic treatment of severe acute pain in physician’s routine clinical practice. Materials and methods: In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18–60 years with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at baseline, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. Results: A total of 351 patients (mean age 44.2 years; male 43%; female 57% were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (p<0.0001. The number of patients with severe intensity of pain reduced from 100% at baseline to 18.3% at day 2 and 6.96% at day 5. According to the patient assessment, 68.36% of patients reported tolerability as “very good to good”, whereas according to physician’s assessment, “very good to good” tolerability was reported in 68.27% of patients. Five (1.43 % patients discontinued the study because of adverse drug reaction. Five patients developed nine GI-related events of moderate intensity. Two patients

  11. Electronic Approval of Invoices (AEF)

    CERN Multimedia

    2003-01-01

    With a view to the simplification of administrative procedures, AS and FI Divisions have drawn up a new procedure for the electronic approval of invoices via the EDH application. The aim of this new procedure is to rationalise the invoice approval process, notably by eliminating paper copies from the approval circuit. This will simplify the processing of invoices and facilitate their timely settlement, while at the same time maintaining a high level of security. This new procedure, in its current phase, will be gradually implemented from 1 November 2003 onwards. For clarification and further information, please see: http://ais.cern.ch/projs/AEF/help/help.htm . Finance Division, Accounts Payable Tel.: 7.22.95

  12. Unstable child welfare permanent placements and early adolescent physical and mental health: The roles of adverse childhood experiences and post-traumatic stress.

    Science.gov (United States)

    Villodas, Miguel T; Cromer, Kelly D; Moses, Jacqueline O; Litrownik, Alan J; Newton, Rae R; Davis, Inger P

    2016-12-01

    Although researchers have found that child welfare placement disruptions are associated with elevated youth physical and mental health problems, the mechanisms that explain this association have not been previously studied. The present study built on a previous investigation of the physical and behavioral consequences of long-term permanent placement patterns among youth who participated in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). The current investigation (n=251) aimed to (a) report the early adolescent living situations of youth with different long-term placement patterns, and (b) to delineate the roles of adverse childhood experiences (ACEs) and post-traumatic stress (PTS) reactions in the association between unstable long-term placement patterns and physical and mental health problems during the transition to adolescence. Information about youth's living situations, ACEs, and physical and mental health was gathered prospectively from child protective services records and biannual caregiver and youth interviews when youth were 4-14 years old. The majority of youth remained with the same caregiver during early adolescence, but youth with chronically unstable permanent placement patterns continued to experience instability. Path analyses revealed that ACEs mediated the association between unstable placement patterns and elevated mental, but not physical, health problems during late childhood. Additionally, late childhood PTS mediated the association between unstable placement patterns and subsequent escalations in physical and mental health problems during the transition to adolescence. Findings highlight the importance of long-term permanency planning for youth who enter the child welfare system and emphasize the importance of trauma-focused assessment and intervention for these youth. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related Adverse Events

    Directory of Open Access Journals (Sweden)

    Keisuke Imafuku

    2017-04-01

    Full Text Available Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD pattern. Oral corticosteroids improved chest shadow of CT scan in both cases. However, when nivolumab was re-administrated, case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From our cases, it is difficult to re-administrate nivolumab for the patients with pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve their symptoms.

  14. Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text

    Science.gov (United States)

    Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

    2013-01-01

    Objective Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Materials and methods Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. Results The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. Discussion The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. Conclusions The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives. PMID:23703825

  15. Nurse practitioner's and certified nurse midwives' knowledge, opinions and practice behaviors regarding periodontal disease and adverse pregnancy outcomes.

    Science.gov (United States)

    Wooten, Katherine T; Lee, Jessica; Jared, Heather; Boggess, Kim; Wilder, Rebecca S

    2011-01-01

    The purpose of this study was to assess the knowledge, opinions and practice behaviors of nurse practitioners (NP) and certified nurse midwives (CNM) regarding periodontal disease and adverse pregnancy outcomes. A 45 item survey was developed, approved, pretested, revised and mailed to 404 North Carolina NPs and CNMs who provide prenatal care. Data was entered into an excel database and transferred to SPSS for Windows for complete analysis. Linear regression modeling was used to determine statistical significance. A total of 219 NPs and CNMs responded to the mailed survey, achieving a response rate of 54%. NPs and CNMs reported having limited knowledge regarding oral health. The majority felt they should collaborate with oral health care professionals to screen patients for periodontal disease. Most agreed they needed more information about periodontal disease and adverse pregnancy outcomes. NPs and CNMs who frequently examine women could serve an important role in screening for oral health problems and making appropriate dental health referrals. Increased basic and continuing education could prepare these professionals for collaborative care with oral health care professionals. This study suggests that collaboration between NPs and CNMs with dental professionals could lead to improved oral health care for pregnant patients.

  16. 40 CFR 350.21 - Adverse health effects.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the adverse health effects associated with each of the chemicals claimed as trade secret and shall make this...

  17. CYTOKINE PROFILE IN VISCERAL OBESITY AND ADVERSE CARDIOVASCULAR PROGNOSIS OF MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    O. V. Gruzdeva

    2015-01-01

    Full Text Available Presence of myocardial infarction in patients with obesity can lead to an uncontrolled increase in proinflammatory cytokines and unfavorable course of the pathological process. Objective: to study the relationship of key inflammatory factors and the development of complications at different terms after myocardial infarction in patients with visceral obesity. The study involved 94 men with myocardial infarction. Visceral obesity was diagnosed by multi-slice computed tomography (LightspeedVCT 64 ,General Electric,USA. On the 1st and 12th day of hospitalization, we determined serum concentrations of interleukins (TNFα, IL-1β, IL-6, IL-8 IL-10 and IL-12, and C-reactive protein. Adverse cardiovascular events were documented during the next year. The most informative indicators were identified by a stepwise logistic regression analysis. In patients with myocardial infarction an imbalance of cytokine profile revealed, i.e., an increase in proinflammatory markers (TNFα, IL-1β, IL-6, IL-8, IL-12, CRP, along with decrease in IL-10, being more pronounced in cases of visceral obesity. Among the studied markers, closest relationship was observed between visceral obesity and serum concentrations of IL-6 and CRP. Over the year, adverse cardiovascular events proved to be more frequent in patients with visceral obesity. Post-infarction complication risk was associated with higher concentrations of IL-6, IL-12 and IL-10 deficiency. Hence, development of adverse cardiovascular events within a year after myocardial infarction is more typical to the patients with visceral obesity, and is accompanied by activation of proinflammatory cytokines and IL-10 deficiency.

  18. Post-mortem analysis of suicide victims shows ABCB1 haplotype 1236T-2677T-3435T as a candidate predisposing factor behind adverse drug reactions in females.

    Science.gov (United States)

    Rahikainen, Anna-Liina; Palo, Jukka U; Haukka, Jari; Sajantila, Antti

    2018-04-01

    Genetic variation in efflux transporter, permeability glycoprotein (P-gp), has recently been associated with completed violent suicides and also violent suicide attempts. As depression is known to be a risk factor for suicide and many antidepressants are P-gp substrates, it has been speculated that inadequate antidepressant treatment response or adverse side effects could be involved. The aim of this study was to investigate whether there is an association between the P-gp coding ABCB1 gene and completed suicides in citalopram users. Also, the effect of sex and suicide method used (violent vs. non-violent) was evaluated. All cases included in the study population, 349 completed suicide victims and 284 controls, were shown to be positive for antidepressant citalopram in a post-mortem toxicological drug screen. ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms were determined by TaqMan genotyping assays. Haplotypes were constructed from genotype data using the PHASE software. The association between the manner of death and the ABCB1 haplotype was tested with logistic regression analysis. No statistically significant differences were observed in the ABCB1 allele or genotype frequencies between the suicide and control groups. However, the ABCB1 1236T-2677T-3435T haplotype was associated with completed suicides of female citalopram users (odds ratio: 2.23; 95% confidence interval: 1.22-4.07; P=0.009). After stratification by the method used for suicide, the association emerged in fatal intoxications (odds ratio: 2.51; 95% confidence interval: 1.29-4.87; P=0.007). In other groups, no statistically significant associations were observed. Our results suggest that female citalopram users with ABCB1 1236T-2677T-3435T are more vulnerable to adverse effects of the drugs as this haplotype was enriched in non-violent suicides of female citalopram users. Even though the biological mechanism behind this observation is unknown, the results provide another example of the importance

  19. 20 CFR 655.207 - Adverse effect rates.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Adverse effect rates. 655.207 Section 655.207... Agricultural Employment § 655.207 Adverse effect rates. (a) Except as otherwise provided in this section, the adverse effect rates for all agricultural and logging employment shall be the prevailing wage rates in the...

  20. Trends in global approvals of biotech crops (1992–2014)

    Science.gov (United States)

    Aldemita, Rhodora R; Reaño, Ian Mari E; Solis, Renando O; Hautea, Randy A

    2015-01-01

    ABSTRACT With the increasing number of genetically modified (GM) events, traits, and crops that are developed to benefit the global population, approval of these technologies for food, feed, cultivation and import in each country may vary depending on needs, demand and trade interest. ISAAA established a GMO Approval Database to document global approvals of biotech crops. GM event name, crops, traits, developer, year of approval for cultivation, food/feed, import, and relevant dossiers were sourced from credible government regulatory websites and biosafety clearinghouses. This paper investigates the trends in GM approvals for food, feed and cultivation based on the number of approving countries, GM crops, events, and traits in the last 23 y (1992–2014), rationale for approval, factors influencing approvals, and their implications in GM crop adoption. Results show that in 2014, there was an accumulative increase in the number of countries granting approvals at 29 (79% developing countries) for commercial cultivation and 31 (70% developing countries) for food and 19 (80% developing developing) for feed; 2012 had the highest number of approving countries and cultivation approvals; 2011 had the highest number of country approvals for feed, and 2014 for food approvals. Herbicide tolerance trait had the highest events approved, followed by insect tolerance traits. Approvals for food product quality increased in the second decade. Maize had the highest number of events approved (single and stacked traits), and stacked traits product gradually increased which is already 30% of the total trait approvals. These results may indicate understanding and acceptance of countries to enhance regulatory capability to be able to benefit from GM crop commercialization. Hence, the paper provided information on the trends on the growth of the GM crop industry in the last 23 y which may be vital in predicting future GM crops and traits. PMID:26039675

  1. Cognition- and Dementia-Related Adverse Effects With Sacubitril-Valsartan: Analysis of the FDA Adverse Event Report System Database.

    Science.gov (United States)

    Perlman, Amichai; Hirsh Raccah, Bruria; Matok, Ilan; Muszkat, Mordechai

    2018-05-07

    Because neprilysin is involved in the degradation of amyloid-beta, there is concern that the angiotensin-neprilysin inhibitor sacubitril-valsartan could increase the risk for dementia. We analyzed adverse event cases submitted to the Food and Drug Administration Adverse Event Report System from July 2015 to March 2017. Cognition- and dementia-related adverse event cases were defined with the use of broad and narrow structured medical queries. During the period evaluated, 9,004 adverse event reports (out of a total of 2,249,479) involved the use of sacubitril-valsartan. Based on the broad definition, sacubitril-valsartan was associated with cognition- and dementia-related adverse events in 459 reports (5.1%), but this was lower than the proportion of these reports among other medications (6.6%, reporting odds ratio [ROR] 0.72, 95% confidence interval [CI] 0.65-0.79). Restricting the comparison to cases with age >60 years and with the use of a comparator group with heart failure resulted in no association between sacubitril-valsartan and dementia-related adverse events, with the use of both the broad and the narrow definitions (ROR 0.87, 95% CI 0.76-1.02, and ROR 1.06, 95% CI 0.4-3.16, respectively). Sacubitril-valsartan is not associated with a disproportionately high rate of short-term dementia-related adverse effect reports. Long-term studies assessing cognitive outcomes are required to better establish the medication's cognition effects. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Psychosocial risk factors and treatment of new onset and recurrent depression during the post-partum period.

    Science.gov (United States)

    Kettunen, Pirjo; Hintikka, Jukka

    2017-07-01

    When developing maternity care services, it is important to know how psychosocial factors affect the course of post-partum depression (PPD), and how depressed mothers are treated. The aim of this study is to assess how adverse childhood experiences, poor present support and violence, and low socioeconomic status (SES) associate with PPD, specifically in new onset and recurrent post-partum depression. The second aim is to assess the treatment received for PPD. This is a cross-sectional study. The study group comprises 104 mothers with a current episode of PPD, and a control group of 104 mothers without an episode. The Structured Clinical Interview for DSM-IV Axis I Disorders was used for data collection. Psychosocial risk factors, treatment issues, and the course of depression were assessed with a structured self-report questionnaire. In age-adjusted multivariate analyses, adverse childhood experiences, a low level of present support in close relationships, and a poor SES were associated significantly with PPD. Childhood adversity was associated with both new onset and recurrent depression. Nevertheless, a low level of support and a poor SES were also associated with recurrent depression. A quarter of mothers with a major depressive episode in the post-partum period attended psychiatric services. In mothers with new onset depression, the proportion was only 5%. There is an urgent need to develop the diagnostics of depression in maternity care services. An awareness of psychosocial risk factors might help in this. More depressed mothers should be referred to psychiatric services.

  3. Childhood adversity and midlife suicidal ideation.

    Science.gov (United States)

    Stansfeld, S A; Clark, C; Smuk, M; Power, C; Davidson, T; Rodgers, B

    2017-01-01

    Childhood adversity predicts adolescent suicidal ideation but there are few studies examining whether the risk of childhood adversity extends to suicidal ideation in midlife. We hypothesized that childhood adversity predicts midlife suicidal ideation and this is partially mediated by adolescent internalizing disorders, externalizing disorders and adult exposure to life events and interpersonal difficulties. At 45 years, 9377 women and men from the UK 1958 British Birth Cohort Study participated in a clinical survey. Childhood adversity was prospectively assessed at the ages of 7, 11 and 16 years. Suicidal ideation at midlife was assessed by the depressive ideas subscale of the Revised Clinical Interview Schedule. Internalizing and externalizing disorders were measured by the Rutter scales at 16 years. Life events, periods of unemployment, partnership separations and alcohol dependence were measured through adulthood. Illness in the household, paternal absence, institutional care, parental divorce and retrospective reports of parental physical and sexual abuse predicted suicidal ideation at 45 years. Three or more childhood adversities were associated with suicidal ideation at 45 years [odds ratio (OR) 4.31, 95% confidence interval (CI) 2.67-6.94]. Psychological distress at 16 years partially mediated the associations of physical abuse (OR 3.41, 95% CI 2.29-5.75), sexual abuse (OR 4.99, 95% CI 2.90-11.16) with suicidal ideation. Adult life events partially mediated the association of parental divorce (OR 6.34, 95% CI -7.16 to 36.75) and physical (OR 9.59, 95% CI 4.97-27.88) and sexual abuse (OR 6.59, 95% CI 2.40-38.36) with suicidal ideation at 45 years. Adversity in childhood predicts suicidal ideation in midlife, partially mediated by adolescent internalizing and externalizing disorders, adult life events and interpersonal difficulties. Understanding the pathways from adversity to suicidal ideation can inform suicide prevention and the targeting of preventive

  4. HyApproval - Handbook for the approval of hydrogen refuelling stations - First preliminary achievements

    Energy Technology Data Exchange (ETDEWEB)

    Wurster, R.; Vandendungen, G.; Guichard, J.; Molag, M.; Barron, J.; Reijalt, M.; Hill, H.J.; Landinger, H.

    2007-05-15

    The EU-funded project HyApproval [www.hyapproval.org] aims at developing a universal Handbook to facilitate the approval process of Hydrogen Refuelling Stations (HRS) in Europe. The main goal of the HyApproval partnership with 22 partners from Europe and one each from China, Japan and the USA is to provide a Handbook of technical and regulatory requirements to assist authorisation officials, companies and organisations in the safe implementation and operation of HRS. Achievements during the first 15 months: analyses of HRS technology concepts and of equipment and safety distances/ Intermediate Design Paper/ Regulations, Codes and Standards (RCS) review and comparison/ first Handbook draft and first review sessions with HySafe experts/ safety matrix/ identification of accident scenarios/ agreement on safety documentation/ critical review of reliability data from collections and risk studies/ risk assessment (RA) criteria definition and RA/ matrix of acceptability and awareness levels/ database of Fire Associations and First Responders/ calendar of hydrogen events/ general description of CGH{sub 2} interfaces. (au)

  5. Prevalence rates and socioeconomic characteristics of post-partum depression in Hungary.

    Science.gov (United States)

    Nagy, Emese; Molnar, Peter; Pal, Attila; Orvos, Hajnalka

    2011-01-30

    The rapid socioeconomic transition in post-communist Hungary adversely affected the overall morbidity and mortality rates in the 1990s. Prevalence data on depressive disorders from the region are still scarce, however. This study reports the findings of the first epidemiological survey, using the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory (BDI), on the prevalence of post-partum depression and the associated risk factors in Hungary. A total of 1030 mothers who delivered their babies between May and July 1999 in 16 counties in Hungary were screened for depressive symptoms 3-26 weeks post-partum. The survey found that 10.81% of the sample was above the cut-off score of 13, and the EPDS detected post-partum depressive symptoms with 76% (95% confidence interval (CI)=60.5-87.1) sensitivity and 92% (95% CI=90.5-94.1) specificity. In addition, 24 socio-demographic, socio-psychiatric data and personal and obstetric variables were surveyed. Results of a hierarchical logistic regression analysis showed that depression of the mother during pregnancy was the strongest predictor of depressive symptoms post-partum. Depression before pregnancy, housing conditions, marital relationship status and family history of alcohol problems were also identified as predictors for post-partum depressive symptoms. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Adverse reactions associated with acetylcysteine.

    Science.gov (United States)

    Sandilands, E A; Bateman, D N

    2009-02-01

    Paracetamol (acetaminophen) is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetylcysteine is widely acknowledged as the antidote of choice for paracetamol poisoning, but its use is not without risk. Adverse reactions, often leading to treatment delay, are frequently associated with both intravenous and oral acetylcysteine and are a common source of concern among treating physicians. A systematic literature review investigating the incidence, clinical features, and mechanisms of adverse effects associated with acetylcysteine. A variety of adverse reactions to acetylcysteine have been described ranging from nausea to death, most of the latter due to incorrect dosing. The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms. The precise nature of this reaction remains unclear. Histamine now seems to be an important mediator of the response, and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. Quantity of paracetamol ingestion, measured through serum paracetamol concentration, is also important as higher paracetamol concentrations protect patients against anaphylactoid effects. Most anaphylactoid reactions occur at the start of acetylcysteine treatment when concentrations are highest. Acetylcysteine also affects clotting factor activity, and this affects the interpretation of minor disturbances in the International Normalized Ratio in the context of paracetamol overdose. This review discusses the incidence, clinical features, underlying pathophysiological mechanisms, and

  7. Analysis of the Education Program Approval Process: A Program Evaluation.

    Science.gov (United States)

    Fountaine, Charles A.; And Others

    A study of the education program approval process involving the Veterans Administration (VA) and the State Approving Agencies (SAAs) had the following objectives: to describe the present education program approval process; to determine time and costs associated with the education program approval process; to describe the approval process at…

  8. Adverse allergic reactions to linear ionic gadolinium-based contrast agents: experience with 194, 400 injections

    International Nuclear Information System (INIS)

    Aran, S.; Shaqdan, K.W.; Abujudeh, H.H.

    2015-01-01

    Aim: To report the authors' experience with the administration of four gadolinium-based contrast agents (GBCA; gadopentetate dimeglumine, gadofosveset trisodium, gadoxetate disodium and gadobenate dimeglumine) in a large study population at a single, large academic medical centre. Materials and methods: The institutional review board approved this retrospective study in which data in the electronic incident reporting system were searched. A total of 194, 400 intravenous administrations of linear ionic GBCAs were assessed for the incidence of adverse reactions and risk factors from 1 January 2007 to 14 January 2014. The severity of reactions (mild, moderate, and severe), patient type (outpatients, inpatients, and emergency), examination type, and treatment options were also investigated. Results: In total, 204/194400 (0.1%) patients (mean age 45.7 ± 14.9) showed adverse reactions, consisting of 6/746 (0.80%), 10/3200 (0.31%), 14/6236 (0.22%) and 174/184218 (0.09%), for gadofosveset trisodium, gadoxetate disodium, gadobenate dimeglumine, and gadopentetate dimeglumine, respectively. An overall significant difference was found between different GBCAs regarding the total number of reactions (p < 0.0001). When comparing the GBCAs together, significant differences were found between gadofosveset trisodium versus gadopentetate dimeglumine (p < 0.0001), gadofosveset trisodium versus gadobenate dimeglumine (p = 0.0051), gadoxetate disodium versus gadopentetate dimeglumine (p < 0.0001) and gadopentetate dimeglumine versus gadobenate dimeglumine (p = 0.0013). Rate of reaction was higher in females (F: 146/113187, 0.13%/M: 58/81213, 0.07%; p < 0.0001). Rate of reactions was higher in outpatient (180/158885, 0.11%), emergency (10/10413, 0.10%), and inpatients (14/25102, 0.05%), respectively (p < 0.0001). Most of the patients had mild symptoms 171/204 (83.8%). Abdomen–pelvis, liver, and thoracic examinations had highest rates of reactions (0.17 versus 0

  9. Social relationships and social support among post-war youth in Northern Uganda.

    Science.gov (United States)

    De Nutte, Leen; Okello, James; Derluyn, Ilse

    2017-08-01

    Although social relationships and social support are salient factors for post-war adolescents' psychosocial coping and adjustment, there is only limited information regarding war-affected adolescents' views on social support and the relationships within which social support is provided. This study therefore explored both elements among a clinical sample of 20 adolescents living in post-war Northern Uganda. Following Braun and Clarke's thematic analysis, we found a prominent role of the biological mother and other primary biological family members in the upbringing of our participants. Spiritual and material support were perceived to be the most important type of support, respectively, while the adolescents were growing up and in their current lives. These findings provide support for the perception that caregiving systems are adaptable to particular sociocultural contexts. Further, the importance of particular functions of social support could signify a potentially selective buffering effect of these functions in adverse contexts. Because of the importance of the primary biological family and the salient role of parent-child relationships in the face of adversity, future research needs to focus on this particular kind of social relationship in contexts of prolonged collective violence. © 2015 International Union of Psychological Science.

  10. Do Changes in Patellofemoral Joint Offset Lead to Adverse Outcomes in Total Knee Arthroplasty With Patellar Resurfacing? A Radiographic Review.

    Science.gov (United States)

    Matz, Jacob; Howard, James L; Morden, David J; MacDonald, Steven J; Teeter, Matthew G; Lanting, Brent A

    2017-03-01

    Patellofemoral joint biomechanics contribute to anterior knee pain, instability, and dysfunction following total knee arthroplasty (TKA). Information about specific factors leading to anterior knee pain and dysfunction is currently limited. Changes in patellofemoral joint offset (PFO) refers to a mismatch between the preoperative and postoperative anteroposterior geometry of the patellofemoral joint. It remains unclear whether these changes lead to adverse outcomes in TKA. A retrospective radiographic review of 970 knees pre-TKA and post-TKA was completed to correlate the radiographic and clinical outcomes of changing the PFO using a posterior-stabilized single knee design with patellar resurfacing. A total of 970 patients were reviewed. Postoperatively, the anterior femoral offset, anteroposterior femoral size, and anterior patellar offset were changed in 40%, 60%, and 71% of knees, respectively, compared to preoperative values. The Western Ontario and McMasters Osteoarthritis Index total score as well as subscale scores for pain and function were not significantly affected by an increase or decrease in PFO. Similarly, Knee Society Scores and range of motion were not significantly affected. Increased anterior patellar offset was, however, associated with increased postoperative patellar tilt. Postoperative patellar tilt was not correlated with adverse patient satisfaction scores or loss of range of motion. Changes in PFO (decreased, maintained, or increased) are common post-TKA and are not associated with a difference in clinical outcomes. Increases in anterior patellar offset led to increased patellar tilt, which was not associated with adverse patient satisfaction scores. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Fludarabine plus alemtuzumab (FA) front-line treatment in young patients with chronic lymphocytic leukemia (CLL) and an adverse biologic profile.

    Science.gov (United States)

    Mauro, Francesca R; Molica, Stefano; Laurenti, Luca; Cortelezzi, Agostino; Carella, Angelo M; Zaja, Francesco; Chiarenza, Annalisa; Angrilli, Francesco; Nobile, Francesco; Marasca, Roberto; Musolino, Caterina; Brugiatelli, Maura; Piciocchi, Alfonso; Vignetti, Marco; Fazi, Paola; Gentile, Giuseppe; De Propris, Maria S; Della Starza, Irene; Marinelli, Marilisa; Chiaretti, Sabina; Del Giudice, Ilaria; Nanni, Mauro; Albano, Francesco; Cuneo, Antonio; Guarini, Anna; Foà, Robin

    2014-02-01

    In 45, ≤ 60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab(®)) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Tissue factor pathway inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study.

    Directory of Open Access Journals (Sweden)

    Aurélie Di Bartolomeo

    Full Text Available The study aimed to evaluate if the rate of tissue factor pathway inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women.This was a prospective multicentre cohort study of 200 patients at a high risk of occurrence or recurrence of placenta-mediated adverse pregnancy outcomes conducted between June 2008 and October 2010. Measurements of tissue factor pathway inhibitor resistance (normalized ratio and tissue factor pathway inhibitor activity were performed for the last 72 patients at 20, 24, 28, 32, and 36 weeks of gestation and during the postpartum period.Overall, 15 patients presented a placenta-mediated adverse pregnancy outcome. There was no difference in normalized tissue factor pathway inhibitor ratios between patients with and without placenta-mediated adverse pregnancy outcomes during pregnancy and in the post-partum period. Patients with placenta-mediated adverse pregnancy outcomes had tissue factor pathway inhibitor activity rates that were significantly higher than those in patients without at as early as 24 weeks of gestation. The same results were observed following delivery.Among high-risk women, the tissue factor pathway inhibitor activity of patients with gestational vascular complications is higher than that in other patients. Hence, these markers could augment a screening strategy that includes an analysis of angiogenic factors as well as clinical and ultrasound imaging with Doppler measurement of the uterine arteries.

  13. Transdermal rivastigmine: management of cutaneous adverse events and review of the literature.

    Science.gov (United States)

    Greenspoon, Jill; Herrmann, Nathan; Adam, David N

    2011-07-01

    Alzheimer's disease is a chronic neurodegenerative disorder resulting in part from the degeneration of cholinergic neurons in the brain. Rivastigmine, a cholinesterase inhibitor, is commonly used as a treatment for dementia due to its ability to moderate cholinergic neurotransmission; however, treatment with oral rivastigmine can lead to gastrointestinal adverse effects such as nausea and vomiting. Transdermal administration of rivastigmine can minimize these adverse effects by providing continuous delivery of the medication, while maintaining the effectiveness of the oral treatment. While the transdermal form of rivastigmine has been found to have fewer systemic adverse effects compared with the oral form, cutaneous reactions, such as contact dermatitis, can lead to discontinuation of the drug in its transdermal form. Lack of patient compliance with regard to applying the patch to the designated site, applying the patch for the correct length of time or rotating patch application sites increases the risk of cutaneous adverse reactions. This article outlines the diagnosis and management of irritant contact dermatitis and allergic contact dermatitis secondary to transdermal rivastigmine. The large majority of reactions to transdermal patches are of an irritant type, which can be diagnosed clinically by the presence of a pruritic, erythematous, eczematous plaque strictly confined to the borders of the patch. In contrast, an allergic reaction can be differentiated by the presence of vesicles and/or oedema, erythema beyond the boundaries of the transdermal patch and lack of improvement of the lesion 48 hours after removal of the offending treatment. By encouraging the patient to follow a regular rotation schedule for the patch, and using lipid-based emollients for irritant dermatitis and pre- and post-treatment topical corticosteroids for allergic dermatitis, cutaneous reactions can often be alleviated and patients can continue with their medication regimen. Other

  14. Patient-Centered Drug Approval: The Role of Patient Advocacy in the Drug Approval Process.

    Science.gov (United States)

    Mattingly, T Joseph; Simoni-Wastila, Linda

    2017-10-01

    Recent approval of eteplirsen for Duchenne muscular dystrophy (DMD), a rare disease with few treatment alternatives, has reignited the debate over the U.S. drug approval process. The evolution of legal and regulatory restrictions to the marketing and sale of pharmaceuticals has spanned more than a century, and throughout this history, patient advocacy has played a significant role. Scientific evidence from clinical trials serves as the foundation for drug approval, but the patient voice has become increasingly influential. Although the gold standard for establishing safety and efficacy through randomized controlled trials has been in place for more than 50 years, it poses several limitations for rare disorders where patient recruitment for traditional clinical trials is a major barrier. Organized efforts by patient advocacy groups to help patients with rare diseases access investigational therapy have had a legislative and regulatory effect. After approval by the FDA, patient access to therapy may still be limited by cost. A managed care organization (MCO) with the fiduciary responsibility of managing the health of a population must weigh coverage decisions for costly therapies with questionable effectiveness against alternatives within the constraint of a finite budget. Even when the FDA deems a drug safe and effective, an MCO may determine that the drug should only be made available at a tier level where out-of-pocket costs are still too high for many patients. This limitation of availability may be due to cost, other treatment alternatives, or outcomes from existing clinical evidence. However, if the MCO makes a costly new treatment for a rare disease readily available, it may temporarily satisfy a small contingency at the cost of all of its members. This article examines the risks and benefits of patient-centered drug approval and the potential economic effect of patient-centered drug approval on population health. There is no funding to disclose. Mattingly

  15. 49 CFR 1522.109 - TSA review and approval.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false TSA review and approval. 1522.109 Section 1522.109..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program...

  16. 49 CFR 1522.115 - Renewal of TSA approval.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Renewal of TSA approval. 1522.115 Section 1522.115..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program...

  17. 29 CFR 1952.157 - Changes to approved plan.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS North Carolina § 1952.157 Changes to approved plan. (a) Legislation. (1) On March 29, 1994, the Assistant Secretary approved North Carolina's... section 17 of the Act as amended on November 5, 1990. (2) [Reserved] (b) The Voluntary Protection Program...

  18. 48 CFR 2922.103-4 - Approvals.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Approvals. 2922.103-4 Section 2922.103-4 Federal Acquisition Regulations System DEPARTMENT OF LABOR SOCIOECONOMIC PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Basic Labor Policies 2922.103-4 Approvals. The “agency...

  19. 38 CFR 21.7220 - Course approval.

    Science.gov (United States)

    2010-07-01

    ...) VOCATIONAL REHABILITATION AND EDUCATION All Volunteer Force Educational Assistance Program (Montgomery GI...; Pub. L. 98-525) (b) Course approval criteria. In administering benefits payable under 38 U.S.C...) Section 21.4265—Practical training approved as institutional training or on-job training; (10) Section 21...

  20. Cinnamon: A systematic review of adverse events.

    Science.gov (United States)

    Hajimonfarednejad, Mahdie; Ostovar, Mohadeseh; Raee, Mohammad Javad; Hashempur, Mohammad Hashem; Mayer, Johannes Gottfried; Heydari, Mojtaba

    2018-04-05

    Cinnamon, from the genus Cinnamomum and Lauraceae family, has been used as a popular spice for thousands of years around the world. Many studies have shown therapeutic effects of cinnamon including its antimicrobial, antiviral, antifungal, antioxidant, antitumor, antihypertensive, antilipemic, antidiabetic, gastroprotective, and immunomodulatory effects. Due to popular use of cinnamon and several human reports on adverse events associated with short or long term use of cinnamon, we aimed to systematically review its human reports of adverse event. Databases including Medline, Scopus, Science Direct, Embase, PubMed Central and Google scholar were searched using the key words "cinnamon" or "cinnamomum" for clinical trials, case reports and case series. Also spontaneous reports about adverse effects of cinnamon were collected from five national and international spontaneous reporting schemes. Thirty eight clinical trials were found, five of them reported adverse events. Twenty case reports and seven case series, as well as, spontaneous reports including 160 adverse events were also included. The most frequent adverse events were gastrointestinal disorders and allergic reactions which were self-limiting in the majority of cases. The available data suggests that despite the safety of cinnamon use as a spice and/or flavoring agent, its use may be associated with significant adverse effects in medicinal uses with larger doses or longer duration of use and should be clinically monitored. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  1. 33 CFR 115.70 - Advance approval of bridges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Advance approval of bridges. 115... BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.70 Advance approval of bridges. (a) The General Bridge Act of 1946 requires the approval of the location and plans of bridges prior...

  2. Environmental change challenges decision-making during post-market environmental monitoring of transgenic crops.

    Science.gov (United States)

    Sanvido, Olivier; Romeis, Jörg; Bigler, Franz

    2011-12-01

    The ability to decide what kind of environmental changes observed during post-market environmental monitoring of genetically modified (GM) crops represent environmental harm is an essential part of most legal frameworks regulating the commercial release of GM crops into the environment. Among others, such decisions are necessary to initiate remedial measures or to sustain claims of redress linked to environmental liability. Given that consensus on criteria to evaluate 'environmental harm' has not yet been found, there are a number of challenges for risk managers when interpreting GM crop monitoring data for environmental decision-making. In the present paper, we argue that the challenges in decision-making have four main causes. The first three causes relate to scientific data collection and analysis, which have methodological limits. The forth cause concerns scientific data evaluation, which is controversial among the different stakeholders involved in the debate on potential impacts of GM crops on the environment. This results in controversy how the effects of GM crops should be valued and what constitutes environmental harm. This controversy may influence decision-making about triggering corrective actions by regulators. We analyse all four challenges and propose potential strategies for addressing them. We conclude that environmental monitoring has its limits in reducing uncertainties remaining from the environmental risk assessment prior to market approval. We argue that remaining uncertainties related to adverse environmental effects of GM crops would probably be assessed in a more efficient and rigorous way during pre-market risk assessment. Risk managers should acknowledge the limits of environmental monitoring programmes as a tool for decision-making.

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

    Science.gov (United States)

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

    1996-12-01

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

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

    Science.gov (United States)

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

    2017-06-03

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

  5. Cannabidiol: a potential treatment for post Ebola syndrome?

    Science.gov (United States)

    Reznik, Sandra E; Gardner, Eliot L; Ashby, Charles R

    2016-11-01

    Patients recovered from Ebola virus infection may experience short- and long-term physical, neuropsychological and social sequelae, including arthralgia, musculoskeletal pain, ophthalmic inflammation, auditory problems, fatigue, confusion, insomnia, short-term memory impairment, anxiety, depression and anorexia, all lasting from two weeks to more than two years. Currently there are no treatments for post Ebola sequelae. We hypothesize that cannabidiol (CBD) may attenuate some of these post Ebola sequelae, several of which have been postulated to result from inflammation and/or an autoimmune response. CBD has anti-inflammatory actions in various animal models. Clinical studies have shown that oral administration of CBD, compared to placebo, significantly reduces anxiety, has antinociceptive and anticonvulsant actions, and may be therapeutic for insomnia. Overall, CBD has a number of pharmacological effects that may significantly improve the mental and somatic health of patients suffering from post Ebola sequelae. In humans, CBD, at therapeutic doses, does not: 1) elicit dependence or tolerance; 2) significantly alter heart rate or blood pressure; 3) affect gastrointestinal transit; 4) produce significant cognitive or psychomotor impairments. Mild sedation and nausea are the most commonly reported adverse effects associated with CBD.CBD, based on its pharmacological effects and favorable safety profile, should be considered as a treatment for individuals with post Ebola sequelae. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Analysis of adverse events with Essure hysteroscopic sterilization reported to the Manufacturer and User Facility Device Experience database.

    Science.gov (United States)

    Al-Safi, Zain A; Shavell, Valerie I; Hobson, Deslyn T G; Berman, Jay M; Diamond, Michael P

    2013-01-01

    The Manufacturer and User Facility Device Experience database may be useful for clinicians using a Food and Drug Administration-approved medical device to identify the occurrence of adverse events and complications. We sought to analyze and investigate reports associated with the Essure hysteroscopic sterilization system (Conceptus Inc., Mountain View, CA) using this database. Retrospective review of the Manufacturer and User Facility Device Experience database for events related to Essure hysteroscopic sterilization from November 2002 to February 2012 (Canadian Task Force Classification III). Online retrospective review. Online reports of patients who underwent Essure tubal sterilization. Essure tubal sterilization. Four hundred fifty-seven adverse events were reported in the study period. Pain was the most frequently reported event (217 events [47.5%]) followed by delivery catheter malfunction (121 events [26.4%]). Poststerilization pregnancy was reported in 61 events (13.3%), of which 29 were ectopic pregnancies. Other reported events included perforation (90 events [19.7%]), abnormal bleeding (44 events [9.6%]), and microinsert malposition (33 events [7.2%]). The evaluation and management of these events resulted in an additional surgical procedure in 270 cases (59.1%), of which 44 were hysterectomies. Sixty-one unintended poststerilization pregnancies were reported in the study period, of which 29 (47.5%) were ectopic gestations. Thus, ectopic pregnancy must be considered if a woman becomes pregnant after Essure hysteroscopic sterilization. Additionally, 44 women underwent hysterectomy after an adverse event reported to be associated with the use of the device. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

  7. Psychosocial functioning in patients with schizophrenia treated with aripiprazole - an office-based real-world setting. Results from the German post-marketing surveillance study.

    Science.gov (United States)

    Bergmann, F; Zacher, A; Nass, A; Urban, R; Werner, C; Spevakné-Göröcs, T; Kungel, M; Ebrecht, M; Modell, S

    2009-05-01

    Aripiprazole (ABILIFY) is an effective antipsychotic used in a dose range from 10 to 30 mg, administered once daily. Soon after its approval in Germany for treatment of schizophrenia, a 12-month post-marketing surveillance study was initiated that included 1 096 patients cared for by 408 office-based psychiatrists and/or neurologists in private practice. The aim was to gain further insights into safety and efficacy of aripiprazole in an outpatient real-life setting focusing on general health, well-being and psychosocial functioning. Efficacy was rated by using standard CGI, SF-12 and SIWM-PsySo instruments for severity of disease, physical and mental health outcomes and psychosocial state, respectively. Safety was evaluated according to the reports of adverse events. Mean total daily dose of aripiprazole increased from 15.4 mg at the visit after 1 month to 17.6 mg at the visits after 6 to 12 months, the most frequently administered maintenance dose being 15 mg. Within the observation period significant improvements of CGI, SF-12 and SIWM-PsySo scores over time versus baseline values were observed (pmuch" or "very much" improved. Aripiprazole was overall well tolerated; 19.9% of patients discontinued treatment after 12 months. Adverse effects in general were moderate to mild and corresponded to the known tolerability profile of aripiprazole. Psychotic side effects reported were probably due to a recurrence of the underlying schizophrenic disorder. The results indicate that aripiprazole may be an efficacious and safe treatment option for pre-treated patients with schizophrenia also in a naturalistic psychiatrist/neurologist practice setting with effects on health and psychosocial functioning and a comparably low dropout rate.

  8. E-Approval Plans in Research Libraries

    Science.gov (United States)

    Pickett, Carmelita; Tabacaru, Simona; Harrell, Jeanne

    2014-01-01

    Research libraries have long invested in approval plan services, which offer an economical way to acquire scholarly and scientific publications. Traditional approval plans have evolved and now enable libraries to expand their e-book offerings to better serve researchers. Publishers offer a myriad of e-book purchasing options. These range from…

  9. Premarket Approvals (PMA)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Premarket approval by FDA is the required process of scientific review to ensure the safety and effectiveness of all devices classified as Class III devices. An...

  10. 75 FR 28814 - FHA Lender Approval, Annual Renewal, Periodic Updates and Required Reports From FHA Approved Lenders

    Science.gov (United States)

    2010-05-24

    ... proposal. This information is required for: (1) FHA lender approval, (2) Annual renewal of each FHA lender... following information: Title of Proposal: FHA Lender Approval, Annual Renewal, Periodic Updates and Required... and HUD-92001-C. Description of the Need for the Information and Its Proposed Use: This information is...

  11. Adverse Cutaneous Reactions to Psychotropic Drugs: A Review

    Directory of Open Access Journals (Sweden)

    Filipa Novais

    2015-11-01

    Full Text Available Introduction: Psychotropic drugs are often implicated in cutaneous adverse drug reactions. While most of these reactions have a benign character, it is still important, however, to consider its role in the increasing stigma and treatment adherence. A small number of the cutaneous adverse drug reactions can develop into serious and potentially fatal conditions. Objectives: This article aims to review the most common cutaneous adverse drug reactions in patients taking psychotropic drugs. Methods: In this study, a search was carried out in the MEDLINE database for English language articles published , from 1999 to 2014, using as keywords: psychiatric, psychotropic, cutaneous, adverse reaction, antidepressive agents, antipsychotics, benzodiazepines, mood stabilizers, anticonvulsant, dementia. Information available from the Portuguese regulatory and supervising agency (Infarmed was also included.Results: 121 articles were found with reference to cutaneous adverse drug reactions associated with psychotropic drugs. The drugs most frequently reported as associated with such adverse effects were anticonvulsants used as mood stabilizers, followed by the antipsychotics . The antidementia drugs were rarely associated with serious cutaneous adverse reactions. Discussion and Conclusion: Cutaneous drug adverse reactions are common in psychiatric clinical practice and typically are minor in severity. The most severe reactions are most often associated with the use of mood stabilizing medications. Some of these side effects can be solved with reduction or drug discontinuation. More severe cases should be referred to a specialist in dermatology.

  12. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    Directory of Open Access Journals (Sweden)

    Herxheimer Andrew

    2002-03-01

    Full Text Available Abstract Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis.

  13. Non-hemorrhage-related adverse effects of rivaroxaban

    OpenAIRE

    Christopoulou, Eliza C.; Filippatos, Theodosios D.; Elisaf, Moses S.

    2017-01-01

    The direct oral anticoagulant rivaroxaban is useful in various indications that include venous deep vein thrombosis prophylaxis/treatment after knee/hip replacement surgery and prevention of stroke in patients with non-valvular atrial fibrillation. Its mechanism of action has been mostly associated with hemorrhage-related adverse effects; thus a number of non-hemorrhage-related adverse effects of the drug have received less attention or go unrecognized. These adverse effects mainly include li...

  14. 16 CFR 901.7 - Adverse determination.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Adverse determination. 901.7 Section 901.7... APPLICATION FOR EXEMPTION FROM THE PROVISIONS OF THE ACT § 901.7 Adverse determination. (a) If, after... of the information before it that it cannot make a favorable determination in connection with the...

  15. Data handling and post-reconstruction analysis at next generation experiments

    International Nuclear Information System (INIS)

    Fischler, M.; Lammel, S.

    1995-11-01

    A new generation of experiments in high energy physics is approaching. With the approval of the LHC at CERN and the revised Main Injector project at Fermilab, high statistics experiments will start operation within 5 to 10 years. With luminosities Up to 10 34 /cm 2 /sec and several hundred thousand readout channels, data most likely cannot be handled and analysed using traditional HEP approaches. The CAP group at Fermilab is investigating different approaches to data handling and organization for post-reconstruction analysis. We discuss the approaches considered, their strengths and weaknesses, integration with hierarchical storage, and sharing of primary data resources

  16. 7 CFR 1710.105 - State regulatory approvals.

    Science.gov (United States)

    2010-01-01

    ... and Basic Policies § 1710.105 State regulatory approvals. (a) In States where a borrower is required... loans are approved by RUS: (1) Loans requiring an Environmental Impact Statement; (2) Loans to finance...

  17. Perspectives used for gaining approval of budgets.

    Science.gov (United States)

    Franks-Joiner, G L

    1990-01-01

    Nurse executives think about problems using a certain perspective which may influence decisions on budgetary matters. The nurse executives' perspective used in decision-making may influence which budget proposals are developed and approved. A study was performed to determine the perspective used by nurse executives in decision-making on supplementary budget item proposals and whether perspective use influenced approval. Findings showed that use of the system view or dual-domain perspective in a proposal may enhance nurse executives' changes of gaining approval.

  18. Endocrine active agents: implications of adverse and non-adverse changes.

    Science.gov (United States)

    Foster, Paul M D; McIntyre, Barry S

    2002-01-01

    The US Environmental Protection Agency (EPA) is currently in the process of developing screening and testing methodologies for the assessment of agents that may possess endocrine-like activity--the so-called endocrine disruptors. Moreover, the EPA has signaled its intention of placing information arising from such studies on the worldwide web. This has created significant interest in how such information may be used in risk assessment and by policymakers and the public in the potential regulation or deselection of specific chemical agents. The construction of lists of endocrine disruptors, although fulfilling the requirements of some parties, is really of little use when the nature of the response, the dose level employed, and the lifestage of the test species used are not given. Thus, we have already seen positive in vitro information available on the interaction with a receptor being used as a key indicator when the results of large, high quality in vivo studies showing no adverse changes have been ignored. Clearly a number of in vitro systems are available to ascertain chemical interaction with specific (mainly steroid) hormone receptors including a number of reporter gene assays. These assays only provide indicators of potential problems and should not be, in isolation, indicators of toxicity. Likewise, short-term in vivo screens such as the uterotrophic and Hershberger studies are frequently conducted in castrated animals and thus indicate the potential for a pharmacological response in vivo rather than an adverse effect. A number of new end points have been added to standard rodent testing protocols in the belief of providing more sensitivity to detect endocrine related changes. These include the measurement of anogenital distance (AGD), developmental landmarks [vaginal opening (VO), preputial separation (PPS)], and in some studies the counting of nipples and areolae on males. AGD, VO, and PPS are all affected by the size of the pup in which they are measured

  19. Adversity and Resilience: A Synthesis of International Research

    Science.gov (United States)

    Noltemeyer, Amity L.; Bush, Kevin R.

    2013-01-01

    Children and adolescents worldwide experience a variety of adversities that have the potential to disrupt typical development. However, some of these individuals exhibit resilience, evidencing normal development in the face of adversity. Here we review research on these constructs of risk, adversity, and resilience; synthesize international…

  20. 15 CFR 971.602 - Significant adverse environmental effects.

    Science.gov (United States)

    2010-01-01

    ... Environmental Effects § 971.602 Significant adverse environmental effects. (a) Determination of significant adverse environmental effects. The Administrator will determine the potential for or the occurrence of any significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106...

  1. 78 FR 2315 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2013-01-10

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  2. 78 FR 15402 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2013-03-11

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  3. 78 FR 11947 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2013-02-20

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  4. 78 FR 17281 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2013-03-20

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  5. 77 FR 16317 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2012-03-20

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  6. 77 FR 66909 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2012-11-07

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... below, receiving approval for the consumptive use of water pursuant to the Commission's approval by rule...

  7. 77 FR 21143 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2012-04-09

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  8. 77 FR 25010 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2012-04-26

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... below, receiving approval for the consumptive use of water pursuant to the Commission's approval by rule...

  9. 77 FR 34455 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2012-06-11

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  10. 77 FR 55891 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2012-09-11

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  11. 77 FR 55892 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2012-09-11

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  12. 77 FR 59239 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2012-09-26

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

  13. Adverse events associated with pediatric exposures to dextromethorphan.

    Science.gov (United States)

    Paul, Ian M; Reynolds, Kate M; Kauffman, Ralph E; Banner, William; Bond, G Randall; Palmer, Robert B; Burnham, Randy I; Green, Jody L

    2017-01-01

    Dextromethorphan is the most common over-the-counter (OTC) antitussive medication. We sought to characterize adverse events associated with dextromethorphan in children dextromethorphan with ≥1 adverse event from multiple U.S. sources (National Poison Data System, FDA Adverse Event Reporting System, manufacturer safety reports, news/media, medical literature) reported between 2008 and 2014. An expert panel determined the relationship between exposure and adverse events, estimated dose ingested, intent of exposure, and identified contributing factors to exposure. 1716 cases contained ≥1 adverse event deemed at least potentially related to dextromethorphan; 1417 were single product exposures. 773/1417 (55%) involved only one single-ingredient dextromethorphan product (dextromethorphan-only). Among dextromethorphan-only cases, 3% followed ingestion of a therapeutic dose; 78% followed an overdose. 69% involved unsupervised self-administration and 60% occurred in children dextromethorphan-only ingestion. Adverse events were predominantly associated with overdose, most commonly affecting the central nervous and autonomic systems.

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

    Science.gov (United States)

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

    2016-05-01

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

  15. CDC Wonder Vaccine Adverse Event Reporting System

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Vaccine Adverse Event Reporting System (VAERS) online database on CDC WONDER provides counts and percentages of adverse event case reports after vaccination,...

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

    Science.gov (United States)

    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.

  17. Asymmetric Information in Iranian’s Health Insurance Market: Testing of Adverse Selection and Moral Hazard

    Science.gov (United States)

    Lotfi, Farhad; Gorji, Hassan Abolghasem; Mahdavi, Ghadir; Hadian, Mohammad

    2015-01-01

    Background: Asymmetric information is one of the most important issues in insurance market which occurred due to inherent characteristics of one of the agents involved in insurance contracts; hence its management requires designing appropriate policies. This phenomenon can lead to the failure of insurance market via its two consequences, namely, adverse selection and moral hazard. Objective: This study was aimed to evaluate the status of asymmetric information in Iran’s health insurance market with respect to the demand for outpatient services. Materials/sPatients and Methods: This research is a cross sectional study conducted on households living in Iran. The data of the research was extracted from the information on household’s budget survey collected by the Statistical Center of Iran in 2012. In this study, the Generalized Method of Moment model was used and the status of adverse selection and moral hazard was evaluated through calculating the latent health status of individuals in each insurance category. To analyze the data, Excel, Eviews and stata11 software were used. Results: The estimation of parameters of the utility function of the demand for outpatient services (visit, medicine, and Para-clinical services) showed that households were more risk averse in the use of outpatient care than other goods and services. After estimating the health status of households based on their health insurance categories, the results showed that rural-insured people had the best health status and people with supplementary insurance had the worst health status. In addition, the comparison of the conditional distribution of latent health status approved the phenomenon of adverse selection in all insurance groups, with the exception of rural insurance. Moreover, calculation of the elasticity of medical expenses to reimbursement rate confirmed the existence of moral hazard phenomenon. Conclusions: Due to the existence of the phenomena of adverse selection and moral hazard

  18. Toward multimodal signal detection of adverse drug reactions.

    Science.gov (United States)

    Harpaz, Rave; DuMouchel, William; Schuemie, Martijn; Bodenreider, Olivier; Friedman, Carol; Horvitz, Eric; Ripple, Anna; Sorbello, Alfred; White, Ryen W; Winnenburg, Rainer; Shah, Nigam H

    2017-12-01

    Improving mechanisms to detect adverse drug reactions (ADRs) is key to strengthening post-marketing drug safety surveillance. Signal detection is presently unimodal, relying on a single information source. Multimodal signal detection is based on jointly analyzing multiple information sources. Building on, and expanding the work done in prior studies, the aim of the article is to further research on multimodal signal detection, explore its potential benefits, and propose methods for its construction and evaluation. Four data sources are investigated; FDA's adverse event reporting system, insurance claims, the MEDLINE citation database, and the logs of major Web search engines. Published methods are used to generate and combine signals from each data source. Two distinct reference benchmarks corresponding to well-established and recently labeled ADRs respectively are used to evaluate the performance of multimodal signal detection in terms of area under the ROC curve (AUC) and lead-time-to-detection, with the latter relative to labeling revision dates. Limited to our reference benchmarks, multimodal signal detection provides AUC improvements ranging from 0.04 to 0.09 based on a widely used evaluation benchmark, and a comparative added lead-time of 7-22 months relative to labeling revision dates from a time-indexed benchmark. The results support the notion that utilizing and jointly analyzing multiple data sources may lead to improved signal detection. Given certain data and benchmark limitations, the early stage of development, and the complexity of ADRs, it is currently not possible to make definitive statements about the ultimate utility of the concept. Continued development of multimodal signal detection requires a deeper understanding the data sources used, additional benchmarks, and further research on methods to generate and synthesize signals. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Applying for ethical approval for research: the main issues.

    Science.gov (United States)

    Gelling, Leslie

    2016-01-13

    The need to obtain research ethical approval is common to all research involving human participants. This approval must be obtained before research participants can be approached and before data collection can begin. The process of ethical review is one way that research participants can be confident that possible risks have been considered, minimised and deemed acceptable. This article outlines some of the main issues researchers should consider when planning an application for research ethical approval by answering the following six questions: 'Do I need research ethical approval?', 'How many applications will I need to make?', 'Where should I apply for research ethical approval?', 'What do I need to include in my application?', 'What do research ethics committees look for?' and 'What other approvals might I need?' Answering these questions will enable researchers to navigate the ethical review process.

  20. Poet Marion Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-North Manchester, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable

  1. Poet Portland Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves the petition, with modifications, from Poet Biorefining-Portland, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel

  2. Poet Alexandria Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-Alexandria, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel

  3. Poet Laddonia Approval

    Science.gov (United States)

    This update Auugust 9, 2016 letter from EPA approves with modifications, the petition from Poet Biorefining Laddonia, Poet Laddonia Facility, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act f

  4. CareTrack Kids—part 3. Adverse events in children's healthcare in Australia: study protocol for a retrospective medical record review

    Science.gov (United States)

    Hibbert, Peter D; Hallahan, Andrew R; Muething, Stephen E; Lachman, Peter; Hooper, Tamara D; Wiles, Louise K; Jaffe, Adam; White, Les; Wheaton, Gavin R; Runciman, William B; Dalton, Sarah; Williams, Helena M; Braithwaite, Jeffrey

    2015-01-01

    Introduction A high-quality health system should deliver care that is free from harm. Few large-scale studies of adverse events have been undertaken in children's healthcare internationally, and none in Australia. The aim of this study is to measure the frequency and types of adverse events encountered in Australian paediatric care in a range of healthcare settings. Methods and analysis A form of retrospective medical record review, the Institute of Healthcare Improvement's Global Trigger Tool, will be modified to collect data. Records of children aged <16 years managed during 2012 and 2013 will be reviewed. We aim to review 6000–8000 records from a sample of healthcare practices (hospitals, general practices and specialists). Ethics and dissemination Human Research Ethics Committee approvals have been received from the Sydney Children's Hospital Network, Children's Health Queensland Hospital and Health Service, and the Women's and Children's Hospital Network in South Australia. An application is under review with the Royal Australian College of General Practitioners. The authors will submit the results of the study to relevant journals and undertake national and international oral presentations to researchers, clinicians and policymakers. PMID:25854978

  5. Assessment of Adverse Events in Protocols, Clinical Study Reports, and Published Papers of Trials of Orlistat: A Document Analysis.

    Directory of Open Access Journals (Sweden)

    Jeppe Bennekou Schroll

    2016-08-01

    Full Text Available Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials.We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were "bothersome," a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal, which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of

  6. Data-driven prediction of adverse drug reactions induced by drug-drug interactions.

    Science.gov (United States)

    Liu, Ruifeng; AbdulHameed, Mohamed Diwan M; Kumar, Kamal; Yu, Xueping; Wallqvist, Anders; Reifman, Jaques

    2017-06-08

    via DDIs. This allowed us to identify potential DDI-induced ADRs not yet clinically reported. The ability of the models to quantify adverse effects between drug classes also suggests that we may be able to select drug combinations that minimize the risk of ADRs. Almost all information on DDI-induced ADRs is generated after drug approval. This situation poses significant health risks for vulnerable patient populations with comorbidities. To help mitigate the risks, we developed a robust probabilistic approach to prospectively predict DDI-induced ADRs. Based on this approach, we developed prediction models for 1,096 ADRs and used them to predict the propensity of all pairwise combinations of nearly 800 drugs to be associated with these ADRs via DDIs. We made the predictions publicly available via internet access.

  7. Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Sakaeda

    Full Text Available OBJECTIVE: Adverse event reports (AERs submitted to the US Food and Drug Administration (FDA were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors (statins and to attempt to determine the rank-order of the association. METHODS: After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. RESULTS: Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. CONCLUSIONS: Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

  8. Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

    Science.gov (United States)

    Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

    2011-01-01

    Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

  9. Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder: post-hoc analysis of randomized, double-blind, placebo-controlled trials.

    Science.gov (United States)

    Thase, Michael E; Edwards, John; Durgam, Suresh; Chen, Changzheng; Chang, Cheng-Tao; Mathews, Maju; Gommoll, Carl P

    2017-09-01

    Treatment-emergent suicidal ideation and behavior are ongoing concerns with antidepressants. Vilazodone, currently approved for the treatment of major depressive disorder (MDD) in adults, has also been evaluated in generalized anxiety disorder (GAD). Post-hoc analyses of vilazodone trials were carried out to examine its effects on suicidal ideation and behavior in adults with MDD or GAD. Data were pooled from vilazodone trials in MDD (four studies) and GAD (three studies). The incidence of suicide-related events was analyzed on the basis of treatment-emergent adverse event reporting and Columbia-Suicide Severity Rating Scale (C-SSRS) monitoring. Treatment-emergent suicidal ideation was analyzed on the basis of a C-SSRS category shift from no suicidal ideation/behavior (C-SSRS=0) at baseline to suicide ideation (C-SSRS=1-5) during treatment. In pooled safety populations (MDD, n=2233; GAD, n=1475), suicide-related treatment-emergent adverse events occurred in less than 1% of vilazodone-treated and placebo-treated patients. Incidences of C-SSRS suicidal ideation were as follows: MDD (vilazodone=19.9%, placebo=24.7%); GAD (vilazodone=7.7%, placebo=9.4%). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment were as follows: MDD (vilazodone=9.4%, placebo=10.3%); GAD (vilazodone=4.4%, placebo=6.1%). Data from placebo-controlled studies indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD or GAD. Nevertheless, all patients should be monitored for suicidal thoughts and behaviors during antidepressant treatment.

  10. FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

    Science.gov (United States)

    Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

    2015-11-01

    On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

  11. Effects of various etching protocols on the flexural properties and surface topography of fiber-reinforced composite dental posts.

    Science.gov (United States)

    Aksornmuang, Juthatip; Chuenarrom, Chanya; Chittithaworn, Natjira

    2017-09-26

    The purpose of this study was to evaluate the flexural properties and surface topography of fiber posts surface-treated with various etching protocols. Seventy each of three types of fiber posts: RelyX Fiber Post, Tenax Fiber Trans, and D.T. Light-Post Illusion X-Ro, were randomly divided into 7 groups: no surface treatment, surface treated with hydrofluoric acid (HF) 4.5% for 60 s, HF 4.5% for 120 s, HF 9.6% for 15 s, HF 9.6% for 60 s, HF 9.6% for 120 s, and treated with H 2 O 2 24% for 10 min. The specimens were then subjected to a three-point bending test. Surface topographies of the posts were observed using a SEM. The results indicate that fiber post surface pretreatments had no adverse effects on the flexural properties. However, the fiber posts treated with high HF concentrations or long etching times seemed to have more surface irregularities.

  12. Adverse health effects of non-medical cannabis use.

    Science.gov (United States)

    Hall, Wayne; Degenhardt, Louisa

    2009-10-17

    For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.

  13. Bias in spontaneous reporting of adverse drug reactions in Japan.

    Directory of Open Access Journals (Sweden)

    Shinichi Matsuda

    Full Text Available Attitudes of healthcare professionals regarding spontaneous reporting of adverse drug reactions (ADRs in Japan are not well known, and Japan's unique system of surveillance, called early post-marketing phase vigilance (EPPV, may affect these reporting attitudes. Our objectives were to describe potential effects of EPPV and to test whether ADR seriousness, prominence, and frequency are related to changes in reporting over time.A manufacturer's database of spontaneous ADR reports was used to extract data from individual case safety reports for 5 drugs subject to EPPV. The trend of reporting and the time lag between ADR onset and reporting to the manufacturer were examined. The following indices for ADRs occurring with each drug were calculated and analyzed to assess reporting trends: Serious:Non-serious ratio, High prominence:Low prominence ratio, and High frequency:Low frequency ratio.For all 5 drugs, the time lag between ADR onset and reporting to the manufacturer was shorter in the EPPV period than in the post-EPPV period. All drugs showed higher Serious:Non-serious ratios in the post-EPPV period. No specific patterns were observed for the High prominence:Low prominence ratio. The High frequency:Low frequency ratio for peginterferon alpha-2a and sevelamer hydrochloride decreased steadily throughout the study period.Healthcare professionals may be more likely to report serious ADRs than to report non-serious ADRs, but the effect of event prominence on reporting trends is still unclear. Factors associated with ADR reporting attitude in Japan might be different from those in other countries because of EPPV and the involvement of medical representatives in the spontaneous reporting process. Pharmacovigilance specialists should therefore be cautious when comparing data between different time periods or different countries. Further studies are needed to elucidate the underlying mechanism of spontaneous ADR reporting in Japan.

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

    Science.gov (United States)

    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.

  15. Poet Fostoria Approval

    Science.gov (United States)

    This August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-Fostoria, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6)

  16. Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial.

    Science.gov (United States)

    Slow, Sandy; Florkowski, Christopher M; Chambers, Stephen T; Priest, Patricia C; Stewart, Alistair W; Jennings, Lance C; Livesey, John H; Camargo, Carlos A; Scragg, Robert; Murdoch, David R

    2014-12-15

    To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Opportunistic addition to an established randomised double blind placebo controlled trial. Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Participants were randomised to receive an oral dose of either 200,000 IU vitamin D3 monthly for two months then 100,000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of "psychological" adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ(2) P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ(2) P=0.03). The number of psychological adverse events-such as fatigue, stress, anxiety, and insomnia-that participants reported at their usual monthly appointments was significantly

  17. Pengaruh Negative Framing dan Adverse Selection terhadap Eskalasi Komitmen

    OpenAIRE

    Arimawan, Muhammad Sandi; Sukirno, Sukirno

    2014-01-01

    Penelitian ini dilakukan bertujuan untuk mengetahui: (1) Pengaruh negative framing terhadap eskalasi komitmen, (2) Pengaruh adverse selection terhadap eskalasi komitmen, (3) Pengaruh negative framing dan adverse selection secara bersama-sama terhadap eskalasi komitmen, (4) Pengaruh negative framing terhadap eskalasi komitmen dimoderasi locus of control, (5) Pengaruh adverse selection terhadap eskalasi komitmen dimoderasi locus of control, (6) Pengaruh negative framing dan adverse selection se...

  18. Poet Leipsic Approval

    Science.gov (United States)

    This August 9, 2016 letter from EPA approves,wtih modifications, the petition from Poet Biorefining-Leipsic, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs

  19. Adverse event reporting in cancer clinical trial publications.

    Science.gov (United States)

    Sivendran, Shanthi; Latif, Asma; McBride, Russell B; Stensland, Kristian D; Wisnivesky, Juan; Haines, Lindsay; Oh, William K; Galsky, Matthew D

    2014-01-10

    Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated. A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness. A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores. Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.

  20. Guidance for package approvals in the United Kingdom

    International Nuclear Information System (INIS)

    Morgan-Warren, E.J.

    2004-01-01

    Approval is required under the transport regulations for a wide range of package designs and operations, and applications for competent authority approval and validation are received from many sources, both in the UK and overseas. To assist package designers and applicants for approval, and to promote consistency in applications and their assessment, the UK Department for Transport issues guidance on the interpretation of the transport regulations and the requirements of an application for approval and its supporting safety case. The general guidance document, known as the Guide to an Application for UK Competent Authority Approval of Radioactive Material in Transport, has been issued for many years and updated to encompass the provisions of each successive edition of the IAEA transport regulations. The guide has been referred to in a number of international fora, including PATRAM, and was cited as a 'good practice' in the report of the IAEA TRANSAS appraisal of the UK in 2002. Specialist guides include the Guide to the Suitability of Elastomeric Seal Materials, which is the subject of a separate paper in this conference, and the Guide to the Approval of Freight Containers as Types IP-2 and IP-3 Packages. This paper discusses the guidance material and summarises the administrative and technical information required in support of applications for approval of package designs, special form and low-dispersible radioactive materials, shipments, special arrangements, modifications and validations. (author)

  1. Consequenses of childhood adversity on health concerns in adulthood

    African Journals Online (AJOL)

    Consequenses of childhood adversity on health concerns in adulthood. ... childhood adversity have similar levels of depression, acute and chronic health. ... to explain the pathways linking childhood adversity to physical health in adulthood.

  2. Adverse drug reactions induced by cardiovascular drugs in outpatients.

    Science.gov (United States)

    Gholami, Kheirollah; Ziaie, Shadi; Shalviri, Gloria

    2008-01-01

    Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs) induced by this class of medicinal products seems necessary. To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3%) patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5%) and the lowest rate with Atenolol (3%). Headache was the most frequent detected ADR (23%). Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, PPearson=0.259, P<0.05). Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

  3. Retrospective case note review of chronic spontaneous urticaria outcomes and adverse effects in patients treated with omalizumab or ciclosporin in UK secondary care.

    Science.gov (United States)

    Savic, Sinisa; Marsland, Alexander; McKay, David; Ardern-Jones, Michael R; Leslie, Tabi; Somenzi, Olivier; Baldock, Laura; Grattan, Clive

    2015-01-01

    Omalizumab is approved in the UK as add-on treatment for chronic spontaneous urticaria (CSU) in patients with inadequate response to H1-antihistamines. Ciclosporin is an established but unlicensed 3rd line option for CSU. Two parallel retrospective observational studies were conducted to describe outcomes of treatment and adverse events with omalizumab or ciclosporin for CSU treatment. Data from UK specialist centres prescribing omalizumab (five centres) or ciclosporin (three centres) in CSU patients were collected from hospital records by clinical staff and pooled for analysis. Forty-six patients prescribed omalizumab and 72 patients prescribed ciclosporin were included. Twenty-two (48%) omalizumab-treated patients had paired Urticaria Activity Scores (UAS7), showing a 25.4 point improvement during treatment (P making causality assignment difficult, whereas those for ciclosporin were consistent with its known adverse effect profile. Validated patient-reported measures of disease severity and quality of life should be used routinely in CSU management. Based on clinician comments and DLQI scores, symptoms and quality of life showed a greater improvement in the omalizumab-treated cohort than in the ciclosporin-treated cohort.

  4. Post-Closure Inspection Report for Corrective Action Unit 424: Area 3 Landfill Complexes Tonopah Test Range, Nevada Calendar Year 2001; TOPICAL

    International Nuclear Information System (INIS)

    K. B. Campbell

    2002-01-01

    Corrective Action Unit (CAU) 424, the Area 3 Landfill Complexes at Tonopah Test Range, consists of eight Corrective Action Sites (CASs), seven of which are landfill cells that were closed previously by capping. (The eighth CAS, A3-7, was not used as a landfill site and was closed without taking any corrective action.) Figure 1 shows the general location of the landfill cells. Figure 2 shows in more detail the location of the eight landfill cells. CAU 424 closure activities included removing small volumes of soil containing petroleum hydrocarbons, repairing cell covers that were cracked or had subsided, and installing above-grade and at-grade monuments marking the comers of the landfill cells. Post-closure monitoring requirements for CAU 424 are detailed in Section 5.0, Post-Closure Inspection Plan, contained in the Closure Report for Corrective Action Unit 424: Area 3 Landfill Complexes, Tonopah Test Range, Nevada, report number DOE/NV-283, July 1999. The Closure Report (CR) was approved by the Nevada Division of Environmental Protection (NDEP) in July 1999. The CR includes compaction and permeability results of soils that cap the seven landfill cells. As stated in Section 5.0 of the NDEP-approved CR, post-closure monitoring at CAU 424 consists of the following: (1) Site inspections conducted twice a year to evaluate the condition of the unit. (2) Verification that landfill markers and warning signs are in-place, intact, and readable. (3) Notice of any subsidence, erosion, unauthorized use, or deficiencies that may compromise the integrity of the landfill covers. (4) Remedy of any deficiencies within 90 days of discovery. (5) Preparation and submittal of an annual report. Site inspections were conducted on May 16, 2001, and November 6, 2001. The inspections were preformed after the NDEP approval of the CR. This report includes copies of the inspection checklist, photographs, recommendations, and conclusions. The Post-Closure Inspection Checklists are found in

  5. 45 CFR 95.611 - Prior approval conditions.

    Science.gov (United States)

    2010-10-01

    ... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GENERAL ADMINISTRATION... for Department approval, signed by the appropriate State official, to the Director, Administration for... of procurement activities beyond that approved in the APD; (D) A change in system concept, or a...

  6. 8 CFR 207.6 - Control over approved refugee numbers.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Control over approved refugee numbers. 207... ADMISSION OF REFUGEES § 207.6 Control over approved refugee numbers. Current numerical accounting of approved refugees is maintained for each special group designated by the President. As refugee status is...

  7. 47 CFR 400.5 - Approval and award.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Approval and award. 400.5 Section 400.5 Telecommunication NATIONAL TELECOMMUNICATIONS AND INFORMATION ADMINISTRATION, DEPARTMENT OF COMMERCE, AND NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION E-911 GRANT PROGRAM § 400.5 Approval...

  8. 12 CFR 614.4470 - Loans subject to bank approval.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Loans subject to bank approval. 614.4470 Section 614.4470 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM LOAN POLICIES AND OPERATIONS Loan Approval Requirements § 614.4470 Loans subject to bank approval. (a) The following loans...

  9. An Overview of Risk Factors Associated to Post-partum Depression in Asia.

    Science.gov (United States)

    Mehta, Shubham; Mehta, Nidhi

    2014-03-04

    Post partum depression (PPD) is an important complication of child-bearing. It requires urgent interventions as it can have long-term adverse consequences if ignored, for both mother and child. If PPD has to be prevented by a public health intervention, the recognition and timely identification of its risk factors is must. We in this review have tried to synthesize the results of Asian studies examining the risk factors of PPD. Some risk factors, which are unique to Asian culture, have also been identified and discussed. We emphasize on early identification of these risk factors as most of these are modifiable and this can have significant implications in prevention of emergence of post partum depression, a serious health issue of Asian women.

  10. An overview of risk factors associated to post-partum depression in Asia

    Directory of Open Access Journals (Sweden)

    Shubham Mehta

    2014-03-01

    Full Text Available Post partum depression (PPD is an important complication of child-bearing. It requires urgent interventions as it can have long-term adverse consequences if ignored, for both mother and child. If PPD has to be prevented by a public health intervention, the recognition and timely identification of its risk factors is must. We in this review have tried to synthesize the results of Asian studies examining the risk factors of PPD. Some risk factors, which are unique to Asian culture, have also been identified and discussed. We emphasize on early identification of these risk factors as most of these are modifiable and this can have significant implications in prevention of emergence of post partum depression, a serious health issue of Asian women.

  11. Addendum to the post-closure permit application for the Bear Creek hydrogeologic regime at the Y-12 plant: Walk-in pits

    International Nuclear Information System (INIS)

    1995-04-01

    In June 1987, the Resource Conservation and Recovery Act (RCRA) Closure/Post-Closure Plan for the Bear Creek Burial Grounds (BCBG) located at the Y-12 Plant on the Oak Ridge Reservation in Oak Ridge, Tennessee was submitted to the Tennessee Department of Environment and Conservation (TDEC) for review and approval.The Closure Plan has been modified and revised several times. This document is an addendum to the Post-Closure Permit Application submitted to TDEC in June, 1994. This addendum contains information on the Walk-In Pits of the BCBG which is meant to supplement the information provided in the Post-Closure Permit Application submitted for the BCBG. This document is not intended to be a stand-alone document.

  12. Etanercept An Overview of Dermatologic Adverse Events

    NARCIS (Netherlands)

    Lecluse, Lidian L. A.; Dowlatshahi, Emmilia A.; Limpens, C. E. Jacqueline M.; de Rie, Menno A.; Bos, Jan D.; Spuls, Phyllis I.

    2011-01-01

    Objectives: To provide a comprehensive overview of dermatologic adverse events of etanercept described in the literature (including all study types, case reports, and surveys) and to present information on the occurrence, severity, treatment, and course of these adverse events. Data Sources: MEDLINE

  13. 48 CFR 52.222-16 - Approval of Wage Rates.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Approval of Wage Rates. 52....222-16 Approval of Wage Rates. As prescribed in 22.407(b), insert the following clause: Approval of Wage Rates (FEB 1988) All straight time wage rates, and overtime rates based thereon, for laborers and...

  14. 7 CFR 1717.609 - RUS approval of general manager.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false RUS approval of general manager. 1717.609 Section... Operational Controls § 1717.609 RUS approval of general manager. (a) If a borrower's mortgage or loan contract... general manager of the borrower's system, such approval is hereby granted provided that the borrower is in...

  15. 28 CFR 551.11 - Authority to approve a marriage.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Authority to approve a marriage. 551.11... MISCELLANEOUS Marriages of Inmates § 551.11 Authority to approve a marriage. (a) The Warden may approve the marriage of a federal inmate confined in a federal institution. This authority may not be delegated below...

  16. Fatigue associated with newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: an up-to-date meta-analysis.

    Science.gov (United States)

    Li, Jing; Gu, Jian

    2017-10-01

    The fatigue associated with five newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) is poorly understood. We conducted this systematic review to fully investigate the fatigue associated with these VEGFR-TKIs in cancer patients. Relevant studies of randomized controlled trials in cancer patients treated with the five VEGFR-TKIs were retrieved and a systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until March 2017. Thirteen randomized controlled trials and 4395 patients were included. The current analysis suggested that the use of five newly approved VEGFR-TKIs increased the risk of all-grade fatigue (1.43; 95% CI 1.23-1.66; p fatigue (1.97; 95% CI1.44-2.70; p fatigue varied significantly within drug type, but high-grade fatigue did not. The RR of all-grade and high-grade fatigue did not vary significantly according to cancer type, treatment line, and treatment duration. The risk of high-grade fatigue may vary with treatment duration, whereas all-grade fatigue may not. The available data suggest that the use of the five newly approved VEGFR-TKIs is associated with a significantly increased risk of fatigue in cancer patients. Physicians should be aware of this adverse effect and should monitor cancer patients receiving these drugs.

  17. 2016 in review: FDA approvals of new molecular entities.

    Science.gov (United States)

    Griesenauer, Rebekah H; Kinch, Michael S

    2017-11-01

    An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of mergers and acquisitions decreased the total number of organizations with past approval experience and continued research and development (R&D) activities to 102, divided evenly between more established pharmaceutical and newer biotechnology companies. Despite these substantial differences, the industry continued to pursue regulatory incentives, as evidenced by a continued increase in the fraction of NMEs approved using an orphan or priority designation, and almost all oncology drugs approved in 2016 utilized these mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. [Efficacy of tramadol/acetaminophen medication for central post-stroke pain].

    Science.gov (United States)

    Tanei, Takafumi; Kajita, Yasukazu; Noda, Hiroshi; Takebayashi, Shigenori; Hirano, Masaki; Nakahara, Norimoto; Wakabayashi, Toshihiko

    2013-08-01

    Central post-stroke pain(CPSP)is the most difficult type of central neuropathic pain to control with medical treatment. Opioids are commonly used for chronic neuropathic pain, but their efficacy in treating central neuropathic pain, particularly CPSP, is not clear. Tramadol is an opioid analgesic that, in combination with acetaminophen, has been approved since 2011 for the treatment of non-cancer pain in Japan. In this study we evaluated the efficacy of tramadol/acetaminophen medication for CPSP. We retrospectively reviewed nine cases of CPSP that received oral tramadol/acetaminophen medication. All cases received tramadol/acetaminophen medication after first taking pregabalin then antidepressant medication. Pain levels were assessed before tramadol/acetaminophen medication began and one month after a maintenance dose was reached, using a visual analogue scale(VAS)and the McGill pain questionnaire(MPQ). The mean dose of tramadol was 121±61.6 mg/day. Tramadol/acetaminophen medication was effective in reducing pain in seven of nine cases(77.8%). The VAS improved 32.9±13.8% from pre-to post-medication, and the MPQ improved from 15.4±9.1 pre-medication to 8.1±4.7 post-medication(ppain levels in patients with CPSP, and is a medication option for the treatment of CPSP.

  19. Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions.

    Science.gov (United States)

    Casey, Christine; Vellozzi, Claudia; Mootrey, Gina T; Chapman, Louisa E; McCauley, Mary; Roper, Martha H; Damon, Inger; Swerdlow, David L

    2006-02-03

    CDC and the U.S. Food and Drug Administration rely on state and local health departments, health-care providers, and the public to report the occurrence of adverse events after vaccination to the Vaccine Adverse Event Reporting System. With such data, trends can be accurately monitored, unusual occurrences of adverse events can be detected, and the safety of vaccination intervention activities can be evaluated. On January 24, 2003, the U.S. Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a biologic terrorism event. As part of the DHHS Smallpox Preparedness and Response Program, CDC in consultation with experts, established surveillance case definitions for adverse events after smallpox vaccination. Adverse reactions after smallpox vaccination identified during the 1960s surveillance activities were classified on the basis of clinical description and included eczema vaccinatum; fetal vaccinia; generalized vaccinia; accidental autoinoculation, nonocular; ocular vaccinia; progressive vaccinia; erythema multiforme major; postvaccinial encephalitis or encephalomyelitis; and pyogenic infection of the vaccination site. This report provides uniform criteria used for the surveillance case definition and classification for these previously recognized adverse reactions used during the DHHS Smallpox Preparedness and Response Program. Inadvertent inoculation was changed to more precisely describe this event as inadvertent autoinoculation and contact transmission, nonocular and ocular vaccinia. Pyogenic infection also was renamed superinfection of the vaccination site or regional lymph nodes. Finally, case definitions were developed for a new cardiac adverse reaction (myo/pericarditis) and for a cardiac adverse event (dilated cardiomyopathy) and are included in this report. The smallpox vaccine surveillance case

  20. Rare and very rare adverse effects of clozapine

    Directory of Open Access Journals (Sweden)

    De Fazio P

    2015-08-01

    Full Text Available Pasquale De Fazio,1 Raffaele Gaetano,1 Mariarita Caroleo,1 Gregorio Cerminara,1 Francesca Maida,2 Antonio Bruno,3 Maria Rosaria Muscatello,3 Maria Jose Jaén Moreno,4 Emilio Russo,2 Cristina Segura-García1 1Department of Health Sciences, School of Specialization in Psychiatry, 2Department of Health Sciences, School of Specialization in Pharmacology, University “Magna Graecia”, Catanzaro, 3Department of Neurosciences, School of Specialization in Psychiatry, University of Messina, Messina, Italy; 4Department of Social Health Sciences, Radiology and Physical Medicine, University of Cordoba, Cordoba, Spain Abstract: Clozapine (CLZ is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate

  1. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2014

    Energy Technology Data Exchange (ETDEWEB)

    Silvas, A. J. [National Security Technologies, LLC, Las Vegas, NV (United States). Nevada Test Site; Lantow, Tiffany A. [National Security Technologies, LLC, Las Vegas, NV (United States). Nevada Test Site

    2015-03-25

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2014 and includes inspection and repair activities completed at the following CAUs; CAU 400: Bomblet Pit and Five Points Landfill (TTR); CAU 407: Roller Coaster RadSafe Area (TTR); CAU 424: Area 3 Landfill Complexes (TTR); CAU 453: Area 9 UXO Landfill (TTR); and CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved Closure Reports and subsequent correspondence with the Nevada Division of Environmental Protection. The post-closure inspection plans and subsequent correspondence modifying the requirements for each CAU are included in Appendix B. The inspection checklists are included in Appendix C. Photographs taken during inspections are included in Appendix D. The annual post-closure inspections were conducted on May 28, 2014. Maintenance was required at CAU 407. Animal burrows were backfilled and erosion repairs were performed. Vegetation monitoring was performed at CAU 407 in June 2014. The vegetation monitoring report is included in Appendix E.

  2. Early life adversity and telomere length: a meta-analysis.

    Science.gov (United States)

    Ridout, K K; Levandowski, M; Ridout, S J; Gantz, L; Goonan, K; Palermo, D; Price, L H; Tyrka, A R

    2018-04-01

    Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.

  3. New Breast Cancer Treatment Approved | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... Breast Cancer Treatment Approved Follow us New Breast Cancer Treatment Approved Photo: Wikimedia Commons IN THE NEWS - Breast ... Food and Drug Administration approved a new breast cancer treatment that aims to reduce the risk of the ...

  4. Is there a link between childhood adversity, attachment style and Scotland’s excess mortality? Evidence, challenges and potential research

    Directory of Open Access Journals (Sweden)

    M. Smith

    2016-07-01

    Full Text Available Abstract Background Scotland has a persistently high mortality rate that is not solely due to the effects of socio-economic deprivation. This “excess” mortality is observed across the entire country, but is greatest in and around the post-industrial conurbation of West Central Scotland. Despite systematic investigation, the causes of the excess mortality remain the subject of ongoing debate. Discussion Attachment processes are a fundamental part of human development, and have a profound influence on adult personality and behaviour, especially in response to stressors. Many studies have also shown that childhood adversity is correlated with adult morbidity and mortality. The interplay between childhood adversity and attachment is complex and not fully elucidated, but will include socio-economic, intergenerational and psychological factors. Importantly, some adverse health outcomes for parents (such as problem substance use or suicide will simultaneously act as risk factors for their children. Data show that some forms of “household dysfunction” relating to childhood adversity are more prevalent in Scotland: such problems include parental problem substance use, rates of imprisonment, rates of suicide and rates of children being taken into care. However other measures of childhood or family wellbeing have not been found to be substantially different in Scotland compared to England. Summary We suggest in this paper that the role of childhood adversity and attachment experience merits further investigation as a plausible mechanism influencing health in Scotland. A model is proposed which sets out some of the interactions between the factors of interest, and we propose parameters for the types of study which would be required to evaluate the validity of the model.

  5. FDA approves efavirenz. Food and Drug Administration.

    Science.gov (United States)

    Highleyman, L

    1998-10-01

    The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.

  6. Accelerated approval of oncology products: the food and drug administration experience.

    Science.gov (United States)

    Johnson, John R; Ning, Yang-Min; Farrell, Ann; Justice, Robert; Keegan, Patricia; Pazdur, Richard

    2011-04-20

    We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.

  7. Predicting post-vaccination autoimmunity: who might be at risk?

    Science.gov (United States)

    Soriano, Alessandra; Nesher, Gideon; Shoenfeld, Yehuda

    2015-02-01

    Vaccinations have been used as an essential tool in the fight against infectious diseases, and succeeded in improving public health. However, adverse effects, including autoimmune conditions may occur following vaccinations (autoimmune/inflammatory syndrome induced by adjuvants--ASIA syndrome). It has been postulated that autoimmunity could be triggered or enhanced by the vaccine immunogen contents, as well as by adjuvants, which are used to increase the immune reaction to the immunogen. Fortunately, vaccination-related ASIA is uncommon. Yet, by defining individuals at risk we may further limit the number of individuals developing post-vaccination ASIA. In this perspective we defined four groups of individuals who might be susceptible to develop vaccination-induced ASIA: patients with prior post-vaccination autoimmune phenomena, patients with a medical history of autoimmunity, patients with a history of allergic reactions, and individuals who are prone to develop autoimmunity (having a family history of autoimmune diseases; asymptomatic carriers of autoantibodies; carrying certain genetic profiles, etc.). Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2014-08-01

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

  9. 14 CFR 21.8 - Approval of articles.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Approval of articles. 21.8 Section 21.8 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS General § 21.8 Approval of articles. If an article is required to be...

  10. 48 CFR 1819.7203 - Mentor approval process.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Mentor approval process... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7203 Mentor approval process. (a) An entity seeking to participate as a mentor must apply to the NASA Headquarters...

  11. Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up.

    Science.gov (United States)

    Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

    2017-02-01

    Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain. Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which

  12. [Reporting ethics board approval in German medical theses and journals].

    Science.gov (United States)

    Zenz, Michael; Zenz, Julia; Grieger, Maximilian

    2018-06-05

    Since 1975, the Declaration of Helsinki of the World Medical Association (WMA) has clearly required ethics committee approval for research into humans. Nevertheless, this Declaration is violated quite often. As many English-language publications have addressed the theme of ethics board approval in theses and other published works, it is now to be investigated in Germany for the first time.From 2013 to 2014, a total of 1,482 medical theses at four selected universities in addition to three German-language scientific journals were reviewed. In 543 theses, reference to ethics approval would have been required according to the criteria of the Declaration of Helsinki.However, ethics approval was stated in only 58.7% of cases, and even less frequently if the prevailing doctoral regulations or instructions did not refer to the necessity of obtaining ethics approval. Theses on pediatrics mentioned ethics approval most frequently (78.6%), whereas the proportion of surgical papers was the lowest (34.9%). Among the journals, Der Nervenarzt mentioned ethics approval most frequently (59.4%) and Der Chirurg least frequently (30%).Our results point to significant deficits in mentioning ethics approval in medical theses and publications. These deficits could easily be compensated for by a thorough approach of the referees of doctoral regulations and by journal reviewers and editors.

  13. 27 CFR 4.50 - Certificates of label approval.

    Science.gov (United States)

    2010-04-01

    ..., DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Requirements for Approval of Labels of... of exemption from label approval, as well as appeal procedures, see part 13 of this chapter. [T.D...

  14. Post-marketing surveillance of the safety profile of iodixanol in the outpatient CT setting. A prospective, multicenter, observational study of patient risk factors, adverse reactions and preventive measures in 9953 patients

    International Nuclear Information System (INIS)

    Mueller, Frank Hugo Heinz

    2014-01-01

    Non-interventional study in outpatient, contrast-enhanced CT: 1. to determine the extent of preventive measures for risk reduction of adverse drug reactions after contrast-enhanced CT examinations. 2. to prospectively determine the incidence and severity of adverse drug reactions occurring after administration of the iso-osmolar contrast medium iodixanol. 3. to determine a possible influence of preventive measures on the incidence/severity of adverse drug reactions. Evaluable documentation was provided for 9953 patients from 66 radiology centers across Germany. Patient characteristics, aspects of iodixanol administration, and adverse events with an at least 'possible' relationship were documented on a standardized case report form (CRF) and were evaluated up to seven days after contrast medium administration. About 55.5% of patients showed one or more risk factors (e.g. impaired renal function 4.4%, diabetes mellitus 8.5%, hypertension 20.6%). One third of the sites did not implement any preventive measures. Patients with a known risk for an allergy-like reaction were more likely to receive pharmacologic preventive treatment (0.5-50.5%). Oral hydration was the main preventive measure in patients with renal risk factors (<8%) followed by intravenous hydration (1%). Adverse drug reactions, mainly hypersensitivity reactions, occurred in 77 patients (0.74%), but were classified as serious in only 3 patients (0.03%). No statistically significant correlation between risk factors, preventive measures, and adverse reactions could be found. The use of preventive measures for CT examinations in this outpatient setting was generally low with risk patients being pre-medicated more often, depending on their history. In the routine outpatient setting, iso-osmolar iodixanol was very well tolerated in almost 10 000 patients undergoing diagnostic CT. The rate of acute and delayed adverse reactions was low. No correlation could be found between risk factors, preventive measures and

  15. Post-marketing surveillance of the safety profile of iodixanol in the outpatient CT setting. A prospective, multicenter, observational study of patient risk factors, adverse reactions and preventive measures in 9953 patients

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Frank Hugo Heinz [Radiology and Nuclear Medicine Center, Ludwigshafen (Germany)

    2014-11-15

    Non-interventional study in outpatient, contrast-enhanced CT: 1. to determine the extent of preventive measures for risk reduction of adverse drug reactions after contrast-enhanced CT examinations. 2. to prospectively determine the incidence and severity of adverse drug reactions occurring after administration of the iso-osmolar contrast medium iodixanol. 3. to determine a possible influence of preventive measures on the incidence/severity of adverse drug reactions. Evaluable documentation was provided for 9953 patients from 66 radiology centers across Germany. Patient characteristics, aspects of iodixanol administration, and adverse events with an at least 'possible' relationship were documented on a standardized case report form (CRF) and were evaluated up to seven days after contrast medium administration. About 55.5% of patients showed one or more risk factors (e.g. impaired renal function 4.4%, diabetes mellitus 8.5%, hypertension 20.6%). One third of the sites did not implement any preventive measures. Patients with a known risk for an allergy-like reaction were more likely to receive pharmacologic preventive treatment (0.5-50.5%). Oral hydration was the main preventive measure in patients with renal risk factors (<8%) followed by intravenous hydration (1%). Adverse drug reactions, mainly hypersensitivity reactions, occurred in 77 patients (0.74%), but were classified as serious in only 3 patients (0.03%). No statistically significant correlation between risk factors, preventive measures, and adverse reactions could be found. The use of preventive measures for CT examinations in this outpatient setting was generally low with risk patients being pre-medicated more often, depending on their history. In the routine outpatient setting, iso-osmolar iodixanol was very well tolerated in almost 10 000 patients undergoing diagnostic CT. The rate of acute and delayed adverse reactions was low. No correlation could be found between risk factors, preventive

  16. The cost of nurse-sensitive adverse events.

    Science.gov (United States)

    Pappas, Sharon Holcombe

    2008-05-01

    The aim of this study was to describe the methodology for nursing leaders to determine the cost of adverse events and effective levels of nurse staffing. The growing transparency of quality and cost outcomes motivates healthcare leaders to optimize the effectiveness of nurse staffing. Most hospitals have robust cost accounting systems that provide actual patient-level direct costs. These systems allow an analysis of the cost consumed by patients during a hospital stay. By knowing the cost of complications, leaders have the ability to justify the cost of improved staffing when quality evidence shows that higher nurse staffing improves quality. An analysis was performed on financial and clinical data from hospital databases of 3,200 inpatients. The purpose was to establish a methodology to determine actual cost per case. Three diagnosis-related groups were the focus of the analysis. Five adverse events were analyzed along with the costs. A regression analysis reported that the actual direct cost of an adverse event was dollars 1,029 per case in the congestive heart failure cases and dollars 903 in the surgical cases. There was a significant increase in the cost per case in medical patients with urinary tract infection and pressure ulcers and in surgical patients with urinary tract infection and pneumonia. The odds of pneumonia occurring in surgical patients decreased with additional registered nurse hours per patient day. Hospital cost accounting systems are useful in determining the cost of adverse events and can aid in decision making about nurse staffing. Adverse events add costs to patient care and should be measured at the unit level to adjust staffing to reduce adverse events and avoid costs.

  17. The relationship between post traumatic stress disorder and post traumatic growth: gender differences in PTG and PTSD subgroups.

    Science.gov (United States)

    Jin, Yuchang; Xu, Jiuping; Liu, Dongyue

    2014-12-01

    This study investigated the post traumatic stress disorder (PTSD) and post traumatic growth (PTG) in 2,300 earthquake survivors 1 year after the 2008 Wenchuan earthquake. This study aimed to investigate the relationship between PTSD and PTG and also tested for the gender differences in PTSD and PTG subgroups. A stratification random sampling strategy and questionnaires were used to collect the data. The PTSD was assessed using the PTSD Check list-Civilian and the PTG was assessed using the Post traumatic growth inventory. 2,300 individuals were involved in the initial survey with 2,080 completing the final questionnaire, a response rate of 90.4%. One-way ANOVA analyses were performed to investigate the gender differences in the PTSD and PTG subgroups. One year following the earthquake, 40.1 and 51.1% of survivors reported PTSD and PTG, respectively. A bivariate correlation analysis indicated that there was a positive association between PTG and PTSD. The PTG and PTSD variance analysis conducted on female and male subgroups suggested that women were more affected than men. Given the relatively high PTG prevalence, it was concluded that researchers need to pay more attention to the positive outcomes of an earthquake rather than just focusing on the negative effects. The surveys and analyses indicated that psychological intervention and care for the earthquake disaster survivors should focus more on females and older people, who tend to be more adversely affected.

  18. 14 CFR 21.609 - Approval for deviation.

    Science.gov (United States)

    2010-01-01

    ... deviation. (a) Each manufacturer who requests approval to deviate from any performance standard of a TSO shall show that the standards from which a deviation is requested are compensated for by factors or... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Approval for deviation. 21.609 Section 21...

  19. Ordinal Position, Approval Motivation, and Interpersonal Attraction

    Science.gov (United States)

    Nowicki, Stephen, Jr.

    1971-01-01

    Results of the study suggest that birth-order effects might be included within the wider framework of approval-dependency theory. Females tend to account for a significant share of birth-order effects. More particularly, firstborn females accounted for much of the differences in expressed attraction as well as need for social approval. (Author)

  20. Ventral striatal activity links adversity and reward processing in children

    Directory of Open Access Journals (Sweden)

    Niki H. Kamkar

    2017-08-01

    Full Text Available Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain’s sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children.

  1. Family Adversity and Resilience Measures in Pediatric Acute Care Settings.

    Science.gov (United States)

    O'Malley, Donna M; Randell, Kimberly A; Dowd, M Denise

    2016-01-01

    Adverse childhood experiences (ACEs) impact health across the life course. The purpose of this study was to identify caregiver ACEs, current adversity, and resilience in families seeking care in pediatric acute care settings. Study aims included identifying demographic characteristics, current adversities, and resilience measures associated with caregiver ACEs ≥4. A cross-sectional survey study design was used and a convenience sample (n = 470) recruited at emergency and urgent care settings of a large Midwest pediatric hospital system. Measures were self-reported. The original 10-item ACEs questionnaire measured caregiver past adversity. Current adversity was measured using the 10-item IHELP. The six-item Brief Resiliency Scale measured resilience, and WHO-5 Well-Being Index was used to measure depressive affect. Compared to participants with ACEs score of 0-3 participants with ACEs ≥4 were more likely to have multiple current adversities, increased risk of depression, and lower resilience. Caregivers using pediatric acute care settings carry a high burden of ACEs and current adversities. Caregiver ACEs are associated with current child experiences of adversity. Caregivers socioeconomic status and education level may not be an accurate indicator of a family's risks or needs. Pediatric acute care settings offer opportunities to access, intervene, and prevent childhood adversity. © 2016 Wiley Periodicals, Inc.

  2. Reliability of the peer-review process for adverse event rating.

    Directory of Open Access Journals (Sweden)

    Alan J Forster

    Full Text Available Adverse events are poor patient outcomes caused by medical care. Their identification requires the peer-review of poor outcomes, which may be unreliable. Combining physician ratings might improve the accuracy of adverse event classification.To evaluate the variation in peer-reviewer ratings of adverse outcomes; determine the impact of this variation on estimates of reviewer accuracy; and determine the number of reviewers who judge an adverse event occurred that is required to ensure that the true probability of an adverse event exceeded 50%, 75% or 95%.Thirty physicians rated 319 case reports giving details of poor patient outcomes following hospital discharge. They rated whether medical management caused the outcome using a six-point ordinal scale. We conducted latent class analyses to estimate the prevalence of adverse events as well as the sensitivity and specificity of each reviewer. We used this model and Bayesian calculations to determine the probability that an adverse event truly occurred to each patient as function of their number of positive ratings.The overall median score on the 6-point ordinal scale was 3 (IQR 2,4 but the individual rater median score ranged from a minimum of 1 (in four reviewers to a maximum median score of 5. The overall percentage of cases rated as an adverse event was 39.7% (3798/9570. The median kappa for all pair-wise combinations of the 30 reviewers was 0.26 (IQR 0.16, 0.42; Min = -0.07, Max = 0.62. Reviewer sensitivity and specificity for adverse event classification ranged from 0.06 to 0.93 and 0.50 to 0.98, respectively. The estimated prevalence of adverse events using a latent class model with a common sensitivity and specificity for all reviewers (0.64 and 0.83 respectively was 47.6%. For patients to have a 95% chance of truly having an adverse event, at least 3 of 3 reviewers are required to deem the outcome an adverse event.Adverse event classification is unreliable. To be certain that a case

  3. Common adverse drug reactions with psychiatric medications and ...

    African Journals Online (AJOL)

    Common adverse drug reactions with psychiatric medications and an approach to their management: Adverse drug reactions are as important in psychiatric practice as they are in any other branch of medicine.

  4. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  5. 42 CFR 102.73 - Approval of benefits.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Approval of benefits. 102.73 Section 102.73 Public... PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that benefits will be paid to a requester and has calculated the type and amount of such benefits, he will...

  6. 76 FR 66117 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2011-10-25

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... notice lists the projects, described below, receiving approval for the consumptive use of water pursuant...

  7. 76 FR 53526 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2011-08-26

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... lists the projects, described below, receiving approval for the consumptive use of water pursuant to the...

  8. 76 FR 42159 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2011-07-18

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... lists the projects, described below, receiving approval for the consumptive use of water pursuant to the...

  9. 77 FR 4859 - Projects Approved for Consumptive Uses of Water

    Science.gov (United States)

    2012-01-31

    ... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... notice lists the projects, described below, receiving approval for the consumptive use of water pursuant...

  10. Diffusion-weighted imaging properties of uterine fibroids pre- and post-uterine fibroid embolisation

    Energy Technology Data Exchange (ETDEWEB)

    Kirpalani, Anish, E-mail: kirpalania@smh.ca [Department of Medical Imaging, University of Toronto, St. Michael’s Hospital, 30 Bond Street, 3CC, Toronto, ON M5B 1W8 (Canada); Chong, Jennifer [Department of Medical Imaging, University of Toronto, St. Michael’s Hospital, 30 Bond Street, 3CC, Toronto, ON M5B 1W8 (Canada); Yang, Natalie [Department of Radiology, Austin Health, Heidelberg, Victoria 3084 (Australia); Jenkins, Sarah J. [Department of Radiology, Memorial University of Newfoundland, St. John’s, NL A1B 3V6 (Canada); Nisenbaum, Rosane [Centre for Research on Inner City Health, the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Dalla Lana School of Public Health, University of Toronto, 30 Bond Street, Toronto, ON M5B 1W8 (Canada); Prabhudesai, Vikramaditya; Anthwal, Shalini; Colak, Errol [Department of Medical Imaging, University of Toronto, St. Michael’s Hospital, 30 Bond Street, 3CC, Toronto, ON M5B 1W8 (Canada)

    2014-09-15

    Highlights: • Change in ADC and contrast enhancement of uterine fibroids following UFE was studied. • ADC of fibroids rises post-UFE. Previous studies assessing this change have conflicting results. • ADC rise post-UFE is associated with degree of loss of contrast enhancement. • ADC measurement using DWI is not yet a proven replacement for GBCA-enhanced MRI. - Abstract: Objective: To determine the change in apparent diffusion coefficient (ADC) of uterine fibroids following uterine fibroid embolisation (UFE), and if the ADC change correlates with either volume loss or degree of contrast enhancement post-UFE. Materials and methods: This study was approved by our institutional review board with waiver of consent. The pelvic MRI examinations, including diffusion-weighted MRI (DWI) using 4 b-values, of 50 consecutive patients prior to and 6 months post-UFE were analyzed. The volume, ADC and amount of enhancement were calculated for each fibroid both pre- and post-UFE. The percent residual enhancement for each fibroid was categorized as either: no (0–1%) residual enhancement or residual (>1%) enhancement. Statistical analysis compared ADC, enhancement and volume for each fibroid pre- and post-UFE using paired t-tests and Pearson correlation coefficients. Results: The mean ADC of all (n = 88) fibroids pre-UFE was 1.30 ± 0.20 × 10{sup −3} mm{sup 2}/s, and increased to 1.68 ± 0.24 × 10{sup −3} mm{sup 2}/s post-UFE (p < 0.0001). Lower pre-UFE ADC correlated with greater ADC change post-UFE (r = −0.50; p < 0.0001). There was no correlation between ADC change and volume change post-UFE (r = 0.07; p = 0.59). However, fibroids with no residual enhancement post-UFE had larger ADC change than those with residual enhancement (p = 0.003). Conclusion: The ADC of fibroids rises post-UFE. ADC change post-UFE is associated with the degree of loss of enhancement and may therefore be valuable in predicting response to treatment in pre-procedural counseling.

  11. CDC WONDER: Vaccine Adverse Event Reporting System (VAERS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Vaccine Adverse Event Reporting System (VAERS) online database on CDC WONDER provides counts and percentages of adverse event case reports after vaccination, by...

  12. Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.

    Science.gov (United States)

    Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

    2014-10-01

    In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed. Project HOPE—The People-to-People Health Foundation, Inc.

  13. Childhood adversities and clinical symptomatology in first-episode psychosis.

    Science.gov (United States)

    Lindgren, Maija; Mäntylä, Teemu; Rikandi, Eva; Torniainen-Holm, Minna; Morales-Muñoz, Isabel; Kieseppä, Tuula; Mantere, Outi; Suvisaari, Jaana

    2017-12-01

    In addition to severe traumatic experiences, milder, more common childhood adversities reflecting psychosocial burden may also be common in people with psychotic disorders and have an effect on symptomatology and functioning. We explored eleven negative childhood experiences and their influence on clinical symptoms among young adults with first-episode psychosis (FEP, n = 75) and matched population controls (n = 51). Individuals with FEP reported more adversities than controls. Specifically serious conflicts within the family, bullying at school, maternal mental health problems, and one's own and parents' serious illness during childhood were experienced by the patients more often than by controls. In the FEP group, the severity of adversity was associated with increased anxiety, manic, and obsessive-compulsive symptoms, but not with the severity of positive psychotic symptoms. Adversity produced a more pronounced effect on symptoms in male patients than in female patients. To conclude, in line with earlier studies of more chronic psychosis, a majority of the participants with FEP reported exposure to childhood adversities, with the FEP group reporting more adversities than controls. High levels of mood and anxiety symptoms in patients with FEP may be related to cumulative exposure to childhood adversities. This should be taken into account in the treatment for FEP. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Stress Level and Adversity Quotient among Single Working Mothers

    Directory of Open Access Journals (Sweden)

    Dianne Bautista Solis

    2015-12-01

    Full Text Available The study identified the profile of the single working mothers in terms of number of children, number of years as a single parent and reason for being a single parent; assessed the single mothers’ stress level and adversity quotient; determined the significant difference of stress level and adversity quotient of single mothers when grouped according to profile variables; determined the best predictor of stress level and adversity quotient. Moreover this research endeavoured to test significant relationship between the adversity quotient and stress level of single working mothers. Lastly, it proposed a stress management program for single working mothers for them to cope with their stress and adversities in life. The researcher employed quantitative method using standardized questionnaires namely Depression, Anxiety, Stress Scale (DASS and Adversity Response Profile (ARP. The respondents were twenty five (25 single working mothers of the students of Batangas State University. From the results, majority of the respondents have 3 children, widow and in early years as single parent; with a normal level of stress and an average adversity quotient.. There are no significant differences on the stress level and adversity quotient of the respondents when grouped according to profile variables. Finally, stress level has no significant effect on adversity quotient of single working mothers. From the findings, the researcher further recommends that the Office of Guidance and Counseling should update the student information database to determine students with a single working mother. The Parent-Teacher Association may form a single-parent subgroup for the single working mothers to be able to identify to other mothers with same situation. Moreover, the proposed stress management program may be reviewed and implemented by the Office of Guidance and Counseling in coordination with the Parent-Teacher Association of Batangas State University. Future researchers

  15. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  16. Ventral striatal activity links adversity and reward processing in children.

    Science.gov (United States)

    Kamkar, Niki H; Lewis, Daniel J; van den Bos, Wouter; Morton, J Bruce

    2017-08-01

    Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. The approval mechanism solves the prisoner's dilemma theoretically and experimentally

    OpenAIRE

    Tatsuyoshi Saijo; Yoshitaka Okano; Takafumi Yamakawa

    2015-01-01

    Consider a situation where players in a prisoner's dilemma game can approve or reject the other's choice such as cooperation or defection. If both players approve the other's choice, the outcome is the one they chose, whereas if either one rejects the other's choice, the outcome is the one when both defect, which we name the approval mechanism herein (this is inspired by the Cold War doctrine of mutually assured destruction). Experimentally, we find that the cooperation rate with the approval...

  18. Adverse reactions of α2-adrenoceptor agonists in cats reported in 2003-2013 in Finland.

    Science.gov (United States)

    Raekallio, Marja R; Virtanen, Marika; Happonen, Irmeli; Vainio, Outi M

    2017-07-01

    To describe suspected adverse drug reactions in cats associated with use of α 2 -adrenoceptor agonists. Retrospective study. A total of 90 cats. Data were collected from reports on adverse reactions to veterinary medicines sent to the Finnish Medicines Agency during 2003-2013. All reports of suspected adverse reactions associated with use of α 2 -adrenoceptor agonists in cats were included. Probable pulmonary oedema was diagnosed based on post mortem or radiological examination, or presence of frothy or excess fluid from the nostrils or trachea. If only dyspnoea and crackles on auscultation were reported, possible pulmonary oedema was presumed. Pulmonary oedema was suspected in 61 cases. Of these cats, 37 were categorised as probable and 24 as possible pulmonary oedema. The first clinical signs had been noted between 1 minute and 2 days (median, 15 minutes) after α 2 -adrenoceptor agonist administration. Many cats probably had no intravenous overhydration when the first clinical signs were detected, as either they presumably had no intravenous cannula or the signs appeared before, during or immediately after cannulation. Of the 61 cats, 43 survived, 14 died and for four the outcome was not clearly stated. Pulmonary oedema is a perilous condition that may appear within minutes of an intramuscular administration of sedative or anaesthetic agent in cats. The symptoms were not caused by intravenous overhydration, at least in cats having no venous cannula when the first clinical signs were detected. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  19. [Description of contributing factors in adverse events related to patient safety and their preventability].

    Science.gov (United States)

    Guerra-García, María Mercedes; Campos-Rivas, Beatriz; Sanmarful-Schwarz, Alexandra; Vírseda-Sacristán, Alicia; Dorrego-López, M Aránzazu; Charle-Crespo, Ángeles

    2017-11-25

    To assess the extent of healthcare related adverse events (AEs), their effect on patients, and their seriousness. To analyse the factors leading to the development of AEs, their relationship with the damage caused, and their degree of preventability. Retrospective descriptive study. Porriño, Pontevedra, Spain, Primary Care Service, from January-2014 to April-2016. Reported AEs were entered into the Patient Safety Reporting and Learning System (SiNASP). The variables measured were: Near Incident (NI) an occurrence with no effect or harm on the patient; Adverse Event (AE) an occurrence that affects or harms a patient. The level of harm is classified as minimal, minor, moderate, critical, and catastrophic. Preventability was classified as little evidence of being preventable, 50% preventable, and sound evidence of being preventable. percentages and Chi-squared test for qualitative variables; P<.05 with SPSS.15. SiNASP. Ethical considerations: approved by the Research Ethics Committee (2016/344). There were 166 recorded AEs (50.6% in males, and 46.4% in women. The mean age was 60.80years). Almost two-thirds 62.7% of AEs affected the patient, with 45.8% causing minimal damage, while 2.4% caused critical damages. Healthcare professionals were a contributing factor in 71.7% of the AEs, with the trend showing that poor communication and lack of protocols were related to the damage caused. Degree of preventability: 96.4%. Most AEs affected the patient, and were related to medication, diagnostic tests, and laboratory errors. The level of harm was related to communication problems, lack of, or deficient, protocols and a poor safety culture. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  20. Arabic translation and cultural adaptation of Liverpool Adverse ...

    African Journals Online (AJOL)

    Keywords: Adverse drug event, Epilepsy, Older adults, Cronbach's alpha, Liverpool Adverse Events. Profile, Seizure ... uncommon symptoms such as memory loss [5]. Age is a known .... to control seizures and minimize their side effects. [22].

  1. Peroral endoscopic myotomy as salvation technique post-Heller: International experience.

    Science.gov (United States)

    Tyberg, Amy; Sharaiha, Reem Z; Familiari, Pietro; Costamagna, Guido; Casas, Fernando; Kumta, Nikhil A; Barret, Maximilien; Desai, Amit P; Schnoll-Sussman, Felice; Saxena, Payal; Martínez, Guadalupe; Zamarripa, Felipe; Gaidhane, Monica; Bertani, Helga; Draganov, Peter V; Balassone, Valerio; Sharata, Ahmed; Reavis, Kevin; Swanstrom, Lee; Invernizzi, Martina; Seewald, Stefan; Minami, Hitomi; Inoue, Haruhiro; Kahaleh, Michel

    2018-01-01

    Treatment for achalasia has traditionally been Heller myotomy (HM). Despite its excellent efficacy rate, a number of patients remain symptomatic post-procedure. Limited data exist as to the best management for recurrence of symptoms post-HM. We present an international, multicenter experience evaluating the efficacy and safety of post-HM peroral endoscopic myotomy (POEM). Patients who underwent POEM post-HM from 13 centers from January 2012 to January 2017 were included as part of a prospective registry. Technical success was defined as successful completion of the myotomy. Clinical success was defined as an Eckardt score of ≤3 on 12-month follow up. Adverse events (AE) including anesthesia-related, operative, and postoperative complications were recorded. Fifty-one patients were included in the study (mean age 54.2, 47% male). Technical success was achieved in 100% of patients. Clinical success on long-term follow up was achieved in 48 patients (94%), with a mean change in Eckardt score of 6.25. Seven patients (13%) had AE: six experienced periprocedural mucosal defect treated endoscopically and two patients developed mediastinitis treated conservatively. For patients with persistent symptoms after HM, POEM is a safe salvation technique with good short-term efficacy. As a result of the challenge associated with repeat HM, POEM might become the preferred technique in this patient population. Further studies with longer follow up are needed. © 2017 Japan Gastroenterological Endoscopy Society.

  2. REVIEW OF NRC APPROVED DIGITAL CONTROL SYSTEMS ANALYSIS

    International Nuclear Information System (INIS)

    Markman, D.W.

    1999-01-01

    Preliminary design concepts for the proposed Subsurface Repository at Yucca Mountain indicate extensive reliance on modern, computer-based, digital control technologies. The purpose of this analysis is to investigate the degree to which the U. S. Nuclear Regulatory Commission (NRC) has accepted and approved the use of digital control technology for safety-related applications within the nuclear power industry. This analysis reviews cases of existing digitally-based control systems that have been approved by the NRC. These cases can serve as precedence for using similar types of digitally-based control technologies within the Subsurface Repository. While it is anticipated that the Yucca Mountain Project (YMP) will not contain control systems as complex as those required for a nuclear power plant, the review of these existing NRC approved applications will provide the YMP with valuable insight into the NRCs review process and design expectations for safety-related digital control systems. According to the YMP Compliance Program Guidance, portions of various NUREGS, Regulatory Guidelines, and nuclear IEEE standards the nuclear power plant safety related concept would be applied to some of the designs on a case-by-case basis. This analysis will consider key design methods, capabilities, successes, and important limitations or problems of selected control systems that have been approved for use in the Nuclear Power industry. An additional purpose of this analysis is to provide background information in support of further development of design criteria for the YMP. The scope and primary objectives of this analysis are to: (1) Identify and research the extent and precedence of digital control and remotely operated systems approved by the NRC for the nuclear power industry. Help provide a basis for using and relying on digital technologies for nuclear related safety critical applications. (2) Identify the basic control architecture and methods of key digital control

  3. Lactobacillus-deficient vaginal microbiota dominate post-partum women in rural Malawi.

    Science.gov (United States)

    Doyle, Ronan; Gondwe, Austridia; Fan, Yue-Mei; Maleta, Kenneth; Ashorn, Per; Klein, Nigel; Harris, Kathryn

    2018-01-05

    The bacterial community found in the vagina is an important determinant of a woman's health and disease. A healthy vaginal microbiota is associated with a lower species richness and high proportions of one of a number of different Lactobacillus spp.. When disrupted the resulting abnormal vaginal microbiota is associated with a number of disease states and poor pregnancy outcomes. Studies up until now have concentrated on relatively small numbers of American and European populations which may not capture the full complexity of the community, nor adequately predict what constitutes a healthy microbiota in all populations. In this study we sampled and characterised the vaginal microbiota from a cohort of 1107 women in rural Malawi found on vaginal swabs taken post-partum. We found a population dominated by Gardnerella vaginalis and devoid of the most common vaginal Lactobacillus species, even if the vagina was sampled over a year post-partum. The Lactobacillus -deficient anaerobic community commonly labelled community state type (CST) 4 could be sub-divided into four further communities. A Lactobacillus iners dominated vaginal microbiota became more common the longer after delivery the vagina was sampled, but G. vaginalis remained the dominant organism. These results outline the difficulty in all-encompassing definitions of what a healthy or abnormal vaginal microbiota is post-partum. Previous identification of community state types and associations between bacterial species, bacterial vaginosis and adverse birth outcomes may not represent the complex heterogeneity of the microbiota present. Importance A bacterial community in the vaginal tract that is dominated by small number of bacterial Lactobacillus species and when they are not present, there is a greater incidence of inflammatory conditions and adverse birth outcomes. A switch to a vaginal bacterial community lacking in Lactobacillus species is common after pregnancy. In this study we characterised the vaginal

  4. Filtering Entities to Optimize Identification of Adverse Drug Reaction From Social Media: How Can the Number of Words Between Entities in the Messages Help?

    Science.gov (United States)

    Abdellaoui, Redhouane; Schück, Stéphane; Texier, Nathalie; Burgun, Anita

    2017-06-22

    With the increasing popularity of Web 2.0 applications, social media has made it possible for individuals to post messages on adverse drug reactions. In such online conversations, patients discuss their symptoms, medical history, and diseases. These disorders may correspond to adverse drug reactions (ADRs) or any other medical condition. Therefore, methods must be developed to distinguish between false positives and true ADR declarations. The aim of this study was to investigate a method for filtering out disorder terms that did not correspond to adverse events by using the distance (as number of words) between the drug term and the disorder or symptom term in the post. We hypothesized that the shorter the distance between the disorder name and the drug, the higher the probability to be an ADR. We analyzed a corpus of 648 messages corresponding to a total of 1654 (drug and disorder) pairs from 5 French forums using Gaussian mixture models and an expectation-maximization (EM) algorithm . The distribution of the distances between the drug term and the disorder term enabled the filtering of 50.03% (733/1465) of the disorders that were not ADRs. Our filtering strategy achieved a precision of 95.8% and a recall of 50.0%. This study suggests that such distance between terms can be used for identifying false positives, thereby improving ADR detection in social media. ©Redhouane Abdellaoui, Stéphane Schück, Nathalie Texier, Anita Burgun. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 22.06.2017.

  5. An Overview of Risk Factors Associated to Post-partum Depression in Asia

    OpenAIRE

    Mehta, Shubham; Mehta, Nidhi

    2014-01-01

    Post partum depression (PPD) is an important complication of child-bearing. It requires urgent interventions as it can have long-term adverse consequences if ignored, for both mother and child. If PPD has to be prevented by a public health intervention, the recognition and timely identification of its risk factors is must. We in this review have tried to synthesize the results of Asian studies examining the risk factors of PPD. Some risk factors, which are unique to Asian culture, have also b...

  6. Effect of Safety Issues with HIV Drugs on the Approval Process of Other Drugs in the Same Class An Analysis of European Public Assessment Reports : an analysis of European public assessment reports

    NARCIS (Netherlands)

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

    2011-01-01

    Background: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required >= 1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval. Objective:

  7. 42 CFR 8.6 - Withdrawal of approval of accreditation bodies.

    Science.gov (United States)

    2010-10-01

    ... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Accreditation § 8.6 Withdrawal of approval of... 42 Public Health 1 2010-10-01 2010-10-01 false Withdrawal of approval of accreditation bodies. 8.6... to establish that the problems that were grounds for withdrawal of approval have been resolved. (2...

  8. Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Amarilyo, Gil; Furst, Daniel E; Woo, Jennifer M P

    2016-01-01

    BACKGROUND: Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website. OBJECTIVES: This study sought to determine if there are differences between the FDA assessments and journal...... reports on biologic agents developed for the treatment of rheumatoid arthritis. METHODS: Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American...... College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report...

  9. Comparative study on the immunogenicity and safety of a purified chick embryo cell rabies vaccine (PCECV) administered according to two different simulated post exposure intramuscular regimens (Zagreb versus Essen).

    Science.gov (United States)

    Mahendra, B J; Narayana, Dh Ashwath; Agarkhedkar, Sharad; Ravish, H S; Harish, B R; Agarkhedkar, Shalaka; Madhusudana, S N; Belludi, Ashwin; Ahmed, Khaleel; Jonnalagedda, Rekha; Vakil, Hoshang; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

    2015-01-01

    Despite availability of effective rabies vaccines, India has the highest global mortality rate for rabies. Low socio-economic communities are most affected due to lack of awareness of the disease and poor compliance to post-exposure prophylactic regimens. Currently, the only approved intramuscular regimen for post-exposure prophylaxis (PEP) against rabies in India is the Essen regimen, which consists of 5 injections administered over 5 separate days in a period of one month. The high number of doses and clinical visits, however, are major reasons for non-compliance, and thus a shorter regimen would be beneficial. In a simulated PEP trial in healthy, adult subjects, this study evaluated whether purified chick embryo cell vaccine (PCECV), administered according to the WHO-recommended 4-dose/3 visit Zagreb vaccination regimen is of equal immunogenicity and safety as the standard Essen regimen in Indian subjects. Two hundred and 50 healthy adults were enrolled and randomized into a Zagreb or Essen group, each receiving PCECV according to their respective regimen. Blood samples were collected on Days 0, 7, 14 and 42 and analyzed using the rapid fluorescent focus inhibition test (RFFIT). By Day 14, all subjects across both groups attained rabies virus neutralizing antibody (RVNA) concentrations of ≥ 0.5IU/ml. The Zagreb regimen was then demonstrated to be immunologically non-inferior to the Essen regimen by Day 14, which was the primary endpoint of the study. No safety issues were noted and the occurrence of adverse events was similar in both groups (17% and 15%, respectively). NCT01365494. CTRI No.: CTRI/2011/07/001857.

  10. Establishment approval in international trade of animal products

    NARCIS (Netherlands)

    Rau, M.L.; Ge, L.; Valeeva, N.I.; Wagenberg, van C.P.A.

    2012-01-01

    This report provides an overview of different approaches of establishment approval as well as its implementation and organisation in international agrifood trade. The focus is on animal products as establishment approval is particularly used for exporting these products. Based on trade data, 8

  11. Safety update on the use of recombinant activated factor VII in approved indications.

    Science.gov (United States)

    Neufeld, Ellis J; Négrier, Claude; Arkhammar, Per; Benchikh el Fegoun, Soraya; Simonsen, Mette Duelund; Rosholm, Anders; Seremetis, Stephanie

    2015-06-01

    This updated safety review summarises the large body of safety data available on the use of recombinant activated factor VII (rFVIIa) in approved indications: haemophilia with inhibitors, congenital factor VII (FVII) deficiency, acquired haemophilia and Glanzmann's thrombasthenia. Accumulated data up to 31 December 2013 from clinical trials as well as post-marketing data (registries, literature reports and spontaneous reports) were included. Overall, rFVIIa has shown a consistently favourable safety profile, with no unexpected safety concerns, in all approved indications. No confirmed cases of neutralising antibodies against rFVIIa have been reported in patients with congenital haemophilia, acquired haemophilia or Glanzmann's thrombasthenia. The favourable safety profile of rFVIIa can be attributed to the recombinant nature of rFVIIa and its localised mechanism of action at the site of vascular injury. Recombinant FVIIa activates factor X directly on the surface of activated platelets, which are present only at the site of injury, meaning that systemic activation of coagulation is avoided and the risk of thrombotic events (TEs) thus reduced. Nonetheless, close monitoring for signs and symptoms of TE is warranted in all patients treated with any pro-haemostatic agent, including rFVIIa, especially the elderly and any other patients with concomitant conditions and/or predisposing risk factors to thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Poet North Manchester Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-North Manchester, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable

  13. Adverse effects of iodine thyroid blocking: A systematic review

    International Nuclear Information System (INIS)

    Spallek, L.; Krille, L.; Reiners, C.; Schneider, R.; Yamashita, S.; Zeeb, H.

    2008-01-01

    131 I, when released in a radiological or nuclear accident as happened recently in Fukushima (Japan)), may cause thyroid cancer as a long-term consequence. Iodine thyroid blocking (ITB) is known to reduce the risk of developing thyroid cancer. Potential adverse effects of ITB have not been systematically investigated so far. This article summarises the results of a review on adverse effects of ITB based on a systematic literature search in scientific medical databases. A meta-analysis was not performed as identified studies displayed major heterogeneity. The search resulted in 14 articles relevant to the topic, reporting mostly on surveys, ecological and intervention studies. Only one study from Poland focused on effects (both desired and adverse) of an ITB intervention following the Chernobyl accident. All other studies reported on iodine administration in a different context. Overall, the studies did not reveal severe adverse reactions to potassium iodide in the general public. Since ITB is a protective measure only applied in very specific circumstances, scientifically sound studies of adverse effects are scarce and consequently the evidence base is weak. The assessment of adverse effects of ITB relies on indirect evidence from related areas. This study may contribute to ongoing developments in pharmaco-epidemiology aiming to better quantify adverse effects of medications and health care interventions including ITB. All rights reserved. (authors)

  14. Risk Factors for Post-treatment Complex Regional Pain Syndrome (CRPS)

    DEFF Research Database (Denmark)

    Petersen, Pelle B; Mikkelsen, Kim Lyngby; Lauritzen, Jes B

    2018-01-01

    OBJECTIVES: 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......, 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...... normal neurophysiology. CONCLUSIONS: 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...

  15. Cognitive Properties of Approval Voting : an Experimental Approach

    Directory of Open Access Journals (Sweden)

    Krzysztof Przybyszewski

    2011-01-01

    Full Text Available The paper summarizes two series of experiments demonstrating the cognitive properties of approval voting. The former series is devoted to mental processes induced in decision makers who use the method of approval voting. Based on cognitive effort, the use of choice strategies is presented in this paper. The observations of respondents show that most of them use relatively effortless strategy of eliminating alternatives and attributes. Few respondents use more sophisticated methods. The other series of experiments analyses the number of alternatives chosen in approval voting. It appears that the average number is not constant, even for similar votes but it depends on the subject of voting. The number of chosen alternatives and the subjective significance of the scope of voting are negatively or positively correlated in the case of special votes. The analyzed experiments show that the cognitive properties of approval voting have a diverse structure. (original abstract

  16. Delighted when approved by others, to pieces when rejected: children's social anxiety magnifies the linkage between self- and other-evaluations.

    Science.gov (United States)

    Reijntjes, Albert; Thomaes, Sander; Boelen, Paul; van der Schoot, Menno; de Castro, Bram Orobio; Telch, Michael J

    2011-07-01

    Socially anxious children tend to attach great importance to others' evaluations of them. However, the extent to which they base their momentary feelings of self-worth (i.e., state self-esteem) on social (dis)approval is unclear. It is also unclear whether this exceedingly approval-based self-esteem is a common correlate of social anxiety and depression, or specifically linked to one or the other. Changes in children's state self-esteem were obtained in response to a manipulated peer evaluation outcome. Participants (N = 188) aged 10 to 13 took part in a rigged online computer contest and were randomized to receive positive or negative peer feedback. Self-reported state self-esteem was assessed via computer at baseline and immediately post-feedback. The predictive effects of self-reported social anxiety and depression symptoms on changes in state self-esteem were investigated. Hierarchical multiple regression analyses showed that children with higher social anxiety, as indexed by the fear of negative evaluation component, experienced significantly stronger increases in state self-esteem following peer approval (β = .26, p self-esteem following peer disapproval (β = -.23, p self-esteem (ps > .20). Socially anxious children's state self-esteem is strongly contingent on social approval. Because basing one's self-esteem on external validation has multiple negative consequences, these findings highlight the importance of teaching these children skills (e.g., making cognitive reappraisals) to weaken the linkage between other- and self-evaluations. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.

  17. 7 CFR 1717.159 - Applications for RUS approvals of mergers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Applications for RUS approvals of mergers. 1717.159... ELECTRIC LOANS Mergers and Consolidations of Electric Borrowers § 1717.159 Applications for RUS approvals of mergers. If a proposed merger requires RUS approval according to RUS regulations and/or the loan...

  18. 7 CFR 4290.510 - Approval of RBIC's Investment Adviser/Manager.

    Science.gov (United States)

    2010-01-01

    ... INVESTMENT COMPANY (âRBICâ) PROGRAM Managing the Operations of a RBIC Management and Compensation § 4290.510... approval of the management contract. Approval of an Investment Adviser/Manager for one RBIC does not... 7 Agriculture 15 2010-01-01 2010-01-01 false Approval of RBIC's Investment Adviser/Manager. 4290...

  19. 30 CFR 250.119 - Will MMS approve subsurface gas storage?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Will MMS approve subsurface gas storage? 250....119 Will MMS approve subsurface gas storage? The Regional Supervisor may authorize subsurface storage of gas on the OCS, on and off-lease, for later commercial benefit. To receive MMS approval you must...

  20. Adverse childhood experiences of low-income urban youth.

    Science.gov (United States)

    Wade, Roy; Shea, Judy A; Rubin, David; Wood, Joanne

    2014-07-01

    Current assessments of adverse childhood experiences (ACEs) may not adequately encompass the breadth of adversity to which low-income urban children are exposed. The purpose of this study was to identify and characterize the range of adverse childhood experiences faced by young adults who grew up in a low-income urban area. Focus groups were conducted with young adults who grew up in low-income Philadelphia neighborhoods. Using the nominal group technique, participants generated a list of adverse childhood experiences and then identified the 5 most stressful experiences on the group list. The most stressful experiences identified by participants were grouped into a ranked list of domains and subdomains. Participants identified a range of experiences, grouped into 10 domains: family relationships, community stressors, personal victimization, economic hardship, peer relationships, discrimination, school, health, child welfare/juvenile justice, and media/technology. Included in these domains were many but not all of the experiences from the initial ACEs studies; parental divorce/separation and mental illness were absent. Additional experiences not included in the initial ACEs but endorsed by our participants included single-parent homes; exposure to violence, adult themes, and criminal behavior; personal victimization; bullying; economic hardship; and discrimination. Gathering youth perspectives on childhood adversity broadens our understanding of the experience of stress and trauma in childhood. Future work is needed to determine the significance of this broader set of adverse experiences in predisposing children to poor health outcomes as adults. Copyright © 2014 by the American Academy of Pediatrics.

  1. [Advantages and disadvantages of applying yttrium stabilized zirconium-dioxide post and core restorations].

    Science.gov (United States)

    Pétercsák, Anita; Radics, Tünde; Hegedus, Csaba

    2014-03-01

    Full ceramic restorations are associated with metal free post and core prosthodontics for teeth with seriously destroyed clinical crowns. Using custom made zirconium-dioxide post and cores can be flattering not only to give a good aesthetic result, but also to provide excellent retention. As none of the post systems stands all demands, prudent planning is mandatory. Our paper deals with favourable and unfavourable conditions as well as common causes of failures of post and core restorations. We took morphological, esthetical and functional considerations that can help to achieve the best results. Amongst them individual anatomic constitution, shape, width and length of the root and root canal, shape of the clinical crown, direction and magnitude of chewing forces are the most important factors. To give examples we present two cases of zirconium-dioxide post and core restorations. In our first case the missing clinical crown and a too wide root canal entrance created a questionable prognosis. To minimize adverse effect of the missing ferrule effect we applied custom-made zirconium-dioxide post and core and an additional abutment. After 7 years the restoration is still functioning. The second case represented a much favourable situation with 1,5 mm clinical crown height. The restoration was a custom-made zirconia post and core and a full-ceramic crown as a single tooth restoration. Although in this case we expected a better prognosis, 15 months later the patient showed up with a post fracture for applying extreme forces on the crown.

  2. Assessing Subjectivity in Sensor Data Post Processing via a Controlled Experiment

    Science.gov (United States)

    Jones, A. S.; Horsburgh, J. S.; Eiriksson, D.

    2017-12-01

    Environmental data collected by in situ sensors must be reviewed to verify validity, and conducting quality control often requires making edits in post processing to generate approved datasets. This process involves decisions by technicians, data managers, or data users on how to handle problematic data. Options include: removing data from a series, retaining data with annotations, and altering data based on algorithms related to adjacent data points or the patterns of data at other locations or of other variables. Ideally, given the same dataset and the same quality control guidelines, multiple data quality control technicians would make the same decisions in data post processing. However, despite the development and implementation of guidelines aimed to ensure consistent quality control procedures, we have faced ambiguity when performing post processing, and we have noticed inconsistencies in the practices of individuals performing quality control post processing. Technicians with the same level of training and using the same input datasets may produce different results, affecting the overall quality and comparability of finished data products. Different results may also be produced by technicians that do not have the same level of training. In order to assess the effect of subjective decision making by the individual technician on the end data product, we designed an experiment where multiple users performed quality control post processing on the same datasets using a consistent set of guidelines, field notes, and tools. We also assessed the effect of technician experience and training by conducting the same procedures with a group of novices unfamiliar with the data and the quality control process and compared their results to those generated by a group of more experienced technicians. In this presentation, we report our observations of the degree of subjectivity in sensor data post processing, assessing and quantifying the impacts of individual technician as

  3. 75 FR 36301 - Review and Approval of Projects

    Science.gov (United States)

    2010-06-25

    ... SUSQUEHANNA RIVER BASIN COMMISSION 18 CFR Parts 806 and 808 Review and Approval of Projects AGENCY... document contains proposed rules that would amend the project review regulations of the Susquehanna River... the scope of withdrawals requiring review and approval; improve notice procedures for all project...

  4. Editorial: Ethics approval: responsibilities of journal editors, authors ...

    African Journals Online (AJOL)

    Meaningful progress of medicine depends on research that must ultimately involve human subjects. Obtaining ethical approval therefore, especially in medical sciences, should be a moral reflex for researchers. This unfortunately is not the case, with numerous researchers bypassing the ethics approval procedure, or simply ...

  5. 42 CFR 422.256 - Review, negotiation, and approval of bids.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Review, negotiation, and approval of bids. 422.256... Information and Plan Approval § 422.256 Review, negotiation, and approval of bids. (a) Authority. Subject to... submitted under § 422.252 and conduct negotiations with MA organizations regarding these bids (including the...

  6. Linaclotide: first global approval.

    Science.gov (United States)

    McWilliams, Vanessa; Whiteside, Glenn; McKeage, Kate

    2012-11-12

    Linaclotide is a once-daily, orally administered, first-in-class agonist of guanylate cyclase-C that is minimally absorbed. It is being developed to treat gastrointestinal disorders by Ironwood Pharmaceuticals and its partners, Forest Laboratories (North America), Almirall (Europe) and Astellas Pharma (Asia-Pacific). Linaclotide has received its first global approval in the US for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC), and a marketing submission has been filed in the EU for IBS-C. This article summarizes the milestones in the development of linaclotide leading to this first approval for IBS-C and CIC. This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

  7. Clinical survey on adverse reaction of contrast media, final report

    International Nuclear Information System (INIS)

    Katayama, Hitoshi; Ishida, Osamu; Osawa, Tadashi

    1988-01-01

    This report is a final analysis of adverse reactions to iodinated contrast media examined in 33,440 patients from 11 hospitals during the period from October 1983 through June 1986. Adverse reactions, such as nausea, exanthema and vomiting, to contrast media occurred in 2,523 patients (7.5 %), with the higher number occuring in patients aged 40 - 60, irrespective of sex. There were no significant alternations in vital signs. Patients positive for pretesting and having a history of allergy had higher incidences of adverse reactions (48 % and 52 %, respectively). A history of allergy is the most potential predictor for adverse reactions to contrast media. There was no definitive correlation between prior medication of contrast media and the occurrence of their adverse reactions. The relationship between the occurrence of adverse reactions and both kinds and dosage of contrast media was unknown. (Namekawa, K.)

  8. Participant-centred active surveillance of adverse events following immunisation: a narrative review.

    Science.gov (United States)

    Cashman, Patrick; Macartney, Kristine; Khandaker, Gulam; King, Catherine; Gold, Michael; Durrheim, David N

    2017-05-01

    The importance of active, participant-centred monitoring of adverse events following immunisation (AEFI) is increasingly recognised as a valuable adjunct to traditional passive AEFI surveillance. The databases OVID Medline and OVID Embase were searched to identify all published articles referring to AEFI. Only studies which sought participant response after vaccination were included. A total of 6060 articles published since the year 2000 were identified. After the application of screening inclusion and exclusion criteria, 25 articles describing 23 post-marketing AEFI systems were identified. Most countries had a single system: Ghana, Japan, China, Korea, Netherlands, Singapore, Brazil, Cambodia, Sri Lanka, Turkey and Cameroon except the USA (2), Canada (4) and Australia (6). Data were collected from participants with and without AEFI in all studies reviewed with denominator data enabling AEFI rate calculations. All studies considered either a single vaccine or specified vaccines or were time limited except one Australian system, which provides continuous automated participant-centred active surveillance of all vaccines. Post-marketing surveillance systems using solicited patient feedback are emerging as a novel AEFI monitoring tool. A number of exploratory systems utilising e-technology have been developed and their potential for scaling up and application in low and middle income countries deserves further investigation. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  9. A drug's life: the pathway to drug approval.

    Science.gov (United States)

    Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

    2013-10-01

    In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

  10. Adverse childhood experience and asthma onset: a systematic review.

    Science.gov (United States)

    Exley, Daniel; Norman, Alyson; Hyland, Michael

    2015-06-01

    Adverse childhood experiences such as abuse and neglect are associated with subsequent immune dysregulation. Some studies show an association between adverse childhood experiences and asthma onset, although significant disparity in results exists in the published literature. We aimed to review available studies employing a prospective design that investigates associations between adverse childhood experience and asthma. A search protocol was developed and studies were drawn from four electronic journal databases. Studies were selected in accordance with pre-set inclusion criteria and relevant data were extracted. 12 studies, assessing data from a total of 31 524 individuals, were identified that investigate the impact of a range of adverse childhood experiences on the likelihood of developing asthma. Evidence suggests that chronic stress exposure and maternal distress in pregnancy operate synergistically with known triggers such as traffic-related air pollution to increase asthma risk. Chronic stress in early life is associated with an increased risk of asthma onset. There is evidence that adverse childhood experience increases the impact of traffic-related air pollution and inconsistent evidence that adverse childhood experience has an independent effect on asthma onset. Copyright ©ERS 2015.

  11. Ventral striatal activity links adversity and reward processing in children

    NARCIS (Netherlands)

    Kamkar, N.H.; Lewis, D.J.; van den Bos, W.; Morton, J.B.

    2017-01-01

    Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive

  12. Estimating post-marketing exposure to pharmaceutical products using ex-factory distribution data.

    Science.gov (United States)

    Telfair, Tamara; Mohan, Aparna K; Shahani, Shalini; Klincewicz, Stephen; Atsma, Willem Jan; Thomas, Adrian; Fife, Daniel

    2006-10-01

    The pharmaceutical industry has an obligation to identify adverse reactions to drug products during all phases of drug development, including the post-marketing period. Estimates of population exposure to pharmaceutical products are important to the post-marketing surveillance of drugs, and provide a context for assessing the various risks and benefits, including drug safety, associated with drug treatment. This paper describes a systematic approach to estimating post-marketing drug exposure using ex-factory shipment data to estimate the quantity of medication available, and dosage information (stratified by indication or other factors as appropriate) to convert the quantity of medication to person time of exposure. Unlike the non-standardized methods often used to estimate exposure, this approach provides estimates whose calculations are explicit, documented, and consistent across products and over time. The methods can readily be carried out by an individual or small group specializing in this function, and lend themselves to automation. The present estimation approach is practical and relatively uncomplicated to implement. We believe it is a useful innovation. Copyright 2006 John Wiley & Sons, Ltd.

  13. The adversative connectives aber and but in conversational corpora.

    Science.gov (United States)

    Gülzow, Insa; Bartlitz, Victoria; Kuehnast, Milena; Golcher, Felix; Bittner, Dagmar

    2018-03-09

    We analyzed the conversational corpora of two German and two English children to investigate how the different use types of the adversative connectives aber and but influence the probability of monologically versus dialogically constructed utterances in the first year of use. Our findings show that children produce adversative connectives mainly in dialogic structures for illocutionary and theme-management purposes, but that the use types of adversative connectives lead to a different distribution of monologic and dialogic clause combinations. The results suggest that monologic and dialogic realizations as a function of text type must be considered when describing the developmental trajectory of the different use types of adversative connectives.

  14. Post-construction monitoring for birds and bats : an examination of methods and issues

    International Nuclear Information System (INIS)

    Ebner, D.; Korpijaakko, C.

    2009-01-01

    The Canadian Environmental Assessment Act (CEAA) stipulates that bird and bat monitoring studies should be conducted following the construction of most wind turbine projects in Canada. The objectives of the monitoring studies are to verify the accuracy of the environmental assessment; determine the effectiveness of any measures taken to mitigate the adverse environmental effects of a project; and to evaluate the cumulative effects on species diversity and numbers. This presentation discussed post-construction monitoring for birds and bats and provided an examination of methods and issues. It emphasized why post-construction monitoring is important. Environmental effects that were examined in the presentation were changes in breeding birds; changes in passage migrants or wintering birds; changes in bat activity; and mortality monitoring/carcass surveys. The key issues regarding the design and implementation of post-construction monitoring programs include variation in field and analytical methods; protocols implemented that can add uncertainty and bias to estimates of mortality; and comparisons of project-specific results with other projects. Other topics that were addressed included federal requirements; provincial requirements; post-construction surveys and carcass searches; search efficiency and analysis. The presentation concluded with a discussion regarding the need for standardization. figs.

  15. Post-construction monitoring for birds and bats : an examination of methods and issues

    Energy Technology Data Exchange (ETDEWEB)

    Ebner, D.; Korpijaakko, C. [Stantec Consulting Ltd., Surrey, BC (Canada)

    2009-07-01

    The Canadian Environmental Assessment Act (CEAA) stipulates that bird and bat monitoring studies should be conducted following the construction of most wind turbine projects in Canada. The objectives of the monitoring studies are to verify the accuracy of the environmental assessment; determine the effectiveness of any measures taken to mitigate the adverse environmental effects of a project; and to evaluate the cumulative effects on species diversity and numbers. This presentation discussed post-construction monitoring for birds and bats and provided an examination of methods and issues. It emphasized why post-construction monitoring is important. Environmental effects that were examined in the presentation were changes in breeding birds; changes in passage migrants or wintering birds; changes in bat activity; and mortality monitoring/carcass surveys. The key issues regarding the design and implementation of post-construction monitoring programs include variation in field and analytical methods; protocols implemented that can add uncertainty and bias to estimates of mortality; and comparisons of project-specific results with other projects. Other topics that were addressed included federal requirements; provincial requirements; post-construction surveys and carcass searches; search efficiency and analysis. The presentation concluded with a discussion regarding the need for standardization. figs.

  16. Approved Drug Products with Therapuetic Equivalence Evaluations (Orange Book)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The publication Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book) identifies drug products approved on...

  17. U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab.

    Science.gov (United States)

    Hazarika, Maitreyee; Chuk, Meredith K; Theoret, Marc R; Mushti, Sirisha; He, Kun; Weis, Shawna L; Putman, Alexander H; Helms, Whitney S; Cao, Xianhua; Li, Hongshan; Zhao, Hong; Zhao, Liang; Welch, Joel; Graham, Laurie; Libeg, Meredith; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2017-07-15

    On December 22, 2014, the FDA granted accelerated approval to nivolumab (OPDIVO; Bristol-Myers Squibb) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on a clinically meaningful, durable objective response rate (ORR) in a non-comparative analysis of 120 patients who received 3 mg/kg of nivolumab intravenously every 2 weeks with at least 6-month follow-up in an ongoing, randomized, open-label, active-controlled clinical trial. The ORR as assessed by a blinded independent review committee per RECIST v1.1 was 31.7% (95% confidence interval, 23.5-40.8). Ongoing responses were observed in 87% of responding patients, ranging from 2.6+ to 10+ months. In 13 patients, the response duration was 6 months or longer. The risks of nivolumab, including clinically significant immune-mediated adverse reactions (imARs), were assessed in 268 patients who received at least one dose of nivolumab. The FDA review considered whether the ORR and durations of responses were reasonably likely to predict clinical benefit, the adequacy of the safety database, and systematic approaches to the identification, description, and patient management for imARs in product labeling. Clin Cancer Res; 23(14); 3484-8. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Admissions and Readmissions Related to Adverse Events, 2007-2014

    Science.gov (United States)

    2015-12-01

    DRG is a classification system primarily used for billing purposes. It uses the principle and secondary diagnoses to assign clinical conditions to...This study assessed adverse events as they relate to readmissions in the Military Health System (MHS). Among 142,579 admissions with an adverse event...The following study retrospectively assessed admissions and readmissions for adverse events in the Military Health System (MHS) by quantifying

  19. 44 CFR 78.9 - Planning grant approval process.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program FLOOD MITIGATION ASSISTANCE § 78.9 Planning grant approval process. The State POC will evaluate and approve applications for Planning Grants. Funds will be provided only for the flood portion of any mitigation plan, and...

  20. 7 CFR 1703.121 - Approved purposes for grants.

    Science.gov (United States)

    2010-01-01

    ... Approved purposes for grants. For distance learning and telemedicine projects, grants shall finance only... studies relating to the establishment or expansion of the phase of the project that is being financed with... initial capital assets associated with the project. The following are approved grant purposes: (a...