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Sample records for acute health endpoints

  1. COMPARISON OF ILLNESS ENDPOINTS IN SWIMMERS' HEALTH STUDIES

    EPA Science Inventory

    Prospective epidemiological studies on swimmers¿ health that were conducted by the U.S. Environmental Protection Agency (U.S. EPA) between 1973 and 1980 defined highly credible gastrointestinal illness (HCGI) as the occurrence of one or more of the following set of symptoms: (1) ...

  2. QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP (QSAR) MODELS TO PREDICT CHEMICAL TOXICITY FOR VARIOUS HEALTH ENDPOINTS

    EPA Science Inventory

    Although ranking schemes based on exposure and toxicity have been developed to aid in the prioritization of research funds for identifying chemicals of regulatory concern, there are significant gaps in the availability of experimental toxicity data for most health endpoints. Pred...

  3. Developing Outcomes Assessments as Endpoints for Registrational Clinical Trials of Antibacterial Drugs: 2015 Update From the Biomarkers Consortium of the Foundation for the National Institutes of Health

    PubMed Central

    Talbot, George H.; Powers, John H.; Hoffmann, Steven C.

    2016-01-01

    One important component in determining the benefits and harms of medical interventions is the use of well-defined and reliable outcome assessments as endpoints in clinical trials. Improving endpoints can better define patient benefits, allowing more accurate assessment of drug efficacy and more informed benefit-vs-risk decisions; another potential plus is facilitating efficient trial design. Since our first report in 2012, 2 Foundation for the National Institutes of Health Biomarkers Consortium Project Teams have continued to develop outcome assessments for potential uses as endpoints in registrational clinical trials of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. In addition, the teams have initiated similar work in the indications of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. This report provides an update on progress to date in these 4 diseases. PMID:26668337

  4. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans.

    PubMed

    Swan, Shanna H

    2008-10-01

    After briefly discussing human exposure to phthalates--diesters of 1,2-benzenedicarboxylic acid (phthalic acid)--this article first presents recent findings from the Study for Future Families, a multi-center pregnancy study in which the human analogue of the phthalate syndrome was first identified. This is one of an increasing number of studies that have investigated human endpoints in relation to environmental exposure to these ubiquitous compounds. This literature, which includes a range of human health endpoints following prenatal, neonatal, childhood, and adult exposures, is then summarized. At least one significant association has been reported for urinary metabolites of di-n-butyl phthalate (DBP), butylbenzyl phthalate (BzBP), diethyl phthlate (DEP), and di-isononyl phthalate (DINP) and for three of the urinary metabolites of di(2-ethylhexyl) phthalate (DEHP). Many of the findings reported in humans--most of which have been in males--are consistent with the anti-androgenic action that has been demonstrated for several phthalates. Replication of the results described here and further mechanistic studies are needed to strengthen links between phthalates and adverse health outcomes.

  5. Acute effects of a prooxidant herbicide on the microalga Chlamydomonas reinhardtii: Screening cytotoxicity and genotoxicity endpoints.

    PubMed

    Esperanza, Marta; Cid, Ángeles; Herrero, Concepción; Rioboo, Carmen

    2015-08-01

    Since recent evidence has demonstrated that many types of chemicals exhibit oxidative and/or genotoxic potential on living organisms, reactive oxygen species (ROS) formation and DNA damage are currently the best accepted paradigms to assess the potential hazardous biological effects of a wide range of contaminants. The goal of this study was to evaluate the sensitivity of different cytotoxicity and genotoxicity responses on the model microalga Chlamydomonas reinhardtii exposed to the prooxidant herbicide paraquat. In addition to the growth endpoint, cell viability, mitochondrial membrane potential and presence of reactive oxygen species (ROS) were assayed as potential markers of cytotoxicity using flow cytometry (FCM). To study the effects of paraquat on C. reinhardtii DNA, several genotoxicity approaches were implemented for the first time in an ecotoxicological study on microalgae. Oxidative DNA base damage was analysed by measuring the oxidative DNA lesion 8-OHdG by FCM. DNA fragmentation was analysed by different methods: comet assay, and cell cycle analysis by FCM, with a particular focus on the presence of subG1-nuclei. Finally, effects on morphology of nuclei were monitored through DAPI staining. The evaluation of these endpoints showed that several physiological and biochemical parameters reacted to oxidative stress disturbances with greater sensitivity than integrative parameters such as growth rates or cell viability. The experiments revealed concentration-dependent cytotoxicity (ROS formation, depolarization of mitochondrial membrane), genotoxicity (oxidative DNA damage, DNA strand breakage, alterations in nuclear morphology), and cell cycle disturbances (subG1-nuclei, decrease of 4N population) in paraquat-treated cells. Overall, the genotoxicity results indicate that the production of ROS caused by exposure to paraquat induces oxidative DNA damage followed by DNA single- and double-strand breaks and cell cycle alterations, possibly leading to apoptosis

  6. Hazardous waste transportation risk assessment for the US Department of Energy Environmental Restoration and Waste Management Programmatic Environmental Impact Statement -- human health endpoints

    SciTech Connect

    Hartmann, H.M.; Policastro, A.J.; Lazaro, M.A.

    1994-03-01

    In this presentation, a quantitative methodology for assessing the risk associated with the transportation of hazardous waste (HW) is proposed. The focus is on identifying air concentrations of HW that correspond to specific human health endpoints.

  7. Review of Dredging Elutriate Application Factors: Relevance to Acute-to-Chronic Protection, Contaminant, and Endpoint Specificity

    DTIC Science & Technology

    2015-07-01

    Particularly, use of the default AF is overly conservative when high levels of nonpersistent chemicals such as ammonia are present in elutriate... ammonia toxicity and the development toxicity test endpoint. DISCLAIMER: The contents of this report are not to be used for advertising, publication, or...Importance of ammonia in determining elutriate toxicity results ............................................. 6 Development toxicity tests and use of

  8. Summary of a workshop on regulatory acceptance of (Q)SARs for human health and environmental endpoints.

    PubMed Central

    Jaworska, Joanna S; Comber, M; Auer, C; Van Leeuwen, C J

    2003-01-01

    The "Workshop on Regulatory Use of (Q)SARs for Human Health and Environmental Endpoints," organized by the European Chemical Industry Council and the International Council of Chemical Associations, gathered more than 60 human health and environmental experts from industry, academia, and regulatory agencies from around the world. They agreed, especially industry and regulatory authorities, that the workshop initiated great potential for the further development and use of predictive models, that is, quantitative structure-activity relationships [(Q)SARs], for chemicals management in a much broader scope than is currently the case. To increase confidence in (Q)SAR predictions and minimization of their misuse, the workshop aimed to develop proposals for guidance and acceptability criteria. The workshop also described the broad outline of a system that would apply that guidance and acceptability criteria to a (Q)SAR when used for chemical management purposes, including priority setting, risk assessment, and classification and labeling. PMID:12896859

  9. OSIRIS, a quest for proof of principle for integrated testing strategies of chemicals for four human health endpoints.

    PubMed

    Vermeire, Theo; Aldenberg, Tom; Buist, Harrie; Escher, Sylvia; Mangelsdorf, Inge; Pauné, Eduard; Rorije, Emiel; Kroese, Dinant

    2013-11-01

    Chemical substances policies in Europe are aiming towards chemical safety and at the same time a reduction in animal testing. These goals are alleged to be reachable by mining as many relevant data as possible, evaluate these data with regard to validity, reliability and relevance, and use of these data in so-called Integrated Testing Strategies (ITS). This paper offers an overview of four human health endpoints that were part of the EU-funded OSIRIS project, aiming to develop ITS fit for the EU chemicals legislation REACH. The endpoints considered cover their categorical as well as continuous characteristics: skin sensitisation, repeated dose toxicity, mutagenicity and carcinogenicity. Detailed papers are published elsewhere in this volume. The stepwise ITS approach developed takes advantage of existing information, groups information about similar substances and integrates exposure considerations. The different and possibly contradictory information is weighted and the respective uncertainties taken into account in a weight of evidence (WoE) approach. In case of data gaps, the ITS proposes the most appropriate method to acquire the missing information. Each building block for the ITS, i.e. each in vivo test, in vitro test, (Q)SAR model or human evidence, is evaluated with regard to quality.

  10. Erythritol Is More Effective Than Xylitol and Sorbitol in Managing Oral Health Endpoints

    PubMed Central

    Mäkinen, Kauko; Honkala, Eino; Saag, Mare; Kennepohl, Elke

    2016-01-01

    Objective. To provide a comprehensive overview of published evidence on the impact of erythritol, a noncaloric polyol bulk sweetener, on oral health. Methods. A literature review was conducted regarding the potential effects of erythritol on dental plaque (biofilm), dental caries, and periodontal therapy. The efficacy of erythritol on oral health was compared with xylitol and sorbitol. Results. Erythritol effectively decreased weight of dental plaque and adherence of common streptococcal oral bacteria to tooth surfaces, inhibited growth and activity of associated bacteria like S. mutans, decreased expression of bacterial genes involved in sucrose metabolism, reduced the overall number of dental caries, and served as a suitable matrix for subgingival air-polishing to replace traditional root scaling. Conclusions. Important differences were reported in the effect of individual polyols on oral health. The current review provides evidence demonstrating better efficacy of erythritol compared to sorbitol and xylitol to maintain and improve oral health. PMID:27635141

  11. Comparing the acute sensitivity of growth and photosynthetic endpoints in three Lemna species exposed to four herbicides.

    PubMed

    Park, Jihae; Brown, Murray T; Depuydt, Stephen; Kim, Jang K; Won, Dam-Soo; Han, Taejun

    2017-01-01

    An ecological impact assessment of four herbicides (atrazine, diuron, paraquat and simazine) was assessed using the aquatic floating vascular plants, Lemna gibba, Lemna minor and Lemna paucicostata as test organisms. The sensitivity of several ecologically relevant parameters (increase in frond area, root length after regrowth, maximum and effective quantum yield of PSII and maximum electron transport rate (ETRmax), were compared after a 72 h exposure to herbicides. The present test methods require relatively small sample volume (3 mL), shorter exposure times (72 h), simple and quick analytical procedures as compared with standard Lemna assays. Sensitivity ranking of endpoints, based on EC50 values, differed depending on the herbicide. The most toxic herbicides were diuron and paraquat and the most sensitive endpoints were root length (6.0-12.3 μg L(-1)) and ETRmax (4.7-10.3 μg L(-1)) for paraquat and effective quantum yield (6.8-10.4 μg L(-1)) for diuron. Growth and chlorophyll a fluorescence parameters in all three Lemna species were sensitive enough to detect toxic levels of diuron and paraquat in water samples in excess of allowable concentrations set by international standards. CV values of all EC50s obtained from the Lemna tests were in the range of 2.8-24.33%, indicating a high level of repeatability comparable to the desirable level of <30% for adoption of toxicity test methods as international standards. Our new Lemna methods may provide useful information for the assessment of toxicity risk of residual herbicides in aquatic ecosystems.

  12. Usefulness of biomarkers as intermediate endpoints in health risks posed by occupational lead exposure.

    PubMed

    Borghini, Andrea; Gianicolo, Emilio Antonio; Andreassi, Maria Grazia

    2016-01-01

    The article concerns potential harmful effects of exposure to lead. Although the occurrence of severe lead poisoning has receded in several countries, occupational exposure resulting in moderate and clinically symptomatic toxicity is still common. An earlier and precise characterization of an individual response is obligatory in order to assess the possible risks for human health. Biomarkers may fill important gaps in the path from exposure to a disease. Specifically speaking, emerging (DNA double strand breaks and telomeric DNA erosion) and validated (micronuclei induction and chromosomal aberrations) biomarkers of genotoxicity seem to provide evidence for the assessment of molecular and cellular damage. Moreover, identification of genetic variability with a key role in modulating genotoxic damage may help minimize risks for susceptible subjects. Further investigations are naturally needed to properly define their diagnostic and/or prognostic value as "early warning" signs of a long-term risk for a subsequent clinically overt disease.

  13. Neurofunctional endpoints assessed in human neuroblastoma SH-SY5Y cells for estimation of acute systemic toxicity

    SciTech Connect

    Gustafsson, Helena; Runesson, Johan; Lundqvist, Jessica; Lindegren, Helene; Axelsson, Viktoria; Forsby, Anna

    2010-06-01

    The objective of the EU-funded integrated project ACuteTox is to develop a strategy in which general cytotoxicity, together with organ-specific toxicity and biokinetic features, are used for the estimation of human acute systemic toxicity. Our role in the project is to characterise the effect of reference chemicals with regard to neurotoxicity. We studied cell membrane potential (CMP), noradrenalin (NA) uptake, acetylcholine esterase (AChE) activity, acetylcholine receptor (AChR) signalling and voltage-operated calcium channel (VOCC) function in human neuroblastoma SH-SY5Y cells after exposure to 23 pharmaceuticals, pesticides or industrial chemicals. Neurotoxic alert chemicals were identified by comparing the obtained data with cytotoxicity data from the neutral red uptake assay in 3T3 mouse fibroblasts. Furthermore, neurotoxic concentrations were correlated with estimated human lethal blood concentrations (LC50). The CMP assay was the most sensitive assay, identifying eight chemicals as neurotoxic alerts and improving the LC50 correlation for nicotine, lindane, atropine and methadone. The NA uptake assay identified five neurotoxic alert chemicals and improved the LC50 correlation for atropine, diazepam, verapamil and methadone. The AChE, AChR and VOCC assays showed limited potential for detection of acute toxicity. The CMP assay was further evaluated by testing 36 additional reference chemicals. Five neurotoxic alert chemicals were generated and orphendrine and amitriptyline showed improved LC50 correlation. Due to the high sensitivity and the simplicity of the test protocol, the CMP assay constitutes a good candidate assay to be included in an in vitro test strategy for prediction of acute systemic toxicity.

  14. Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions

    PubMed Central

    Mehus, Aaron A.; Reed, Rustin J.; Lee, Vivien S. T.; Littau, Sally R.; Hu, Chengcheng; Lutz, Eric A.

    2015-01-01

    Objective: To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. Methods: We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting—lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. Results: B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Conclusions: Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use. PMID:26147538

  15. In vivo quantification of active decitabine-triphosphate metabolite: a novel pharmacoanalytical endpoint for optimization of hypomethylating therapy in acute myeloid leukemia.

    PubMed

    Wang, Hongyan; Chen, Ping; Wang, Jiang; Santhanam, Ramasamy; Aimiuwu, Josephine; Saradhi, U V Vijaya; Liu, Zhongfa; Schwind, Sebastian; Mims, Alice; Byrd, John C; Grever, Michael R; Villalona-Calero, Miguel A; Klisovic, Rebecca; Walker, Alison; Garzon, Ramiro; Blum, William; Chan, Kenneth K; Marcucci, Guido

    2013-01-01

    Decitabine (DAC) is used for treatment of patients with myelodysplastic syndromes and acute myeloid leukemia (AML). Following cellular uptake, DAC is activated to DAC-triphosphate (TP) and incorporated into DNA. Once incorporated into the DNA, DAC-TP binds and inactivates DNA methyltransferases (DNMTs), thereby leading to hypomethylation and re-expression of epigenetically silenced tumor suppressor genes and ultimately antileukemia activity. However, direct evidence of in vivo DAC-TP occurrence in DAC-treated patients has been difficult to demonstrate due to a lack of suitable validated analytical methodology. Thus, we developed and validated a nonradioactive sensitive and specific LC-MS/MS assay for quantification of DAC-TP. The assay is linear from 50 to 1,000 nM and from 1 to 10 μM and has a lower limit of quantitation of 50 nM and a coefficient of variation for both within- and between-day precision <20%. Following DAC treatment, we detected DAC-TP in parental and DAC-resistant AML cells (in vitro) and bone marrow (BM) and spleen of normal and leukemic mice (in vivo). Downregulation of DNMTs and correlation of DAC-TP concentration with proteins involved in mechanisms of DAC resistance were also demonstrated. The clinical applicability of this method was proven by measuring DAC-TP level in BM and blood mononuclear cells from DAC-treated AML patients. Higher levels are seemingly associated with clinical response. Monitoring the DAC-TP intracellular level may serve as a novel pharmacological endpoint for designing more effective DAC-based regimens.

  16. Estimation of the acute inhalation hazards of chemicals based on route-to-route and local endpoint extrapolation: experience from bulk maritime transport.

    PubMed

    Höfer, Thomas; James, Derek; Syversen, Tore; Bowmer, Tim

    2011-12-01

    Data on acute lethal inhalation toxicity from animal studies are commonly required for assessing the hazards to human health of volatile, gaseous and dusty chemicals or their mixtures. The International Maritime Organisation (IMO) made the provision of acute inhalation toxicity data a mandatory requirement for the carriage of bulk liquid chemicals transported by sea in tank ships, thereby creating the need for inhalation data on many hundreds of chemicals in bulk maritime transport. Taking note of previously published proposals for estimating acute inhalation toxicity hazards for chemicals, and the paucity of measured experimental data, an extrapolation method has been developed by the Group of Experts on the Scientific Aspects of Marine Environmental Protection (GESAMP) to partly fulfil this need. This method should be seen as a pragmatic approach to the challenge of missing measured experimental test data, with the added benefit of reducing tests in experimental animals. The method is based on a route-to-route (i.e. between-route) extrapolation of information on acute oral and/or dermal toxicity, in combination with data on the potential for irritation and/or corrosion to skin and eyes. The validation of this method was based on the individual evaluation of inhalation toxicity studies for 330 chemicals, including mixtures and many important chemical groups, for which the IMO holds public and industry-confidential data. The authors contend that this extrapolation method offers a reliable basis for hazard evaluation in the context of bulk maritime transport, and the 'GESAMP inhalation toxicity extrapolation method' has become part of the IMO regulatory system for the carriage of bulk liquids (i.e. noxious liquid substances) on board tank ships.

  17. Analyzing the "correct" endpoint.

    PubMed

    Atherton, Pamela J; Novotny, Paul J; Tan, Angelina D

    2006-01-01

    The choice of QOL endpoints for a study should be based on which score will most likely change if the treatment is favorable. How the QOL change is calculated should be based on the expected amount of missing data, how many time points data will be collected, and whether extreme outliers in the scores impact results. The study should have sufficient power to detect a meaningful difference between arms (typically 10 points on a 0-100 point scale) in the chosen QOL endpoint. At the conclusion of a study, several secondary endpoints can be analyzed which can provide additional information and confirm primary endpoint results.

  18. [Immunological surrogate endpoints to evaluate vaccine efficacy].

    PubMed

    Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai

    2015-12-01

    An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description.

  19. Assessment of the Acute and Chronic Health Hazards of Hydraulic Fracturing Fluids.

    PubMed

    Wattenberg, Elizabeth V; Bielicki, Jeffrey M; Suchomel, Ashley E; Sweet, Jessica T; Vold, Elizabeth M; Ramachandran, Gurumurthy

    2015-01-01

    There is growing concern about how hydraulic fracturing affects public health because this activity involves handling large volumes of fluids that contain toxic and carcinogenic constituents, which are injected under high pressure through wells into the subsurface to release oil and gas from tight shale formations. The constituents of hydraulic fracturing fluids (HFFs) present occupational health risks because workers may be directly exposed to them, and general public health risks because of potential air and water contamination. Hazard identification, which focuses on the types of toxicity that substances may cause, is an important step in the complex health risk assessment of hydraulic fracturing. This article presents a practical and adaptable tool for the hazard identification of HFF constituents, and its use in the analysis of HFF constituents reported to be used in 2,850 wells in North Dakota between December 2009 and November 2013. Of the 569 reported constituents, 347 could be identified by a Chemical Abstract Service Registration Number (CASRN) and matching constituent name. The remainder could not be identified either because of trade secret labeling (210) or because of an invalid CASRN (12). Eleven public databases were searched for health hazard information on thirteen health hazard endpoints for 168 identifiable constituents that had at least 25 reports of use. Health hazard counts were generated for chronic and acute endpoints, including those associated with oral, inhalation, ocular, and dermal exposure. Eleven of the constituents listed in the top 30 by total health hazard count were also listed in the top 30 by reports of use. This includes naphthalene, which along with benzyl chloride, has the highest health hazard count. The top 25 constituents reportedly used in North Dakota largely overlap with those reported for Texas and Pennsylvania, despite different geologic formations, target resources (oil vs. gas), and disclosure requirements

  20. Examination of Inter-relationships among Atmospheric Transport Patterns, Ozone Concentrations, and Human Health Endpoints in New York State

    NASA Astrophysics Data System (ADS)

    Garcia, Valerie Cover

    In its mission to protect human health and the environment, the United States (U.S.) Environmental Protection Agency (EPA) implemented the NOx Budget Trading Program (NBP) to reduce the emissions of nitrogen oxides (NOx) in the Eastern U.S., with the intent of reducing ambient concentrations of both NOx and the secondarily-formed ozone chemicals. These pollutants and their precursors can be transported downwind, contributing to pollutant levels at locations much farther from the emission sources, potentially impacting human health in downwind areas. This study investigates the health risks in New York State (NYS) from exposure to polluted air parcels transported from the Midwest. Back-trajectories are performed from several sites within NYS for ten summers (June, July and August from 1997 to 2006) to identify days that the air parcel passed through the Ohio River Valley (ORV) region within 48 hours back in time. The ORV zone is defined as a boundary encompassing relatively high-emitting power plants in the Midwest and is used as an indicator variable to represent the transport of ozone from this area into NYS in an epidemiology analysis. The ORV zone variable and the daily maximum 8-hr average ozone concentrations are then used as the main health effects in a Generalized Additive Model (GAM) to investigate potential associations between these two variables and respiratory-related hospital admissions. The results of the analysis indicate that the risk of being admitted to the hospital for a respiratory-related illness on days that air parcels are transported from the Midwest is elevated in NYS sub-regions 2, 3 and 6. In addition, the risk of respiratory-related hospital admission from exposure to ozone is elevated in Regions 2 and 4. Two time periods before the implementation of the NBP and after the implementation of the NBP (summers of 1997 -- 2000 and 2004 -- 2006, respectively) were also examined, but an analysis of the number of summers needed to conduct the

  1. Health Impacts from Acute Radiation Exposure

    SciTech Connect

    Strom, Daniel J.

    2003-09-30

    Absorbed doses above1-2 Gy (100-200 rads) received over a period of a day or less lead to one or another of the acute radiation syndromes. These are the hematopoietic syndrome, the gastrointestinal (GI) syndrome, the cerebrovascular (CV) syndrome, the pulmonary syndrome, or the cutaneous syndrome. The dose that will kill about 50% of the exposed people within 60 days with minimal medical care, LD50-60, is around 4.5 Gy (450 rads) of low-LET radiation measured free in air. The GI syndrome may not be fatal with supportive medical care and growth factors below about 10 Gy (1000 rads), but above this is likely to be fatal. Pulmonary and cutaneous syndromes may or may not be fatal, depending on many factors. The CV syndrome is invariably fatal. Lower acute doses, or protracted doses delivered over days or weeks, may lead to many other health outcomes than death. These include loss of pregnancy, cataract, impaired fertility or temporary or permanent sterility, hair loss, skin ulceration, local tissue necrosis, developmental abnormalities including mental and growth retardation in persons irradiated as children or fetuses, radiation dermatitis, and other symptoms listed in Table 2 on page 12. Children of parents irradiated prior to conception may experience heritable ill-health, that is, genetic changes from their parents. These effects are less strongly expressed than previously thought. Populations irradiated to high doses at high dose rates have increased risk of cancer incidence and mortality, taken as about 10-20% incidence and perhaps 5-10% mortality per sievert of effective dose of any radiation or per gray of whole-body absorbed dose low-LET radiation. Cancer risks for non-uniform irradiation will be less.

  2. Using backup generators for meeting peak electricity demand: a sensitivity analysis on emission controls, location, and health endpoints.

    PubMed

    Gilmore, Elisabeth A; Adams, Peter J; Lave, Lester B

    2010-05-01

    Generators installed for backup power during blackouts could help satisfy peak electricity demand; however, many are diesel generators with nonnegligible air emissions that may damage air quality and human health. The full (private and social) cost of using diesel generators with and without emission control retrofits for fine particulate matter (PM2.5) and nitrogen oxides (NOx) were compared with a new natural gas turbine peaking plant. Lower private costs were found for the backup generators because the capital costs are mostly ascribed to reliability. To estimate the social costs from air quality, the changes in ambient concentrations of ozone (O3) and PM2.5 were modeled using the Particulate Matter Comprehensive Air Quality Model with extensions (PMCAMx) chemical transport model. These air quality changes were translated to their equivalent human health effects using concentration-response functions and then into dollars using estimates of "willingness-to-pay" to avoid ill health. As a case study, 1000 MW of backup generation operating for 12 hr/day for 6 days in each of four eastern U.S. cities (Atlanta, Chicago, Dallas, and New York) was modeled. In all cities, modeled PM2.5 concentrations increased (up to 5 microg/m3) due mainly to primary emissions. Smaller increases and decreases were observed for secondary PM2.5 with more variation between cities. Increases in NOx, emissions resulted in significant nitrate formation (up to 1 microg/m3) in Atlanta and Chicago. The NOx emissions also caused O3 decreases in the urban centers and increases in the surrounding areas. For PM2.5, a social cost of approximately $2/kWh was calculated for uncontrolled diesel generators in highly populated cities but was under 10 cent/kWh with PM2.5 and NOx controls. On a full cost basis, it was found that properly controlled diesel generators are cost-effective for meeting peak electricity demand. The authors recommend NOx and PM2.5 controls.

  3. In vitro sensitivity of granulo-monocytic progenitors as a new toxicological cell system and endpoint in the ACuteTox Project

    SciTech Connect

    Cerrato, Laura; Valeri, Antonio; Bueren, Juan A.; Albella, Beatriz

    2009-07-15

    The ACuteTox Project (part of the EU 6th Framework Programme) was started up in January 2005. The aim of this project is to develop a simple and robust in vitro strategy for prediction of human acute systemic toxicity, which could replace animal tests used for regulatory purposes. Our group is responsible for the characterization of the effect of the reference chemicals on the hematopoietic tissue. CFU-GM assay based on the culture of human mononuclear cord blood cells has been used to characterize the effects of the selected compounds on the myeloid progenitors. Previous results have shown the relevance of the CFU-GM assay for the prediction of human acute neutropenia after treatment of antitumoral compounds, and this assay has been recently approved by the ECVAM's Scientific Advisory Committee. Among the compounds included in the study there were pharmaceuticals, environmental pollutants and industrial chemicals. Eleven out of 55 chemicals did not show any cytotoxic effect at the maximum concentration tested. The correlation coefficients of CFU-GM IC50, IC70 and IC90 values with human LC50 values (50% lethal concentration calculated from time-related sublethal and lethal human blood concentrations) were 0.4965, 0.5106 and 0.5142 respectively. Although this correlation is not improve respect to classical in vitro basal cytotoxicity tests such as 3T3 Neutral Red Uptake, chemicals which deviate substantially in the correlation with these assays (colchicine, digoxin, 5-Fluorouracil and thallium sulfate) fitted very well in the linear regression analysis of the CFU-GM progenitors. The results shown in the present study indicate that the sensitivity of CFU-GM progenitors correlates better than the sensitivity of HL-60 cells with human LC50 values and could help to refine the predictability for human acute systemic toxicity when a given chemical may affect to the hematopoietic myeloid system.

  4. A Phase II study of acute toxicity for Celebrex{sup TM} (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: Primary endpoint analysis of RTOG 0128

    SciTech Connect

    Gaffney, David K. . E-mail: david.gaffney@hci.utah.edu; Winter, Kathryn M.S.; Dicker, Adam P.; Miller, Brigitte; Eifel, Patricia J.; Ryu, Janice; Avizonis, Vilija; Fromm, Mitch; Greven, Kathryn

    2007-01-01

    Purpose: To determine treatment-related acute toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, i.v. cisplatin and 5-FU, and concurrent pelvic radiation therapy. Methods and Materials: Eligible patients on this RTOG Phase I-II study for advanced cervix cancer included FIGO Stage IIB-IVA or patients with FIGO Stage IB through IIA with biopsy proven pelvic node metastases or tumor size {>=}5 cm. Patients were treated with pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at 400 mg twice daily beginning on day 1 for 1 year. Cisplatin (75 mg/m2) and 5-FU (1g/m2 for 4 days) were administered every 3 weeks times 3. The primary end point of the study was treatment related toxicity. Results: Between August 2001 and March 2004, 84 patients were accrued to the study and 77 patients were evaluable for toxicity. Regarding the primary end point, toxicities were observed in the following areas: blood/bone marrow (16), gastrointestinal (14), pain (7), renal/genitourinary (6), cardiovascular (3), hemorrhage (1), and neurologic (1). For the first 75 evaluable patients, a toxicity failure was identified in 36 patients for a rate of 48%. Conclusions: Celecoxib at 400 mg twice daily together with concurrent cisplatin and 5-FU and pelvic radiotherapy has a high incidence of acute toxicities. The most frequent toxicities were hematologic. Albeit, the toxicity was deemed excessive in this trial, the rate of toxicities was not too different compared to other recent experiences with concurrent chemoradiation for advanced cervix cancer.

  5. Acute mental health nurses: comprehensive practitioners or specialist therapists?

    PubMed

    Mathers, B

    2012-02-01

    This paper examines the aids and barriers to implementing the psychosocial interventions (PSI) which trainees learned on two teaching modules. The main purpose of the modules is to teach trainees PSI to help them be more effective in their care of patients with severe mental illness. The trainees were qualified nurses working in acute mental health wards in various London hospitals. PSI has been found to be helpful for patients with psychotic symptoms in community contexts. In this study, the implementation of PSI specific to acute inpatient mental health settings is explored. This was achieved by conducting semi-structured audiotaped interviews with all 20 trainees from a single cohort. The data were analysed by categories and themes to elicit not only the problems but also helpful strategies which can be used when working with PSI in acute inpatient mental health settings. The paper concludes by offering recommendations for future good practice for this area of mental health service.

  6. Assaying Pharmacodynamic Endpoints with Targeted Therapy: Flavopiridol and 17AAG Induced Dephosphorylation of Histone H1.5 in Acute Myeloid Leukemia

    PubMed Central

    Wang, Liwen; Harshman, Sean W.; Liu, Shujun; Ren, Chen; Xu, Hua; Sallans, Larry; Grever, Michael; Byrd, John C.; Marcucci, Guido; Freitas, Michael A.

    2011-01-01

    Histone H1 is commonly used to assay kinase activity in vitro. As many promising targeted therapies affect kinase activity of specific enzymes involved in cancer transformation, H1 phosphorylation can serve as potential pharmacodynamic marker for drug activity within the cell. In this report we utilized a phosphoproteomic workflow to characterize histone H1 phosphorylation changes associated with two targeted therapies in the Kasumi-1 Acute Myeloid Leukemia (AML) cell line. The phosphoproteomic workflow was first validated with standard casein phosphoproteins and then applied to the direct analysis of histone H1 from Kasumi-1 nuclear lysates. Ten H1 phosphorylation sites were identified on the H1 variants, H1.2, H1.3, H1.4, H1.5 and H1.x. Liquid chromatography mass spectrometry profiling of intact H1s demonstrated global dephosphorylation of H1.5 associated with therapy by the cyclin dependent kinase inhibitor, flavopiridol, and the Hsp90 inhibitor, 17AAG (17-(Allylamino)-17-demethoxygeldanamycin). In contrast, independent treatments with a nucleotide analog, proteosome inhibitor and histone deacetylase inhibitor did not exhibit decreased H1.5 phosphorylation. The data presented herein demonstrate that potential of histones to assess the cellular response of reagents that have direct and indirect effects on kinase activity that alters histone phosphorylation. As such, this approach may be a highly informative marker for response to targeted therapies influencing histone phosphorylation. PMID:21110323

  7. Assaying pharmacodynamic endpoints with targeted therapy: flavopiridol and 17AAG induced dephosphorylation of histone H1.5 in acute myeloid leukemia.

    PubMed

    Wang, Liwen; Harshman, Sean W; Liu, Shujun; Ren, Chen; Xu, Hua; Sallans, Larry; Grever, Michael; Byrd, John C; Marcucci, Guido; Freitas, Michael A

    2010-12-01

    Histone H1 is commonly used to assay kinase activity in vitro. As many promising targeted therapies affect kinase activity of specific enzymes involved in cancer transformation, H1 phosphorylation can serve as potential pharmacodynamic marker for drug activity within the cell. In this study we utilized a phosphoproteomic workflow to characterize histone H1 phosphorylation changes associated with two targeted therapies in the Kasumi-1 acute myeloid leukemia cell line. The phosphoproteomic workflow was first validated with standard casein phosphoproteins and then applied to the direct analysis of histone H1 from Kasumi-1 nuclear lysates. Ten H1 phosphorylation sites were identified on the H1 variants, H1.2, H1.3, H1.4, H1.5 and H1.x. LC MS profiling of intact H1s demonstrated global dephosphorylation of H1.5 associated with therapy by the cyclin-dependent kinase inhibitor, flavopiridol and the Heat Shock Protein 90 inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin. In contrast, independent treatments with a nucleotide analog, proteosome inhibitor and histone deacetylase inhibitor did not exhibit decreased H1.5 phosphorylation. The data presented herein demonstrate that potential of histones to assess the cellular response of reagents that have direct and indirect effects on kinase activity that alters histone phosphorylation. As such, this approach may be a highly informative marker for response to targeted therapies influencing histone phosphorylation.

  8. Acute kidney injury: global health alert.

    PubMed

    Li, Philip Kam Tao; Burdmann, Emmanuel A; Mehta, Ravindra L

    2013-05-01

    Acute kidney injury (AKI) is increasingly prevalent in developing and developed countries and is associated with severe morbidity and mortality. Most etiologies of AKI can be prevented by interventions at the individual, community, regional and in-hospital levels. Effective measures must include community-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, as well as early recognition and management. Efforts should be focused on minimizing causes of AKI, increasing awareness of the importance of serial measurements of serum creatinine in high-risk patients, and documenting urine volume in acutely ill people to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers. Protocols need to be developed to systematically manage prerenal conditions and specific infections. More accurate data about the true incidence and clinical impact of AKI will help to raise the importance of the disease in the community, and increase awareness of AKI by governments, the public, general and family physicians and other healthcare professionals to help prevent the disease. Prevention is the key to avoid the heavy burden of mortality and morbidity associated with AKI.

  9. Acute and long term health effects of radiation

    SciTech Connect

    Voelz, G.L.

    1986-11-19

    This paper covers selected aspects of the acute and long term health effects excluding acute radiation syndrome and carcinogenesis, resulting from exposure to ionizing radiation. The changes addressed in this paper are those witnessed within an organ or whole body rather than at the molecular or even cellular level. They include acute and late health effects. Some of these effects are threshold effects, meaning that the dose must exceed a certain threshold before one sees these effects. Less than the threshold dose results in no observable organ or whole body effect. The severity of the effects correlate directly with the amount of cell damage or cell death that has occurred. 15 refs., 4 figs., 8 tabs.

  10. Acute Health Delivery, Energy Impact, and Rural Texas.

    ERIC Educational Resources Information Center

    Milburn, Lonna; And Others

    To examine what changes occurred in the acute health care delivery systems of rural Texas energy impact communities from 1978 to 1983, a retrospective survey was used to acquire data from which a database could be generated that could provide information for community and state policy decisions. From a pool of communities chosen by a panel of…

  11. [Intermediate endpoints in clinical research].

    PubMed

    Peters, Sanne A E; Groenwold, Rolf H H; Bots, Michiel L

    2013-01-01

    An intermediate variable such as blood pressure is part of the causal pathway of mechanisms to a clinical outcome, e.g. myocardial infarction. An intervention affects a clinical outcome through its effect on that intermediate variable. In studies designed to assess the effects of interventions an intermediate variable may be used as surrogate for clinical outcomes. Such an endpoint is also known as an intermediate endpoint. Intervention studies with intermediate endpoints are commonly performed in medical research to evaluate the effects of an intervention on clinical outcomes. Intervention studies with an intermediate endpoint are conducted in a smaller study population and with a shorter duration of follow-up than studies using clinical outcomes. An intermediate variable is not eligible as an intermediate endpoint when the intervention also affects other biological mechanisms that subsequently affect the clinical endpoint. Due to a smaller sample size and shorter study duration, side effects of intervention are more difficult to evaluate in studies with an intermediate endpoint than in studies with clinical endpoints.

  12. Acute Health Impact of Air Pollution in China

    NASA Astrophysics Data System (ADS)

    Feng, T.; Zhao, Y.; Zheng, M.

    2014-12-01

    Air pollution not only has long term health impact, but can affect health through acute exposure. This paper, using air pollution index (API) as overall evaluation of air quality, blood pressure and vital capacity as health outcomes, focuses on the acute health impact of air pollution in China. Current result suggests that after controlling smoking history, occupational exposure, income and education, API is positively associated with blood pressure and negatively associated with vital capacity. The associations became stronger for people with hypertension or pulmonary functional diseases, which indicates that these people are more sensitive to air pollution. Among three pollutants which API measures, that is inhalable particles (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2), PM10 is most statistically associated with blood pressure increase and vital capacity decrease. Further study will focusing on the following two questions. The first question is how various time lags affect the associations among API, blood pressure and vital capacity. The second question is how differently people in various cohorts reacts to acute exposure to air pollution. The differences in reactions of blood pressure and vital capacity between people in urban and rural areas, genders, various age cohorts, distinct income and education groups will be further studied.

  13. Mental health nurses' views of recovery within an acute setting.

    PubMed

    Cleary, Michelle; Horsfall, Jan; O'Hara-Aarons, Maureen; Hunt, Glenn E

    2013-06-01

    How the principles of a recovery-oriented mental health service are incorporated in the day-to-day nursing practice of mental health nurses in inpatient settings is unclear. In this study, we interviewed 21 mental health nurses working in acute inpatient mental health units about a range of recovery-focused topics. Three overlapping themes were identified: (i) the perception of recovery; (ii) congruent humanistic approaches; and (iii) practical realities. Only four interviewees had some formal training about recovery. Most respondents recognize that positive attitudes, person-centred care, hope, education about mental illness, medication and side-effects, and the acknowledgement of individual recovery pathways are necessary to prevent readmission, and are central to a better life for people who live with a mental illness. This research supports the view that ideas and practices associated with the recovery movement have been adopted to some degree by nurses working at the acute end of the services continuum. However, most saw the recovery orientation as rhetoric rather than as an appropriately resourced, coordinated, and integrated program. These nurses, however, speak of much more detailed aspects of working with patients and being required to prepare them for the exigencies of living in the community post-discharge.

  14. Spatial and temporal dynamics of lake whitefish (Coregonus clupeaformis) health indicators: linking individual-based indicators to a management-relevant endpoint

    USGS Publications Warehouse

    Wagner, Tyler; Jones, Michael L.; Ebener, Mark P.; Arts, Michael T.; Brenden, Travis O.; Honeyfield, Dale C.; Wright, Gregory M.; Faisal, Mohamed

    2010-01-01

    We examined the spatial and temporal dynamics of health indicators in four lake whitefish (Coregonus clupeaformis) stocks located in northern lakes Michigan and Huron from 2003 to 2006. The specific objectives were to (1) quantify spatial and temporal variability in health indicators; (2) examine relationships among nutritional indicators and stock-specific spatial and temporal dynamics of pathogen prevalence and intensity of infection; and (3) examine relationships between indicators measured on individual fish and stock-specific estimates of natural mortality. The percent of the total variation attributed to spatial and temporal sources varied greatly depending on the health indicator examined. The most notable pattern was a downward trend in the concentration of highly unsaturated fatty acids (HUFAs), observed in all stocks, in the polar lipid fraction of lake whitefish dorsal muscle tissue over the three study years. Variation among stocks and years for some indicators were correlated with the prevalence and intensity of the swimbladder nematode Cystidicola farionis, suggesting that our measures of fish health were related, at some level, with disease dynamics. We did not find relationships between spatial patterns in fish health indicators and estimates of natural mortality rates for the stocks. Our research highlights the complexity of the interactions between fish nutritional status, disease dynamics, and natural mortality in wild fish populations. Additional research that identifies thresholds of health indicators, below (or above) which survival may be reduced, will greatly help in understanding the relationship between indicators measured on individual fish and potential population-level effects.

  15. Surrogate Endpoints in Suicide Research

    ERIC Educational Resources Information Center

    Wortzel, Hal S.; Gutierrez, Peter M.; Homaifar, Beeta Y.; Breshears, Ryan E.; Harwood, Jeri E.

    2010-01-01

    Surrogate endpoints frequently substitute for rare outcomes in research. The ability to learn about completed suicides by investigating more readily available and proximate outcomes, such as suicide attempts, has obvious appeal. However, concerns with surrogates from the statistical science perspective exist, and mounting evidence from…

  16. Establishing a group of endpoints to support collective operations without specifying unique identifiers for any endpoints

    DOEpatents

    Archer, Charles J.; Blocksom, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanghon

    2016-02-02

    A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

  17. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity. 601.41 Section 601.41 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  18. Acute health effects of accidental chlorine gas exposure

    PubMed Central

    2014-01-01

    Objectives This study was conducted to report the course of an accidental release of chlorine gas that occurred in a factory in Gumi-si, South Korea, on March 5, 2013. We describe the analysis results of 2 patients hospitalized because of chlorine-induced acute health problems, as well as the clinical features of 209 non-hospitalized patients. Methods We analyzed the medical records of the 2 hospitalized patients admitted to the hospital, as well as the medical records and self-report questionnaires of 209 non-hospitalized patients completed during outpatient treatment. Results Immediately after the exposure, the 2 hospitalized patients developed acute asthma-like symptoms such as cough and dyspnea, and showed restrictive and combined pattern ventilatory defects on the pulmonary function test. The case 1 showed asthma-like symptoms over six months and diurnal variability in peak expiratory flow rate was 56.7%. In case 2, his FEV1 after treatment (93%) increased by 25% compared to initial FEV1 (68%). Both cases were diagnosed as chlorine-induced reactive airways dysfunction syndrome (RADS) on the basis of these clinical features. The most frequent chief complaints of the 209 non-hospitalized patients were headache (22.7%), followed by eye irritation (18.2%), nausea (11.2%), and sore throat (10.8%), with asymptomatic patients accounting for 36.5%. The multiple-response analysis of individual symptom revealed headache (42.4%) to be the most frequent symptom, followed by eye irritation (30.5%), sore throat (30.0%), cough (29.6%), nausea (27.6%), and dizziness (27.3%). Conclusions The 2 patients hospitalized after exposure to chlorine gas at the leakage site showed a clinical course corresponding to RADS. All of the 209 non-hospitalized patients only complained of symptoms of the upper airways and mucous membrane irritation. PMID:25852940

  19. Comparative endpoint sensitivity of in vitro estrogen agonist assays.

    PubMed

    Dreier, David A; Connors, Kristin A; Brooks, Bryan W

    2015-07-01

    Environmental and human health implications of endocrine disrupting chemicals (EDCs), particularly xenoestrogens, have received extensive study. In vitro assays are increasingly employed as diagnostic tools to comparatively evaluate chemicals, whole effluent toxicity and surface water quality, and to identify causative EDCs during toxicity identification evaluations. Recently, the U.S. Environmental Protection Agency (USEPA) initiated ToxCast under the Tox21 program to generate novel bioactivity data through high throughput screening. This information is useful for prioritizing chemicals requiring additional hazard information, including endocrine active chemicals. Though multiple in vitro and in vivo techniques have been developed to assess estrogen agonist activity, the relative endpoint sensitivity of these approaches and agreement of their conclusions remain unclear during environmental diagnostic applications. Probabilistic hazard assessment (PHA) approaches, including chemical toxicity distributions (CTD), are useful for understanding the relative sensitivity of endpoints associated with in vitro and in vivo toxicity assays by predicting the likelihood of chemicals eliciting undesirable outcomes at or above environmentally relevant concentrations. In the present study, PHAs were employed to examine the comparative endpoint sensitivity of 16 in vitro assays for estrogen agonist activity using a diverse group of compounds from the USEPA ToxCast dataset. Reporter gene assays were generally observed to possess greater endpoint sensitivity than other assay types, and the Tox21 ERa LUC BG1 Agonist assay was identified as the most sensitive in vitro endpoint for detecting an estrogenic response. When the sensitivity of this most sensitive ToxCast in vitro endpoint was compared to the human MCF-7 cell proliferation assay, a common in vitro model for biomedical and environmental monitoring applications, the ERa LUC BG1 assay was several orders of magnitude less

  20. Behavioral endpoints for radiation injury

    NASA Astrophysics Data System (ADS)

    Rabin, B. M.; Joseph, J. A.; Hunt, W. A.; Dalton, T. B.; Kandasamy, S. B.; Harris, A. H.; Ludewig, B.

    1994-10-01

    The relative behavioral effectiveness of heavy particles was evaluated. Using the taste aversion paradigm in rats, the behavioral toxicity of most types of radiation (including 20Ne and 40Ar) was similar to that of 60Co photons. Only 56Fe and 93Nb particles and fission neutrons were significantly more effective. Using emesis in ferrets as the behavioral endpoint, 56Fe particles and neutrons were again the most effective; however, 60Co photons were significantly more effective than 18 MeV electrons. These results suggest that LET does not completely predict behavioral effectiveness. Additionally, exposing rats to 10 cGy of 56Fe particles attenuated amphetamine-induced taste aversion learning. This behavior is one of a broad class of behaviors which depends on the integrity of the dopaminergic system and suggests the possibility of alterations in these behaviors following exposure to heavy particles in a space radiation environment.

  1. Statistical analysis of histopathological endpoints.

    PubMed

    Green, John W; Springer, Timothy A; Saulnier, Amy N; Swintek, Joe

    2014-05-01

    Histopathological assessments of fish from aquatic ecotoxicology studies are being performed with increasing frequency. Aquatic ecotoxicology studies performed for submission to regulatory agencies are usually conducted with multiple subjects (e.g., fish) in each of multiple vessels (replicates) within a water control and within each of several concentrations of a test substance. A number of histopathological endpoints are evaluated in each fish, and a severity score is generally recorded for each endpoint. The severity scores are often recorded using a nonquantitative scale of 0 to 4, with 0 indicating no effect, 1 indicating minimal effect, through 4 for severe effect. Statistical methods often used to analyze these scores suffer from several shortcomings: computing average scores as though scores were quantitative values, considering only the frequency of abnormality while ignoring severity, ignoring any concentration-response trend, and ignoring the possible correlation between responses of individuals within test vessels. A new test, the Rao-Scott Cochran-Armitage by Slices (RSCABS), is proposed that incorporates the replicate vessel experimental design and the biological expectation that the severity of the effect tends to increase with increasing doses or concentrations, while retaining the individual subject scores and taking into account the severity as well as frequency of scores. A power simulation and examples demonstrate the performance of the test. R-based software has been developed to carry out this test and is available free of charge at www.epa.gov/med/Prods_Pubs/rscabs.htm. The SAS-based RSCABS software is available from the first and third authors.

  2. Health utility indexes in patients with acute coronary syndromes

    PubMed Central

    Gencer, Baris; Rodondi, Nicolas; Auer, Reto; Nanchen, David; Räber, Lorenz; Klingenberg, Roland; Pletscher, Mark; Jüni, Peter; Windecker, Stephan; Matter, Christian M; Lüscher, Thomas F; Mach, François; Perneger, Thomas V; Girardin, François R

    2016-01-01

    Background Acute coronary syndromes (ACS) have been associated with lower health utilities (HUs) compared with the general population. Given the prognostic improvements after ACS with the implementation of coronary angiography (eg, percutaneous coronary intervention (PCI)), contemporary HU values derived from patient-reported outcomes are needed. Methods We analysed data of 1882 patients with ACS 1 year after coronary angiography in a Swiss prospective cohort. We used the EuroQol five-dimensional questionnaire (EQ-5D) and visual analogue scale (VAS) to derive HU indexes. We estimated the effects of clinical factors on HU using a linear regression model and compared the observed HU with the average values of individuals of the same sex and age in the general population. Results Mean EQ-5D HU 1-year after coronary angiography for ACS was 0.82 (±0.16) and mean VAS was 0.77 (±0.18); 40.9% of participants exhibited the highest utility values. Compared with population controls, the mean EQ-5D HU was similar (expected mean 0.82, p=0.58) in patients with ACS, but the mean VAS was slightly lower (expected mean 0.79, p<0.001). Patients with ACS who are younger than 60 years had lower HU than the general population (<0.001). In patients with ACS, significant differences were found according to the gender, education and employment status, diabetes, obesity, heart failure, recurrent ischaemic or incident bleeding event and participation in cardiac rehabilitation (p<0.01). Conclusions At 1 year, patients with ACS with coronary angiography had HU indexes similar to a control population. Subgroup analyses based on patients' characteristics and further disease-specific instruments could provide better sensitivity for detecting smaller variations in health-related quality of life. PMID:27252878

  3. Health Care Seeking Behavior of Persons with Acute Chagas Disease in Rural Argentina: A Qualitative View

    PubMed Central

    Dinardi, Graciela; Canevari, Cecilia; Torabi, Nahal

    2016-01-01

    Chagas disease (CD) is a tropical parasitic disease largely underdiagnosed and mostly asymptomatic affecting marginalized rural populations. Argentina regularly reports acute cases of CD, mostly young individuals under 14 years old. There is a void of knowledge of health care seeking behavior in subjects experiencing a CD acute condition. Early treatment of the acute case is crucial to limit subsequent development of disease. The article explores how the health outcome of persons with acute CD may be conditioned by their health care seeking behavior. The study, with a qualitative approach, was carried out in rural areas of Santiago del Estero Province, a high risk endemic region for vector transmission of CD. Narratives of 25 in-depth interviews carried out in 2005 and 2006 are analyzed identifying patterns of health care seeking behavior followed by acute cases. Through the retrospective recall of paths for diagnoses, weaknesses of disease information, knowledge at the household level, and underperformance at the provincial health care system level are detected. The misdiagnoses were a major factor in delaying a health care response. The study results expose lost opportunities for the health care system to effectively record CD acute cases. PMID:27829843

  4. Self-reported acute health symptoms and exposure to companion animals

    EPA Science Inventory

    Background: In order to understand the etiological burden of disease associated with acute health symptoms (e.g. gastrointestinal [GI], respiratory, dermatological), it is important to understand how common exposures influence these symptoms. Exposures to familiar and unfamiliar ...

  5. The education and training needs of qualified mental health nurses working in acute adult mental health services.

    PubMed

    Jones, Julia; Lowe, Trevor

    2003-11-01

    This paper presents findings from a research study that investigated the education and training needs of qualified mental health nurses who work in acute adult mental health services in the UK. The study aimed to address a key knowledge 'gap' highlighted by recent Department of Health reports () that suggest that little is known regarding the education and training expectations, priorities and needs of mental health nurses who work in acute adult mental health services. This study aimed to identify (i) what type of post-registration education and training mental health nurses working in acute settings need; (ii) how the nurses want education and training to be delivered; and (iii) what qualifications and accreditation the nurses want to receive? The research consisted of two methods: focus groups and a questionnaire survey. This paper reports on the findings from the questionnaire survey. The results of the survey demonstrate that there is a real need for post-registration education and training for this group of nurses; to equip them with the relevant knowledge and skills to nurse people in the acute phase of their mental illness in acute inpatient settings.

  6. School Nurse Workload: A Scoping Review of Acute Care, Community Health, and Mental Health Nursing Workload Literature

    ERIC Educational Resources Information Center

    Endsley, Patricia

    2017-01-01

    The purpose of this scoping review was to survey the most recent (5 years) acute care, community health, and mental health nursing workload literature to understand themes and research avenues that may be applicable to school nursing workload research. The search for empirical and nonempirical literature was conducted using search engines such as…

  7. Surrogate endpoint analysis: an exercise in extrapolation.

    PubMed

    Baker, Stuart G; Kramer, Barnett S

    2013-03-06

    Surrogate endpoints offer the hope of smaller or shorter cancer trials. It is, however, important to realize they come at the cost of an unverifiable extrapolation that could lead to misleading conclusions. With cancer prevention, the focus is on hypothesis testing in small surrogate endpoint trials before deciding whether to proceed to a large prevention trial. However, it is not generally appreciated that a small surrogate endpoint trial is highly sensitive to a deviation from the key Prentice criterion needed for the hypothesis-testing extrapolation. With cancer treatment, the focus is on estimation using historical trials with both surrogate and true endpoints to predict treatment effect based on the surrogate endpoint in a new trial. Successively leaving out one historical trial and computing the predicted treatment effect in the left-out trial yields a standard error multiplier that summarizes the increased uncertainty in estimation extrapolation. If this increased uncertainty is acceptable, three additional extrapolation issues (biological mechanism, treatment following observation of the surrogate endpoint, and side effects following observation of the surrogate endpoint) need to be considered. In summary, when using surrogate endpoint analyses, an appreciation of the problems of extrapolation is crucial.

  8. Closeness, chaos and crisis: the attractions of working in acute mental health care.

    PubMed

    Deacon, M; Warne, T; McAndrew, S

    2006-12-01

    This paper makes a case for the attractiveness of acute mental health inpatient nursing (acute nursing) and argues that an altered perception of this work is essential if we are to provide the most acutely mentally ill and vulnerable people with a stable and expert nursing workforce. The discussion draws on an ethnographic study conducted in an inner-city psychiatric unit in England and the advantages of this method for understanding nursing work are described. Within our findings, we set out two overarching themes: the contextual realities of the contemporary acute ward and features of attraction that encourage nurses to work in the acute care setting. The former includes nurses' responsibility for the total ward environment and the latter the 'comfort of closeness' and 'surviving and thriving in chaos and crisis'. In conclusion, we argue that despite the unpopularity of the acute inpatient mental health environment, the highly sophisticated skills employed by acute nurses actually ensure the promotion of health for the majority of service users.

  9. Self-reported acute health symptoms and exposure to companion animals#

    EPA Science Inventory

    Self-reported acute health symptoms and exposure to companion animalsWhitney S. Krueger1,2, Elizabeth D. Hilborn2, Timothy J. Wade21Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA2Environmental Public Health Division, Office of Research and Development, U...

  10. Endpoints for Mouse Abdominal Tumor Models: Refinement of Current Criteria

    PubMed Central

    Paster, Eden V; Villines, Kimberly A; Hickman, Debra L

    2009-01-01

    Accurate, rapid, and noninvasive health assessments are required to establish more appropriate endpoints in mouse cancer models where tumor size is not easily measured. We evaluated potential endpoints in mice with experimentally induced peritoneal lymphoma, an abdominal tumor model, by comparing body weight, body condition, and behavior with those of a control group of mice not developing lymphoma. Our hypothesis was that body weight would increase or plateau, whereas body condition and behavioral scores would decrease, as disease progressed. Results indicated that body weight did not differ significantly between the control and experimental groups, but the experimental group experienced significant decreases in both body condition and behavioral scores. Our results support the use of body condition and behavioral scoring as adjunctive assessment methods for mice involved in abdominal lymphoma tumor studies in which health may decline despite an increase or plateau in body weight. PMID:19619413

  11. Comparing Laboratory and Field Measured Bioaccumulation Endpoints

    EPA Science Inventory

    The report presents an approach that allows comparisons of all laboratory and field bioaccumulation endpoints measurements. The approach will enable the inclusion of large amounts of field data into evaluations of bioaccumulation potential for legacy chemicals. Currently, these...

  12. Critical endpoint behavior: A Wang Landau study

    NASA Astrophysics Data System (ADS)

    Landau, D. P.; Wang, Fugao; Tsai, Shan-Ho

    2008-07-01

    We study the critical endpoint behavior using an asymmetric Ising model with two- and three-body interactions on a triangular lattice, in the presence of an external field. The simulation method we use is Wang-Landau sampling in a two-dimensional parameter space. We observe a clear divergence of the curvature of the spectator phase boundary and of the magnetization coexistence diameter derivative at the critical endpoint, and the exponents for both divergences agree well with previous theoretical predictions.

  13. Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans

    PubMed Central

    Yang, Zhendong; Xue, Kathy S.; Sun, Xiulan; Tang, Lili; Wang, Jia-Sheng

    2015-01-01

    Aflatoxins B1 (AFB1), deoxynivalenol (DON), fumonisin B1 (FB1), T-2 toxin (T-2), and zearalenone (ZEA) are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB1 toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB1, FB1, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model. PMID:26633509

  14. Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans.

    PubMed

    Yang, Zhendong; Xue, Kathy S; Sun, Xiulan; Tang, Lili; Wang, Jia-Sheng

    2015-12-02

    Aflatoxins B₁ (AFB₁), deoxynivalenol (DON), fumonisin B₁ (FB₁), T-2 toxin (T-2), and zearalenone (ZEA) are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB₁ toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB₁, FB₁, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model.

  15. A Method for Quantifying the Acute Health Impacts of Residential Non-Biological Exposure Via Inhalation

    SciTech Connect

    Logue, Jennifer M.; Sherman, Max H.; Singer, Bret C.

    2014-08-01

    The inability to monetize the health costs of acute exposures in homes and the benefits of various control options is a barrier to justifying policies and approaches that can reduce exposure and improve health.We synthesized relationships between short-term outdoor concentration changes and health outcomes to estimate the health impacts of short-term in-home exposures. Damage and cost impacts of specific health outcomes were taken from the literature. We assessed the impact of vented and non-vented residential natural gas cooking burners on Southern California occupants for two pollutants (NO2 and CO).

  16. Public Health Response Systems In-Action: Learning from Local Health Departments’ Experiences with Acute and Emergency Incidents

    PubMed Central

    Hunter, Jennifer C.; Yang, Jane E.; Crawley, Adam W.; Biesiadecki, Laura; Aragón, Tomás J.

    2013-01-01

    As part of their core mission, public health agencies attend to a wide range of disease and health threats, including those that require routine, acute, and emergency responses. While each incident is unique, the number and type of response activities are finite; therefore, through comparative analysis, we can learn about commonalities in the response patterns that could improve predictions and expectations regarding the resources and capabilities required to respond to future acute events. In this study, we interviewed representatives from more than 120 local health departments regarding their recent experiences with real-world acute public health incidents, such as infectious disease outbreaks, severe weather events, chemical spills, and bioterrorism threats. We collected highly structured data on key aspects of the incident and the public health response, particularly focusing on the public health activities initiated and community partners engaged in the response efforts. As a result, we are able to make comparisons across event types, create response profiles, and identify functional and structural response patterns that have import for future public health preparedness and response. Our study contributes to clarifying the complexity of public health response systems and our analysis reveals the ways in which these systems are adaptive to the character of the threat, resulting in differential activation of functions and partners based on the type of incident. Continued and rigorous examination of the experiences of health departments throughout the nation will refine our very understanding of what the public health response system is, will enable the identification of organizational and event inputs to performance, and will allow for the construction of rich, relevant, and practical models of response operations that can be employed to strengthen public health systems. PMID:24236137

  17. Establishing a group of endpoints in a parallel computer

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanhong

    2016-02-02

    A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

  18. Catastrophic health expenditure on acute coronary events in Asia: a prospective study

    PubMed Central

    Lee, Stephen W-L; Sawhney, Jitendra PS; Ong, Tiong K; Chin, Chee Tang; Kim, Hyo-Soo; Krittayaphong, Rungroj; Nhan, Vo T; Itoh, Yohji; Huo, Yong

    2016-01-01

    Abstract Objective To estimate out-of-pocket costs and the incidence of catastrophic health expenditure in people admitted to hospital with acute coronary syndromes in Asia. Methods Participants were enrolled between June 2011 and May 2012 into this observational study in China, India, Malaysia, Republic of Korea, Singapore, Thailand and Viet Nam. Sites were required to enrol a minimum of 10 consecutive participants who had been hospitalized for an acute coronary syndrome. Catastrophic health expenditure was defined as out-of-pocket costs of initial hospitalization > 30% of annual baseline household income, and it was assessed six weeks after discharge. We assessed associations between health expenditure and age, sex, diagnosis of the index coronary event and health insurance status of the participant, using logistic regression models. Findings Of 12 922 participants, 9370 (73%) had complete data on expenditure. The mean out-of-pocket cost was 3237 United States dollars. Catastrophic health expenditure was reported by 66% (1984/3007) of those without insurance versus 52% (3296/6366) of those with health insurance (P < 0.05). The occurrence of catastrophic expenditure ranged from 80% (1055/1327) in uninsured and 56% (3212/5692) of insured participants in China, to 0% (0/41) in Malaysia. Conclusion Large variation exists across Asia in catastrophic health expenditure resulting from hospitalization for acute coronary syndromes. While insurance offers some protection, substantial numbers of people with health insurance still incur financial catastrophe. PMID:26966330

  19. Changing the endpoints for determining effective obesity management.

    PubMed

    Ross, Robert; Blair, Steve; de Lannoy, Louise; Després, Jean-Pierre; Lavie, Carl J

    2015-01-01

    Health authorities worldwide recommend weight loss as a primary endpoint for effective obesity management. Despite a growing public awareness of the importance of weight loss and the spending of billions of dollars by Americans in attempts to lose weight, obesity prevalence continues to rise. In this report we argue that effective obesity management in today's environment will require a shift in focus from weight loss as the primary endpoint, to improvements in the causal behaviors; diet and exercise/physical activity (PA). We reason that increases in PA combined with a balanced diet are associated with improvement in many of the intermediate risk factors including cardiorespiratory fitness (CRF) associated with obesity despite minimal or no weight loss. Consistent with this notion, we suggest that a focus on healthy behaviors for the prevention of additional weight gain may be an effective way of managing obesity in the short term.

  20. [Telemedicine in acute stroke care--a health economics view].

    PubMed

    Günzel, F; Theiss, S; Knüppel, P; Halberstadt, S; Rose, G; Raith, M

    2010-05-01

    Specialized stroke units offer optimal treatment of patients with an acute stroke. Unfortunately, their installation is limited by an acute lack of experienced neurologists and the small number of stroke patients in sparsely populated rural areas. This problem is increasingly being solved by the use of telemedicine, so that neurological expertise is made available to basic and regular care. It has been demonstrated by national and international pilot studies that solidly based and rapid decisions can be made by telemedicine regrading the use of thrombolysis, as the most important acute treatment, but also of other interventions. So far studies have only evaluated improvement in the quality of care achieved by networking, but not of any lasting effect on any economic benefit. Complementary to a medical evaluation, the qualitative economic assessment presented here of German and American concepts of telemetric care indicate no difference in efficacy between various ways of networking. Most noteworthy, when comparing two large American and German studies, is the difference in their priorities. While the American networks achieved targeted improvements in efficacy of care that go beyond the immediate wishes of the doctors involved, this was of only secondary importance in the German studies. Also, in contrast to several American networks, the German telemetry networks have not tended to be organized for future growth. In terms of economic benefits, decentralized organized networks offer a greater potential of efficacy than purely local ones. Furthermore, the integration of inducements into the design of business models is a fundamental factor for achieving successful and lasting existence, especially within a highly competitive market.

  1. Determining acute health hazard ratings in the absence of applicable toxicological data.

    PubMed

    Simmons, Fred; Quigley, David; Freshwater, Dave; Whyte, Helena; Boada-Clista, Lydia; Laul, J C

    2007-11-01

    Health, safety, and emergency planning professionals have a responsibility to identify acute hazards associated with chemicals and to find a way to transmit that information to chemical users, emergency responders, and others. Various organizations such as the Department of Energy are considering acute health hazard ratings as triggers that would mandate various activities. A paradigm shift away from a "lists" based approach to determining whether a chemical is sufficiently hazardous to require further analysis for emergency planning purposes is under way. Various toxicological data sources and approaches in use to develop an acute health hazard rating are discussed. Methods of extrapolating data from published and unpublished supporting documentation to develop an acute health hazard rating in the absence of toxicological data by animal species, chemical structure similarities, MSDS estimated values, and data mining are discussed. The process described analyzes applicable data and allows the analyst to determine reasonable health hazard rating numbers for chemicals without published hazard ratings and for mixtures of chemicals. The level and amount of resources available will determine which methods will be used in the process.

  2. Acute stress and cardiovascular health: is there an ACE gene connection?

    PubMed

    Holman, E Alison

    2012-10-01

    Cardiovascular disorders (CVD) are associated with acute and posttraumatic stress responses, yet biological processes underlying this association are poorly understood. This study examined whether renin-angiotensin-aldosterone system activity, as indicated by a functional single nucleotide polymorphism (SNP) in the angiotensin converting enzyme (ACE) gene, is associated with both CVD and acute stress related to the September 11, 2001 (9/11) terrorist attacks. European-American respondents (N = 527) from a nationally representative longitudinal study of coping following 9/11 provided saliva for genotyping. Respondents had completed health surveys before 9/11 and annually for 3 years after, and acute stress assessments 9 to 23 days after 9/11. Respondents with rs4291 AA or TT genotypes reported high acute stress twice as often as those with the AT genotype. Individuals with the TT genotype were 43% more likely to report increased physician-diagnosed CVD over 3 years following 9/11, when the following variables were included in the model: (a) pre-9/11 CVD, mental health, and non-CVD ailments; (b) cardiac risk factors; (c) ongoing endocrine disorders; and (d) significant demographics. The ACE rs4291 TT genotype, which has been associated with HPA axis hyperactivity and higher levels of serum angiotensin converting enzyme (ACE), predicted acute stress response and reports of physician-diagnosed CVD in a national sample following collective stress. ACE gene function may be associated with both mental and physical health disorders following collective stress.

  3. Indoor air pollution: Acute adverse health effects and host susceptibility

    SciTech Connect

    Zummo, S.M.; Karol, M.H.

    1996-01-01

    Increased awareness of the poor quality of indoor air compared with outdoor air has resulted in a significant amount of research on the adverse health effects and mechanisms of action of indoor air pollutants. Common indoor air agents are identified, along with resultant adverse health effects, mechanisms of action, and likely susceptible populations. Indoor air pollutants range from biological agents (such as dust mites) to chemical irritants (such as nitrogen dioxide, carbon monoxide, sulfur dioxide, formaldehyde, and isocyanates). These agents may exert their effects through allergic as well as nonallergic mechanisms. While the public does not generally perceive poor indoor air quality as a significant health risk, increasing reports of illness related to indoor air and an expanding base of knowledge on the health effects of indoor air pollution are likely to continue pushing the issue to the forefront.

  4. Molecular pathology endpoints useful for aging studies.

    PubMed

    Niedernhofer, L J; Kirkland, J L; Ladiges, W

    2016-10-06

    The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome. But for a new chemical entity, knowing what endpoints to measure remains a formidable challenge. For economy's sake, and to achieve results in a reasonable time frame, surrogate markers of lifespan and healthy aging are desperately needed. This review provides a comprehensive analysis of molecular endpoints that are currently being used as indices of age-related phenomena (e.g., morbidity, frailty, mortality) and proposes an approach for validating and prioritizing these endpoints.

  5. Exploring the impact of health information technology on communication and collaboration in acute care nursing.

    PubMed

    Cashen, Margaret S; Bradley, Victoria; Farrell, Ann; Murphy, Judy; Schleyer, Ruth; Sensmeier, Joyce; Dykes, Patricia C

    2006-01-01

    A focus group using nursing informatics experts as informants was conducted to guide development of a survey to explore the impact of health information technology on the role of nurses and interdisciplinary communication in acute care settings. Through analysis of focus group transcripts, five key themes emerged: information, communication, care coordination, interdisciplinary relationships, workflow, and practice effectiveness and efficiency. This served as the basis for development of a survey that will investigate perceptions of acute care providers across the United States regarding the impact of health information technology on the role of nurses and interdisciplinar communication in acute care settings. The purpose of this paper is to describe the process of survey development including analysis of transcripts, emergence of key themes, and the processes by which the themes will be employed to inform survey development.

  6. Fear of Severe Acute Respiratory Syndrome (SARS) among Health Care Workers

    ERIC Educational Resources Information Center

    Ho, Samuel M. Y.; Kwong-Lo, Rosalie S. Y.; Mak, Christine W. Y.; Wong, Joe S.

    2005-01-01

    In this study, the authors examined fear related to severe acute respiratory syndrome (SARS) among 2 samples of hospital staff in Hong Kong. Sample 1 included health care workers (n = 82) and was assessed during the peak of the SARS epidemic. Sample 2 included hospital staff who recovered from SARS (n = 97). The results show that participants in…

  7. Observations on Three Endpoint Properties and Their Relationship to Regulatory Outcomes of European Oncology Marketing Applications

    PubMed Central

    Stolk, Pieter; McAuslane, James Neil; Schellens, Jan; Breckenridge, Alasdair M.; Leufkens, Hubert

    2015-01-01

    Background. Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy’s clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. Materials and Methods. We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013). Results. Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments. There was no difference (p = .3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p < .05) improvements in primary endpoints (p < .0001 difference between the approved and failed groups). Conclusion. Three key endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint outcome, and its statistical significance) are consistent with the European Medicines Agency guidance and, notwithstanding the contribution of unique disease-specific circumstances, are associated with a predictable positive outcome for oncology MAAs. Implications for Practice: Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many

  8. Enabling communication concurrency through flexible MPI endpoints

    DOE PAGES

    Dinan, James; Grant, Ryan E.; Balaji, Pavan; ...

    2014-09-23

    MPI defines a one-to-one relationship between MPI processes and ranks. This model captures many use cases effectively; however, it also limits communication concurrency and interoperability between MPI and programming models that utilize threads. Our paper describes the MPI endpoints extension, which relaxes the longstanding one-to-one relationship between MPI processes and ranks. Using endpoints, an MPI implementation can map separate communication contexts to threads, allowing them to drive communication independently. Also, endpoints enable threads to be addressable in MPI operations, enhancing interoperability between MPI and other programming models. Furthermore, these characteristics are illustrated through several examples and an empirical study thatmore » contrasts current multithreaded communication performance with the need for high degrees of communication concurrency to achieve peak communication performance.« less

  9. Enabling communication concurrency through flexible MPI endpoints

    SciTech Connect

    Dinan, James; Grant, Ryan E.; Balaji, Pavan; Goodell, David; Miller, Douglas; Snir, Marc; Thakur, Rajeev

    2014-09-23

    MPI defines a one-to-one relationship between MPI processes and ranks. This model captures many use cases effectively; however, it also limits communication concurrency and interoperability between MPI and programming models that utilize threads. Our paper describes the MPI endpoints extension, which relaxes the longstanding one-to-one relationship between MPI processes and ranks. Using endpoints, an MPI implementation can map separate communication contexts to threads, allowing them to drive communication independently. Also, endpoints enable threads to be addressable in MPI operations, enhancing interoperability between MPI and other programming models. Furthermore, these characteristics are illustrated through several examples and an empirical study that contrasts current multithreaded communication performance with the need for high degrees of communication concurrency to achieve peak communication performance.

  10. Mental and social health during and after acute emergencies: emerging consensus?

    PubMed Central

    van Ommeren, Mark; Saxena, Shekhar; Saraceno, Benedetto

    2005-01-01

    Mental health care programmes during and after acute emergencies in resource-poor countries have been considered controversial. There is no agreement on the public health value of the post-traumatic stress disorder concept and no agreement on the appropriateness of vertical (separate) trauma-focused services. A range of social and mental health intervention strategies and principles seem, however, to have the broad support of expert opinion. Despite continuing debate, there is emerging agreement on what entails good public health practice in respect of mental health. In terms of early interventions, this agreement is exemplified by the recent inclusion of a "mental and social aspects of health" standard in the Sphere handbook's revision on minimal standards in disaster response. This affirmation of emerging agreement is important and should give clear messages to health planners. PMID:15682252

  11. Congenital adrenal hyperplasia: classification of studies employing psychological endpoints.

    PubMed

    Stout, Stephanie A; Litvak, Margarita; Robbins, Natashia M; Sandberg, David E

    2010-01-01

    Psychological outcomes in persons with congenital adrenal hyperplasia (CAH) have received substantial attention. The objectives of this paper were to (1) catalog psychological endpoints assessed in CAH outcome studies and (2) classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68%) investigated endpoints related to psychosexual differentiation. The preponderance of studies (76%) examined a direct relationship (i.e., inferring causality) between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development.

  12. Public Health Consequences on Vulnerable Populations from Acute Chemical Releases

    PubMed Central

    Ruckart, Perri Zeitz; Orr, Maureen F.

    2008-01-01

    Data from a large, multi-state surveillance system on acute chemical releases were analyzed to describe the type of events that are potentially affecting vulnerable populations (children, elderly and hospitalized patients) in order to better prevent and plan for these types of incidents in the future. During 2003–2005, there were 231 events where vulnerable populations were within ¼ mile of the event and the area of impact was greater than 200 feet from the facility/point of release. Most events occurred on a weekday during times when day care centers or schools were likely to be in session. Equipment failure and human error caused a majority of the releases. Agencies involved in preparing for and responding to chemical emergencies should work with hospitals, nursing homes, day care centers, and schools to develop policies and procedures for initiating appropriate protective measures and managing the medical needs of patients. Chemical emergency response drills should involve the entire community to protect those that may be more susceptible to harm. PMID:21572842

  13. Design Considerations for Post-Acute Care mHealth: Patient Perspectives.

    PubMed

    Sanger, Patrick; Hartzler, Andrea; Lober, William B; Evans, Heather L; Pratt, Wanda

    2014-01-01

    Many current mobile health applications ("apps") and most previous research have been directed at management of chronic illnesses. However, little is known about patient preferences and design considerations for apps intended to help in a post-acute setting. Our team is developing an mHealth platform to engage patients in wound tracking to identify and manage surgical site infections (SSI) after hospital discharge. Post-discharge SSIs are a major source of morbidity and expense, and occur at a critical care transition when patients are physically and emotionally stressed. Through interviews with surgical patients who experienced SSI, we derived design considerations for such a post-acute care app. Key design qualities include: meeting basic accessibility, usability and security needs; encouraging patient-centeredness; facilitating better, more predictable communication; and supporting personalized management by providers. We illustrate our application of these guiding design considerations and propose a new framework for mHealth design based on illness duration and intensity.

  14. Management of acute respiratory infections by community health volunteers: experience of Bangladesh Rural Advancement Committee (BRAC).

    PubMed Central

    Hadi, Abdullahel

    2003-01-01

    OBJECTIVE: To assess the role of management practices for acute respiratory infections (ARIs) in improving the competency of community health volunteers in diagnosing and treating acute respiratory infections among children. METHODS: Data were collected by a group of research physicians who observed the performance of a sample of 120 health volunteers in 10 sub-districts in Bangladesh in which Bangladesh Rural Advancement Committee (BRAC) had run a community-based ARI control programme since mid-1992. Standardized tests were conducted until the 95% interphysician reliability on the observation of clinical examination was achieved. FINDINGS:The sensitivity, specificity, and overall agreement rates in diagnosing and treating ARIs were significantly higher among the health volunteers who had basic training and were supervised routinely than among those who had not. CONCLUSION: Diagnosis and treatment of ARIs at the household level in developing countries are possible if intensive basic training and the close supervision of service providers are ensured. PMID:12764514

  15. Acute health effects after exposure to chlorine gas released after a train derailment.

    PubMed

    Van Sickle, David; Wenck, Mary Anne; Belflower, Amy; Drociuk, Dan; Ferdinands, Jill; Holguin, Fernando; Svendsen, Erik; Bretous, Lena; Jankelevich, Shirley; Gibson, James J; Garbe, Paul; Moolenaar, Ronald L

    2009-01-01

    In January 2005, a train derailment on the premises of a textile mill in South Carolina released 42 to 60 tons of chlorine gas in the middle of a small town. Medical records and autopsy reports were reviewed to describe the clinical presentation, hospital course, and pathology observed in persons hospitalized or deceased as a result of chlorine gas exposure. Eight persons died before reaching medical care; of the 71 persons hospitalized for acute health effects as a result of chlorine exposure, 1 died in the hospital. The mean age of the hospitalized persons was 40 years (range, 4 months-76 years); 87% were male. The median duration of hospitalization was 4 days (range, 1-29 days). Twenty-five (35%) persons were admitted to the intensive care unit; the median length of stay was 3 days. Many surviving victims developed significant pulmonary signs and severe airway inflammation; 41 (58%) hospitalized persons met PO2/FiO2 criteria for acute respiratory distress syndrome or acute lung injury. During their hospitalization, 40 (57%) developed abnormal x-ray findings, 74% of those within the first day. Hypoxia on room air and PO2/FiO2 ratio predicted severity of outcome as assessed by the duration of hospitalization and the need for intensive care support. This community release of chlorine gas caused widespread exposure and resulted in significant acute health effects and substantial health care requirements. Pulse oximetry and arterial blood gas analysis provided early indications of outcome severity.

  16. Acute Recurrent Pancreatitis in Children: A Study From the Pediatric Health Information System.

    PubMed

    Pant, Chaitanya; Sferra, Thomas J; Lee, Brian R; Cocjin, Jose T; Olyaee, Mojtaba

    2016-03-01

    We investigated acute recurrent pancreatitis (ARP) in children using a national health care database. From 2002 to 2014, 26,435 children had a diagnosis of acute pancreatitis (AP); 10,648 discharges were index hospitalizations. A total of 6159 children had a single hospitalization for AP, whereas 4489 (42%) children underwent 15,787 rehospitalizations. Children experienced a median of 2 ARP-related hospitalizations with a median time between admissions of 86 days. Younger patients with a more severe index episode of AP were at a higher risk of ARP. ARP-related hospitalizations had an increased requirement for intensive care unit care compared with an index episode of AP.

  17. Shift endpoint trace selection algorithm and wavelet analysis to detect the endpoint using optical emission spectroscopy

    NASA Astrophysics Data System (ADS)

    Ben Zakour, Sihem; Taleb, Hassen

    2016-06-01

    Endpoint detection (EPD) is very important undertaking on the side of getting a good understanding and figuring out if a plasma etching process is done on the right way. It is truly a crucial part of supplying repeatable effects in every single wafer. When the film to be etched has been completely erased, the endpoint is reached. In order to ensure the desired device performance on the produced integrated circuit, many sensors are used to detect the endpoint, such as the optical, electrical, acoustical/vibrational, thermal, and frictional. But, except the optical sensor, the other ones show their weaknesses due to the environmental conditions which affect the exactness of reaching endpoint. Unfortunately, some exposed area to the film to be etched is very low (<0.5%), reflecting low signal and showing the incapacity of the traditional endpoint detection method to determine the wind-up of the etch process. This work has provided a means to improve the endpoint detection sensitivity by collecting a huge numbers of full spectral data containing 1201 spectra for each run, then a new unsophisticated algorithm is proposed to select the important endpoint traces named shift endpoint trace selection (SETS). Then, a sensitivity analysis of linear methods named principal component analysis (PCA) and factor analysis (FA), and the nonlinear method called wavelet analysis (WA) for both approximation and details will be studied to compare performances of the methods mentioned above. The signal to noise ratio (SNR) is not only computed based on the main etch (ME) period but also the over etch (OE) period. Moreover, a new unused statistic for EPD, coefficient of variation (CV), is proposed to reach the endpoint in plasma etches process.

  18. Nurses' attitudes towards the use of PRN psychotropic medications in acute and forensic mental health settings.

    PubMed

    Barr, Lesley; Wynaden, Dianne; Heslop, Karen

    2017-03-24

    Many countries now have national mental health policies and guidelines to decrease or eliminate the use of seclusion and restraint yet the use of Pro Re Nata (PRN) medications has received less practice evaluation. This research aimed to identify mental health nurses' attitudes towards the use of PRN medications with mental health consumers. Participants were working in forensic mental health and non-forensic acute mental health settings. The "Attitudes towards PRN medication use survey" was used and data were collected online. Data were analysed using the Statistical Package Social Sciences, Version 22.0. Practice differences between forensic and other acute mental health settings were identified related to the use of PRN medications to manage symptoms from nicotine, alcohol and other drug withdrawal. Differences related to the useage of comfort rooms and conducting comprehensive assessments of consumers' psychiatric symptoms were also detected. Qualitative findings highlighted the need for increased accountability for the prescribing and administration of PRN medications along with more nursing education/training to use alternative first line interventions. Nurses administering PRN medications should be vigilant regarding the indications for this practice to ensure they are facilitating the consumer's recovery by reducing the use of all forms of potentially restrictive practices in the hospital setting. The reasons for using PRN medications and PRN administration rates must be continually monitored to avoid practices such as high dose antipsychotics use and antipsychotic polypharmacy to ensure the efficacy of the consumers' management plans on their health care outcomes.

  19. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

    PubMed Central

    Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

    2015-01-01

    Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect

  20. Operation Safe Haven: an evaluation of health surveillance and monitoring in an acute setting.

    PubMed

    Bennett, C; Mein, J; Beers, M; Harvey, B; Vemulpad, S; Chant, K; Dalton, C

    2000-02-17

    From May to June 1999, 3,920 ethnic Albanians from Kosovo arrived in Australia as part of Operation Safe Haven. These people were evacuated from refugee camps in the former Yugoslav Republic of Macedonia. Initial processing in Australia occurred at East Hills Reception Centre, and accommodation for the duration of stay was provided in eight Haven Centres in five States. The arrival of a large number of refugees in a short time frame is unprecedented in Australia. A health surveillance system was developed and critical health data were collected to assess health status and needs, plan care, monitor for potential outbreaks of communicable diseases, track service use, to meet international reporting requirements and document our response to this crisis. In this article the health surveillance system is evaluated and suggestions are offered for the formulation of specific guidelines necessary for health surveillance in acute settings.

  1. Enhancing adult therapeutic interpersonal relationships in the acute health care setting: an integrative review

    PubMed Central

    Kornhaber, Rachel; Walsh, Kenneth; Duff, Jed; Walker, Kim

    2016-01-01

    Therapeutic interpersonal relationships are the primary component of all health care interactions that facilitate the development of positive clinician–patient experiences. Therapeutic interpersonal relationships have the capacity to transform and enrich the patients’ experiences. Consequently, with an increasing necessity to focus on patient-centered care, it is imperative for health care professionals to therapeutically engage with patients to improve health-related outcomes. Studies were identified through an electronic search, using the PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO databases of peer-reviewed research, limited to the English language with search terms developed to reflect therapeutic interpersonal relationships between health care professionals and patients in the acute care setting. This study found that therapeutic listening, responding to patient emotions and unmet needs, and patient centeredness were key characteristics of strategies for improving therapeutic interpersonal relationships. PMID:27789958

  2. The Prevalence of Natural Health Product Use in Patients with Acute Cardiovascular Disease

    PubMed Central

    Alherbish, Aws; Charrois, Theresa L.; Ackman, Margaret L.; Tsuyuki, Ross T.; Ezekowitz, Justin A.

    2011-01-01

    Background Natural health products (NHP) use may have implications with respect to adverse effects, drug interactions and adherence yet the prevalence of NHP use by patients with acute cardiovascular disease and the best method to ascertain this information is unknown. Objective To identify the best method to ascertain information on NHP, and the prevalence of use in a population with acute cardiovascular disease. Methods Structured interviews were conducted with a convenience sample of consecutive patients admitted with acute cardiovascular disease to the University of Alberta Hospital during January 2009. NHP use was explored using structured and open-ended questions based on Health Canada's definition of NHP. The medical record was reviewed, and documentation of NHP use by physicians, nurses, and pharmacists, compared against the gold-standard structured interview. Results 88 patients were interviewed (mean age 62 years, standard deviation [SD 14]; 80% male; 41% admitted for acute coronary syndromes). Common co-morbidities included hypertension (59%), diabetes (26%) and renal impairment (19%). NHP use was common (78% of patients) and 75% of NHP users reported daily use. The category of NHP most commonly used was vitamins and minerals (73%) followed by herbal products (20%), traditional medicines including Chinese medicines (9%), homeopathic preparations (1%) and other products including amino acids, essential fatty acids and probiotics (35%). In a multivariable model, only older age was associated with increased NHP use (OR 1.5 per age decile [95%CI 1.03 to 2.2]). When compared to the interview, the highest rate of NHP documentation was the pharmacist history (41%). NHP were documented in 22% of patients by the physician and 19% by the nurse. Conclusions NHP use is common in patients admitted with acute cardiovascular disease. However, health professionals do not commonly identify NHP as part of the medication profile despite its potential importance. Structured

  3. Acute effects of aerobic stretching, health and happiness improving movement exercise on cortical activity of children.

    PubMed

    Choi, Hyungsoo; Park, Sangjun; Kim, Kyekyoon Kevin; Lee, Kwanghee; Rhyu, Hyun-Seung

    2016-08-01

    Acute high-intensity physical exercise is known to improve cognitive performance of children, including those with attention-deficit/hyperactivity disorder (ADHD). In this work, we investigated the acute effect of an aerobic stretching and moderate-intensity, health and happiness improving movement (HHIM) exercise on the cortical activity of children with and without ADHD using electroencephalography (EEG). Children aged 12 to 14 yr with combined-type ADHD and age-matched healthy controls participated in the study, performing two individual movements (n=79, 35 controls) and a single exercise bout (n=45, 18 controls). electroencephalographic signals were recorded before and immediately after each movement, and before and after acute exercise under resting conditions, to obtain absolute and relative power estimates for the theta (3.5-8 Hz), alpha (8-12 Hz), sensory motor rhythm (12-16 Hz), and beta (16-25 Hz) bands. After acute HHIM exercise, all children showed significant changes in their relative EEG, mainly in the theta and alpha bands. Individual movements were found to influence relative theta, alpha and beta, and theta-to-beta ratios. He presents aerobic stretching HHIM exercise has demonstrated acute effect on the cortical activity of children.

  4. Increased systolic blood pressure reactivity to acute stress is related with better self-reported health.

    PubMed

    Wright, Bradley J; O'Brien, Shaun; Hazi, Agnes; Kent, Stephen

    2014-11-13

    The stress reactivity hypothesis posits that the magnitude of cardiovascular reactions to acute stress tasks is related with future blood pressure status, heart hypertrophy, and atherosclerosis. We assessed the stress reactivity hypothesis and aimed to identify which physiological indices (blood pressure, heart-rate, cortisol, salivary immunoglobulin A (sIgA)) related to self-reported mental and physical health. We also assessed if physiological reactions elicited by an acute stressor were more related than basal assessments. Participants provided physiological samples, self-reported stress and health-data before and after an assessed 5-7 minute academic oral presentation. In hierarchical regression models, increased systolic and reduced sIgA reactivity was associated with better perceptions of mental health. Reactivity data were more related to self-reported data than basal data. In line with the only 2 studies to assess the reactivity hypothesis with self-perceived health, increased systolic reactivity was best associated with better perceived physical and mental health. The findings suggest that increased SBP reactivity may also be associated with positive health outcomes. Further research is required to determine if increased or decreased sIgA reactivity is most predictive of future morbidity.

  5. Infectious etiologies of acute febrile illness among patients seeking health care in south-central Cambodia.

    PubMed

    Kasper, Matthew R; Blair, Patrick J; Touch, Sok; Sokhal, Buth; Yasuda, Chadwick Y; Williams, Maya; Richards, Allen L; Burgess, Timothy H; Wierzba, Thomas F; Putnam, Shannon D

    2012-02-01

    The agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. From December 2006 to December 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central Cambodia were enrolled in a study to elucidate the etiologies. Upon enrollment, respiratory specimens, whole blood, and serum were collected. Testing was performed for viral, bacterial, and parasitic pathogens. Etiologies were identified in 38.0% of patients. Influenza was the most frequent pathogen, followed by dengue, malaria, and bacterial pathogens isolated from blood culture. In addition, 3.5% of enrolled patients were infected with more than one pathogen. Our data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia. Data from syndromic-based surveillance studies can help guide public health responses in developing nations.

  6. The Effect of Acute Exercise on Affect and Arousal in Inpatient Mental Health Consumers.

    PubMed

    Stanton, Robert; Reaburn, Peter; Happell, Brenda

    2016-09-01

    Acute exercise performed at a self-selected intensity improves affect and may improve long-term adherence. Similarly, in people with severe depression, acute aerobic exercise performed at self-selected intensity improves affect and arousal. However, the relationship between changes in affect and arousal and perceived exercise intensity in people with mental illness has not been evaluated. Affect and arousal were assessed immediately prior to, and immediately following, a group exercise program performed at a self-selected intensity in 40 inpatient mental health consumers who received a diagnosis of anxiety or bipolar or depressive disorders. Exercise intensity was assessed immediately after exercise. Postexercise affect was significantly improved for people with bipolar and depressive disorders but not for people with anxiety disorders. For the group as a whole, results showed a significant curvilinear relationship between ratings of perceived exertion and postexercise affect. These data will inform the development and delivery of future exercise interventions for inpatient mental health consumers.

  7. Population growth rate determinants for Arbacia: Evaluating ecological relevance of toxicity test endpoints

    SciTech Connect

    Nacci, D.; Gleason, T.; Munns, W.R. Jr.

    1995-12-31

    A population dynamics model for the sea urchin, Arbacia punctulata, was recently developed incorporating life stage endpoints frequently measured in acute and chronic toxicity studies. Model elasticity analysis was used to demonstrate that population growth rate was influenced most by adult survival and least by early life stage success, calling into question the ecological relevance of results from standardized Arbacia fertilization and larval development toxicity tests. Two approaches were used to continue this evaluation. Actual and hypothetical dose-response curves for toxicant exposures over multiple life stages were used to evaluate contributions to population growth rate of stage-specific toxicant effects. Additionally, relationships between critical life stages were developed from laboratory data for Arbacia. The results of this analysis underscore the importance of understanding both endpoint sensitivity to toxicants and sensitivity of population growth rate to test endpoints in determining the ecological relevance of toxicity tests results.

  8. Missing data and measurement variability in assessing progression-free survival endpoint in randomized clinical trials.

    PubMed

    Sridhara, Rajeshwari; Mandrekar, Sumithra J; Dodd, Lori E

    2013-05-15

    Progression-free survival (PFS) is frequently used as the primary efficacy endpoint in the evaluation of cancer treatment that is considered for marketing approval. Missing or incomplete data problems become more acute with a PFS endpoint (compared with overall survival). In a given clinical trial, it is common to observe incomplete data due to premature treatment discontinuation, missed or flawed assessments, change of treatment, lack of follow-up, and unevaluable data. When incomplete data issues are substantial, interpretation of the data becomes tenuous. Plans to prevent, minimize, or properly analyze incomplete data are critical for generalizability of results from the clinical trial. Variability in progressive disease measurement between radiologists further contributes to data problems with a PFS endpoint. The repercussions of this on phase III clinical trials are complex and depend on several factors, including the magnitude of the variability and whether there is a systematic reader evaluation bias favoring one treatment arm particularly in open-label trials.

  9. Scaling for interfacial tensions near critical endpoints.

    PubMed

    Zinn, Shun-Yong; Fisher, Michael E

    2005-01-01

    Parametric scaling representations are obtained and studied for the asymptotic behavior of interfacial tensions in the full neighborhood of a fluid (or Ising-type) critical endpoint, i.e., as a function both of temperature and of density/order parameter or chemical potential/ordering field. Accurate nonclassical critical exponents and reliable estimates for the universal amplitude ratios are included naturally on the basis of the "extended de Gennes-Fisher" local-functional theory. Serious defects in previous scaling treatments are rectified and complete wetting behavior is represented; however, quantitatively small, but unphysical residual nonanalyticities on the wetting side of the critical isotherm are smoothed out "manually." Comparisons with the limited available observations are presented elsewhere but the theory invites new, searching experiments and simulations, e.g., for the vapor-liquid interfacial tension on the two sides of the critical endpoint isotherm for which an amplitude ratio -3.25+/-0.05 is predicted.

  10. A specific endpoint assay for ubiquitin.

    PubMed Central

    Rose, I A; Warms, J V

    1987-01-01

    Simple endpoint assays for free ubiquitin (Ub) and for the Ub-activating enzyme are described. The method for measuring Ub makes use of the reaction of iodoacetamide-treated Ub-activating enzyme (E): [3H]ATP + Ub + E----E X [3H]AMP-Ub + PPi and PPi----2Pi (in the presence of pyrophosphatase). The Ub is then measured by determining the acid-insoluble radioactivity. The reaction is accompanied by a slow enzyme-catalyzed hydrolysis of the complex to AMP plus Ub. The presence of ubiquitin-activating enzyme in excess of Ub by approximately equal to 0.1 microM assures that the steady state will be close to the endpoint for total Ub. A preparation of the activating enzyme from human erythrocytes that does not depend on affinity chromatography is described. Several applications of the assay are presented. PMID:3031643

  11. Psychiatric nurse practitioners' experiences of working with mental health care users presenting with acute symptoms.

    PubMed

    Ngako, Kgalabi J; Van Rensburg, Elsie S J; Mataboge, Sanah M L

    2012-05-30

    Psychiatric nurse practitioners (PNPs) working with mental health care users presenting with acute symptoms work in a complex environment. This environment is characterised by mental health care users who may present with a history of violence, sexual assault and substance misuse. The objectives of this study were twofold: firstly, to explore and describe the experiences of PNPs working with mental health care users (MHCUs) presenting with acute symptoms; and secondly, to make recommendations for the advanced PNPs to facilitate promotion of the mental health of PNPs with reference to nursing practice, research and education. A qualitative, explorative, descriptive and contextual design was used. The target population was PNPs working with MHCUs presenting with acute symptoms in a public mental health care institution in Gauteng. Data were collected by means of four focus group interviews involving 21 PNPs. The researcher made use of drawings, naïve sketches and field notes for the purpose of data triangulation. Data were analysed in accordance with Tesch's method of open coding. The three themes that emerged were: PNPs experienced working with these MHCUs as entering an unsafe world where care became a burden; they experienced negative emotional reactions and attitudes towards these MHCUs that compromised quality nursing care; and they made a plea for a nurturing environment that would enhance quality nursing care. The PNPs suggest skills and competency development, organisational support, and a need for external resources. Creation of a positive environment and mobilisation of resources as well as the identification and bridging of obstacles are essential in the promotion of the overall wellbeing and mental health of PNPs.

  12. School-Based Mental Health Program Evaluation: Children's School Outcomes and Acute Mental Health Service Use

    ERIC Educational Resources Information Center

    Kang-Yi, Christina D.; Mandell, David S.; Hadley, Trevor

    2013-01-01

    Background: This study examined the impact of school-based mental health programs on children's school outcomes and the utilization of acute mental health services. Methods: The study sample included 468 Medicaid-enrolled children aged 6 to 17 years who were enrolled 1 of 2 school-based mental health programs (SBMHs) in a metropolitan area…

  13. Protein patterns as endpoints in environmental remediation

    SciTech Connect

    Bradley, B.; Brown, D.

    1995-12-31

    Biological endpoints can complement chemical analyses in monitoring environmental remediation. In some cases the levels of chemical detection are so low that the costs of clean-up to no detection would be prohibitive. And chemical tests do not indicate the availability of the contaminants to the biota. On the other hand many if not most biological tests lack specificity. The authors have investigated a protein expression assay to establish an endpoint for clean-up of sulfur mustard and breakdown products. Earthworms (Lumbricus terrestris) were exposed to sulfur mustard (SM), a breakdown product thiodiethanol (TDE), and ethylene glycol, the solvent for the two chemicals. Tissue from the lining of the coelomic cavity was taken from each of 6 worms in each treatment class. Soluble proteins were extracted and separated on one and two-dimensional (1D and 2D) gels. The 1 D gels showed no difference by eye but the patterns from control and solvent control worms on 2D gels differed from those of worms exposed to TDE and SM. The 1D gel data were digitized and analyzed by pattern recognition using artificial neural networks. The protein patterns under the two treatments and the two controls were learned in one set of data and successfully recognized in a second. This indicated that what was learned was useful in recognizing patterns induced by SM and TDE. Thus a possible endpoint for remediation would be the protein pattern at no effect levels of chemicals of interest.

  14. Health advisory values for drinking water contaminants and the methodology for determining acute exposure values.

    PubMed

    Donohue, Joyce Morrissey; Lipscomb, John C

    2002-04-08

    The Health Advisory (HA) Program of the Office of Water provides informal technical guidance to Federal, State and local officials responsible for protecting health when emergency spills or contamination situations occur. Under this program, first initiated in 1985, HA values are developed for 1-day, 10-day, longer-term (approx. 7 years) and lifetime exposures based on data describing non- cancer endpoints of toxicity. For substances that are known or probable human carcinogens, lifetime HAs are not recommended. In these situations, the HA document provides an estimate of the drinking water concentration that is equivalent to a l0(-4) 10(-6) cancer risk. US EPA has HA documents for over 175 chemicals dating from 1987 to 1998. A tabular summary of HA values can be accessed through the EPA Office of Science and Technology (OST) web page. The HA support documents provide a concise technical summary of and references for information on chemical, physical and toxicological properties, analytical methods, and treatment technologies. Some of the lifetime HA and cancer values in the HA documents may no longer agree with the most recent Agency assessment for Reference Dose (RfD) and cancer effects. However, the lifetime HA and cancer values presented in the HA tables have been updated to correspond with agency consensus values as presented in the Integrated Risk Information System (IRIS) database.

  15. Study relating residential formaldehyde concentrations and acute health symptoms in adult women

    SciTech Connect

    Zollinger, T.; Godish, T.

    1986-09-01

    This study consisted of a survey of 180 families who requested formaldehyde sampling of their homes through the local health or state health departments in Indiana in 1980-1985. At the time that the air sample was collected, the residents of the house were interviewed regarding the presence and severity of 22 acute health symptoms suspected to be associated with formaldehyde exposure. Surveyed individuals did not know the concentration of formaldehyde in their home at the time of the interview. For the purpose of this report, analysis was limited to the oldest (typically the only) adult woman in the household who was interviewed on the day that the air sample was taken (n = 163). The level of formaldehyde in the samples ranged from less than 0.010 ppm to 0.750 ppm. Comparisons of the formaldehyde concentrations with the health symptoms indicate that formaldehyde levels above 0.050 ppm did not increase the likelihood of the women to report the presence of any of the acute health symptoms studied. However, formaldehyde levels above 0.100 ppm significantly increased the likelihood of the women to report eye and sinus irritation, difficulty in breathing and sleeping, runny nose, and chest pain.

  16. Biomarkers and surrogate endpoints in glaucoma clinical trials.

    PubMed

    Medeiros, Felipe A

    2015-05-01

    Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies.

  17. Pathways to catastrophic health expenditure for acute coronary syndrome in Kerala: ‘Good health at low cost’?

    PubMed Central

    2012-01-01

    Background Universal health coverage through the removal of financial and other barriers to access, particularly for people who are poor, is a global priority. This viewpoint describes the many pathways to catastrophic health expenditure (CHE) for patients with Acute Coronary Syndrome (ACS) based on two case studies and the thematic analysis of field notes regarding 210 patients and their households from a study based in Kerala, India. Discussion There is evidence of the severe financial impact of non-communicable diseases (NCDs), which is in contradiction to the widely acclaimed Kerala model: Good health at low cost. However, it is important to look beyond the out-of-pocket expenditure (OOPE) and CHE to the possible pathways and identify the triggers that make families vulnerable to CHE. The identified pathways include a primary and secondary loop. The primary pathway describes the direct path by which families experience CHE. These include: 1) factors related to the pre-event period that increase the likelihood of experiencing CHE, such as being from the lower socio-economic strata (SES), past financial losses or loans that leave families with no financial shock absorber at the time of illness; 2) factors related to the acute event, diagnosis, treatment and hospitalization and expenditures incurred for the same and; 3) factors related to the post-event period such as loss of gainful employment and means of financing both the acute period and the long-term management particularly through distress financing. The secondary pathway arises from the primary and includes: 1) the impact of distress financing and; 2) the long- and short- term consequences of CHE. These factors ultimately result in a vicious cycle of debt and poverty through non-compliance and repeat acute events. Summary This paper outlines the direct and indirect pathways by which patients with ACS and their families are trapped in a vicious cycle of debt and poverty. It also contradicts the prevailing

  18. Ecosystem Services as Assessment Endpoints in Ecological Risk Assessment

    EPA Science Inventory

    The focus of ecological risk assessment (ERA) is on assessment endpoints, explicit expressions of environmental values to be protected. Traditionally, the ecological entities identified in assessment endpoints have been components of ecosystems deemed by risk assessors to be impo...

  19. Contextual factors associated with health care service utilization for children with acute childhood illnesses in Nigeria

    PubMed Central

    Lilford, Richard J.

    2017-01-01

    Objective To examine the independent contribution of individual, community and state-level factors to health care service utilization for children with acute childhood illnesses in Nigeria. Materials and methods The study was based on secondary analyses of cross-sectional population-based data from the 2013 Nigeria Demographic and Health Survey (DHS). Multilevel logistic regression models were applied to the data on 6,427 under-five children who used or did not use health care service when they were sick (level 1), nested within 896 communities (level 2) from 37 states (level 3). Results About one-quarter of the mothers were between 15 and 24 years old and almost half of them did not have formal education (47%). While only 30% of the children utilized health service when they were sick, close to 67% lived in the rural area. In the fully adjusted model, mothers with higher education attainment (Adjusted odds ratio [aOR] = 1.63; 95% credible interval [CrI] = 1.31–2.03), from rich households (aOR = 1.76; 95% CrI = 1.35–2.25), with access to media (radio, television or magazine) (aOR = 1.18; 95% CrI = 1.08–1.29), and engaging in employment (aOR = 1.18; 95% CrI = 1.02–1.37) were significantly more likely to have used healthcare services for acute childhood illnesses. On the other hand, women who experienced difficulty getting to health facilities (aOR = 0.87; 95% CrI = 0.75–0.99) were less likely to have used health service for their children. Conclusions Our findings highlight that utilization of healthcare service for acute childhood illnesses was influenced by not only maternal factors but also community-level factors, suggesting that public health strategies should recognise this complex web of individual composition and contextual composition factors to guide provision of healthcare services. Such interventions could include: increase in female school enrolment, provision of interest-free loans for small and medium scale enterprises, introduction of

  20. Magnetic-field induced critical endpoint

    NASA Astrophysics Data System (ADS)

    Rechenberger, Stefan

    2017-03-01

    The phase diagram of strong interaction matter is analyzed utilizing the Nambu-Jona-Lasinio model. Special emphasis is placed on its dependence on an external magnetic field and isospin chemical potential. Using flavor mixing induced by instanton effects the influence of isospin breaking due to the magnetic field and the isospin chemical potential is compared. It is found that at low temperatures and large quark chemical potential the magnetic field, depending on its strength, induces a new critical endpoint or a triple point.

  1. Effects of un-ionized ammonia on histological, endocrine, and whole organism endpoints in slimy sculpin (Cottus cognatus).

    PubMed

    Spencer, P; Pollock, R; Dubé, M

    2008-12-11

    mine effluents hold potential to affect the health of slimy sculpin including acute, chronic, histological and endocrine endpoints.

  2. Acute physiology and chronic health evaluation (APACHE II) and Medicare reimbursement

    PubMed Central

    Wagner, Douglas P.; Draper, Elizabeth A.

    1984-01-01

    This article describes the potential for the acute physiology score (APS) of acute physiology and chronic health evaluation (APACHE) II, to be used as a severity adjustment to diagnosis-related groups (DRG's) or other diagnostic classifications. The APS is defined by a relative value scale applied to 12 objective physiologic variables routinely measured on most hospitalized patients shortly after hospital admission. For intensive care patients, APS at admission is strongly related to subsequent resource costs of intensive care for 5,790 consecutive admissions to 13 large hospitals, across and within diagnoses. The APS could also be used to evaluate quality of care, medical technology, and the response to changing financial incentives. PMID:10311080

  3. Nonalcoholic Steatohepatitis and Endpoints in Clinical Trials

    PubMed Central

    Hannah, William N.; Torres, Dawn M.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in developed countries, and the rates of NAFLD continue to rise in conjunction with the obesity pandemic. While the majority of patients with isolated steatosis generally have a benign course, a diagnosis of nonalcoholic steatohepatitis (NASH) carries a significantly higher risk for progression of disease, cirrhosis, and death. Pharmacologic therapeutic interventions in NASH have largely proven to be ineffective or unappealing due to long-term side-effect profiles, and the majority of patients cannot achieve or sustain targeted weight loss goals, necessitating an urgent need for therapeutic trials and drug development. The complex molecular mechanisms leading to NASH and the long duration of time to develop complications of disease are challenges to developing meaningful clinical endpoints. Because of these challenges, surrogate endpoints that are linked to all-cause mortality, liver-related death, and complications of cirrhosis are much more likely to be beneficial in the majority of patients. PMID:28035202

  4. Strategies and Endpoints of Antifibrotic Drug Trials

    PubMed Central

    Torok, Natalie; Dranoff, Jonathan A.; Schuppan, Detlef; Friedman, Scott L.

    2015-01-01

    There is an urgent need to develop antifibrotic therapies for chronic liver disease, and to clarify which endpoints in antifibrotic trials will be acceptable to regulatory agencies. AASLD sponsored an endpoints conference to help accelerate the efficient testing of antifibrotic agents and to develop recommendations on clinical trial design for liver fibrosis. In this review we summarize the salient and novel elements of this conference and provide directions for future clinical trial design. The paper follows the structure of the conference and is organized into five areas: I) Antifibrotic trial design; II) Preclinical proof of concept studies; III) Pharmacologic targets: rationale and lessons to learn; IV) Rational drug design and development; V) Consensus and recommendations on design of clinical trials in liver fibrosis. Expert overviews and collaborative discussions helped to summarize the key unmet needs and directions for the future, including: 1) Greater clarification of at-risk populations and study groups; 2) Standardization of all elements of drug discovery and testing; 3) Standardization of clinical trial approaches; 4) Accelerated development of improved non-invasive markers; 5) Need for exploration of potential off-target toxicities of future antifibrotic drugs. PMID:25626988

  5. Nurses' perceptions of multidisciplinary team work in acute health-care.

    PubMed

    Atwal, Anita; Caldwell, Kay

    2006-12-01

    Multidisciplinary teamwork is viewed as one of the key processes through which care is managed in the British National Health Service, and yet is often viewed as one of the most problematic. Working in a multidisciplinary team requires many skills, which involves understanding not only one's own role but also the role of other professionals. The aim of this study was to explore nurses' perceptions of multidisciplinary teamwork in acute health-care. Nineteen nurses were interviewed using the critical incident approach to obtain their perceptions of multidisciplinary teamwork. Direct observation was conducted to record interactions between nurses and health-care professionals in multidisciplinary teams. In total, 14 meetings were attended in elder care and orthopaedics and seven in acute medicine. The findings of this study identified three barriers that hindered teamwork: (i) differing perceptions of teamwork; (ii) different levels of skills acquisitions to function as a team member; and (iii) the dominance of medical power that influenced interaction in teams. Thus, education establishments and nursing managers need to ensure that the acquisition of team-playing skills is an integral part of continued professional development.

  6. Ready, aim fire! Mental health nurses under siege in acute inpatient facilities.

    PubMed

    Ward, Louise

    2013-04-01

    It has been clearly acknowledged and well-documented that physical, emotional, and psychological violence is a central theme and an expected workplace hazard for registered nurses working in acute inpatient mental health care facilities. Limited research, however, has focused on how registered nurses have been able to cope within this environment and adequately protect themselves from harm. A critical feminist research project recently explored the lived experience of 13 Australian, female, registered nurses working in a busy metropolitan acute inpatient mental health care facility. "Fear" was exposed as the precursor to violence and aggression, both "fear as experienced by the nurse" and "fear as experienced by the patient." The participants reported experiencing a sense of fear when they could not accurately or confidently anticipate a patient response or reaction. They identified this relationship with fear as being "part of the job" and part of the unpredictable nature of caring for people experiencing complex distortions in thinking and behavior. The participants believed, however, that additional workplace pressures complicated the therapeutic environment, resulting in a distraction from patient care and observation. This distraction could lead to nurse-patient miscommunication and the potential for violence. This article discusses a major theme to emerge from this study, "Better the devil you know!" The theme highlights how mental health nurses cope with violence and why they choose to continue working in this complex care environment.

  7. Design Considerations for Post-Acute Care mHealth: Patient Perspectives

    PubMed Central

    Sanger, Patrick; Hartzler, Andrea; Lober, William B.; Evans, Heather L.; Pratt, Wanda

    2014-01-01

    Many current mobile health applications (“apps”) and most previous research have been directed at management of chronic illnesses. However, little is known about patient preferences and design considerations for apps intended to help in a post-acute setting. Our team is developing an mHealth platform to engage patients in wound tracking to identify and manage surgical site infections (SSI) after hospital discharge. Post-discharge SSIs are a major source of morbidity and expense, and occur at a critical care transition when patients are physically and emotionally stressed. Through interviews with surgical patients who experienced SSI, we derived design considerations for such a post-acute care app. Key design qualities include: meeting basic accessibility, usability and security needs; encouraging patient-centeredness; facilitating better, more predictable communication; and supporting personalized management by providers. We illustrate our application of these guiding design considerations and propose a new framework for mHealth design based on illness duration and intensity. PMID:25954465

  8. Public Health Lessons from Severe Acute Respiratory Syndrome a Decade Later

    PubMed Central

    Butler-Jones, David; Tsang, Thomas; Yu, Wang

    2013-01-01

    The outbreak of severe acute respiratory syndrome in 2002–2003 exacted considerable human and economic costs from countries involved. It also exposed major weaknesses in several of these countries in coping with an outbreak of a newly emerged infectious disease. In the 10 years since the outbreak, in addition to the increase in knowledge of the biology and epidemiology of this disease, a major lesson learned is the value of having a national public health institute that is prepared to control disease outbreaks and designed to coordinate a national response and assist localities in their responses. PMID:23739634

  9. An innovative, multidisciplinary, process-driven approach to acute stroke in a community health system network.

    PubMed

    Fessler, Richard D; To, Chiu Yuen; Gordon, Vickie; Stover, Carrie; Dunne, Robert

    2014-01-01

    Stroke is one of the major causes of death and disability in the United States, yet it is undertreated by many major medical centers across the country. Timely recognition and treatment of acute ischemic stroke remains a challenge due to confusing clinical presentations, hospital logistics, communication barriers among providers, and lack of standardized treatment algorithms. By creating a system-wide Code Stroke protocol, St. John Providence Health System improved documentation, increased intravenous tissue plasminogen activator delivery, reduced specialist call-back times, improved door-to-computer tomography scan and door-to-needle time, and identified appropriate patients for endovascular therapy.

  10. Serum and salivary cardiac analytes in acute myocardial infarction related to oral health status

    NASA Astrophysics Data System (ADS)

    Ebersole, Jeffrey L.; Kryscio, Richard J.; Campbell, Charles; Kinane, Denis F.; McDevitt, John T.; Christodoulides, Nicolaos; Floriano, Pierre N.; Miller, Craig S.

    2014-06-01

    With the advent of an increased emphasis on the potential to utilize biomarkers in saliva for systemic diseases, the issue of existing oral disease is an important consideration that could adversely affect the interpretation of diagnostic results obtained from saliva. We addressed the question does a patient's oral inflammation status confound biomarker levels used in diagnosis of acute myocardial infarction (AMI). The results demonstrated that multiple serum biomarkers and a few salivary biomarkers reflected the cardiac event. Importantly, oral health of the individual had minimal impact on the validity of the serum or salivary biomarker effectiveness.

  11. Exploring the Relationships between the Electronic Health Record System Components and Patient Outcomes in an Acute Hospital Setting

    ERIC Educational Resources Information Center

    Wiggley, Shirley L.

    2011-01-01

    Purpose: The purpose of this study was to examine the relationship between the electronic health record system components and patient outcomes in an acute hospital setting, given that the current presidential administration has earmarked nearly $50 billion to the implementation of the electronic health record. The relationship between the…

  12. Acute Bronchitis

    MedlinePlus

    ... can also cause acute bronchitis. To diagnose acute bronchitis, your health care provider will ask about your symptoms and listen to your breathing. You may also have other tests. Treatments include rest, fluids, and aspirin (for adults) or ...

  13. [Access to medicines prescribed for acute health conditions in adults in South and Northeast Brazil].

    PubMed

    Paniz, Vera Maria Vieira; Cechin, Isabel Carolina Coelho Flores; Fassa, Anaclaudia Gastal; Piccini, Roberto Xavier; Tomasi, Elaine; Thumé, Elaine; Silveira, Denise Silva da; Facchini, Luiz Augusto

    2016-01-01

    This was a cross-sectional study within Brazil's Project for the Expansion and Consolidation of Family Health, 2005, with the objective of universal and free access to the medication prescribed in the last medical appointment for acute health problems and to estimate the degree to which access may have improved with inclusion of the medicines in prevailing policies and programs. The sample included 4,060 adults living in the area of primary health care units in 41 municipalities in South and Northeast Brazil. Access was greater in the South (83.2%) than in the Northeast (71%), and free access was similar (37%), with a greater share by the Family Health Program (FHP) when compared to the traditional model, especially in the Northeast. Some 60% of prescribed medicines and 50% of those on the National List of Essential Medicines (RENAME) were paid for. No variation was observed in the proportion of medicines present on the prevailing RENAME list and access. However, 40% of the medicines that were paid for can currently be obtained through the Popular Pharmacy Program. The latter program appears to emerge as a new way to guarantee access to medicines prescribed in the health system.

  14. Determining Significant Endpoints for Ecological risk Analyses

    SciTech Connect

    Hinton, Thimas G.; Bedford, Joel

    1999-06-01

    Our interest is in obtaining a scientifically defensible endpoint for measuring ecological risks to populations exposed to chronic, low-level radiation, and radiation with concomitant exposure to chemicals. To do so, we believe that we must understand the extent to which molecular damage is detrimental at the individual and population levels of biological organization. Ecological risk analyses based on molecular damage, without an understanding of the impacts to higher levels of biological organization, could cause cleanup strategies on DOE sites to be overly conservative and unnecessarily expensive. Our goal is to determine the relevancy of sublethal cellular damage to the performance of individuals and populations. We think that we can achieve this by using novel biological dosimeters in controlled, manipulative dose/effects experiments, and by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables such as age-specific survivorship, reproductive output, age at maturity and longevity.

  15. Modeling Acute Health Effects of Astronauts from Exposure to Large Solar Particle Events

    NASA Technical Reports Server (NTRS)

    Hu, Shaowen; Kim, Myung-Hee Y.; Cucinotta, Francis A.

    2011-01-01

    In space exploration outside the Earth s geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possible failure of the mission. Acute risks are of special concern during extra-vehicular activities because of the rapid onset of SPE. However, most SPEs will not lead to acute risks but can lead to mission disruption if accurate projection methods are not available. Acute Radiation Sickness (ARS) is a group of clinical syndromes developing acutely (within several seconds to 3 days) after high dose whole-body or significant partial-body ionizing radiation exposures. The manifestation of these syndromes reflects the disturbance of physiological processes of various cellular groups damaged by radiation. Hematopoietic cells, skin, epithelium, intestine, and vascular endothelium are among the most sensitive tissues of human body to ionizing radiation. Most ARS symptoms are directly related to these tissues and other systems (nervous, endocrine, and cardiovascular, etc.) with coupled regulations. Here we report the progress in bio-mathematical models to describe the dose and time-dependent early human responses to ionizing radiation. The responses include lymphocyte depression, granulocyte modulation, fatigue and weakness syndrome, and upper gastrointestinal distress. The modest dose and dose-rates of SPEs are predicted to lead to large sparing of ARS, however detailed experimental data on a range of proton dose-rates for organ doses from 0.5 to 2 Gy is needed to validate the models. We also report on the ARRBOD code that integrates the BRYNTRN and SUMDOSE codes, which are used to estimate the SPE organ doses for astronauts under various space travel scenarios, with our models of ARS. The more recent effort is to provide easy web access to space radiation risk assessment using the ARRBOD code.

  16. Care Transitions in Long-term Care and Acute Care: Health Information Exchange and Readmission Rates.

    PubMed

    Yeaman, Brian; Ko, Kelly J; Alvarez del Castillo, Rodolfo

    2015-09-30

    Care transitions between settings are a well-known cause of medical errors. A key component of transition is information exchange, especially in long-term care (LTC). However, LTC is behind other settings in adoption of health information technologies (HIT). In this article, we provide some brief background information about care transitions in LTC and concerns related to technology. We describe a pilot project using HIT and secure messaging in LTC to facilitate electronic information exchange during care transitions. Five LTC facilities were included, all located within Oklahoma and serviced by the same regional health system. The study duration was 20 months. Both inpatient readmission and return emergency department (ED) visit rates were lower than baseline following implementation. We provide discussion of positive outcomes, lessons learned, and limitations. Finally, we offer implications for practice and research for implementation of HIT and information exchange across care settings that may contribute to reduction in readmission rates in acute care and ED settings.

  17. Comparing laboratory and field measured bioaccumulation endpoints.

    PubMed

    Burkhard, Lawrence P; Arnot, Jon A; Embry, Michelle R; Farley, Kevin J; Hoke, Robert A; Kitano, Masaru; Leslie, Heather A; Lotufo, Guilherme R; Parkerton, Thomas F; Sappington, Keith G; Tomy, Gregg T; Woodburn, Kent B

    2012-01-01

    An approach for comparing laboratory and field measures of bioaccumulation is presented to facilitate the interpretation of different sources of bioaccumulation data. Differences in numerical scales and units are eliminated by converting the data to dimensionless fugacity (or concentration-normalized) ratios. The approach expresses bioaccumulation metrics in terms of the equilibrium status of the chemical, with respect to a reference phase. When the fugacity ratios of the bioaccumulation metrics are plotted, the degree of variability within and across metrics is easily visualized for a given chemical because their numerical scales are the same for all endpoints. Fugacity ratios greater than 1 indicate an increase in chemical thermodynamic activity in organisms with respect to a reference phase (e.g., biomagnification). Fugacity ratios less than 1 indicate a decrease in chemical thermodynamic activity in organisms with respect to a reference phase (e.g., biodilution). This method provides a holistic, weight-of-evidence approach for assessing the biomagnification potential of individual chemicals because bioconcentration factors, bioaccumulation factors, biota-sediment accumulation factors, biomagnification factors, biota-suspended solids accumulation factors, and trophic magnification factors can be included in the evaluation. The approach is illustrated using a total 2393 measured data points from 171 reports, for 15 nonionic organic chemicals that were selected based on data availability, a range of physicochemical partitioning properties, and biotransformation rates. Laboratory and field fugacity ratios derived from the various bioaccumulation metrics were generally consistent in categorizing substances with respect to either an increased or decreased thermodynamic status in biota, i.e., biomagnification or biodilution, respectively. The proposed comparative bioaccumulation endpoint assessment method could therefore be considered for decision making in a

  18. Reengineering acute episodic and chronic care delivery: the Geisinger Health System experience.

    PubMed

    Slotkin, Jonathan R; Casale, Alfred S; Steele, Glenn D; Toms, Steven A

    2012-07-01

    Comparative effectiveness research (CER) represents an evolution in clinical decision-making research that allows for the study of heterogeneous groups of patients with complex diseases processes. It has foundations in decision science, reliability science, and health care policy research. Health care finance will increasingly rely on CER for guidance in the coming years. There is increasing awareness of the importance of decreasing unwarranted variation in health care delivery. In the past 7 years, Geisinger Health System has performed broad reengineering of its acute episodic and chronic care delivery models utilizing macrosystem-level application of CER principles. These provider-driven process initiatives have resulted in significant improvement across all segments of care delivery, improved patient outcomes, and notable cost containment. These programs have led to the creation of novel pricing models, and when "hardwired" throughout a care delivery system, they can lead to correct medical decision making by 100% of providers in all patient encounters. Neurosurgery as a specialty faces unique challenges and opportunities with respect to broad adoption and application of CER techniques.

  19. Population-scale assessment endpoints in ecological risk assessment part II: selection of assessment endpoint attributes.

    PubMed

    Landis, Wayne G; Kaminski, Laurel A

    2007-07-01

    Because ecological services often are tied to specific species, the risk to populations is a critical endpoint and important feature of ecological risk assessments. In Part 1 of this series it was demonstrated that population scale assessment endpoints are important expressions of the valued components of ecological structures. This commentary reviews several of the characteristics of populations that can be evaluated and used in population scale risk assessments. Two attributes are evaluated as promising. The 1st attribute is the change in potential productivity of the population over a specified time period. The 2nd attribute is the change in the age structure of a population, expressed graphically or as a normalized effects vector (NEV). The NEV is a description of the change in age structure due to a toxicant or other stressor and appears to be characteristic of specific stressor effects.

  20. Ecosystem services as assessment endpoints for ecological risk assessment.

    PubMed

    Munns, Wayne R; Rea, Anne W; Suter, Glenn W; Martin, Lawrence; Blake-Hedges, Lynne; Crk, Tanja; Davis, Christine; Ferreira, Gina; Jordan, Steve; Mahoney, Michele; Barron, Mace G

    2016-07-01

    Ecosystem services are defined as the outputs of ecological processes that contribute to human welfare or have the potential to do so in the future. Those outputs include food and drinking water, clean air and water, and pollinated crops. The need to protect the services provided by natural systems has been recognized previously, but ecosystem services have not been formally incorporated into ecological risk assessment practice in a general way in the United States. Endpoints used conventionally in ecological risk assessment, derived directly from the state of the ecosystem (e.g., biophysical structure and processes), and endpoints based on ecosystem services serve different purposes. Conventional endpoints are ecologically important and susceptible entities and attributes that are protected under US laws and regulations. Ecosystem service endpoints are a conceptual and analytical step beyond conventional endpoints and are intended to complement conventional endpoints by linking and extending endpoints to goods and services with more obvious benefit to humans. Conventional endpoints can be related to ecosystem services even when the latter are not considered explicitly during problem formulation. To advance the use of ecosystem service endpoints in ecological risk assessment, the US Environmental Protection Agency's Risk Assessment Forum has added generic endpoints based on ecosystem services (ES-GEAE) to the original 2003 set of generic ecological assessment endpoints (GEAEs). Like conventional GEAEs, ES-GEAEs are defined by an entity and an attribute. Also like conventional GEAEs, ES-GEAEs are broadly described and will need to be made specific when applied to individual assessments. Adoption of ecosystem services as a type of assessment endpoint is intended to improve the value of risk assessment to environmental decision making, linking ecological risk to human well-being, and providing an improved means of communicating those risks. Integr Environ Assess Manag

  1. Ordered kinematic endpoints for 5-body cascade decays

    NASA Astrophysics Data System (ADS)

    Klimek, Matthew D.

    2016-12-01

    We present expressions for the kinematic endpoints of 5-body cascade decay chains proceeding through all possible combinations of 2-body and 3-body decays, with one stable invisible particle in the final decay stage. When an invariant mass can be formed in multiple ways by choosing different final state particles from a common vertex, we introduce techniques for finding the sub-leading endpoints for all indistinguishable versions of the invariant mass. In contrast to short decay chains, where sub-leading endpoints are linearly related to the leading endpoints, we find that in 5-body decays, they provide additional independent constraints on the mass spectrum.

  2. Voluntary control of static endpoint stiffness during force regulation tasks.

    PubMed

    Perreault, Eric J; Kirsch, Robert F; Crago, Patrick E

    2002-06-01

    The goals of this study were to determine the degree to which subjects could voluntarily modulate static endpoint stiffness orientation and to quantify the effects of simultaneously generated voluntary endpoint forces on this ability. Static endpoint stiffness, which characterizes the relationship between externally imposed displacements of the hand and the elastic forces generated in response, was estimated in real time during the application of planar, stochastic perturbations of endpoint position. This estimation was accomplished using a real-time parametric identification algorithm on measured force and position data. Subjects were provided with real-time visual feedback of endpoint stiffness, and their ability to modulate the orientation of maximum static stiffness was measured for different endpoint force magnitudes and directions. We found that individuals can voluntarily change stiffness orientation but that the magnitude of these changes is small, the range of available stiffness orientations decreases as endpoint force exertion increases, and endpoint force direction significantly constrains direction and magnitude of the stiffness orientations that can be achieved. Given these findings it appears unlikely that static endpoint stiffness orientation is controlled independently of force by voluntary neural mechanisms during postural tasks.

  3. Translational endpoints in fragile X syndrome.

    PubMed

    de Esch, Celine E F; Zeidler, Shimriet; Willemsen, Rob

    2014-10-01

    Fragile X syndrome (FXS) occurs in less than 10% of the intellectually disabled (ID) population. The cause of FXS is a CGG trinucleotide repeat longer than 200 CGG units within the first exon of the FMR1 gene, which leads to hypermethylation and consequently silencing of the FMR1 gene. The lack of FMR1's gene product, the fragile X mental retardation protein (FMRP) in neurons is the cause of the ID in patients with FXS. FMRP plays an important role in local protein synthesis at the synapse including modulation of synaptic plasticity. The advancing knowledge about the cellular function of FMRP has led to the identification of translational endpoints for future therapeutic intervention strategies. This review highlights the challenging routes to the identification of reliable outcome measures in preclinical studies using both cellular models and Fmr1 knockout mice. Finally, clinical studies carried out to correct intellectual and behavioral deficits in patients with FXS, using a variety of existing and new drugs, are discussed.

  4. Acute health effects associated with exposure to volcanic air pollution (vog) from increased activity at Kilauea Volcano in 2008.

    PubMed

    Longo, Bernadette M; Yang, Wei; Green, Joshua B; Crosby, Frederick L; Crosby, Vickie L

    2010-01-01

    In 2008, the Kilauea Volcano on the island of Hawai'i increased eruption activity and emissions of sulfurous volcanic air pollution called vog. The purpose of this study was to promptly assess for a relative increase in cases of medically diagnosed acute illnesses in an exposed Hawaiian community. Using a within-clinic retrospective cohort design, comparisons were made for visits of acute illnesses during the 14 wk prior to the increased volcanic emissions (low exposure) to 14 wk of high vog exposure when ambient sulfur dioxide was threefold higher and averaged 75 parts per billion volume per day. Logistic regression analysis estimated effect measures between the low- and high-exposure cohorts for age, gender, race, and smoking status. There were statistically significant positive associations between high vog exposure and visits for medically diagnosed cough, headache, acute pharyngitis, and acute airway problems. More than a sixfold increase in odds was estimated for visits with acute airway problems, primarily experienced by young Pacific Islanders. These findings suggest that the elevated volcanic emissions in 2008 were associated with increased morbidity of acute illnesses in age and racial subgroups of the general Hawaiian population. Continued investigation is crucial to fully assess the health impact of this natural source of sulfurous air pollution. Culturally appropriate primary- and secondary-level health prevention initiatives are recommended for populations in Hawai'i and volcanically active areas worldwide.

  5. Comparison of acute physiology and chronic health evaluation II and acute physiology and chronic health evaluation IV to predict intensive care unit mortality

    PubMed Central

    Parajuli, Bashu Dev; Shrestha, Gentle S.; Pradhan, Bishwas; Amatya, Roshana

    2015-01-01

    Context: Clinical assessment of severity of illness is an essential component of medical practice to predict the outcome of critically ill-patient. Acute Physiology and Chronic Health Evaluation (APACHE) model is one of the widely used scoring systems. Aims: This study was designed to evaluate the Performance of APACHE II and IV scoring systems in our Intensive Care Unit (ICU). Settings and Design: A prospective study in 6 bedded ICU, including 76 patients all above 15 years. Subjects and Methods: APACHE II and APACHE IV scores were calculated based on the worst values in the first 24 h of admission. All enrolled patients were followed, and outcome was recorded as survivors or nonsurvivors. Statistical Analysis Used: SPSS version 17. Results: The mean APACHE score was significantly higher among nonsurvivors than survivors (P < 0.005). Discrimination for APACHE II and APACHE IV was fair with area under receiver operating characteristic curve of 0.73 and 0.79 respectively. The cut-off point with best Youden index for APACHE II was 17 and for APACHE IV was 85. Above cut-off point, mortality was higher for both models (P < 0.005). Hosmer–Lemeshow Chi-square coefficient test showed better calibration for APACHE II than APACHE IV. A positive correlation was seen between the models with Spearman's correlation coefficient of 0.748 (P < 0.01). Conclusions: Discrimination was better for APACHE IV than APACHE II model however Calibration was better for APACHE II than APACHE IV model in our study. There was good correlation between the two models observed in our study. PMID:25722550

  6. A critical narrative analysis of shared decision-making in acute inpatient mental health care.

    PubMed

    Stacey, Gemma; Felton, Anne; Morgan, Alastair; Stickley, Theo; Willis, Martin; Diamond, Bob; Houghton, Philip; Johnson, Beverley; Dumenya, John

    2016-01-01

    Shared decision-making (SDM) is a high priority in healthcare policy and is complementary to the recovery philosophy in mental health care. This agenda has been operationalised within the Values-Based Practice (VBP) framework, which offers a theoretical and practical model to promote democratic interprofessional approaches to decision-making. However, these are limited by a lack of recognition of the implications of power implicit within the mental health system. This study considers issues of power within the context of decision-making and examines to what extent decisions about patients' care on acute in-patient wards are perceived to be shared. Focus groups were conducted with 46 mental health professionals, service users, and carers. The data were analysed using the framework of critical narrative analysis (CNA). The findings of the study suggested each group constructed different identity positions, which placed them as inside or outside of the decision-making process. This reflected their view of themselves as best placed to influence a decision on behalf of the service user. In conclusion, the discourse of VBP and SDM needs to take account of how differentials of power and the positioning of speakers affect the context in which decisions take place.

  7. Does Acute Maternal Stress in Pregnancy Affect Infant Health Outcomes? Examination of a Large Cohort of Infants Born After the Terrorist Attacks of September 11, 2001

    DTIC Science & Technology

    2009-01-01

    Spandorfer S, Grill E, Davis O, Fasouliotis S, Rosenwaks Z: Septem- ber 11th in New York City (NYC): the effect of a catastrophe on IVF outcome in a...Naval Health Research Center Does acute maternal stress in pregnancy affect infant health outcomes ? Examination of A Large Cohort of Infants Born...California 92106 BioMed CentralBMC Public Health ssOpen AcceResearch article Does acute maternal stress in pregnancy affect infant health outcomes

  8. Acute Coronary Syndrome Treatment Costs from the Perspective of the Supplementary Health System

    PubMed Central

    Teich, Vanessa; Piha, Tony; Fahham, Lucas; Squiassi, Haline Bianca; Paloni, Everton de Matos; Miranda, Paulo; Araújo, Denizar Vianna

    2015-01-01

    Background Acute coronary syndrome (ACS) is defined as a “group of clinical symptoms compatible with acute myocardial ischemia”, representing the leading cause of death worldwide, with a high clinical and financial impact. In this sense, the development of economic studies assessing the costs related to the treatment of ACS should be considered. Objective To evaluate costs and length of hospital stay between groups of patients treated for ACS undergoing angioplasty with or without stent implantation (stent+ / stent-), coronary artery bypass surgery (CABG) and treated only clinically (Clinical) from the perspective of the Brazilian Supplementary Health System (SHS). Methods A retrospective analysis of medical claims of beneficiaries of health plans was performed considering hospitalization costs and length of hospital stay for management of patients undergoing different types of treatment for ACS, between Jan/2010 and Jun/2012. Results The average costs per patient were R$ 18,261.77, R$ 30,611.07, R$ 37,454.94 and R$ 40,883.37 in the following groups: Clinical, stent-, stent+ and CABG, respectively. The average costs per day of hospitalization were R$ 1,987.03, R$ 4,024.72, R$ 6,033.40 and R$ 2,663.82, respectively. The average results for length of stay were 9.19 days, 7.61 days, 6.19 days and 15.20 days in these same groups. The differences were significant between all groups except Clinical and stent- and between stent + and CABG groups for cost analysis. Conclusion Hospitalization costs of SCA are high in the Brazilian SHS, being significantly higher when interventional procedures are required. PMID:26559980

  9. [Attaching importance to study on acute health risk assessment and adaptation of air pollution and climate change].

    PubMed

    Shi, X M

    2017-03-10

    Air pollution and climate change have become key environmental and public health problems around the world, which poses serious threat to human health. How to assess and mitigate the health risks and increase the adaptation of the public have become an urgent topic of research in this area. The six papers in this issue will provide important and rich information on design, analysis method, indicator selection and setting about acute health risk assessment and adaptation study of air pollution and climate change in China, reflecting the advanced conceptions of multi-center and area-specific study and multi-pollutant causing acute effect study. However, the number and type of the cities included in these studies were still limited. In future, researchers should further expand detailed multi-center and multi-area study coverage, conduct area specific predicting and early warning study and strengthen adaptation study.

  10. Computer Model for Prediction of PCB Dechlorination and Biodegradation Endpoints

    SciTech Connect

    Just, E.M.; Klasson, T.

    1999-04-19

    Mathematical modeling of polychlorinated biphenyl (PCB) transformation served as a means of predicting possible endpoints of bioremediation, thus allowing evaluation of several of the most common transformation patterns. Correlation between laboratory-observed and predicted endpoint data was, in some cases, as good as 0.98 (perfect correlation = 1.0).

  11. Acute health effects in a community after a release of hydrofluoric acid

    SciTech Connect

    Wing, J.S.; Brender, J.D.; Sanderson, L.M.; Perrotta, D.M.; Beauchamp, R.A. )

    1991-05-01

    {approximately} 3,000 persons were evacuated from a Texas community after 24,036 kg (53,000 lb) of caustic hydrofluoric acid (HF) were released from a nearby petrochemical plant. Emergency room and hospital records of 939 persons who were seen at two area hospitals were reviewed. Most persons who presented at the emergency rooms were female (56%) or black (60%), and their mean age was 33.9 y. The most frequently reported symptoms were eye irritation (41.5%), burning throat (21%), headache (20.6%), and shortness of breath (19.4%). Physical examination results were normal for 49% of the cases; however, irritation of the eyes, nose, throat, skin, and lungs were noted on other exams. Decreased pulmonary function was demonstrated by pulmonary function tests (forced expiratory volume in the first second, less than 80% of predicted value, 42.3%); hypoxemia (pO2 less than 80 mm Hg, 17.4%) and hypocalcemia (less than 8.5 mg/dl, 16.3%) were also noted. Ninety-four (10%) of the cases were hospitalized, and more than 83% of all cases were discharged with a primary diagnosis of HF exposure. There are several reports of individuals who are acutely and chronically exposed to HF; however, we are unaware of other published reports that describe exposure of a community to HF. This incident represented a unique opportunity to study the immediate health impact on a community of residents who were exposed to a hazardous materials release. Results of this analysis suggest that (a) initial health problems should be followed up, (b) any long-term health effects of HF exposure must be assessed, and (c) the health impact on the population at risk should be determined.

  12. Impact of Advanced Health Care Directives on Treatment Decisions by Physicians in Patients with Acute Stroke

    PubMed Central

    Qureshi, Adnan I; Chaudhry, Saqib A.; Connelly, Bo; Abott, Emily; Janjua, Tariq; Kim, Stanley H.; Miley, Jefferson T.; Rodriguez, Gustavo J.; Uzun, Guven; Watanabe, Masaki

    2012-01-01

    of directives). Intravenous medication and defibrillation for cardiac arrest was withheld in 29% (compared with 19%) of the treatment decisions in the presence of advance health care directives. The two attorney raters found the description of acceptable outcome inadequate in 14 and 21 of 28 advance health care directives reviewed, respectively. The overall mean kappa for agreement regarding adequacy of documentation was modest (43%) for “does the advance health care directive specify which treatments the patient would choose, or refuse to receive if they were diagnosed with an acute, terminal condition?” and lowest (3%) for “description of acceptable outcome”. Conclusions We did not find any prominent differences in most “routine complexity,” “moderate complexity,” or “high complexity” treatment decisions in patient management in the presence of advance health care directives. Presence of advance health care directives also did not reduce the prominent variance among physicians in treatment decisions. PMID:23552508

  13. Building on a national health information technology strategic plan for long-term and post-acute care: comments by the Long Term Post Acute Care Health Information Technology Collaborative.

    PubMed

    Alexander, Gregory L; Alwan, Majd; Batshon, Lynne; Bloom, Shawn M; Brennan, Richard D; Derr, John F; Dougherty, Michelle; Gruhn, Peter; Kirby, Annessa; Manard, Barbara; Raiford, Robin; Serio, Ingrid Johnson

    2011-07-01

    The LTPAC (Long Term Post Acute Care) Health Information Technology (HIT) Collaborative consists of an alliance of long-term services and post-acute care stakeholders. Members of the collaborative are actively promoting HIT innovations in long-term care settings because IT adoption for health care institutions in the United States has become a high priority. One method used to actively promote HIT is providing expert comments on important documents addressing HIT adoption. Recently, the Office of the National Coordinator for HIT released a draft of the Federal Health Information Technology Strategic Plan 2011-2015 for public comment. The following brief is intended to inform about recommendations and comments made by the Collaborative on the strategic plan.

  14. Acute health effects of PM10 pollution on symptomatic and asymptomatic children

    SciTech Connect

    Pope, C.A. 3d.; Dockery, D.W. )

    1992-05-01

    This study assessed the association between daily changes in respiratory health and respirable particulate pollution (PM10) in Utah Valley during the winter of 1990-1991. During the study period, 24-h PM10 concentrations ranged from 7 to 251 micrograms/m3. Participants included symptomatic and asymptomatic samples of fifth- and sixth-grade students. Relatively small but statistically significant (p less than 0.01) negative associations between peak expiratory flow (PEF) and PM10 were observed for both the symptomatic and asymptomatic samples. The association was strongest for the symptomatic children. Large associations between the incidence of respiratory symptoms, especially cough, and PM10 pollution were also observed for both samples. Again the association was strongest for the symptomatic sample. Immediate and delayed PM10 effects were observed. Respiratory symptoms and PEF changes were more closely associated with 5-day moving-average PM10 levels than with concurrent-day levels. These associations were also observed at PM10 levels below the 24-h standard of 150 micrograms/m3. This study indicates that both symptomatic and asymptomatic children may suffer acute health effects of respirable particulate pollution, with symptomatic children suffering the most.

  15. Developing a market orientation in the Health Service: a survey of acute NHS Trusts in Scotland.

    PubMed

    Laing, A W; Galbraith, A

    1996-01-01

    Argues that the introduction of the quasi market mechanism into the Health Service has required that managers within NHS trusts acquire new managerial skills relating to market operations and, more importantly, reorientate their organizations towards the marketplace. Examines the pattern of development which has occurred within acute trusts across Scotland in the past three years, and argues that managers in the majority of trusts have developed a remarkably robust and relevant conceptualization of the nature and application of marketing within the NHS, reflecting the difficulties managers have faced in selling the concept of marketing to a generally sceptical body of clinicians. Notes, in part owing to such professional scepticism, that the development of marketing as an implementable approach to operations has lagged significantly behind the managerial conceptualization, although this cannot be attributed solely to resistance from clinicians and other health care professionals. Rather, suggests that such limited progress in implementing a market orientation reflects a range of "structural" barriers, both within individual trusts and the specific market environment faced by trusts.

  16. Health-related QOL in acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease: a review of the literature.

    PubMed

    Doll, Helen; Miravitlles, Marc

    2005-01-01

    There is a lack of emphasis on health-related QOL (HR-QOL) changes associated with acute exacerbation of chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD). The aim of this review is to examine the use of HR-QOL instruments to evaluate acute exacerbation of CB or COPD, so as to form recommendations for future research.A literature search of papers published between 1966 and July 2003 identified more than 300 articles that used acute exacerbation of CB or COPD as the search term. However, only 21 of these studies employed HR-QOL measures as predictors of outcome or in the assessment of the impact, evolution or treatment of acute exacerbations of COPD or CB. A variety of HR-QOL measures were used, both generic and disease specific. The disease-specific St George's Respiratory Questionnaire (SGRQ), devised for patients with stable CB and with a recall period of 1-12 months, was the most widely used measure, with the Chronic Respiratory disease Questionnaire (CRQ) and the Baseline and Transitional Dyspnoea Index (BDI, TDI) being the only other disease-specific measures used. Most measures, both generic and disease specific, performed adequately when used during acute exacerbation of CB or COPD and indicated poor HR-QOL during acute exacerbation, which improved on resolution of the exacerbation. Relationships were evident between HR-QOL during an acute exacerbation and various outcomes, including post-exacerbation functional status, hospital re- admission for acute exacerbation or COPD, and mortality. There is a need for studies of treatments for acute exacerbation of CB or COPD to include an appropriate HR-QOL instrument to aid in the stratification of patients so as to target the right treatment to the right patient group. While a new instrument could be developed to measure HR-QOL during acute exacerbation of CB or COPD, currently available disease-specific measures such as the CRQ and the SGRQ appear to be acceptable to patients during acute

  17. Facilitators and barriers to doing workplace mental health research: Case study of acute psychological trauma in a public transit system.

    PubMed

    Links, Paul S; Bender, Ash; Eynan, Rahel; O'Grady, John; Shah, Ravi

    2016-03-10

    The Acute Psychological Trauma (APT) Study was a collaboration between an acute care hospital, a specialized multidisciplinary program designed to meet the mental health needs of injured workers, and a large urban public transit system. The overall purpose was to evaluate a Best Practices Intervention (BPI) for employees affected by acute psychological trauma compared to a Treatment as Usual (TAU) group. The specific purpose is to discuss facilitators and barriers that were recognized in implementing and carrying out mental health research in a workplace setting. Over the course of the APT study, a joint implementation committee was responsible for day-to-day study operations and made regular observations on the facilitators and barriers that arose throughout the study. The facilitators to this study included the longstanding relationships among the partners, increased recognition for the need of mental health research in the workplace, and the existence of a community advisory committee. The significant barriers to doing this study of mental health research in the workplace included differences in organizational culture, inconsistent union support, co-interventions, and stigma. Researchers and funding agencies need to be flexible and provide additional resources in order to overcome the barriers that can exist doing workplace mental health research.

  18. Nurse-patient interaction in acute adult inpatient mental health units: a review and synthesis of qualitative studies.

    PubMed

    Cleary, Michelle; Hunt, Glenn E; Horsfall, Jan; Deacon, Maureen

    2012-02-01

    Mental health nurses work with acutely unwell patients, and the busy setting is characterised by unpredictable events. This paper is a report of a review conducted to identify, analyse and synthesize research in adult acute inpatient mental health units, which focused on nurse-patient interaction. Several electronic databases were searched using relevant keywords to identify studies published from 1999-present. Qualitative studies published in English were included if they specifically investigated nurse-patient interaction in acute inpatient care in adult settings. Eighteen studies were included (23 papers). Findings were grouped into the following six categories: 1) sophisticated communication; 2) subtle discriminations; 3) managing security parameters; 4) ordinary communication; 5) reliance on colleagues; and 6) personal characteristics. These studies of acute inpatient mental health units reveal that nurse communication involves interpersonal approaches and modalities that exemplify highly developed communication and personal skills designed specifically for this challenging setting. Further quality research should focus on the conditions that enable the development of therapeutic interactional skills and the relationship of these skills to the nuanced context in which they are practiced.

  19. Ecological risk assessment of bisphenol A in surface waters of China based on both traditional and reproductive endpoints.

    PubMed

    Guo, Lei; Li, Zhengyan; Gao, Pei; Hu, Hong; Gibson, Mark

    2015-11-01

    Bisphenol A (BPA) occurs widely in natural waters with both traditional and reproductive toxicity to various aquatic species. The water quality criteria (WQC), however, have not been established in China, which hinders the ecological risk assessment for the pollutant. This study therefore aims to derive the water quality criteria for BPA based on both acute and chronic toxicity endpoints and to assess the ecological risk in surface waters of China. A total of 15 acute toxicity values tested with aquatic species resident in China were found in published literature, which were simulated with the species sensitivity distribution (SSD) model for the derivation of criterion maximum concentration (CMC). 18 chronic toxicity values with traditional endpoints were simulated for the derivation of traditional criterion continuous concentration (CCC) and 12 chronic toxicity values with reproductive endpoints were for reproductive CCC. Based on the derived WQC, the ecological risk of BPA in surface waters of China was assessed with risk quotient (RQ) method. The results showed that the CMC, traditional CCC and reproductive CCC were 1518μgL(-1), 2.19μgL(-1) and 0.86μgL(-1), respectively. The acute risk of BPA was negligible with RQ values much lower than 0.1. The chronic risk was however much higher with RQ values of between 0.01-3.76 and 0.03-9.57 based on traditional and reproductive CCC, respectively. The chronic RQ values on reproductive endpoints were about threefold as high as those on traditional endpoints, indicating that ecological risk assessment based on traditional effects may not guarantee the safety of aquatic biota.

  20. Equipment management risk rating system based on engineering endpoints.

    PubMed

    James, P J

    1999-01-01

    The equipment management risk ratings system outlined here offers two significant departures from current practice: risk classifications are based on intrinsic device risks, and the risk rating system is based on engineering endpoints. Intrinsic device risks are categorized as physical, clinical and technical, and these flow from the incoming equipment assessment process. Engineering risk management is based on verification of engineering endpoints such as clinical measurements or energy delivery. This practice eliminates the ambiguity associated with ranking risk in terms of physiologic and higher-level outcome endpoints such as no significant hazards, low significance, injury, or mortality.

  1. Development of Effects-Based Nutrient Criteria using Biological Endpoints

    NASA Astrophysics Data System (ADS)

    Miltner, R.

    2005-05-01

    Ohio employs biological endpoints to judge the status of aquatic life in rivers and streams. Specifically, numeric criteria derived from biological indices have been incorporated into Ohio's water quality standards for fish and macroinvertebrate communities. When appropriate, chemical-specific water quality standards derived from dose-response curves are used in concert with the biological indices to ascribe the causes and sources of impairment to polluted streams. However, water quality criteria have not been established for all polluting agents, especially those, like nutrients, that do not elicit a simple dose-response curve. In such cases, where biological impairment is observed, the linkage between the impairment and causal agent is made inferentially. Ohio EPA is currently studying the relationship between nutrient concentrations, periphytic chlorophyll a concentrations, and biological indices to ascertain whether a direct relationship exists between nutrient concentration and the biological health of fish and macroinvertebrate communities, with the eventual goal of adopting effects-based nutrient criteria in Ohio's water quality standards. Results from the first field season show a strong relationship between chlorophyll a concentrations, and physical and land use variables. Additionally, 48 h dissolved oxygen flux correlated with periphytic chlorophyll a concentrations and the degree of canopy cover.

  2. Evaluation of reproduction as an endpoint in chronic toxicity tests with the amphipod Hyalella azteca

    SciTech Connect

    Brunson, E.L.; Dwyer, F.J.; Ingersoll, C.G.

    1995-12-31

    In 1994, USEPA published ``Methods for Measuring the Toxicity and Bioaccumulation of Sediment-associated Contaminants with Freshwater Invertebrates`` (EPA/600/R-94/024). Within that document a Hyalella azteca 10-d survival test for sediments is described. The 10-d survival test provides a measure of acute toxicity from moderately to highly contaminated sediments. In addition to survival, growth during the 10-d test can be measured and could be a more sensitive endpoint. However, the ecological significance of reduced growth is questionable. Reproduction may be a more sensitive endpoint than growth or survival and its ecological importance is not questionable. The objective of this research is to develop a Hyalella azteca sediment toxicity test with a reproductive endpoint. The reproductive test will closely resemble the 10-d test but will be longer in duration and may require isolation of amphipods from the sediment for reproduction. Presently, reproductive effects of different diets and water types have been evaluated. A preliminary test protocol has been developed and is being tested and refined. This presentation will provide the most current results of this ongoing research. This study will be used to develop standard methods for measuring chronic toxicity in sediments using Hyalella azteca.

  3. Human health screening level risk assessments of tertiary-butyl acetate (TBAC): calculated acute and chronic reference concentration (RfC) and Hazard Quotient (HQ) values based on toxicity and exposure scenario evaluations.

    PubMed

    Bus, James S; Banton, Marcy I; Faber, Willem D; Kirman, Christopher R; McGregor, Douglas B; Pourreau, Daniel B

    2015-02-01

    A screening level risk assessment has been performed for tertiary-butyl acetate (TBAC) examining its primary uses as a solvent in industrial and consumer products. Hazard quotients (HQ) were developed by merging TBAC animal toxicity and dose-response data with population-level, occupational and consumer exposure scenarios. TBAC has a low order of toxicity following subchronic inhalation exposure, and neurobehavioral changes (hyperactivity) in mice observed immediately after termination of exposure were used as conservative endpoints for derivation of acute and chronic reference concentration (RfC) values. TBAC is not genotoxic but has not been tested for carcinogenicity. However, TBAC is unlikely to be a human carcinogen in that its non-genotoxic metabolic surrogates tertiary-butanol (TBA) and methyl tertiary butyl ether (MTBE) produce only male rat α-2u-globulin-mediated kidney cancer and high-dose specific mouse thyroid tumors, both of which have little qualitative or quantitative relevance to humans. Benchmark dose (BMD)-modeling of the neurobehavioral responses yielded acute and chronic RfC values of 1.5 ppm and 0.3 ppm, respectively. After conservative modeling of general population and near-source occupational and consumer product exposure scenarios, almost all HQs were substantially less than 1. HQs exceeding 1 were limited to consumer use of automotive products and paints in a poorly ventilated garage-sized room (HQ = 313) and occupational exposures in small and large brake shops using no personal protective equipment or ventilation controls (HQs = 3.4-126.6). The screening level risk assessments confirm low human health concerns with most uses of TBAC and indicate that further data-informed refinements can address problematic health/exposure scenarios. The assessments also illustrate how tier-based risk assessments using read-across toxicity information to metabolic surrogates reduce the need for comprehensive animal testing.

  4. Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background In Ontario, current treatment for eligible patients who have an acute ischemic stroke is intravenous thrombolysis (IVT). However, there are some limitations and contraindications to IVT, and outcomes may not be favourable for patients with stroke caused by a proximal intracranial occlusion. An alternative is mechanical thrombectomy with newer devices, and a number of recent studies have suggested that this treatment is more effective for improving functional independence and clinical outcomes. The objective of this health technology assessment was to evaluate the clinical effectiveness and cost-effectiveness of new-generation mechanical thrombectomy devices (with or without IVT) compared to IVT alone (if eligible) in patients with acute ischemic stroke. Methods We conducted a systematic review of the literature, limited to randomized controlled trials that examined the effectiveness of mechanical thrombectomy using stent retrievers and thromboaspiration devices for patients with acute ischemic stroke. We assessed the quality of the evidence using the GRADE approach. We developed a Markov decision-analytic model to assess the cost-effectiveness of mechanical thrombectomy (with or without IVT) versus IVT alone (if eligible), calculated incremental cost-effectiveness ratios using a 5-year time horizon, and conducted sensitivity analyses to examine the robustness of the estimates. Results There was a substantial, statistically significant difference in rate of functional independence (GRADE: high quality) between those who received mechanical thrombectomy (with or without IVT) and IVT alone (odds ratio [OR] 2.39, 95% confidence interval [CI] 1.88–3.04). We did not observe a difference in mortality (GRADE: moderate quality) (OR 0.80, 95% CI 0.60–1.07) or symptomatic intracerebral hemorrhage (GRADE: moderate quality) (OR 1.11, 95% CI 0.66–1.87). In the base-case cost-utility analysis, which had a 5 year time horizon, the costs and effectiveness for

  5. Alternative Endpoints and Approaches Selected for the Remediation of Contaminated Groundwater at Complex Sites

    NASA Astrophysics Data System (ADS)

    Deeb, R. A.; Hawley, E.

    2011-12-01

    This presentation will focus on findings, statistics, and case studies from a recently-completed report for the Department of Defense's Environmental Security Technology Certification Program (ESTCP) (Project ER-0832) on alternative endpoints and alternative remedial strategies for groundwater remediation under a variety of Federal and state cleanup programs, including technical impracticability (TI) and other Applicable or Relevant and Appropriate Requirement (ARAR) waivers, state and local designations such as groundwater management zones, Alternate Concentration Limits (ACLs), use of monitored natural attenuation (MNA) over long timeframes, and more. The primary objective of the project was to provide environmental managers and regulators with tools, metrics, and information needed to evaluate alternative endpoints for groundwater remediation at complex sites. A statistical analysis of Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) sites receiving TI waivers will be presented as well as case studies of other types of alternative endpoints and alternative remedial strategies to illustrate the variety of approaches used at complex sites and the technical analyses used to predict and document cost, timeframe, and potential remedial effectiveness. Case studies provide examples of the flexible, site-specific, application of alternative endpoints and alternative remedial strategies that have been used in the past to manage and remediate groundwater contamination at complex sites. For example, at least 13 states consider some designation for groundwater containment in their corrective action policies, such as groundwater management zones, containment zones, and groundwater classification exemption areas. These designations typically indicate that groundwater contamination is present above permissible levels. Soil and groundwater within these zones are managed to protect human health and the environment. Lesson learned for the analyses

  6. Modeling the acute health effects of astronauts from exposure to large solar particle events.

    PubMed

    Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

    2009-04-01

    Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed.

  7. Patient reported outcomes as endpoints in medical research.

    PubMed

    Fairclough, Diane L

    2004-04-01

    This review covers a number of the many design and analytic issues associated with clinical trials that incorporate patient reported outcomes as primary or secondary endpoints. We use a clinical trial designed to evaluate a new therapy for the prevention of migraines to illustrate how endpoints are defined by the objectives of the study, the methods for handling longitudinal assessments with multiple scales or outcomes, and the methods of analysis in the presence of missing data.

  8. Acute health impact of the gas release at Lake Nyos, Cameroon, 1986

    NASA Astrophysics Data System (ADS)

    Baxter, Peter J.; Kapila, Mukesh

    1989-11-01

    Available medical evidence on the acute health impact of the gas release at Lake Nyos is summarised, including the results of a survey of medical records of 845 survivors treated at Wum and Nkambe hospitals. The main clinical features were compatible with exposure to an asphyxiant gas such as CO 2 but confirmation of the identity of the gas or gases involved was not possible. Exposure to CO 2 over such a large inhabited area and reversible coma lasting for hours after CO 2 gassing do not appear to have been reported before. In some victims, blistering or ulceration of the skin was present which could not be readily explained by local injury from pressure, or burns from acid, or falling near fires. Further epidemiological studies on survivors are unlikely to be feasible, but the possibility of long-term anoxic brain damage among adults and children who had been rendered comatose by the gas should be considered, though overt evidence of major neurological or respiratory disability was not apparent in survivors in the weeks following the disaster. The inadequacy of the toxicological and forensic evidence obtained points to the need for the rapid mobilisation of medical scientists in future disasters of this kind.

  9. Accurate measurement method for tube's endpoints based on machine vision

    NASA Astrophysics Data System (ADS)

    Liu, Shaoli; Jin, Peng; Liu, Jianhua; Wang, Xiao; Sun, Peng

    2017-01-01

    Tubes are used widely in aerospace vehicles, and their accurate assembly can directly affect the assembling reliability and the quality of products. It is important to measure the processed tube's endpoints and then fix any geometric errors correspondingly. However, the traditional tube inspection method is time-consuming and complex operations. Therefore, a new measurement method for a tube's endpoints based on machine vision is proposed. First, reflected light on tube's surface can be removed by using photometric linearization. Then, based on the optimization model for the tube's endpoint measurements and the principle of stereo matching, the global coordinates and the relative distance of the tube's endpoint are obtained. To confirm the feasibility, 11 tubes are processed to remove the reflected light and then the endpoint's positions of tubes are measured. The experiment results show that the measurement repeatability accuracy is 0.167 mm, and the absolute accuracy is 0.328 mm. The measurement takes less than 1 min. The proposed method based on machine vision can measure the tube's endpoints without any surface treatment or any tools and can realize on line measurement.

  10. Preliminary remediation goals for ecological endpoints

    SciTech Connect

    Efroymson, R.A.; Suter, G.W. II; Sample, B.E.; Jones, D.S.

    1996-07-01

    Preliminary remediation goals (PRGs) are useful for risk assessment and decision making at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) sites. PRGs are upper concentration limits for specific chemicals in specific environmental media that are anticipated to protect human health or the environment. They can be used for multiple remedial investigations at multiple facilities. In addition to media and chemicals of potential concern, the development of PRGs generally requires some knowledge or anticipation of future land use. In Preliminary Remediation Goals for Use at the U.S. Department of Energy Oak Ridge Operations Office (Energy Systems 1995), PRGs intended to protect human health were developed with guidance from Risk Assessment Guidance for Superfund: Volume I - Human Health Evaluation Manual, Part B (RAGS) (EPA 1991). However, no guidance was given for PRGs based on ecological risk. The numbers that appear in this volume have, for the most part, been extracted from toxicological benchmarks documents for Oak Ridge National Laboratory (ORNL) and have previously been developed by ORNL. The sources of the quantities, and many of the uncertainties associated with their derivation, are described in this technical memorandum.

  11. Recording of hospitalizations for acute exacerbations of COPD in UK electronic health care records

    PubMed Central

    Rothnie, Kieran J; Müllerová, Hana; Thomas, Sara L; Chandan, Joht S; Smeeth, Liam; Hurst, John R; Davis, Kourtney; Quint, Jennifer K

    2016-01-01

    Background Accurate identification of hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) within electronic health care records is important for research, public health, and to inform health care utilization and service provision. We aimed to develop a strategy to identify hospitalizations for AECOPD in secondary care data and to investigate the validity of strategies to identify hospitalizations for AECOPD in primary care data. Methods We identified patients with chronic obstructive pulmonary disease (COPD) in the Clinical Practice Research Datalink (CPRD) with linked Hospital Episodes Statistics (HES) data. We used discharge summaries for recent hospitalizations for AECOPD to develop a strategy to identify the recording of hospitalizations for AECOPD in HES. We then used the HES strategy as a reference standard to investigate the positive predictive value (PPV) and sensitivity of strategies for identifying AECOPD using general practice CPRD data. We tested two strategies: 1) codes for hospitalization for AECOPD and 2) a code for AECOPD other than hospitalization on the same day as a code for hospitalization due to unspecified reason. Results In total, 27,182 patients with COPD were included. Our strategy to identify hospitalizations for AECOPD in HES had a sensitivity of 87.5%. When compared with HES, using a code suggesting hospitalization for AECOPD in CPRD resulted in a PPV of 50.2% (95% confidence interval [CI] 48.5%–51.8%) and a sensitivity of 4.1% (95% CI 3.9%–4.3%). Using a code for AECOPD and a code for hospitalization due to unspecified reason resulted in a PPV of 43.3% (95% CI 42.3%–44.2%) and a sensitivity of 5.4% (95% CI 5.1%–5.7%). Conclusion Hospitalization for AECOPD can be identified with high sensitivity in the HES database. The PPV and sensitivity of strategies to identify hospitalizations for AECOPD in primary care data alone are very poor. Primary care data alone should not be used to identify

  12. Do pollution time-series studies contain uncontrolled or residual confounding by risk factors for acute health events?

    PubMed

    Bukowski, John

    2008-07-01

    Acute health effects from air pollution are based largely on weak associations identified in time-series studies comparing daily air pollution levels to daily mortality. Much of this mortality is due to cardiovascular disease. Time-series studies have many potential limitations, but are not thought to be confounded by traditional cardiovascular risk factors (e.g., smoking status or hypertension) because these chronic risk factors are not obviously associated with daily pollution levels. However, acute psychobehavioral variants of these risk factors (e.g., smoking patterns and episodes of stress on any given day) are plausible confounders for the associations observed in time-series studies, given that time-series studies attempt to predict acute rather than chronic health outcomes. There is a fairly compelling literature on the strong link between cardiovascular events and daily "triggers" such as stress. Stress-related triggers are plausibly associated with daily pollution levels through surrogate stressors such as ambient temperature, daily workload, local traffic congestion, or other correlates of air pollution. For example, variables such as traffic congestion and industrial activity increase both stress-related health events and air pollution, suggesting the potential for classical confounding. Support for this argument is illustrated through examples of the well-demonstrated relationship between emotional stress and heart attack/stroke.

  13. National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury

    PubMed Central

    Cronin, Robert M; VanHouten, Jacob P; Siew, Edward D; Eden, Svetlana K; Fihn, Stephan D; Nielson, Christopher D; Peterson, Josh F; Baker, Clifton R; Ikizler, T Alp; Speroff, Theodore

    2015-01-01

    Objective Hospital-acquired acute kidney injury (HA-AKI) is a potentially preventable cause of morbidity and mortality. Identifying high-risk patients prior to the onset of kidney injury is a key step towards AKI prevention. Materials and Methods A national retrospective cohort of 1,620,898 patient hospitalizations from 116 Veterans Affairs hospitals was assembled from electronic health record (EHR) data collected from 2003 to 2012. HA-AKI was defined at stage 1+, stage 2+, and dialysis. EHR-based predictors were identified through logistic regression, least absolute shrinkage and selection operator (lasso) regression, and random forests, and pair-wise comparisons between each were made. Calibration and discrimination metrics were calculated using 50 bootstrap iterations. In the final models, we report odds ratios, 95% confidence intervals, and importance rankings for predictor variables to evaluate their significance. Results The area under the receiver operating characteristic curve (AUC) for the different model outcomes ranged from 0.746 to 0.758 in stage 1+, 0.714 to 0.720 in stage 2+, and 0.823 to 0.825 in dialysis. Logistic regression had the best AUC in stage 1+ and dialysis. Random forests had the best AUC in stage 2+ but the least favorable calibration plots. Multiple risk factors were significant in our models, including some nonsteroidal anti-inflammatory drugs, blood pressure medications, antibiotics, and intravenous fluids given during the first 48 h of admission. Conclusions This study demonstrated that, although all the models tested had good discrimination, performance characteristics varied between methods, and the random forests models did not calibrate as well as the lasso or logistic regression models. In addition, novel modifiable risk factors were explored and found to be significant. PMID:26104740

  14. The dopaminergic response to acute stress in health and psychopathology: A systematic review.

    PubMed

    Vaessen, Thomas; Hernaus, Dennis; Myin-Germeys, Inez; van Amelsvoort, Thérèse

    2015-09-01

    Previous work in animals has shown that dopamine (DA) in cortex and striatum plays an essential role in stress processing. For the first time, we systematically reviewed the in vivo evidence for DAergic stress processing in health and psychopathology in humans. All studies included (n studies=25, n observations=324) utilized DA D2/3 positron emission tomography and measured DAergic activity during an acute stress challenge. The evidence in healthy volunteers (HV) suggests that physiological, but not psychological, stress consistently increases striatal DA release. Instead, increased medial prefrontal cortex (mPFC) DAergic activity in HV was observed during psychological stress. Across brain regions, stress-related DAergic activity was correlated with the physiological and psychological intensity of the stressor. The magnitude of stress-induced DA release was dependent on rearing conditions, personality traits and genetic variations in several SNPs. In psychopathology, preliminary evidence was found for stress-related dorsal striatal DAergic hyperactivity in psychosis spectrum and a blunted response in chronic cannabis use and pain-related disorders, but results were inconsistent. Physiological stress-induced DAergic activity in striatum in HV may reflect somatosensory properties of the stressor and readiness for active fight-or-flight behavior. DAergic activity in HV in the ventral striatum and mPFC may be more related to expectations about the stressor and threat evaluation, respectively. Future studies with increased sample size in HV and psychopathology assessing the functional relevance of stress-induced DAergic activity, the association between cortical and subcortical DAergic activity and the direct comparison of different stressors are necessary to conclusively elucidate the role of the DA system in the stress response.

  15. Association of serum interleukin-6, interleukin-8, and Acute Physiology and Chronic Health Evaluation II score with clinical outcome in patients with acute respiratory distress syndrome

    PubMed Central

    Swaroopa, Deme; Bhaskar, Kakarla; Mahathi, T.; Katkam, Shivakrishna; Raju, Y. Satyanarayana; Chandra, Naval; Kutala, Vijay Kumar

    2016-01-01

    Background and Aim: Studies on potential biomarkers in experimental models of acute lung injury (ALI) and clinical samples from patients with ALI have provided evidence to the pathophysiology of the mechanisms of lung injury and predictor of clinical outcome. Because of the high mortality and substantial variability in outcomes in patients with acute respiratory distress syndrome (ARDS), identification of biomarkers such as cytokines is important to determine prognosis and guide clinical decision-making. Materials and Methods: In this study, we have included thirty patients admitted to Intensive Care Unit diagnosed with ARDS, and serum samples were collected on day 1 and 7 and were analyzed for serum interleukin-6 (IL-6) and IL-8 by ELISA method, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring was done on day 1. Results: The mortality in the patients observed with ARDS was 34%. APACHE II score was significantly higher in nonsurvivors as compared to survivors. There were no significant differences in gender and biochemical and hematological parameters among the survivors and nonsurvivors. Serum IL-6 and IL-8 levels on day 1 were significantly higher in all the ARDS patients as compared to healthy controls and these levels were returned to near-normal basal levels on day 7. The serum IL-6 and IL-8 levels measured on day 7 were of survivors. As compared to survivors, the IL-6 and IL-8 levels were significantly higher in nonsurvivors measured on day 1. Spearman's rank correlation analysis indicated a significant positive correlation of APACHE II with IL-8. By using APACHE II score, IL-6, and IL-8, the receiver operating characteristic curve was plotted and the provided predictable accuracy of mortality (outcome) was 94%. Conclusion: The present study highlighted the importance of measuring the cytokines such as IL-6 and IL-8 in patients with ARDS in predicting the clinical outcome. PMID:27688627

  16. Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition.

    PubMed

    Gilbert, Peter B; Gabriel, Erin E; Huang, Ying; Chan, Ivan S F

    2015-09-01

    A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect

  17. Image Segmentation Using Parametric Contours With Free Endpoints.

    PubMed

    Benninghoff, Heike; Garcke, Harald

    2016-04-01

    In this paper, we introduce a novel approach for active contours with free endpoints. A scheme for image segmentation is presented based on a discrete version of the Mumford-Shah functional where the contours can be both closed and open curves. Additional to a flow of the curves in normal direction, evolution laws for the tangential flow of the endpoints are derived. Using a parametric approach to describe the evolving contours together with an edge-preserving denoising, we obtain a fast method for image segmentation and restoration. The analytical and numerical schemes are presented followed by numerical experiments with artificial test images and with a real medical image.

  18. Image Segmentation Using Parametric Contours With Free Endpoints

    NASA Astrophysics Data System (ADS)

    Benninghoff, Heike; Garcke, Harald

    2016-04-01

    In this paper, we introduce a novel approach for active contours with free endpoints. A scheme is presented for image segmentation and restoration based on a discrete version of the Mumford-Shah functional where the contours can be both closed and open curves. Additional to a flow of the curves in normal direction, evolution laws for the tangential flow of the endpoints are derived. Using a parametric approach to describe the evolving contours together with an edge-preserving denoising, we obtain a fast method for image segmentation and restoration. The analytical and numerical schemes are presented followed by numerical experiments with artificial test images and with a real medical image.

  19. Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

    PubMed

    Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

    2017-03-01

    Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days.

  20. Comparison of thrombolysis in myocardial infarction, Global Registry of Acute Coronary Events, and Acute Physiology and Chronic Health Evaluation II risk scores in patients with acute myocardial infarction who require mechanical ventilation for more than 24 hours.

    PubMed

    Eran, Oren; Novack, Victor; Gilutz, Harel; Zahger, Doron

    2011-02-01

    The ability to provide an accurate prognosis in an intensive care unit is of major importance. Numerous risk scores have been developed to predict hospital mortality based on demographic, physiologic, and clinical data. These scores were universally developed in general medical or surgical intensive care units. Patients admitted to a cardiac care unit differ in many aspects from those admitted to general medical intensive care units. Few patients require mechanical ventilation and prolonged intensive care. Performance of risk scores developed for patients with acute myocardial infarction (AMI) in this subgroup is unknown. We prospectively studied 51 consecutive patients who were admitted to a cardiac care unit from September 2006 to March 2008 for AMI and received mechanical ventilation for >24 hours. Acute Physiology and Chronic Health Evaluation II (APACHE II), Thrombolysis In Myocardial Infarction, and Global Registry of Acute Coronary Events risk scores were calculated for each patient. Mortality rates were extrapolated based on these 3 risk scores. Twenty-two of 51 patients (43%) died in hospital. Age, mean arterial pressure, urea, albumin, hemoglobin, need for vasopressors, and estimated glomerular filtration rate were predictive of mortality. APACHE II and Global Registry of Acute Coronary Events scores were higher in nonsurvivors but Thrombolysis In Myocardial Infarction risk score was not predictive of mortality. APACHE II score had the highest value for area under receiver operator characteristics curve for mortality prediction. In conclusion, patients with AMI requiring mechanical ventilation have a high mortality rate. This risk is predicted by co-morbidities better than by direct cardiac parameters. Consequently, conventional AMI risk scores do not perform well in this very sick population and the APACHE II score better predicts their short-term outcome.

  1. Secondary analysis of data can inform care delivery for Indigenous women in an acute mental health inpatient unit.

    PubMed

    Bradley, Pat; Cunningham, Teresa; Lowell, Anne; Nagel, Tricia; Dunn, Sandra

    2017-02-01

    There is a paucity of research exploring Indigenous women's experiences in acute mental health inpatient services in Australia. Even less is known of Indigenous women's experience of seclusion events, as published data are rarely disaggregated by both indigeneity and gender. This research used secondary analysis of pre-existing datasets to identify any quantifiable difference in recorded experience between Indigenous and non-Indigenous women, and between Indigenous women and Indigenous men in an acute mental health inpatient unit. Standard separation data of age, length of stay, legal status, and discharge diagnosis were analysed, as were seclusion register data of age, seclusion grounds, and number of seclusion events. Descriptive statistics were used to summarize the data, and where warranted, inferential statistical methods used SPSS software to apply analysis of variance/multivariate analysis of variance testing. The results showed evidence that secondary analysis of existing datasets can provide a rich source of information to describe the experience of target groups, and to guide service planning and delivery of individualized, culturally-secure mental health care at a local level. The results are discussed, service and policy development implications are explored, and suggestions for further research are offered.

  2. The habitus of 'rescue' and its significance for implementation of rapid response systems in acute health care.

    PubMed

    Mackintosh, Nicola; Humphrey, Charlotte; Sandall, Jane

    2014-11-01

    The need to focus on patient safety and improve the quality and consistency of medical care in acute hospital settings has been highlighted in a number of UK and international reports. When patients on a hospital ward become acutely unwell there is often a window of opportunity for staff, patients and relatives to contribute to the 'rescue' process by intervening in the trajectory of clinical deterioration. This paper explores the social and institutional processes associated with the practice of rescue, and implications for the implementation and effectiveness of rapid response systems (RRSs) within acute health care. An ethnographic case study was conducted in 2009 in two UK hospitals (focussing on the medical directorates in each organisation). Data collection involved 180 h of observation, 35 staff interviews (doctors, nurses, health care assistants and managers) and documentary review. Analysis was informed by Bourdieu's logic of practice and his relational concept of the 'field' of the general medical ward. Three themes illustrated the nature of rescue work within the field and collective rules which guided associated occupational distinction practices: (1) the 'dirty work' of vital sign recording and its distinction from diagnostic (higher order) interpretive work; (2) the moral order of legitimacy claims for additional help; and (3) professional deference and the selective managerial control of rescue work. The discourse of rescue provided a means of exercising greater control over clinical uncertainty. The acquisition of 'rescue capital' enabled the social positioning of health care assistants, nurses and doctors, and shaped use of the RRS on the wards. Boundary work, professional legitimation and jurisdictional claims defined the social practice of rescue, as clinical staff had to balance safety, professional and organisational concerns within the field. This paper offers a nuanced understanding of patient safety on the front-line, challenging notions of

  3. Sharp bounds on causal effects using a surrogate endpoint.

    PubMed

    Kuroki, Manabu

    2013-11-10

    This paper considers a problem of evaluating the causal effect of a treatment X on a true endpoint Y using a surrogate endpoint S, in the presence of unmeasured confounders between S and Y. Such confounders render the causal effect of X on Y unidentifiable from the causal effect of X on S and the joint probability of S and Y. To evaluate the causal effect of X on Y in such a situation, this paper derives closed-form formulas for the sharp bounds on the causal effect of X on Y based on both the causal effect of X on S and the joint probability of S and Y under various assumptions. In addition, we show that it is not always necessary to observe Y to test the null causal effect of X on Y under the monotonicity assumption between X and S. These bounds enable clinical practitioners and researchers to assess the causal effect of a treatment on a true endpoint using a surrogate endpoint with minimum computational effort.

  4. Predictive Modeling of Apical Toxicity Endpoints Using Data ...

    EPA Pesticide Factsheets

    The US EPA and other regulatory agencies face a daunting challenge of evaluating potential toxicity for tens of thousands of environmental chemicals about which little is currently known. The EPA’s ToxCast program is testing a novel approach to this problem by screening compounds using a variety of in vitro assays and using the results to prioritize chemicals for further, more detailed testing. Phase I of ToxCast is testing 320 chemicals (mainly pesticide active ingredients) against ~400 cell-based and biochemical assays. In order to anchor these studies, we are using in vivo guideline study data for subchronic, chronic, cancer, reproductive and developmental endpoints. This data is compiled in the EPA toxicity reference database, ToxRefDB. The main goal of ToxCast is the discovery and validation of “signatures” linking in vitro assay data to in vivo toxicity endpoints. These signatures will be collections of assays that are correlated with particular endpoints. These assay collections should also help define molecular-and cellular-level mechanisms of toxicity. This talk will discuss our strategy to use a combination of statistical and machine learning methods, coupled with biochemical network or systems biology approaches. Our initial examples will focus signatures for endpoints from 2 year rodent cancer bioassays. Most of the data we have analyzed is in dose or concentration response series, so to effectively use this data we have developed novel appro

  5. Is Suicide Ideation a Surrogate Endpoint for Geriatric Suicide?

    ERIC Educational Resources Information Center

    Links, Paul S.; Heisel, Marnin J.; Quastel, Adam

    2005-01-01

    The present study explored the validity of treating suicide ideation as a surrogate endpoint that can serve as a proxy for suicide in clinical intervention research with suicidal seniors. Two criteria; that suicide ideation is modulated by the proposed intervention and that modulation of suicide ideation leads to a quantitative reduction in…

  6. Developing a Cognition Endpoint for Traumatic Brain Injury Clinical Trials.

    PubMed

    Silverberg, Noah D; Crane, Paul K; Dams-O'Connor, Kristen; Holdnack, James; Ivins, Brian J; Lange, Rael T; Manley, Geoffrey T; McCrea, Michael; Iverson, Grant L

    2017-01-15

    Cognitive impairment is a core clinical feature of traumatic brain injury (TBI). After TBI, cognition is a key determinant of post-injury productivity, outcome, and quality of life. As a final common pathway of diverse molecular and microstructural TBI mechanisms, cognition is an ideal endpoint in clinical trials involving many candidate drugs and nonpharmacological interventions. Cognition can be reliably measured with performance-based neuropsychological tests that have greater granularity than crude rating scales, such as the Glasgow Outcome Scale-Extended, which remain the standard for clinical trials. Remarkably, however, there is no well-defined, widely accepted, and validated cognition endpoint for TBI clinical trials. A single cognition endpoint that has excellent measurement precision across a wide functional range and is sensitive to the detection of small improvements (and declines) in cognitive functioning would enhance the power and precision of TBI clinical trials and accelerate drug development research. We outline methodologies for deriving a cognition composite score and a research program for validation. Finally, we discuss regulatory issues and the limitations of a cognition endpoint.

  7. ECOLOGICAL ENDPOINT MODELING: EFFECTS OF SEDIMENT ON FISH POPULATIONS

    EPA Science Inventory

    Sediment is one of the main stressors of concern for TMDLs (Total Maximum Daily Loads) for streams, and often it is a concern because of its impact on biological endpoints. The National Research Council (NRC) has recommended that the EPA promote the development of models that ca...

  8. Expanding the ecotoxicological toolbox: the inclusion of polychaete reproductive endpoints.

    PubMed

    Lewis, Ceri; Watson, Gordon J

    2012-04-01

    In the last 15 years the diversity of pollutants and routes of impact have increased. However, the polychaete families, species and endpoints investigated have remained fairly constant. Reproductive outputs are more ecologically relevant than adult physiological or biochemical changes. Nevertheless, there remains a paucity of data on the reproductive responses of the popular species to pollutants which limits our ability to understand the true ecological impacts of such contaminants on natural populations. We highlight the current knowledge gaps in our understanding of the impacts of pollutants on the 'model' species' reproductive biology and therefore the potential ecological impacts of such contaminants on their natural populations, and the potential benefits of a wider use of polychaete reproductive endpoints for ecotoxicological assessments. The following priority areas are suggested for inclusion in the polychaete ecotoxicology toolbox: 1. Include reproductive endpoints as assessments of ecotoxicology for the traditional 'model' species and those that have different reproductive traits to ensure broad ecological relevance. 2. Nereids and Arenicola marina should be used to investigate the interaction of pollutants with the endocrine/environmental control of reproduction. 3. Polychaetes are ideal for addressing the under representation of male eco-toxicity effects. 4. Emerging pollutants should be assessed with reproductive endpoints together with the traditional biomarkers. 5. Effects of pollutants on larval behaviour need to be explored considering the limited but equivocal results so far.

  9. Comparison and Evaluation of Laboratory and Field Measured Bioaccumulation Endpoints

    EPA Science Inventory

    Evaluation of bioaccumulation endpoints on a fugacity basis allows provides a framework to assess the biomagnification potential of a chemical and assess data deficiencies, i.e., uncertainties and lack of data. In addition, it is suggested that additional guidance is needed in o...

  10. Improving Endpoint Detection to Support Automated Systematic Reviews

    PubMed Central

    Lucic, Ana; Blake, Catherine L.

    2016-01-01

    Authors of biomedical articles use comparison sentences to communicate the findings of a study, and to compare the results of the current study with earlier studies. The Claim Framework defines a comparison claim as a sentence that includes at least two entities that are being compared, and an endpoint that captures the way in which the entities are compared. Although automated methods have been developed to identify comparison sentences from the text, identifying the role that a specific noun plays (i.e. entity or endpoint) is much more difficult. Automated methods have been successful at identifying the second entity, but classification models were unable to clearly differentiate between the first entity and the endpoint. We show empirically that establishing if head noun is an amount or measure provides a statistically significant improvement that increases the endpoint precision from 0.42 to 0.56 on longer and from 0.51 to 0.58 on shorter sentences and recall from 0.64 to 0.71 on longer and from 0.69 to 0.74 on shorter sentences. The differences were not statistically significant for the second compared entity. PMID:28269949

  11. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... well-controlled clinical trials establishing that the biological product has an effect on a...

  12. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... well-controlled clinical trials establishing that the biological product has an effect on a...

  13. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based...

  14. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... well-controlled clinical trials establishing that the biological product has an effect on a...

  15. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based...

  16. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based...

  17. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based...

  18. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... well-controlled clinical trials establishing that the biological product has an effect on a...

  19. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity. 314.510 Section 314.510...

  20. Automatic endpoint detection to support the systematic review process.

    PubMed

    Blake, Catherine; Lucic, Ana

    2015-08-01

    Preparing a systematic review can take hundreds of hours to complete, but the process of reconciling different results from multiple studies is the bedrock of evidence-based medicine. We introduce a two-step approach to automatically extract three facets - two entities (the agent and object) and the way in which the entities are compared (the endpoint) - from direct comparative sentences in full-text articles. The system does not require a user to predefine entities in advance and thus can be used in domains where entity recognition is difficult or unavailable. As with a systematic review, the tabular summary produced using the automatically extracted facets shows how experimental results differ between studies. Experiments were conducted using a collection of more than 2million sentences from three journals Diabetes, Carcinogenesis and Endocrinology and two machine learning algorithms, support vector machines (SVM) and a general linear model (GLM). F1 and accuracy measures for the SVM and GLM differed by only 0.01 across all three comparison facets in a randomly selected set of test sentences. The system achieved the best performance of 92% for objects, whereas the accuracy for both agent and endpoints was 73%. F1 scores were higher for objects (0.77) than for endpoints (0.51) or agents (0.47). A situated evaluation of Metformin, a drug to treat diabetes, showed system accuracy of 95%, 83% and 79% for the object, endpoint and agent respectively. The situated evaluation had higher F1 scores of 0.88, 0.64 and 0.62 for object, endpoint, and agent respectively. On average, only 5.31% of the sentences in a full-text article are direct comparisons, but the tabular summaries suggest that these sentences provide a rich source of currently underutilized information that can be used to accelerate the systematic review process and identify gaps where future research should be focused.

  1. Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

    PubMed Central

    Plewes, Katherine; Maude, Richard J.; Hanson, Josh; Herdman, M. Trent; Leopold, Stije J.; Ngernseng, Thatsanun; Charunwatthana, Prakaykaew; Phu, Nguyen Hoan; Ghose, Aniruddha; Hasan, M. Mahtab Uddin; Fanello, Caterina I.; Faiz, Md Abul; Hien, Tran Tinh; Day, Nicholas P. J.; White, Nicholas J.; Dondorp, Arjen M.

    2017-01-01

    Background Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. Methods Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African ‘AQUAMAT’ trial comparing artesunate and quinine (children), and the Vietnamese ‘AQ’ study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures. Results Improvements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the ‘AQUAMAT’ study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery. Conclusions The relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid

  2. Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients

    PubMed Central

    Bank, J. R.; Rabelink, T. J.; de Fijter, J. W.; Reinders, M. E. J.

    2015-01-01

    Despite excellent short-term graft survival after renal transplantation, the long-term graft outcome remains compromised. It has become evident that a combination of sustained alloreactivity and calcineurin-inhibitor- (CNI-) related nephrotoxicity results in fibrosis and consequently dysfunction of the graft. New immunosuppressive regimens that can minimize or eliminate side effects, while maintaining efficacy, are required to improve long-term graft survival. In this perspective mesenchymal stromal cells (MSCs) are an interesting candidate, since MSCs have immunosuppressive and regenerative properties. The first clinical trials with MSCs in renal transplantation showed safety and feasibility and displayed promising results. Recently, the first phase II studies have been started. One of the most difficult and challenging aspects in those early phase trials is to define accurate endpoints that can measure safety and efficacy of MSC treatment. Since both graft losses and acute rejection rates declined, alternative surrogate markers such as renal function, histological findings, and immunological markers are used to measure efficacy and to provide mechanistic insight. In this review, we will discuss the current status of MSCs in renal transplantation with a focus on the endpoints used in the different experimental and clinical studies. PMID:26258149

  3. Identifying and designing chemicals with minimal acute aquatic toxicity.

    PubMed

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T; Zimmerman, Julie Beth

    2015-05-19

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure-activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical-chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard.

  4. Severe Acute Respiratory Syndrome Epidemic and Change of People's Health Behavior in China

    ERIC Educational Resources Information Center

    Tan, Xiaodong; Li, Shiyue; Wang, Chunhong; Chen, Xiaoqing; Wu, Xiaomin

    2004-01-01

    Severe Acute Respiratory Syndrome (SARS) has become a new worldwide epidemic whose origin was until recently unknown. It is the unpredictable nature of this epidemic that makes people want answers to some important questions about what they can do to protect themselves. This study presents an inquiry into peoples knowledge and self-reported…

  5. Acute and Chronic Whole-Body Vibration Exercise does not Induce Health-Promoting Effects on The Blood Profile

    PubMed Central

    Theodorou, Anastasios A.; Gerodimos, Vassilis; Karatrantou, Konstantina; Paschalis, Vassilis; Chanou, Konstantina; Jamurtas, Athanasios Z.; Nikolaidis, Michalis G.

    2015-01-01

    Whole-body vibration (WBV) exercise is an alternative, popular and easy exercise that can be followed by general public. Therefore, the aim of the present study was to investigate the influence of acute and chronic WBV exercise on health-related parameters. Twenty-eight women were allocated into a control group (n=11, mean ±SEM: age, 43.5 ±1.5 yr; body mass, 66.1 ±3.1 kg; height, 160.6 ±1.5 cm) and a vibration group (n=17, mean ±SEM: age, 44.0 ±1.0 yr; body mass, 67.1 ±2.2 kg; height, 162.5 ±1.5 cm). After baseline assessments, participants of the experimental group performed WBV training 3 times/week for 8 weeks. Before and after the chronic WBV exercise, the participants of the vibration group performed one session of acute WBV exercise. Blood chemistry measurements (hematology, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, glucose, insulin, triacylglycerols, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B and lipoprotein, thiobarbituric-acid reactive substances, protein carbonyls, total antioxidant capacity, uric acid, albumin and bilirubin) were assessed pre-exercise and post-exercise at the first and eighth week of WBV exercise in both control and vibration groups. The results failed to support any effect of both acute and chronic WBV exercise on biochemical health-related parameters. However, it seems that WBV exercise is a safe way of training without a negative impact on muscle and liver functionality. PMID:26240654

  6. Acute adverse event signalling scheme using the Saskatchewan Administrative health care utilization datafiles: results for two benzodiazepines.

    PubMed

    Rawson, N S; Rawson, M J

    1999-01-01

    Linked administrative health care utilization databases offer potential benefits for postmarketing surveillance. The value of the Saskatchewan datafiles in an acute adverse event signalling scheme has been evaluated using two benzodiazepines. The first 20,000 patients dispensed lorazepam and the first 8525 patients dispensed alprazolam were followed through the datafiles over the year after their initial prescription of the relevant drug, and all medical services occurring during treatment were recorded. The most frequent adverse drug reactions to benzodiazepines are drowsiness, depression, impaired intellectual function and memory, lethargy, impaired coordination, dizziness, nausea and/or vomiting, skin rash, and respiratory disturbance. Data from our study showed that sleep disorders, depressive disorders, dizziness and/or vertigo, respiratory symptoms, esophagus and stomach disorders, and inflammatory skin conditions occurred significantly more often in the first 30 days after the initial prescription than in the succeeding six months in both drug groups, indicating that they are important adverse events. There are several limitations to the methodology; however, the results of the analysis indicate that the use of administrative health care utilization datafiles in a systematic assessment to signal potential acute adverse drug reactions is a feasible proposition, but further studies are required to assess whether events are real adverse reactions.

  7. Reduced acute inpatient care was largest savings component of Geisinger Health System's patient-centered medical home.

    PubMed

    Maeng, Daniel D; Khan, Nazmul; Tomcavage, Janet; Graf, Thomas R; Davis, Duane E; Steele, Glenn D

    2015-04-01

    Early evidence suggests that the patient-centered medical home has the potential to improve patient outcomes while reducing the cost of care. However, it is unclear how this care model achieves such desirable results, particularly its impact on cost. We estimated cost savings associated with Geisinger Health System's patient-centered medical home clinics by examining longitudinal clinic-level claims data from elderly Medicare patients attending the clinics over a ninety-month period (2006 through the first half of 2013). We also used these data to deconstruct savings into its main components (inpatient, outpatient, professional, and prescription drugs). During this period, total costs associated with patient-centered medical home exposure declined by approximately 7.9 percent; the largest source of this savings was acute inpatient care ($34, or 19 percent savings per member per month), which accounts for about 64 percent of the total estimated savings. This finding is further supported by the fact that longer exposure was also associated with lower acute inpatient admission rates. The results of this study suggest that patient-centered medical homes can lead to sustainable, long-term improvements in patient health outcomes and the cost of care.

  8. Acute service delivery in a police-mental health program for children exposed to violence and trauma.

    PubMed

    Murphy, Robert A; Rosenheck, Robert A; Berkowitz, Steven J; Marans, Steven R

    2005-01-01

    The Child Development Community Policing Program represents a national model of community-based collaboration between police and mental health professionals for violence-exposed and traumatized children. Administrative data from clinical records of a 24-hour consultation service were examined through stepwise multivariate logistic regression to identify child and event characteristics associated with a direct, in-person response at the time of police contact. Of 2361 children, 809 (34.3%) received a direct, in-person response. Relative to Caucasian children, Hispanic youth were more likely to receive this form of response (OR = 1.36). An acute clinical response was more likely for incidents of gang involvement (OR = 8.12), accidents (OR = 5.21), felony assaults (OR = 2.97), property crimes (OR = 2.30), family violence (OR = 1.53) and psychiatric crises (OR = 1.29). Acute response was less likely when juvenile conduct problems (OR = 0.61), fires (OR = 0.59), child maltreatment (OR = 0.57), and domestic violence (OR = 0.44) were involved. Incidents that were more severe or involved a primary mental health component were related to utilization of intensive CDCP resources.

  9. A Review of Chronic and Acute Physical Activity Participation on Neuroelectric Measures of Brain Health and Cognition during Childhood

    PubMed Central

    Hillman, Charles H.; Kamijo, Keita; Scudder, Mark

    2011-01-01

    Background A growing body of research has detailed the beneficial relation of chronic participation in- and acute responses to- physical activity on aspects of cognition that underlie scholastic achievement. Here, we review the relevant neuroelectric findings on this beneficial relation in children, providing support for the influence of physical activity on specific cognitive processes that comprise academic performance. Method A review of studies examining physical activity and neuroelectric concomitants of cognition during childhood is described. When applicable, research involving adult populations is also described to better inform on this relationship in children. Results Collectively, the data support a beneficial relation of chronic and acute participation in physical activity to brain health and cognition. The results suggest more effective allocation of cognitive processes involved in stimulus engagement and action monitoring during tasks requiring variable amounts of cognitive control in children. Conclusion Physical activity may influence brain health and cognition in children, leading to enhanced scholastic performance and greater overall effective functioning across the lifespan. PMID:21281669

  10. Cost-effectiveness of the community-based management of severe acute malnutrition by community health workers in southern Bangladesh.

    PubMed

    Puett, Chloe; Sadler, Kate; Alderman, Harold; Coates, Jennifer; Fiedler, John L; Myatt, Mark

    2013-07-01

    This study assessed the cost-effectiveness of adding the community-based management of severe acute malnutrition (CMAM) to a community-based health and nutrition programme delivered by community health workers (CHWs) in southern Bangladesh. The cost-effectiveness of this model of treatment for severe acute malnutrition (SAM) was compared with the cost-effectiveness of the 'standard of care' for SAM (i.e. inpatient treatment), augmented with community surveillance by CHWs to detect cases, in a neighbouring area. An activity-based cost model was used, and a societal perspective taken, to include all costs incurred in the programme by providers and participants for the management of SAM in both areas. Cost data were coupled with programme effectiveness data. The community-based strategy cost US$26 per disability-adjusted life year (DALY) averted, compared with US$1344 per DALY averted for inpatient treatment. The average cost to participant households for their child to recover from SAM in community treatment was one-sixth that of inpatient treatment. These results suggest that this model of treatment for SAM is highly cost-effective and that CHWs, given adequate supervision and training, can be employed effectively to expand access to treatment for SAM in Bangladesh.

  11. Gender differences in pre-event health status of young patients with acute myocardial infarction: A VIRGO study analysis

    PubMed Central

    Dreyer, Rachel P; Smolderen, Kim G; Strait, Kelly M; Beltrame, John F; Lichtman, Judith H; Lorenze, Nancy P; D’Onofrio, Gail; Bueno, Héctor; Krumholz, Harlan M; Spertus, John A

    2015-01-01

    Aims We assessed gender differences in pre-event health status (symptoms, functioning, quality of life) in young patients with acute myocardial infarction (AMI), and whether or not this association persists following sequential adjustment for important covariates. We also evaluated the interaction between gender and prior coronary artery disease (CAD), given that aggressive symptom control is a cornerstone of care in those with known coronary disease. Methods and Results A total of 3,501 AMI patients (2,349 women) aged 18–55 years were enrolled from 103 United States/24 Spanish hospitals (2008–2012). Clinical/health status information was obtained by medical record abstraction and patient interviews. Pre-event health status was measured by generic [Short Form-12 (SF-12), EuroQoL [EQ-5D)] and disease-specific [Seattle angina questionnaire (SAQ)] measures. T-test/chi-square and multivariable linear/logistic regression analysis was utilized, sequentially adjusting for covariates. Women had more co-morbidities and significantly lower generic mean health scores than men [SF-12 physical health =43±12 vs. 46±11 and mental health= 44±13 vs. 48±11]; EQ-5D utility index=0.7±0.2 vs. 0.8±0.2, and visual analog scale=63±22 vs. 67±20, P<0.0001 for all. Their disease-specific health status was also worse, with more angina [SAQ angina frequency=83±22 vs. 87±18], worse physical function [physical limitation=78±27 vs. 87±21] and poorer quality of life [55±25 vs. 60±22, P<0.0001 for all]. In multivariable analysis, the association between female gender and worse generic physical/mental health persisted, as well as worse disease-specific physical limitation and quality of life. The interaction between gender and prior CAD was not significant in any of the health status outcomes. Conclusion Young women have worse pre-event health status as compared with men, regardless of their CAD history. While future studies of gender differences should adjust for baseline health

  12. A new end-point for ELISA titrations.

    PubMed

    Vidal, José

    2004-01-01

    This report describes a new ELISA procedure based on end-point titrations. This end-point ELISA takes advantage of the change of color intensity that occurs when peroxidase-containing wells of an ELISA plate are revealed with diaminobenzidine-nickel and further intensification with silver: as antibody concentration and, therefore, peroxidase concentration, decreased, the color became stronger in some wells and, afterwards (i.e., at lower antibody and peroxidase concentrations), the color faded toward clear background. It is proposed that the reciprocal of the sample dilution at which the color intensifies can be used as a measure of the sample antibody content. This report verifies the validity and precision of that procedure.

  13. World Health Organization Grade II Oligodendroglioma Occurring after Successful Treatment for Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Yoon, Sang-In; Park, Dong-Hyuk; Kang, Shin-Hyuk; Park, Jung-Yul; Chung, Yong-Gu

    2016-01-01

    When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms are a significant long term problem. Radiation is generally accepted to be a major cause of the development of secondary neoplasms. Following treatment for ALL, a variety of secondary tumors, including brain tumors, hematologic malignancies, sarcomas, thyroid cancers, and skin cancers have been reported. However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we present a case of secondary oligodendroglioma occurring 13 years after the end of ALL treatment. PMID:27867928

  14. Research priorities in biomarkers and surrogate end-points.

    PubMed

    Aronson, Jeffrey K

    2012-06-01

    Ideal tests of the effects of therapeutic interventions measure the desired outcomes; however, the desired outcomes are not always easily measured or may be long-term objectives. Biomarkers and surrogate end-points are often cheaper and easier to measure and can be measured over a shorter time span. They can be used in screening, diagnosing, staging, and monitoring diseases, in monitoring responses to interventions, and in various aspects of drug discovery and development. They can be extrinsic to the body or intrinsic, and can relate to any point in the pharmacological chain, at the molecular, cellular, tissue, or organ level. Problems arise when the relation between the pathophysiology of the disease and the mechanism of action of the intervention is not properly understood; when adverse effects obviate therapeutic effects; when confounding factors, such as other drugs, alter the surrogate independently of the final end-point; when a biomarker persists after resolution of the disease; and when the concentration-effect curves for the effects of an intervention on the primary outcome and the surrogate are different. Use of biomarkers may also be hindered by poor reproducibility of measurement techniques. Challenges for clinical pharmacologists are to devise biomarker tests that are reliable, reproducible, sensitive, and specific, and surrogate end-points that are associated with the clinical outcomes of concern and useful. A robust taxonomy is needed of the relations that link the pathophysiology of disease, the mechanisms of action of interventions and their adverse effects, the desired clinical outcomes, and the surrogate end-points that predict them.

  15. Modeling Robot Dynamic Performance for Endpoint Force Control

    DTIC Science & Technology

    1988-08-01

    we consider is robot endpoint force control, also known as manipulator compliant motion control. Force control research has been quite popular...manipulator through a programmed trajectory consisting of a sequence of joint positions and velocities. Position and velocity sensors located at the robot ...may be located. 1.1 Force Control Research Background Research in robot compliant motion control has been in these areas: " Passive compliance schemes

  16. Challenges assessing clinical endpoints in early Huntington disease

    PubMed Central

    Paulsen, Jane S.; Wang, Chiachi; Duff, Kevin; Barker, Roger; Nance, Martha; Beglinger, Leigh; Moser, David; Williams, Janet K.; Simpson, Sheila; Langbehn, Douglas; van Kammen, Daniel P.

    2010-01-01

    The primary aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest-studied HD participants likely to be recruited into clinical trials. Since the advent of genetic testing for HD, it is possible to identify gene carriers prior to the diagnosis of disease, which opens up the possibility of clinical trials of disease-modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multi-national, 32-site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene-positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real-life function. PMID:20623772

  17. Exposing the cancer genome atlas as a SPARQL endpoint

    PubMed Central

    Deus, Helena F.; Veiga, Diogo F.; Freire, Pablo R.; Weinstein, John N.; Mills, Gordon B.; Almeida, Jonas S.

    2011-01-01

    The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. PMID:20851208

  18. Special endpoint and product specific considerations in pharmaceutical acceptable daily exposure derivation.

    PubMed

    Gould, Janet; Callis, Courtney M; Dolan, David G; Stanard, Brad; Weideman, Patricia A

    2016-08-01

    Recently, a guideline has been published by the European Medicines Agency (EMA) on setting safe limits, permitted daily exposures (PDE) [also called acceptable daily exposures (ADE)], for medicines manufactured in multi-product facilities. The ADE provides a safe exposure limit for inadvertent exposure of a drug due to cross-contamination in manufacturing. The ADE determination encompasses a standard risk assessment, requiring an understanding of the toxicological and pharmacological effects, the mechanism of action, drug compound class, and the dose-response as well as the pharmacokinetic properties of the compound. While the ADE concept has broad application in pharmaceutical safety there are also nuances and specific challenges associated with some toxicological endpoints or drug product categories. In this manuscript we discuss considerations for setting ADEs when the following specific adverse health endpoints may constitute the critical effect: genotoxicity, developmental and reproductive toxicity (DART), and immune system modulation (immunostimulation or immunosuppression), and for specific drug classes, including antibody drug conjugates (ADCs), emerging medicinal therapeutic compounds, and compounds with limited datasets. These are challenging toxicological scenarios that require a careful evaluation of all of the available information in order to establish a health-based safe level.

  19. Impact of integrated health system changes, accelerated due to an earthquake, on emergency department attendances and acute admissions: a Bayesian change-point analysis

    PubMed Central

    Schluter, Philip J; Hamilton, Greg J; Deely, Joanne M; Ardagh, Michael W

    2016-01-01

    Objective To chart emergency department (ED) attendance and acute admission following a devastating earthquake in 2011 which lead to Canterbury's rapidly accelerated integrated health system transformations. Design Interrupted time series analysis, modelling using Bayesian change-point methods, of ED attendance and acute admission rates over the 2008–2014 period. Setting ED department within the Canterbury District Health Board; with comparison to two other district health boards unaffected by the earthquake within New Zealand. Participants Canterbury's health system services ∼500 000 people, with around 85 000 ED attendances and 37 000 acute admissions per annum. Main outcome measures De-seasoned standardised population ED attendance and acute admission rates overall, and stratified by age and sex, compared before and after the earthquake. Results Analyses revealed five global patterns: (1) postearthquake, there was a sudden and persisting decrease in the proportion of the population attending the ED; (2) the growth rate of ED attendances per head of population did not change between the pre-earthquake and postearthquake periods; (3) postearthquake, there was a sudden and persisting decrease in the proportion of the population admitted to hospital; (4) the growth rate of hospital admissions per head of the population declined between pre-earthquake and postearthquake periods and (5) the most dramatic reduction in hospital admissions growth after the earthquake occurred among those aged 65+ years. Extrapolating from the projected and fitted deseasoned rates for December 2014, ∼676 (16.8%) of 4035 projected hospital admissions were avoided. Conclusions While both necessarily and opportunistically accelerated, Canterbury's integrated health systems transformations have resulted in a dramatic and sustained reduction in ED attendances and acute hospital admissions. This natural intervention experiment, triggered by an earthquake, demonstrated that

  20. Evaluation of a multi-endpoint assay in rats, combining the bone-marrow micronucleus test, the Comet assay and the flow-cytometric peripheral blood micronucleus test.

    PubMed

    Bowen, Damian E; Whitwell, James H; Lillford, Lucinda; Henderson, Debbie; Kidd, Darren; Mc Garry, Sarah; Pearce, Gareth; Beevers, Carol; Kirkland, David J

    2011-05-18

    With the publication of revised draft ICH guidelines (Draft ICH S2), there is scope and potential to establish a combined multi-end point in vivo assay to alleviate the need for multiple in vivo assays, thereby reducing time, cost and use of animals. Presented here are the results of an evaluation trial in which the bone-marrow and peripheral blood (via MicroFlow(®) flow cytometry) micronucleus tests (looking at potential chromosome breakage and whole chromosome loss) in developing erythrocytes or young reticulocytes were combined with the Comet assay (measuring DNA strand-breakage), in stomach, liver and blood lymphocytes. This allowed a variety of potential target tissues (site of contact, site of metabolism and peripheral distribution) to be assessed for DNA damage. This combination approach was performed with minimal changes to the standard and regulatory recommended sampling times for the stand-alone assays. A series of eight in vivo genotoxins (2-acetylaminofluorene, benzo[a]pyrene, carbendazim, cyclophosphamide, dimethylnitrosamine, ethyl methanesulfonate, ethyl nitrosourea and mitomycin C), which are known to act via different modes of action (direct- and indirect-acting clastogens, alkylating agents, gene mutagens, cross-linking and aneugenic compounds) were tested. Male rats were dosed at 0, 24 and 45 h, and bone marrow and peripheral blood (micronucleus endpoint), liver, whole blood and stomach (Comet endpoint) were sampled at three hours after the last dose. Comet and micronucleus responses were as expected based on available data for conventional (acute) stand-alone assays. All compounds were detected as genotoxic in at least one of the endpoints. The importance of evaluating both endpoints was highlighted by the uniquely positive responses for certain chemicals (benzo[a]pyrene and 2-acetylaminofluorene) with the Comet endpoint and certain other chemicals (carbendazim and mitomycin C) with the micronucleus endpoint. The data generated from these

  1. The risky reliance on small surrogate endpoint studies when planning a large prevention trial.

    PubMed

    Baker, Stuart G; Kramer, Barnett S

    2013-02-01

    The definitive evaluation of treatment to prevent a chronic disease with low incidence in middle age, such as cancer or cardiovascular disease, requires a trial with a large sample size of perhaps 20,000 or more. To help decide whether to implement a large true endpoint trial, investigators first typically estimate the effect of treatment on a surrogate endpoint in a trial with a greatly reduced sample size of perhaps 200 subjects. If investigators reject the null hypothesis of no treatment effect in the surrogate endpoint trial they implicitly assume they would likely correctly reject the null hypothesis of no treatment effect for the true endpoint. Surrogate endpoint trials are generally designed with adequate power to detect an effect of treatment on surrogate endpoint. However, we show that a small surrogate endpoint trial is more likely than a large surrogate endpoint trial to give a misleading conclusion about the beneficial effect of treatment on true endpoint, which can lead to a faulty (and costly) decision about implementing a large true endpoint prevention trial. If a small surrogate endpoint trial rejects the null hypothesis of no treatment effect, an intermediate-sized surrogate endpoint trial could be a useful next step in the decision-making process for launching a large true endpoint prevention trial.

  2. Symptoms, functioning and quality of life after treatment in a residential sub-acute mental health service in Australia.

    PubMed

    Thomas, Kerry A; Rickwood, Debra J; Brown, Patricia M

    2017-01-01

    The aim of this study was to assess clients' and service providers' perspectives on changes in mental health after an admission to a residential recovery-focused, sub-acute service, in Australia. Clients were either step-up clients, entering the service directly from the community, or step-down clients who were transitioning from an inpatient unit to home. During the 30-month period of data collection (August 2011 to January 2014) all clients (N = 102) were invited to participate in the longitudinal study and 41 clients consented to be involved (38% response rate). At admission and exit, participants completed the Behaviour and Symptom Identification Scale (Basis-32) and service providers completed the Life Skills Profile-16 and Health of the Nations Outcome Scales. Follow-up data 3 months after exit were available for 12 clients, including the Basis-32 and a self-report measure of quality of life (Assessment of Quality of Life 8-dimension). Both client groups reported positive improvements between admission and exit in the areas of relation to self and others, psychosis, daily living and presence of depression or anxiety symptoms. Service providers reported gains for clients in the areas of self-care, level of symptoms and presence of social problems. At 3 months, clients generally reported positive quality of life, although there was no significant change in symptoms and functioning. This study demonstrates that after an admission to a sub-acute service, step-up clients experience an improvement in their symptoms and functioning, have avoided a hospital admission and are well enough to return home. Step-down clients also experience further improvements in their symptoms and functioning, indicating that the service has assisted them in their transition to independent living after a hospital admission. Sub-acute residential units provide a continuation of care for inpatients preparing to return home, and people with a mental health problem living in the

  3. Loss of quality adjusted days as a trial endpoint: effect of early thrombolytic treatment in suspected myocardial infarction. Grampion Region Early Anistreplase Trial (GREAT).

    PubMed Central

    Rawles, J; Light, J

    1993-01-01

    STUDY OBJECTIVES--(1) To measure the quality of life and the loss of quality adjusted days (QADS) after suspected acute myocardial infarction in patients who received thrombolytic treatment either at home or in hospital. (2) To compare the loss of QADS as a trial endpoint with the conventional endpoints of mortality and Q-wave infarction. DESIGN--Randomised double blind parallel group trial of anistreplase (30 U given intravenously) and placebo given either at home or in hospital. SETTING--Rural practices in Grampian admitting patients to teaching hospitals in Aberdeen. PATIENTS--A total of 311 patients with suspected acute myocardial infarction and no contraindications to thrombolytic treatment seen at home within four hours of the onset of symptoms. MEASUREMENTS AND MAIN RESULTS--Loss of quality adjusted days (QADS) in the first 100 days after suspected myocardial infarction (365 QADS = 1 QALY) was the main outcome measure. Compared with later administration in hospital, anistreplase at home resulted in a relative reduction of mortality of 49% (95% confidence interval 3.95%, 2p = 0.04), and a relative reduction of 26% in the proportion of survivors with infarction who had Q-waves (95% CI 7.44%, 2p = 0.007). During the 100 day follow up, the median loss of QADS was 25 for all patients. This loss was significantly greater in those who died than in survivors (65 v 18, 2p < 0.001), and in survivors with infarction than in survivors without infarction (26 v 13, 2p < 0.01). However, there was no significant difference in loss of QADS in those with infarction with or without Q-waves (29 v 21, NS), and the median loss of QADS was not significantly different in those who had thrombolytic treatment at home or in hospital (median difference 0, 95% CI -5, +4 QADS). CONCLUSIONS--Loss of QADS had two serious limitations as an outcome measure: it was less sensitive than mortality and it failed to reflect physiological benefit. Palliative treatment with no physiological effect

  4. The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress

    PubMed Central

    Antic, Nick A.; Heeley, Emma; Anderson, Craig S.; Luo, Yuanming; Wang, Jiguang; Neal, Bruce; Grunstein, Ron; Barbe, Ferran; Lorenzi-Filho, Geraldo; Huang, Shaoguang; Redline, Susan; Zhong, Nanshan; McEvoy, R. Doug

    2015-01-01

    The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. Clinical Trials Registration Number: NCT00738179. Australia New Zealand Clinical Trials Registry Number: ACTRN12608000409370. Citation: Antic NA, Heeley E, Anderson CS, Luo Y, Wang J, Neal B, Grunstein R, Barbe F, Lorenzi-Filho G, Huang S, Redline S, Zhong N, McEvoy RD. The sleep apnea cardiovascular endpoints (SAVE) trial: rationale, ethics, design, and progress. SLEEP 2015;38(8):1247–1257. PMID:25669180

  5. Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

    DOEpatents

    Archer, Charles J; Blocksome, Michael E; Ratterman, Joseph D; Smith, Brian E

    2014-02-11

    Endpoint-based parallel data processing in a parallel active messaging interface ('PAMI') of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective opeartion through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

  6. Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

    2014-08-12

    Endpoint-based parallel data processing in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective operation through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

  7. Clinical research and methodology: What usage and what hierarchical order for secondary endpoints?

    PubMed

    Laporte, Silvy; Diviné, Marine; Girault, Danièle

    2016-02-01

    In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of concluding that there is a benefit for one of these endpoints when such benefit does not exist (inflation of type I error risk). There are mainly two methods used to control the risk of drawing erroneous conclusions for secondary endpoints. The first method consists of distributing the risk over several co-primary endpoints, so as to maintain an overall risk of 5%. The second is the hierarchical test procedure, which consists of first establishing a hierarchy of the endpoints, then evaluating each endpoint in succession according to this hierarchy while the endpoints continue to show statistical significance. This simple method makes it possible to show the additional advantages of treatments and to identify the factors that differentiate them.

  8. Perspectives for integration into the local health system of community-based management of acute malnutrition in children under 5 years: a qualitative study in Bangladesh

    PubMed Central

    2014-01-01

    Background Acute malnutrition is a major cause of death among under-five children in low- and middle-income countries. United Nations agencies recommend the integration of community-based management of acute malnutrition (CMAM) into the local health systems for sustainability. The objective of the study was to assess the preparedness of the health system to implement CMAM targeting children under-five years in two sub-districts of Bangladesh. Methods The assessment was performed through direct observation of 44 health centres, individual interviews of seven policy makers, three donors, four health and nutrition implementing partners, 29 health workers, and review of secondary data. Assessment themes, derived from the WHO six Building Blocks, were nutrition governance, nutrition financing, health service delivery, human resources, equipment and supply, referral, monitoring and supervision mechanism. They were subdivided into 16 criteria. Findings were compared with CMAM operational recommendations according to WHO, Valid International and Food and Nutrition Technical Assistance guidelines. Results The government of Bangladesh has developed inpatient and outpatient CMAM guidelines, and a policy offering free-of-charge health care for under-five children. Nutrition coordination was not under full government leadership. Most of funds (74%) dedicated to CMAM were provided by donors, for short-term interventions. Of the total 44 health centres assessed, 39 (88.6%) were active, among which 4 (10.2%) delivered inpatient services, 35 (89.8%) outpatient services, and 24 (61.5%) outreach services. These were regarded as opportunities to include CMAM activities. There were 48.9% vacant positions and the health workers were not trained for management of acute malnutrition. Equipment and supplies did not meet the operational recommendations for management of acute malnutrition. Conclusion Implementing CMAM through the health centres of both sub-districts would warrant

  9. Who experiences seclusion? An examination of demographics and duration in a public acute inpatient mental health service.

    PubMed

    Chavulak, Jacinta; Petrakis, Melissa

    2017-03-21

    Restrictive interventions such as seclusion may occur during an acute mental health crisis. Such interventions are experienced by people as traumatic and counter to recovery. The current study aimed to investigate the use of seclusion and who was secluded amongst patients presenting with psychotic symptomology. All acute inpatient admissions were examined across a 12-month period January-December 2013. Electronic and paper records were accessed and audited for all 655 admissions. There were 91 admissions that included a seclusion and 200 seclusion events. There were 79 unique patients who experienced seclusion. For those experiencing seclusion: two-thirds were male, 49% were either homeless or had no fixed abode, 32% received case management in the community prior to their inpatient stay, and 56% were unemployed or not in the workforce. The median and mode duration of seclusion was 4 h. By understanding seclusion interventions better, changes can be made to enhance practice. This descriptive research into seclusion has clarified the demographics of who is most likely to experience seclusion, for how long, and the implications for reducing restrictive interventions. How the social work role could contribute to reforms to protect and enhance the rights and well-being of marginalized members of our communities, at their most vulnerable, is considered.

  10. Resistance to changing practice from pro re nata prescriptions to patient group directions in acute mental health settings.

    PubMed

    Price, O; Baker, J A

    2013-09-01

    Poor practice associated with pro re nata (PRN) prescriptions in mental health is known to be common and can increase the risk of serious and potentially fatal side effects. A contributing factor to poor practice is the lack of a clear chain of accountability between the decision to prescribe and administer PRN prescriptions. To address this problem, a patient group direction (PGD) for acute behavioural disturbance (lorazepam 0.5-2 mg) and staff training materials were developed. The intention was to replace PRN prescriptions with the PGD in two mental health trusts. One of the potential benefits of this would be the removal of the contribution of PRN to high and combined dose antipsychotic prescriptions. This proposal, however, was met with significant resistance in both trusts and did not replace PRN as a result. A series of interviews and focus groups were conducted with 16 RMNs working in the two trusts, to explore the reasons why the PGD was met with resistance. Senior nurses perceived resistance to be associated with anxieties over increased responsibility for decision making. Junior nurses reported concerns regarding the medicalization of the nursing role, the paperwork associated with the PGD and the training approach used. Future efforts to implement PGDs in mental health settings must carefully consider the methods for engaging effectively with participating organizations, in terms of managing change and completing the necessary groundwork for successful implementation.

  11. Delirium Detection and Impact of Comorbid Health Conditions in a Post-Acute Rehabilitation Hospital Setting

    PubMed Central

    Stelmokas, Julija; Gabel, Nicolette; Flaherty, Jennifer M.; Rayson, Katherine; Tran, Kathileen; Anderson, Jason R.; Bieliauskas, Linas A.

    2016-01-01

    Misdiagnosis and under-detection of delirium may occur in many medical settings. This is important to address as delirium clearly increases risk of morbidity and mortality in such settings. This study assessed whether Veterans who screened positive on a delirium severity measure (Memorial Delirium Assessment Scale; MDAS) differed from those with and without corresponding medical documentation of delirium in terms of cognitive functioning, psychiatric/medical history, and medication use. A medical record review of 266 inpatients at a VA post-acute rehabilitation unit found that 10.9% were identified as delirious according to the MDAS and/or medical records. Of the Veterans who screened positive on the MDAS (N = 19), 68.4% went undetected by medical screening. Undetected cases had a higher number of comorbid medical conditions as measured by the Age-Adjusted Charlson Index (AACI) scores (median = 9, SD = 3.15; U = 5.5, p = .003) than medically documented cases. For Veterans with a score of 7 or greater on the AACI, the general relative risk for delirium was 4.46. Delirium is frequently under-detected in a post-acute rehabilitation unit, particularly for Veterans with high comorbid illness. The relative risk of delirium is up to 4.46 for those with high medical burden, suggesting the need for more comprehensive delirium screening in these patients. PMID:27902744

  12. Leveraging Big Data and Electronic Health Records to Enhance Novel Approaches to Acute Kidney Injury Research and Care.

    PubMed

    Sutherland, Scott M; Goldstein, Stuart L; Bagshaw, Sean M

    2017-03-08

    While acute kidney injury (AKI) has been poorly defined historically, a decade of effort has culminated in a standardized, consensus definition. In parallel, electronic health records (EHRs) have been adopted with greater regularity, clinical informatics approaches have been refined, and the field of EHR-enabled care improvement and research has burgeoned. Although both fields have matured in isolation, uniting the 2 has the capacity to redefine AKI-related care and research. This article describes how the application of a consistent AKI definition to the EHR dataset can accurately and rapidly diagnose and identify AKI events. Furthermore, this electronic, automated diagnostic strategy creates the opportunity to develop predictive approaches, optimize AKI alerts, and trace AKI events across institutions, care platforms, and administrative datasets.

  13. The Impact of Acute Urinary Retention After Iodine-125 Prostate Brachytherapy on Health-Related Quality of Life

    SciTech Connect

    Roeloffzen, Ellen M.A.; Hinnen, Karel A.; Battermann, Jan J.; Monninkhof, Evelyn M.; Roermund, Joep G.H. van; Gellekom, Marion van; Frank, Steven J.; Vulpen, Marco van

    2010-08-01

    Purpose: To evaluate the impact of acute urinary retention (AUR) in patients treated with {sup 125}I prostate brachytherapy on short- and long-term health-related quality of life (HRQOL); and to assess whether pretreatment HRQOL has additional value in the prediction of AUR. Methods and Materials: For 127 patients treated with {sup 125}I brachytherapy for localized prostate cancer between December 2000 and June 2003, toxicity and HRQOL data were prospectively collected. Patients received a HRQOL questionnaire at five time points: before and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30), the tumor-specific EORTC prostate cancer module (EORTC QLQ-PR25), and the American Urological Association (AUA) symptom index. Results: Of 127 patients, 13 (10.2%) developed AUR. Patients with AUR had a significantly worse urinary QOL at all time points compared with patients without AUR. The mean difference over time (6 years) between both groups for the EORTC QLQ-PR25 urinary symptom score was 13.0 points (p < 0.001) and for the AUA urinary symptom score was 15.7 points (p = 0.001). Global QOL scores (EORTC QLQ-C30) over time for patients who developed AUR were significantly worse compared with patients without AUR (mean difference 6.7 points; p = 0.043). In multivariate logistic regression analysis, pretreatment International Prostate Symptom Score (p = 0.004) and neoadjuvant hormonal treatment (p = 0.034) were predictors of AUR. Quality of life did not have added predictive value. Conclusion: Acute urinary retention after prostate brachytherapy has a significant negative impact on patient's HRQOL up to 6 years after treatment, in terms of both global QOL measures and urinary symptom scores. Furthermore, our results suggest limited value of pretreatment HRQOL measures for the prediction of AUR.

  14. New science-based endpoints to accelerate oncology drug development.

    PubMed

    Kelloff, Gary J; Sigman, Caroline C

    2005-03-01

    Although several new oncology drugs have reached the market, more than 80% of drugs for all indications entering clinical development do not get marketing approval, with many failing late in development often in Phase III trials, because of unexpected safety issues or difficulty determining efficacy, including confounded outcomes. These factors contribute to the high costs of oncology drug development and clearly show the need for faster, more cost-effective strategies for evaluating oncology drugs and better definition of patients who will benefit from treatment. Remarkable advances in the understanding of neoplastic progression at the cellular and molecular levels have spurred the discovery of molecularly targeted drugs. This progress along with advances in imaging and bioassay technologies are the basis for describing and evaluating new biomarker endpoints as well as for defining other biomarkers for identifying patient populations, potential toxicity, and providing evidence of drug effect and efficacy. Definitions and classifications of these biomarkers for use in oncology drug development are presented in this paper. Science-based and practical criteria for validating biomarkers have been developed including considerations of mechanistic plausibility, available methods and technology, and clinical feasibility. New promising tools for measuring biomarkers have also been developed and are based on genomics and proteomics, direct visualisation by microscopy (e.g., confocal microscopy and computer-assisted image analysis of cellular features), nanotechnologies, and direct and remote imaging (e.g., fluorescence endoscopy and anatomical, functional and molecular imaging techniques). The identification and evaluation of potential surrogate endpoints and other biomarkers require access to and analysis of large amounts of data, new technologies and extensive research resources. Further, there is a requirement for a convergence of research, regulatory and drug developer

  15. World Trade Center Health Program; Addition of New-Onset Chronic Obstructive Pulmonary Disease and WTC-Related Acute Traumatic Injury to the List of WTC-Related Health Conditions. Final rule.

    PubMed

    2016-07-05

    The World Trade Center (WTC) Health Program conducted a review of published, peer-reviewed epidemiologic studies regarding potential evidence of chronic obstructive pulmonary disease (COPD) and acute traumatic injury among individuals who were responders to or survivors of the September 11, 2001, terrorist attacks. The Administrator of the WTC Health Program (Administrator) found that these studies provide substantial evidence to support a causal association between each of these health conditions and 9/11 exposures. As a result, the Administrator is publishing a final rule to add both new-onset COPD and WTC-related acute traumatic injury to the List of WTC-Related Health Conditions eligible for treatment coverage in the WTC Health Program.

  16. Exploring a possible origin of the QCD critical endpoint

    SciTech Connect

    Bugaev, K. A. Petrov, V. K. Zinovjev, G. M.

    2013-03-15

    We develop a new model of the QCD critical endpoint by matching the deconfinement phase transition line of quark-gluon bags with the similar line at which the bag surface tension coefficient vanishes. Unlike all previous studies of such models the deconfined phase in our approach is defined not by an essential singularity of the isobaric partition function but its simple pole. As an unexpected result we find out that the first-order phase transition which is usually defined by a discontinuity of the first derivative of the bag system pressure results from a discontinuity of the derivative of surface tension coefficient of quark-gluon bags.

  17. Two-temperature LATE-PCR endpoint genotyping

    PubMed Central

    Sanchez, J Aquiles; Abramowitz, Jessica D; Salk, Jesse J; Reis, Arthur H; Rice, John E; Pierce, Kenneth E; Wangh, Lawrence J

    2006-01-01

    Background In conventional PCR, total amplicon yield becomes independent of starting template number as amplification reaches plateau and varies significantly among replicate reactions. This paper describes a strategy for reconfiguring PCR so that the signal intensity of a single fluorescent detection probe after PCR thermal cycling reflects genomic composition. The resulting method corrects for product yield variations among replicate amplification reactions, permits resolution of homozygous and heterozygous genotypes based on endpoint fluorescence signal intensities, and readily identifies imbalanced allele ratios equivalent to those arising from gene/chromosomal duplications. Furthermore, the use of only a single colored probe for genotyping enhances the multiplex detection capacity of the assay. Results Two-Temperature LATE-PCR endpoint genotyping combines Linear-After-The-Exponential (LATE)-PCR (an advanced form of asymmetric PCR that efficiently generates single-stranded DNA) and mismatch-tolerant probes capable of detecting allele-specific targets at high temperature and total single-stranded amplicons at a lower temperature in the same reaction. The method is demonstrated here for genotyping single-nucleotide alleles of the human HEXA gene responsible for Tay-Sachs disease and for genotyping SNP alleles near the human p53 tumor suppressor gene. In each case, the final probe signals were normalized against total single-stranded DNA generated in the same reaction. Normalization reduces the coefficient of variation among replicates from 17.22% to as little as 2.78% and permits endpoint genotyping with >99.7% accuracy. These assays are robust because they are consistent over a wide range of input DNA concentrations and give the same results regardless of how many cycles of linear amplification have elapsed. The method is also sufficiently powerful to distinguish between samples with a 1:1 ratio of two alleles from samples comprised of 2:1 and 1:2 ratios of the

  18. Adverse effect of agroecosystem pond water on biological endpoints of common toad (Rhinella arenarum) tadpoles.

    PubMed

    Babini, María Selene; Bionda, Clarisa de Lourdes; Salas, Nancy Edith; Martino, Adolfo Ludovico

    2016-08-01

    Chemical prroducts used in farming and wastes from livestock can contaminate pond water in agroecosystems due to runoff. Amphibians using these ponds for breeding are probably exposed to pollutants, and serious consequences might be observed afterward at the population level. Assessment biological endpoints of anuran to water quality give a realistic estimate of the probability of occurrence of adverse effects and provide an early warning signal. In this study, the ecotoxicity of agroecosystem ponds from the south of Córdoba province, Argentina, was investigated. Ponds in four sites with different degrees of human disturbance were selected: three agroecosystems (A1, A2, A3) and a site without crops or livestock (SM). The effect of pond water quality on the biological endpoint of Rhinella arenarum tadpoles was examined using microcosms with pond water from sites. Biological endpoints assessed were as follows: mortality, growth, development, morphological abnormalities (in body shape, gut, and labial tooth row formula), behavior, and blood cell parameters (micronucleus and nuclear abnormalities). Results indicated that water from agroecosystems has adverse effect on early life stage of R. arenarum. High mortality and fewer metamorphs were recorded in the A1 and A3 treatments. Tadpoles and metamorphs from A1 and A2 treatments had lower body condition. Tadpoles from A1 and A3 showed the highest prevalence of morphological abnormalities. The lowest amount of tadpoles feeding and the highest percentage of tadpoles swimming on the surface were observed in treatments with agroecosystem pond water. The higher frequencies of micronuclei and nuclear abnormalities were recorded in tadpoles from A1, A2, and A3 treatments. We check the sensitivity of the biological endpoints of R. arenarum tadpoles like early warning indicators of water quality. We found that the poor water quality of agroecosystem ponds has impact on the health of the tadpoles, and this could affect the

  19. Alternative Endpoints and Approaches for the Remediation of Contaminated Groundwater at Complex Sites - 13426

    SciTech Connect

    Deeb, Rula A.; Hawley, Elisabeth L.

    2013-07-01

    alternative endpoints for groundwater remediation at complex sites. A statistical analysis of Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) sites receiving TI waivers will be presented as well as case studies of other types of alternative endpoints and alternative remedial strategies that illustrate the variety of approaches used at complex sites and the technical analyses used to predict and document cost, time frame, and potential remedial effectiveness. This presentation is intended to inform DOE program managers, state regulators, practitioners and other stakeholders who are evaluating technical cleanup challenges within their own programs, and establishing programmatic approaches to evaluating and implementing long-term management approaches. Case studies provide examples of long-term management designations and strategies to manage and remediate groundwater at complex sites. At least 13 states consider some designation for groundwater containment in their corrective action policies, such as groundwater management zones, containment zones, and groundwater classification exemption areas. Long-term management designations are not a way to 'do nothing' or walk away from a site. Instead, soil and groundwater within the zone is managed to be protective of human health and the environment. Understanding when and how to adopt a long-term management approach can lead to cost savings and the more efficient use of resources across DOE and at numerous other industrial and military sites across the U.S. This presentation provides context for assessing the use and appropriate role of alternative endpoints and supporting long-term management designations in final remedies. (authors)

  20. The Identification of Seniors at Risk (ISAR) score to predict clinical outcomes and health service costs in older people discharged from UK acute medical units

    PubMed Central

    Edmans, Judi; Bradshaw, Lucy; Gladman, John R. F.; Franklin, Matthew; Berdunov, Vladislav; Elliott, Rachel; Conroy, Simon P.

    2013-01-01

    Background: tools are required to identify high-risk older people in acute emergency settings so that appropriate services can be directed towards them. Objective: to evaluate whether the Identification of Seniors At Risk (ISAR) predicts the clinical outcomes and health and social services costs of older people discharged from acute medical units. Design: an observational cohort study using receiver–operator curve analysis to compare baseline ISAR to an adverse clinical outcome at 90 days (where an adverse outcome was any of death, institutionalisation, hospital readmission, increased dependency in activities of daily living (decrease of 2 or more points on the Barthel ADL Index), reduced mental well-being (increase of 2 or more points on the 12-point General Health Questionnaire) or reduced quality of life (reduction in the EuroQol-5D) and high health and social services costs over 90 days estimated from routine electronic service records. Setting: two acute medical units in the East Midlands, UK. Participants: a total of 667 patients aged ≥70 discharged from acute medical units. Results: an adverse outcome at 90 days was observed in 76% of participants. The ISAR was poor at predicting adverse outcomes (AUC: 0.60, 95% CI: 0.54–0.65) and fair for health and social care costs (AUC: 0.70, 95% CI: 0.59–0.81). Conclusions: adverse outcomes are common in older people discharged from acute medical units in the UK; the poor predictive ability of the ISAR in older people discharged from acute medical units makes it unsuitable as a sole tool in clinical decision-making. PMID:23666405

  1. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model

    PubMed Central

    Gulani, Jatinder; King, Gregory; Hieber, Kevin; Chappell, Mark; Ossetrova, Natalia

    2016-01-01

    Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6–14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2–4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies. PMID:27579862

  2. Integrated versus fragmented implementation of complex innovations in acute health care

    PubMed Central

    Woiceshyn, Jaana; Blades, Kenneth; Pendharkar, Sachin R.

    2017-01-01

    Background: Increased demand and escalating costs necessitate innovation in health care. The challenge is to implement complex innovations—those that require coordinated use across the adopting organization to have the intended benefits. Purpose: We wanted to understand why and how two of five similar hospitals associated with the same health care authority made more progress with implementing a complex inpatient discharge innovation whereas the other three experienced more difficulties in doing so. Methodology: We conducted a qualitative comparative case study of the implementation process at five comparable urban hospitals adopting the same inpatient discharge innovation mandated by their health care authority. We analyzed documents and conducted 39 interviews of the health care authority and hospital executives and frontline managers across the five sites over a 1-year period while the implementation was ongoing. Findings: In two and a half years, two of the participating hospitals had made significant progress with implementing the innovation and had begun to realize benefits; they exemplified an integrated implementation mode. Three sites had made minimal progress, following a fragmented implementation mode. In the former mode, a semiautonomous health care organization developed a clear overall purpose and chose one umbrella initiative to implement it. The integrative initiative subsumed the rest and guided resource allocation and the practices of hospital executives, frontline managers, and staff who had bought into it. In contrast, in the fragmented implementation mode, the health care authority had several overlapping, competing innovations that overwhelmed the sites and impeded their implementation. Practice Implications: Implementing a complex innovation across hospital sites required (a) early prioritization of one initiative as integrative, (b) the commitment of additional (traded off or new) human resources, (c) deliberate upfront planning and

  3. Towards better environmental performance of wastewater sludge treatment using endpoint approach in LCA methodology.

    PubMed

    Alyaseri, Isam; Zhou, Jianpeng

    2017-03-01

    The aim of this study is to use the life cycle assessment method to measure the environmental performance of the sludge incineration process in a wastewater treatment plant and to propose an alternative that can reduce the environmental impact. To show the damages caused by the treatment processes, the study aimed to use an endpoint approach in evaluating impacts on human health, ecosystem quality, and resources due to the processes. A case study was taken at Bissell Point Wastewater Treatment Plant in Saint Louis, Missouri, U.S. The plant-specific data along with literature data from technical publications were used to build an inventory, and then analyzed the environmental burdens from sludge handling unit in the year 2011. The impact assessment method chosen was ReCipe 2008. The existing scenario (dewatering-multiple hearth incineration-ash to landfill) was evaluated and three alternative scenarios (fluid bed incineration and anaerobic digestion with and without land application) with energy recovery from heat or biogas were proposed and analyzed to find the one with the least environmental impact. The existing scenario shows that the most significant impacts are related to depletion in resources and damage to human health. These impacts mainly came from the operation phase (electricity and fuel consumption and emissions related to combustion). Alternatives showed better performance than the existing scenario. Using ReCipe endpoint methodology, and among the three alternatives tested, the anaerobic digestion had the best overall environmental performance. It is recommended to convert to fluid bed incineration if the concerns were more about human health or to anaerobic digestion if the concerns were more about depletion in resources. The endpoint approach may simplify the outcomes of this study as follows: if the plant is converted to fluid bed incineration, it could prevent an average of 43.2 DALYs in human life, save 0.059 species in the area from extinction

  4. Assessment of toxicity test endpoints for freshwater mussel larvae (glochidia).

    PubMed

    Fritts, Andrea K; Barnhart, M Christopher; Bradley, Megan; Liu, Na; Cope, W Gregory; Hammer, Edward; Bringolf, Robert B

    2014-01-01

    The objectives of the present study were to determine if the viability of freshwater mussel larvae (glochidia) is an ecologically relevant endpoint for toxicity tests and to define the appropriate duration of those tests. The authors assessed 1) how viability (the shell closure response to sodium chloride) compares with infectivity (ability to attach to a host fish and successfully metamorphose to the juvenile stage), and 2) the decline of viability and infectivity over time after glochidia were released from female mussels. Glochidia of 7 mussel species were isolated from females, placed in water, and subsampled daily for 2 d to 5 d. Viability, when ≥90%, was generally a good predictor of infectivity; however, when viability was <90%, infectivity was often disproportionately low, especially for glochidia collected near the end of the brooding period. Viability and infectivity declined more rapidly in natural water and sediment compared to reconstituted water. Following 24-h exposure to a toxicant (sodium chloride or copper), infectivity of the viable glochidia did not differ among concentrations of toxicants. The results indicate that viability is a valid proxy for infectivity and an ecologically relevant endpoint for standard toxicity tests with freshwater mussels for any test duration with control viability >90%.

  5. Design and analysis of crossover trials for absorbing binary endpoints.

    PubMed

    Nason, Martha; Follmann, Dean

    2010-09-01

    The crossover is a popular and efficient trial design used in the context of patient heterogeneity to assess the effect of treatments that act relatively quickly and whose benefit disappears with discontinuation. Each patient can serve as her own control as within-individual treatment and placebo responses are compared. Conventional wisdom is that these designs are not appropriate for absorbing binary endpoints, such as death or HIV infection. We explore the use of crossover designs in the context of these absorbing binary endpoints and show that they can be more efficient than the standard parallel group design when there is heterogeneity in individuals' risks. We also introduce a new two-period design where first period "survivors" are rerandomized for the second period. This design combines the crossover design with the parallel design and achieves some of the efficiency advantages of the crossover design while ensuring that the second period groups are comparable by randomization. We discuss the validity of the new designs and evaluate both a mixture model and a modified Mantel-Haenszel test for inference. The mixture model assumes no carryover or period effects while the Mantel-Haenszel approach conditions out period effects. Simulations are used to compare the different designs and an example is provided to explore practical issues in implementation.

  6. Immediate skin responses to laser and light treatments: Warning endpoints: How to avoid side effects.

    PubMed

    Wanner, Molly; Sakamoto, Fernanda H; Avram, Mathew M; Anderson, R Rox

    2016-05-01

    Lasers are versatile, commonly used treatment tools in dermatology. While it is tempting to follow manufacturer's guidelines or other "recipes" for laser treatment, this approach alone can be a recipe for disaster. Specific and immediate skin responses or endpoints exist and are clinically useful because they correlate with underlying mechanisms that are either desirable (ie, therapeutic), undesirable (ie, warning signs of injury or side effects), or incidental. The observation of clinical endpoints is a safe and reliable guide for appropriate treatment. This article presents the warning endpoints during specific dermatologic laser treatments, and the accompanying article presents the therapeutic endpoints, their underlying mechanisms, and the utility of these endpoints.

  7. Refocusing acute psychiatry, performance management, standards and accountability, a new context for mental health nursing.

    PubMed

    Harnett, P J; Bowles, N; Coughlan, A

    2009-06-01

    The term 'performance management' has an aversive 'managerial' aspect, is unappealing to many public sector staff and has an 'image problem'. Perhaps as a consequence, it has failed to make a significant impact on Irish public sector workers, notably mental health nurses. In this paper, performance management is introduced and examined within an Irish healthcare context and with reference to its use in other countries. Some of the challenges faced by Irish mental health nurses and the potential benefits of working within a performance managed workplace are discussed. The paper concludes that performance management is likely to increasingly affect nurses, either as active agents or as passive recipients of a change that is thrust on them. The authors anticipate that the performance management 'image problem' will give way to recognition that this is a fundamental change which has the potential to enable health services to change. This change will bring high standards of transparency, worker involvement in decision making, an explicit value base for health services and individual teams. It provides the potential for clear practice standards and high standards of transparency as well as worker welfare in all aspects, including supporting employment and career progression.

  8. Cooperative Working towards Family-Centred Health Education in Acute Care: Improvement in Client Satisfaction

    ERIC Educational Resources Information Center

    Bastani, Farideh; Golaghaie, Farzaneh; Farahani, Mansoureh A.; Rafeie, Mohammad

    2014-01-01

    Objective: To establish family-centred health education for patients in a neurosurgery unit and to evaluate its impact on patients' and families' satisfaction. Design: Cooperative participatory research through which a group of clinical nurses and an academic researcher engaged in cycles of action and reflection. Setting: The study was conducted…

  9. Treatment and Prevention of Acute Diarrhoea. Guidelines for the Trainers of Health Workers.

    ERIC Educational Resources Information Center

    World Health Organization, Geneva (Switzerland).

    This booklet, intended primarily for the trainers of middle-level community health workers in underdeveloped countries, is designed to help such workers present the topic of diarrhea treatment and prevention in training courses. Divided into five sections, the booklet gives guidelines on treatment and prevention, with particular emphasis on the…

  10. Overview of systematic reviews: yoga as a therapeutic intervention for adults with acute and chronic health conditions.

    PubMed

    McCall, Marcy C; Ward, Alison; Roberts, Nia W; Heneghan, Carl

    2013-01-01

    Objectives. Overview the quality, direction, and characteristics of yoga interventions for treatment of acute and chronic health conditions in adult populations. Methods. We searched for systematic reviews in 10 online databases, bibliographic references, and hand-searches in yoga-related journals. Included reviews satisfy Oxman criteria and specify yoga as a primary intervention in one or more randomized controlled trials for treatment in adults. The AMSTAR tool and GRADE approach evaluated the methodological quality of reviews and quality of evidence. Results. We identified 2202 titles, of which 41 full-text articles were assessed for eligibility and 26 systematic reviews satisfied inclusion criteria. Thirteen systematic reviews include quantitative data and six papers include meta-analysis. The quality of evidence is generally low. Sixteen different types of health conditions are included. Eleven reviews show tendency towards positive effects of yoga intervention, 15 reviews report unclear results, and no, reviews report adverse effects of yoga. Yoga appears most effective for reducing symptoms in anxiety, depression, and pain. Conclusion. Although the quality of systematic reviews is high, the quality of supporting evidence is low. Significant heterogeneity and variability in reporting interventions by type of yoga, settings, and population characteristics limit the generalizability of results.

  11. Efficacy of Acute Intermittent Hypoxia on Physical Function and Health Status in Humans with Spinal Cord Injury: A Brief Review

    PubMed Central

    Astorino, Todd A.; Harness, Eric T.; White, Ailish C.

    2015-01-01

    Spinal cord injury (SCI) results in a loss of motor and sensory function and is consequent with reductions in locomotion, leading to a relatively sedentary lifestyle which predisposes individuals to premature morbidity and mortality. Many exercise modalities have been employed to improve physical function and health status in SCI, yet they are typically expensive, require many trained clinicians to implement, and are thus relegated to specialized rehabilitation centers. These characteristics of traditional exercise-based rehabilitation in SCI make their application relatively impractical considering the time-intensive nature of these regimens and patients' poor access to exercise. A promising approach to improve physical function in persons with SCI is exposure to acute intermittent hypoxia (IH) in the form of a small amount of sessions of brief, repeated exposures to low oxygen gas mixtures interspersed with normoxic breathing. This review summarizes the clinical application of IH in humans with SCI, describes recommended dosing and potential side effects of IH, and reviews existing data concerning the efficacy of relatively brief exposures of IH to modify health and physical function. Potential mechanisms explaining the effects of IH are also discussed. Collectively, IH appears to be a safe, time-efficient, and robust approach to enhance physical function in chronic, incomplete SCI. PMID:26167303

  12. Health-Related Quality of Life, Depression, Anxiety, and Self-Image in Acute Lymphocytic Leukemia Survivors

    PubMed Central

    Baytan, Birol; Aşut, Çiğdem; Çırpan Kantarcıoğlu, Arzu; Sezgin Evim, Melike; Güneş, Adalet Meral

    2016-01-01

    Objective: With increasing survival rates in childhood acute lymphocytic leukemia (ALL), the long-term side effects of treatment have become important. Our aim was to investigate health-related quality of life, depression, anxiety, and self-image among ALL survivors. Materials and Methods: Fifty patients diagnosed with ALL and their siblings were enrolled. The Kovacs Children’s Depression Inventory, State-Trait Anxiety Inventory, Offer Self-Image Questionnaire, and Pediatric Quality of Life InventoryTM were used for collecting data. ANOVA tests were used to determine if there were any significant differences between groups. Results: ALL survivors had higher depression, more anxiety symptoms, lower quality of life, and more negative self-image when compared to their siblings. Conclusion: Continuous diagnostic and interventional mental health services might be necessary for possible emotional side effects of treatment during and after the treatment. Rehabilitation and follow-up programs should be implemented for children during and after treatment for ALL. PMID:27094799

  13. Nurses experiences of delivering care in acute inpatient mental health settings: A narrative synthesis of the literature.

    PubMed

    Wyder, Marianne; Ehrlich, Carolyn; Crompton, David; McArthur, Leianne; Delaforce, Caroline; Dziopa, Fiona; Ramon, Shulamit; Powell, Elizabeth

    2017-03-14

    Inpatient psychiatric care requires a balance between working with consumers' priorities and goals, managing expectations of the community, legal, professional and service responsibilities. In order to improve service delivery within acute mental health units, it is important to understand the constraints and facilitating factors for good care. We conducted a systematic narrative synthesis, where findings of qualitative studies are synthesised to generate new insights. 21 articles were identified. Our results show that personal qualities, professional skills as well as environmental factors all influence the ability to provide recovery focused care. Three overarching themes which either facilitated or hindered were identified. These included: (i) Complexity of the nursing role (clinical care; practical and emotional support: advocacy and education; enforcing aspects of the Mental Health Act. and, maintaining ward safety); (ii) Constraining factors (operational barriers; change in patient characteristic; and competing understandings of care); and (iii) Facilitating factors (ward factors; nursing tools; nurse characteristics; approach to people; approach to work and ability to self-care). We suggest that the therapeutic use of self is central to the provision of recovery oriented care. However person-centred practice can be fragile and fluid and a compassionate system of support is needed to enable an understanding of context and self. It is critical to have a work environment which fosters hope and optimism and is supportive of autonomy, ensures workload balance, and is safe.

  14. Overview of Systematic Reviews: Yoga as a Therapeutic Intervention for Adults with Acute and Chronic Health Conditions

    PubMed Central

    McCall, Marcy C.; Ward, Alison; Roberts, Nia W.; Heneghan, Carl

    2013-01-01

    Objectives. Overview the quality, direction, and characteristics of yoga interventions for treatment of acute and chronic health conditions in adult populations. Methods. We searched for systematic reviews in 10 online databases, bibliographic references, and hand-searches in yoga-related journals. Included reviews satisfy Oxman criteria and specify yoga as a primary intervention in one or more randomized controlled trials for treatment in adults. The AMSTAR tool and GRADE approach evaluated the methodological quality of reviews and quality of evidence. Results. We identified 2202 titles, of which 41 full-text articles were assessed for eligibility and 26 systematic reviews satisfied inclusion criteria. Thirteen systematic reviews include quantitative data and six papers include meta-analysis. The quality of evidence is generally low. Sixteen different types of health conditions are included. Eleven reviews show tendency towards positive effects of yoga intervention, 15 reviews report unclear results, and no, reviews report adverse effects of yoga. Yoga appears most effective for reducing symptoms in anxiety, depression, and pain. Conclusion. Although the quality of systematic reviews is high, the quality of supporting evidence is low. Significant heterogeneity and variability in reporting interventions by type of yoga, settings, and population characteristics limit the generalizability of results. PMID:23762174

  15. Azacitidine for Treating Acute Myeloid Leukaemia with More Than 30 % Bone Marrow Blasts: An Evidence Review Group Perspective of a National Institute for Health and Care Excellence Single Technology Appraisal.

    PubMed

    Tikhonova, Irina A; Hoyle, Martin W; Snowsill, Tristan M; Cooper, Chris; Varley-Campbell, Joanna L; Rudin, Claudius E; Mujica Mota, Ruben E

    2017-03-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The clinical effectiveness data used in the company's economic analysis were derived from a single randomised controlled trial, AZA-AML-001. It was an international, multicentre, controlled, phase III study with an open-label, parallel-group design conducted to determine the efficacy and safety of azacitidine against a conventional care regimen (CCR). The CCR was a composite comparator of acute myeloid leukaemia treatments currently available in the National Health Service: intensive chemotherapy followed by best supportive care (BSC) upon disease relapse or progression, non-intensive chemotherapy followed by BSC and BSC only. In AZA-AML-001, the primary endpoint was overall survival. Azacitidine appeared to be superior to the CCR, with median overall survival of 10.4 and 6.5 months, respectively. However, in the intention-to-treat analysis, the survival advantage associated with azacitidine was not statistically significant. The company submitted a de novo economic evaluation based on a partitioned survival model with four health states: "Remission", "Non-remission", "Relapse/Progressive disease" and "Death". The model time horizon was 10 years. The perspective was the National Health Service and Personal Social Services. Costs and health effects were discounted at the rate of 3.5 % per year. The base-case incremental cost-effectiveness ratio (ICER) of azacitidine

  16. Nutrient reference value: non-communicable disease endpoints--a conference report.

    PubMed

    Lupton, J R; Blumberg, J B; L'Abbe, M; LeDoux, M; Rice, H B; von Schacky, C; Yaktine, A; Griffiths, J C

    2016-03-01

    scientific evidence does exist to confirm a relationship between the intake of a specific bioactive constituent and enhanced health conditions or reduced risk of a chronic disease. Further, research on the putative mechanisms of action of various classes of bioactives is supported by national and pan-national government agencies, and academic institutions, as well as functional food and dietary supplement manufacturers. Consumers are becoming educated and are seeking to purchase products containing bioactives, yet there is no evaluative process in place to let the public know how strong the science is behind the benefits or the quantitative amounts needed to achieve these beneficial health effects or to avoid exceeding the upper level (UL). When one lacks an essential nutrient, overt deficiency with concomitant physiological determents and eventually death are expected. The absence of bioactive substances from the diet results in suboptimal health, e.g., poor cellular and/or physiological function, which is relative and not absolute. Regrettably at this time, there is no DRI process to evaluate bioactives, although a recent workshop convened by the National Institutes of Health (Options for Consideration of Chronic Disease Endpoints for Dietary Reference Intakes (DRIs); March 10-11, 2015; http://health.gov/dietaryguidelines/dri/ ) did explore the process to develop DVs for nutrients, the lack of which result in increased risk of chronic disease (non-communicable disease) endpoints. A final report is expected soon. This conference (CRN-International Scientific Symposium; "Nutrient Reference Value-Non-Communicable Disease (NRV-NCD) Endpoints," 20 November in Kronberg, Germany; http://www.crn-i.ch/2015symposium/ ) explores concepts related to the Codex NRV process, the public health opportunities in setting NRVs for bioactive constituents, and further research and details on the specific class of bioactives, n-3 long-chain polyunsaturated fatty acids (also termed omega-3 fatty

  17. Computation of eigenfunctions and eigenvalues for the Sturm-Liouville problem with Dirichlet boundary conditions at the left endpoint and Neumann conditions at the right endpoint

    NASA Astrophysics Data System (ADS)

    Khapaev, M. M.; Khapaeva, T. M.

    2016-10-01

    A functional-based variational method is proposed for finding the eigenfunctions and eigenvalues in the Sturm-Liouville problem with Dirichlet boundary conditions at the left endpoint and Neumann conditions at the right endpoint. Computations are performed for three potentials: sin(( x-π)2/π), cos(4 x), and a high nonisosceles triangle.

  18. Health effects in those with acute radiation sickness from the Chernobyl accident.

    PubMed

    Mettler, Fred A; Gus'kova, Angelina K; Gusev, Igor

    2007-11-01

    The Chernobyl accident resulted in almost one-third of the reported cases of acute radiation sickness (ARS) reported worldwide. Cases occurred among the plant employees and first responders but not among the evacuated populations or general population. The diagnosis of ARS was initially considered for 237 persons based on symptoms of nausea, vomiting, and diarrhea. Ultimately, the diagnosis of ARS was confirmed in 134 persons. There were 28 short term deaths of which 95% occurred at whole body doses in excess of 6.5 Gy. Underlying bone marrow failure was the main contributor to all deaths during the first 2 mo. Allogenic bone marrow transplantation was performed on 13 patients and an additional six received human fetal liver cells. All of these patients died except one individual who later was discovered to have recovered his own marrow and rejected the transplant. Two or three patients were felt to have died as a result of transplant complications. Skin doses exceeded bone marrow doses by a factor of 10-30, and at least 19 of the deaths were felt to be primarily due to infection from large area beta burns. Internal contamination was of relatively minor importance in treatment. By the end of 2001, an additional 14 ARS survivors died from various causes. Long term treatment has included therapy for beta burn fibrosis and skin atrophy as well as for cataracts.

  19. Israeli Acute Paralysis Virus: Epidemiology, Pathogenesis and Implications for Honey Bee Health

    PubMed Central

    Chen, Yan Ping; Pettis, Jeffery S.; Corona, Miguel; Chen, Wei Ping; Li, Cong Jun; Spivak, Marla; Visscher, P. Kirk; DeGrandi-Hoffman, Gloria; Boncristiani, Humberto; Zhao, Yan; vanEngelsdorp, Dennis; Delaplane, Keith; Solter, Leellen; Drummond, Francis; Kramer, Matthew; Lipkin, W. Ian; Palacios, Gustavo; Hamilton, Michele C.; Smith, Barton; Huang, Shao Kang; Zheng, Huo Qing; Li, Ji Lian; Zhang, Xuan; Zhou, Ai Fen; Wu, Li You; Zhou, Ji Zhong; Lee, Myeong-L.; Teixeira, Erica W.; Li, Zhi Guo; Evans, Jay D.

    2014-01-01

    Israeli acute paralysis virus (IAPV) is a widespread RNA virus of honey bees that has been linked with colony losses. Here we describe the transmission, prevalence, and genetic traits of this virus, along with host transcriptional responses to infections. Further, we present RNAi-based strategies for limiting an important mechanism used by IAPV to subvert host defenses. Our study shows that IAPV is established as a persistent infection in honey bee populations, likely enabled by both horizontal and vertical transmission pathways. The phenotypic differences in pathology among different strains of IAPV found globally may be due to high levels of standing genetic variation. Microarray profiles of host responses to IAPV infection revealed that mitochondrial function is the most significantly affected biological process, suggesting that viral infection causes significant disturbance in energy-related host processes. The expression of genes involved in immune pathways in adult bees indicates that IAPV infection triggers active immune responses. The evidence that silencing an IAPV-encoded putative suppressor of RNAi reduces IAPV replication suggests a functional assignment for a particular genomic region of IAPV and closely related viruses from the Family Dicistroviridae, and indicates a novel therapeutic strategy for limiting multiple honey bee viruses simultaneously and reducing colony losses due to viral diseases. We believe that the knowledge and insights gained from this study will provide a new platform for continuing studies of the IAPV–host interactions and have positive implications for disease management that will lead to mitigation of escalating honey bee colony losses worldwide. PMID:25079600

  20. Israeli acute paralysis virus: epidemiology, pathogenesis and implications for honey bee health.

    PubMed

    Chen, Yan Ping; Pettis, Jeffery S; Corona, Miguel; Chen, Wei Ping; Li, Cong Jun; Spivak, Marla; Visscher, P Kirk; DeGrandi-Hoffman, Gloria; Boncristiani, Humberto; Zhao, Yan; vanEngelsdorp, Dennis; Delaplane, Keith; Solter, Leellen; Drummond, Francis; Kramer, Matthew; Lipkin, W Ian; Palacios, Gustavo; Hamilton, Michele C; Smith, Barton; Huang, Shao Kang; Zheng, Huo Qing; Li, Ji Lian; Zhang, Xuan; Zhou, Ai Fen; Wu, Li You; Zhou, Ji Zhong; Lee, Myeong-L; Teixeira, Erica W; Li, Zhi Guo; Evans, Jay D

    2014-07-01

    Israeli acute paralysis virus (IAPV) is a widespread RNA virus of honey bees that has been linked with colony losses. Here we describe the transmission, prevalence, and genetic traits of this virus, along with host transcriptional responses to infections. Further, we present RNAi-based strategies for limiting an important mechanism used by IAPV to subvert host defenses. Our study shows that IAPV is established as a persistent infection in honey bee populations, likely enabled by both horizontal and vertical transmission pathways. The phenotypic differences in pathology among different strains of IAPV found globally may be due to high levels of standing genetic variation. Microarray profiles of host responses to IAPV infection revealed that mitochondrial function is the most significantly affected biological process, suggesting that viral infection causes significant disturbance in energy-related host processes. The expression of genes involved in immune pathways in adult bees indicates that IAPV infection triggers active immune responses. The evidence that silencing an IAPV-encoded putative suppressor of RNAi reduces IAPV replication suggests a functional assignment for a particular genomic region of IAPV and closely related viruses from the Family Dicistroviridae, and indicates a novel therapeutic strategy for limiting multiple honey bee viruses simultaneously and reducing colony losses due to viral diseases. We believe that the knowledge and insights gained from this study will provide a new platform for continuing studies of the IAPV-host interactions and have positive implications for disease management that will lead to mitigation of escalating honey bee colony losses worldwide.

  1. Modeling acute health risks associated with accidental releases of toxic gases

    SciTech Connect

    Haskin, F.E.; Ding, C.; Summa, K.J.; Young, M.

    1996-09-01

    CHEM{_}MACCS has been developed from the radiological accident consequence code, MACCS, to perform probabilistic calculations of potential off-site consequences of the accidental atmospheric release of hazardous chemicals. The principal phenomena considered in CHEM{_}MACCS are atmospheric transport, mitigative actions based on dose projection, dose accumulation by a number of pathways, and early and latent health effects. CHEM{_}MACCS provides the following capabilities: (1) statistical weather sampling data (8,760 hourly data points per year), (2) population dose and health effect risk calculations based on site-specific population data, (3) health effects calculations including the consideration of potential site specific mitigative actions (evacuation and shielding), and (4) modeling of multiple release segments. Three different sample problems are contained in this report to show how to use CHEM{_}MACCS. Three test problems are run to compare CHEM{_}MACCS and D2PC. The doses versus the downwind centerline distances from the source for the given doses are in very close agreement.

  2. Trends in Utilization of Surrogate Endpoints in Contemporary Cardiovascular Clinical Trials.

    PubMed

    Patel, Ravi B; Vaduganathan, Muthiah; Samman-Tahhan, Ayman; Kalogeropoulos, Andreas P; Georgiopoulou, Vasiliki V; Fonarow, Gregg C; Gheorghiade, Mihai; Butler, Javed

    2016-06-01

    Surrogate endpoints facilitate trial efficiency but are variably linked to clinical outcomes, and limited data are available exploring their utilization in cardiovascular clinical trials over time. We abstracted data regarding primary clinical, intermediate, and surrogate endpoints from all phase II to IV cardiovascular clinical trials from 2001 to 2012 published in the 8 highest Web of Science impact factor journals. Two investigators independently classified the type of primary endpoint. Of the 1,224 trials evaluated, 677 (55.3%) primary endpoints were clinical, 165 (13.5%) intermediate, and 382 (31.2%) surrogate. The relative proportions of these endpoints remained constant over time (p = 0.98). Trials using surrogate endpoints were smaller (187 vs 1,028 patients) and enrolled patients more expeditiously (1.4 vs 0.9 patients per site per month) compared with trials using clinical endpoints (p <0.001 for both comparisons). Surrogate endpoint trials were independently more likely to meet their primary endpoint compared to trials with clinical endpoints (adjusted odds ratio 1.56, 95% CI 1.05 to 2.34; p = 0.03). Rates of positive results in clinical endpoint trials have decreased over time from 66.1% in 2001 to 2003 to 47.2% in 2010 to 2012 (p = 0.001), whereas these rates have remained stable over the same period for surrogate (72.0% to 69.3%, p = 0.27) and intermediate endpoints (74.4% to 71.4%, p = 0.98). In conclusion, approximately a third of contemporary cardiovascular trials use surrogate endpoints. These trials are completed more expeditiously and are more likely to meet their primary outcomes. The overall scientific contribution of these surrogate endpoint trials requires further attention given their variable association with definitive outcomes.

  3. Assessing chronic fish health: An application to a case of an acute exposure to chemically treated crude oil.

    PubMed

    Mauduit, F; Domenici, P; Farrell, A P; Lacroix, C; Le Floch, S; Lemaire, P; Nicolas-Kopec, A; Whittington, M; Zambonino-Infante, J L; Claireaux, G

    2016-09-01

    Human alteration of marine ecosystems is substantial and growing. Yet, no adequate methodology exists that provides reliable predictions of how environmental degradation will affect these ecosystems at a relevant level of biological organization. The primary objective of this study was to develop a methodology to evaluate a fish's capacity to face a well-established environmental challenge, an exposure to chemically dispersed oil, and characterize the long-term consequences. Therefore, we applied high-throughput, non-lethal challenge tests to assess hypoxia tolerance, temperature susceptibility and maximal swimming speed as proxies for a fish's functional integrity. These whole animal challenge tests were implemented before (1 month) and after (1 month) juvenile European sea bass (Dicentrarchus labrax) had been acutely exposed (48h) to a mixture containing 0.08gL(-1) of weathered Arabian light crude oil plus 4% dispersant (Corexit© EC9500A), a realistic exposure concentration during an oil spill. In addition, experimental populations were then transferred into semi-natural tidal mesocosm ponds and correlates of Darwinian fitness (growth and survival) were monitored over a period of 4 months. Our results revealed that fish acutely exposed to chemically dispersed oil remained impaired in terms of their hypoxia tolerance and swimming performance, but not in temperature susceptibility for 1 month post-exposure. Nevertheless, these functional impairments had no subsequent ecological consequences under mildly selective environmental conditions since growth and survival were not impacted during the mesocosm pond study. Furthermore, the earlier effects on fish performance were presumably temporary because re-testing the fish 10 months post-exposure revealed no significant residual effects on hypoxia tolerance, temperature susceptibility and maximal swimming speed. We propose that the functional proxies and correlates of Darwinian fitness used here provide a useful

  4. Role of the steroidogenic acute regulatory protein in health and disease

    PubMed Central

    Manna, Pulak R.; Stetson, Cloyce L.; Slominski, Andrzej T.; Pruitt, Kevin

    2015-01-01

    Steroid hormones are an important class of regulatory molecules that are synthesized in steroidogenic cells of the adrenal, ovary, testis, placenta, brain and skin, and influence a spectrum of developmental and physiological processes. The steroidogenic acute regulatory protein (STAR) predominantly mediates the rate-limiting step in steroid biosynthesis, i.e., the transport of the substrate of all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane. At the inner membrane, cytochrome P450 cholesterol side chain cleavage enzyme cleaves the cholesterol side-chain to form the first steroid, pregnenolone, which is converted by a series of enzymes to various steroid hormones in specific tissues. Both basic and clinical evidence have demonstrated the crucial involvement of the STAR protein in the regulation of steroid biosynthesis. Multiple levels of regulation impinge on STAR action. Recent findings demonstrate that hormone-sensitive lipase, through its action on the hydrolysis of cholesteryl esters, plays an important role in regulating StAR expression and steroidogenesis which involve the liver X receptor pathway. Activation of the latter influences macrophage cholesterol efflux that is a key process in the prevention of atherosclerotic cardiovascular disease. Appropriate regulation of steroid hormones is vital for proper functioning of many important biological activities, which are also paramount for geriatric populations to live longer and healthier. This review summarizes the current level of understanding on tissue-specific and hormone-induced regulation of STAR expression and steroidogenesis, and provides insights into a number of cholesterol and/or steroid coupled physiological and pathophysiological consequences. PMID:26271515

  5. Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy

    PubMed Central

    Faulhaber-Walter, Robert; Scholz, Sebastian; Haller, Herrmann; Kielstein, Jan T; Hafer, Carsten

    2016-01-01

    Background Critically ill patients with acute kidney injury (AKI) in need of renal replacement therapy (RRT) may have a protracted and often incomplete rehabilitation. Their long-term outcome has rarely been investigated. Study design Survivors of the HANnover Dialysis OUTcome (HANDOUT) study were evaluated after 5 years for survival, health status, renal function, and quality of life (QoL). The HANDOUT study had examinded mortality and renal recovery of patients with AKI receiving either standard extendend or intensified dialysis after multi organ failure. Results One hundred fifty-six former HANDOUT participants were analyzed. In-hospital mortality was 56.4%. Five-year survival after AKI/RRT was 40.1% (86.5% if discharged from hospital). Main causes of death were cardiovascular complications and sepsis. A total of 19 survivors presented to the outpatient department of our clinic and had good renal recovery (mean estimated glomerular filtration rate 72.5±30 mL/min/1.73 m2; mean proteinuria 89±84 mg/d). One person required maintenance dialysis. Seventy-nine percent of the patients had a pathological kidney sonomorphology. The Charlson comorbidity score was 2.2±1.4 and adjusted for age 3.3±2.1 years. Numbers of comorbid conditions averaged 2.38±1.72 per patient (heart failure [52%] > chronic kidney disease/myocardial infarction [each 29%]). Median 36-item short form health survey (SF-36™) index was 0.657 (0.69 physical health/0.66 mental health). Quality-adjusted life-years after 5 years were 3.365. Conclusion Mortality after severe AKI is higher than short-term prospective studies show, and morbidity is significant. Kidney recovery as well as general health remains incomplete. Reduction of QoL is minor, and social rehabilitation is very good. Affectivity is heterogeneous, but most patients experience emotional well-being. In summary, AKI in critically ill patients leads to incomplete rehabilitation but acceptable QoL after 5 years. PMID:27284261

  6. Mothers' health-seeking behaviour in acute diarrhoea in Tlaxcala, Mexico.

    PubMed

    Pérez-Cuevas, R; Guiscafré, H; Romero, G; Rodríguez, L; Gutiérrez, G

    1996-12-01

    This study, a cross-sectional survey, was conducted to assess how mothers take care of their children with diarrhoea and to develop a model of health-care seeking behaviour. Multistage sampling was used. Mothers whose children aged less than five years had suffered from diarrhoea in the last fortnight were included. Nurses interviewed the mothers to collect data. Variables included in the interview were: mothers' characteristics, children's characteristics, clinical data, treatment given by the mother, maternal health-seeking behaviour and mothers' information about diarrhoea and dehydration. Variables corresponding to the clinical data were grouped to identify dehydration signs and the need for medical care. Dehydration was defined as the presence of two or more of the following reported signs: thirst, sunken eyes, sunken fontanelle, or scanty urine. The need for medical care was defined as the presence of one or more of the following characteristics: illness lasting more than three days, vomiting, fever, bloody diarrhoea or dehydration. A sample of 747 mothers was obtained. Household treatments consisted of herbal teas to stop diarrhoea (52.3%), liquids to prevent dehydration (92.2%), symptomatic drugs (35.2%) and changes in feeding patterns (36.3%), which consisted in suppressing milk and dairy products and interrupting breast feeding (12.2%). Mothers sought medical assistance when they perceived a worsening of clinical conditions. Clinical signs statistically associated with their decision were: bloody diarrhoea, vomiting, illness longer than three days, weight loss, and fever. The signs of dehydration were not associated with health care-seeking because the mother did not recognise them. It is concluded that maternal educational programmes should emphasise, besides the proper use of oral rehydration therapy, teaching mothers to identify signs of dehydration as an indication to seek timely medical care.

  7. Acute health effects of the Tasman Spirit oil spill on residents of Karachi, Pakistan

    PubMed Central

    Janjua, Naveed Zafar; Kasi, Pashtoon Murtaza; Nawaz, Haq; Farooqui, Sadia Zohra; Khuwaja, Urooj Bakht; Najam-ul-Hassan; Jafri, Syed Nadim; Lutfi, Shahid Ali; Kadir, Muhammad Masood; Sathiakumar, Nalini

    2006-01-01

    Background On July 27 2003, a ship carrying crude oil run aground near Karachi and after two weeks released 37,000 tons of its cargo into the sea. Oil on the coastal areas and fumes in air raised health concerns among people. We assessed the immediate health impact of oil spill from the tanker Tasman Spirit on residents of the affected coastline in Karachi, Pakistan. Methods We conducted a study consisting of an exposed group including adults living in houses on the affected shoreline and two control groups (A and B) who lived at the distance of 2 km and 20 km away from the sea, respectively. We selected households through systematic sampling and interviewed an adult male and female in each household about symptoms relating to eyes, respiratory tract, skin and nervous system, smoking, allergies, beliefs about the effect on their health and anxiety about the health effects. We used logistic regression procedures to model each symptom as an outcome and the exposure status as an independent variable while adjusting for confounders. We also used linear regression procedure to assess the relationship exposure status with symptoms score; calculated by summation of all symptoms. Results Overall 400 subjects were interviewed (exposed, n = 216; group A, n = 83; and group B, n = 101). The exposed group reported a higher occurrence of one or more symptoms compared to either of the control groups (exposed, 96% vs. group A, 70%, group B 85%; P < 0.001). Mean summary symptom scores were higher among the exposed group (14.5) than control group A (4.5) and control group B (3.8, P < 0.001). Logistic regression models indicated that there were statistically significant, moderate-to-strong associations (Prevalence ORs (POR) ranging from 2.3 to 37.0) between the exposed group and the symptoms. There was a trend of decreasing symptom-specific PORs with increase in distance from the spill site. Multiple linear regression model revealed strong relationship of exposure status with the

  8. Emergency Care of Patients with Acute Ischemic Stroke in the Kaiser Permanente Southern California Integrated Health System

    PubMed Central

    Sauser-Zachrison, Kori; Shen, Ernest; Ajani, Zahra; Neil, William P; Sangha, Navdeep; Gould, Michael K; Sharp, Adam L

    2016-01-01

    Context: Tissue plasminogen activator (tPA) is underutilized for treatment of acute ischemic stroke. Objective: To determine whether the probability of tPA administration for patients with ischemic stroke in an integrated health care system improved from 2009 to 2013, and to identify predictors of tPA administration. Design: Retrospective analysis of all ischemic stroke presentations to 14 Emergency Departments between 2009 and 2013. A generalized linear mixed-effects model identified patient and hospital predictors of tPA. Main Outcome Measures: Primary outcome was tPA administration; secondary outcomes were door-to-imaging and door-to-needle times and tPA-related bleeding complications. Results: Of the 11,630 patients, 3.9% received tPA. The likelihood of tPA administration increased with presentation in 2012 and 2013 (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.26–2.43; and OR = 2.58; 95% CI = 1.90–3.51), female sex (OR = 1.27; 95% CI = 1.04–1.54), and ambulance arrival (OR = 2.17; 95% CI = 1.76–2.67), and decreased with prior stroke (OR = 0.47; 95% CI = 0.25–0.89) and increased age (OR = 0.98; 95% CI = 0.97–0.99). Likelihood varied by Medical Center (pseudo-intraclass correlation coefficient 13.5%). Among tPA-treated patients, median door-to-imaging time was 15 minutes (interquartile range, 9–23 minutes), and door-to-needle time was 73 minutes (interquartile range, 55–103 minutes). The rate of intracranial hemorrhage was 4.2% and 0.9% among tPA- and non-tPA treated patients (p < 0.001). Conclusion: Acute ischemic stroke care improved over time in this integrated health system. Better understanding of differences in hospital performance will have important quality-improvement and policy implications. PMID:27043833

  9. Short- and longer-term health-care resource utilization and costs associated with acute ischemic stroke

    PubMed Central

    Johnson, Barbara H; Bonafede, Machaon M; Watson, Crystal

    2016-01-01

    Objectives The mean lifetime cost of ischemic stroke is approximately $140,048 in the United States, placing stroke among the top 10 most costly conditions among Medicare beneficiaries. The objective of this study was to describe the health-care resource utilization and costs in the year following hospitalization for acute ischemic stroke (AIS). Methods This retrospective claims analysis quantifies utilization and costs following inpatient admission for AIS among the commercially insured and Medicare beneficiaries in the Truven Health databases. Patients who were 18 years or older and continuously enrolled for 12 months before and after an AIS event occurring (index) between January 2009 and December 2012 were identified. Patients with AIS in the year preindex were excluded. Demographic and clinical characteristics were evaluated at admission and in the preindex, respectively. Direct costs, readmissions, and inpatient length of stay (LOS) were described in the year postindex. Results The eligible populations comprised 20,314 commercially insured patients and 31,037 Medicare beneficiaries. Average all-cause costs were $61,354 and $44,929 (commercial and Medicare, respectively) in the first year after the AIS. Approximately 50%–55% of total 12-month costs were incurred between day 31 and day 365 following the incident AIS. One quarter (24.6%) of commercially insured patients and 38.8% of Medicare beneficiaries were readmitted within 30 days with 16.6% and 71.7% (commercial and Medicare, respectively) of those having a principal diagnosis of AIS. The average AIS-related readmission length of stay was nearly three times that of the initial hospitalization for both commercially insured patients (3.8 vs 10.8 days) and Medicare beneficiaries (4.0 vs 10.8 days). Conclusion In addition to the substantial costs of the initial hospitalization of an AIS, these costs double within the year following this event. Given the high cost associated with AIS, new interventions

  10. Semi-inclusive hadronic B decays in the endpoint region

    SciTech Connect

    Chay, Junegone; Kim, Chul; Leibovich, Adam K.; Zupan, Jure

    2006-10-01

    We consider in the soft-collinear effective theory semi-inclusive hadronic B decays, B{yields}XM, in which an energetic light meson M near the endpoint recoils against an inclusive jet X. We focus on a subset of decays where the spectator quark from the B meson ends up in the jet. The branching ratios and direct CP asymmetries are computed to next-to-leading order accuracy in {alpha}{sub s} and to leading order in 1/m{sub b}. The contribution of charming penguins is extensively discussed, and a method to extract it in semi-inclusive decays is suggested. Subleading 1/m{sub b} corrections and SU(3) breaking effects are discussed.

  11. DETERMINING SIGNIFICANT ENDPOINTS FOR ECOLOGICAL RISK ANALYS ES

    SciTech Connect

    Hinton, Thomas G.

    2000-12-31

    Our interest is in obtaining a scientifically defensible endpoint for measuring ecological risks to populations exposed to chronic, low-level radiation, and radiation with concomitant exposure to chemicals. To do so, we believe that we must understand the extent to which molecular damage is detrimental at the individual and population levels of biological organization. Ecological risk analyses based on molecular damage, without an understanding of the impacts to higher levels of biological organization, could cause cleanup strategies on DOE sites to be overly conservative and unnecessarily expensive. Our goal is to determine the relevancy of sublethal cellular damage to the performance of individuals and populations. We think that we can achieve this by using novel biological dosimeters in controlled, manipulative dose/effects experiments, and by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables (such as age-specific survivorship, reproductive output, age at maturity and longevity).

  12. Spatial Variable Selection Methods for Investigating Acute Health Effects of Fine Particulate Matter Components

    PubMed Central

    Vock, Laura F. Boehm; Reich, Brian J.; Fuentes, Montserrat; Dominici, Francesca

    2014-01-01

    Summary Multi-site time series studies have reported evidence of an association between short term exposure to particulate matter (PM) and adverse health effects, but the effect size varies across the United States. Variability in the effect may partially be due to differing community level exposure and health characteristics, but also due to the chemical composition of PM which is known to vary greatly by location and time. The objective of this article is to identify particularly harmful components of this chemical mixture. Because of the large number of highly-correlated components, we must incorporate some regularization into a statistical model. We assume that, at each spatial location, the regression coefficients come from a mixture model with the flavor of stochastic search variable selection, but utilize a copula to share information about variable inclusion and effect magnitude across locations. The model differs from current spatial variable selection techniques by accommodating both local and global variable selection. The model is used to study the association between fine PM (PM <2.5 μm) components, measured at 115 counties nationally over the period 2000–2008, and cardiovascular emergency room admissions among Medicare patients. PMID:25303336

  13. Health information technology adoption in U.S. acute care hospitals.

    PubMed

    Zhang, Ning Jackie; Seblega, Binyam; Wan, Thomas; Unruh, Lynn; Agiro, Abiy; Miao, Li

    2013-04-01

    Previous studies show that the healthcare industry lags behind many other economic sectors in the adoption of information technology. The purpose of this study is to understand differences in structural characteristics between providers that do and that do not adopt Health Information Technology (HIT) applications. Publicly available secondary data were used from three sources: American Hospital Association (AHA) annual survey, Healthcare Information and Management Systems Society (HIMSS) analytics annual survey, and Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) databases. Fifty-two information technologies were grouped into three clusters: clinical, administrative, and strategic decision making ITs. Negative binomial regression was applied with adoption of technology as the dependent variables and eight organizational and contextual factors as the independent variables. Hospitals adopt a relatively larger proportion of administrative information technology as compared to clinical and strategic IT. Large size, urban location and HMO penetration were found to be the most influential hospital characteristics that positively affect information technology adoption. There are still considerable variations in the adoption of information technology across hospitals and in the type of technology adopted. Organizational factors appear to be more influential than market factors when it comes to information technology adoption. The future research may examine whether the Electronic Health Record (EHR) Incentive Program in 2011 would increase the information technology uses in hospitals as it provides financial incentives for HER adoptions and uses among providers.

  14. Are Hemodynamics Surrogate Endpoints in Pulmonary Arterial Hypertension?

    PubMed Central

    Ventetuolo, Corey E.; Gabler, Nicole B.; Fritz, Jason S.; Smith, K. Akaya; Palevsky, Harold I.; Klinger, James R.; Halpern, Scott D.; Kawut, Steven M.

    2014-01-01

    Background While frequently assessed in trials and clinical practice, hemodynamic response to therapy has never been validated as a surrogate endpoint for clinical events in pulmonary arterial hypertension (PAH). Methods and Results We performed a patient-level pooled analysis of four randomized placebo-controlled trials to determine if treatment-induced changes in hemodynamic values at 12 weeks accounted for the relationship between treatment assignment and the probability of early clinical events (death, lung transplantation, atrial septostomy, PAH hospitalization, withdrawal for clinical worsening, escalation in PAH therapy). We included 1119 subjects with PAH. The median (interquartile range) age was 48 (37 – 59), and 23% were men. 656 (59%) received active therapy (101 [15%] iloprost, 118 [18%] sitaxsentan, 204 [31%] sildenafil, and 233 [36%] subcutaneous treprostinil). Active treatment significantly lowered right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance and increased cardiac output and index (p < 0.01 for all). Changes in hemodynamic values (except for RAP and mPAP) were significantly associated with the risk of a clinical event (p ≤ 0.01 for all). While active treatment approximately halved the odds of a clinical event compared to placebo (p < 0.001), changes in hemodynamics accounted for only 1.2 – 13.9% of the overall treatment effect. Conclusions Treatment-induced changes in hemodynamics at 12 weeks only partially explain the impact of therapy on the probability of early clinical events in PAH. These findings suggest that resting hemodynamics are not valid surrogate endpoints for short-term events in PAH clinical trials. PMID:24951771

  15. [Acute head injuries in primary health care--internet survey conducted with general practitioners].

    PubMed

    Luoto, Teemu M; Artsola, Minna; Helminen, Mika; Liimatainen, Suvi; Kosunen, Elise; Ohman, Juha

    2013-01-01

    Patients with head injury constitute a large population treated in primary health care. It is essential to recognize patients with traumatic brain injury among this notable population to determine the need for more specific evaluation. General practitioners (n=331) in Pirkanmaa hospital district in Finland received an email link to answer the survey. The response rate was 54.1% (n=179). Mean survey score was 20.5 points (max. 25). Only acquaintance with the national traumatic brain injury practice guidelines was associated with greater survey scores. The general practitioners' level of knowledge in managing head injuries was good. Deficiencies were found in the questions dealt with post-traumatic amnesia and the definition of traumatic brain injury.

  16. Interactive toxicity of major ion salts: Comparisons among species and between acute and chronic endpoints

    EPA Science Inventory

    Increased concentrations of major ions (Na, K, Ca, Mg, Cl, SO4, HCO3) in freshwater systems can result from a variety of anthropogenic activities, and can adversely affect aquatic organisms if the increase is sufficiently severe. Laboratory tests have indicated that the toxicity...

  17. Protective effect of Zhuyeqing liquor, a Chinese traditional health liquor, on acute alcohol-induced liver injury in mice

    PubMed Central

    2013-01-01

    The study first evaluated the hepatoprotective effect of Zhuyeqing Liquor (ZYQL) against acute alcohol-induced liver injury in mice. Animals were administered orally with 50% alcohol 12 ml/kg at 4 h after the doses of ZYQL everyday for fourteen consecutive days except mice in normal group. The protective effect was evaluated by biochemical parameters including serum aspartate transaminase (AST), alanine transferase (ALT), total-bilirubin (TBIL) and reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissue. The result were confirmed histopathologically and the expression of TNF-α in mice liver was determined by immunohistochemistry analysis. HPLC-PDA was used for phytochemical analysis of ZYQL, and the plant source of each compound was claritied by UPLC-TOF-MS. The result showed that pretreatment with ZYQL exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes in a dose depended manner. HPLC analysis indicated that ZYQL contained flavonoids, iridoids, terpenoids and phenolic acids, which might be the active chemicals. This study demonstrated the hepatoprotective activity of ZYQL, thus scientifically supported the function of its health care. PMID:24090365

  18. Predicting Patient Advocacy Engagement: A Multiple Regression Analysis Using Data From Health Professionals in Acute-Care Hospitals.

    PubMed

    Jansson, Bruce S; Nyamathi, Adeline; Heidemann, Gretchen; Duan, Lei; Kaplan, Charles

    2015-01-01

    Although literature documents the need for hospital social workers, nurses, and medical residents to engage in patient advocacy, little information exists about what predicts the extent they do so. This study aims to identify predictors of health professionals' patient advocacy engagement with respect to a broad range of patients' problems. A cross-sectional research design was employed with a sample of 94 social workers, 97 nurses, and 104 medical residents recruited from eight hospitals in Los Angeles. Bivariate correlations explored whether seven scales (Patient Advocacy Eagerness, Ethical Commitment, Skills, Tangible Support, Organizational Receptivity, Belief Other Professionals Engage, and Belief the Hospital Empowers Patients) were associated with patient advocacy engagement, measured by the validated Patient Advocacy Engagement Scale. Regression analysis examined whether these scales, when controlling for sociodemographic and setting variables, predicted patient advocacy engagement. While all seven predictor scales were significantly associated with patient advocacy engagement in correlational analyses, only Eagerness, Skills, and Belief the Hospital Empowers Patients predicted patient advocacy engagement in regression analyses. Additionally, younger professionals engaged in higher levels of patient advocacy than older professionals, and social workers engaged in greater patient advocacy than nurses. Limitations and the utility of these findings for acute-care hospitals are discussed.

  19. Mount St Helens eruptions, May 18 to June 12, 1980. An overview of the acute health impact.

    PubMed

    Baxter, P J; Ing, R; Falk, H; French, J; Stein, G F; Bernstein, R S; Merchant, J A; Allard, J

    1981-12-04

    Thirty-five known deaths were caused by the landslide and lateral blast of the May 18 eruption of Mount St Helens and at least 23 persons are missing. In 18 of 23 cases that reached autopsy, asphyxiation from ash inhalation was the cause of death. A rapidly established hospital surveillance system detected increases in the number of emergency room (ER) visits and admissions for asthma and bronchitis in communities with the heaviest ashfall after the May 18 eruption and the eruptions on May 25 and June 12. There were also increases in the number of ER visits for ash-related eye complaints in some areas. laboratory studies indicated that the May 18 ash was not acutely toxic, but the respirable portion contained 3% to 7% of crystalline free silica, a potential pneumoconiosis hazard to certain heavily exposed occupational groups. Continuing volcanic activity of Mount St Helens and future eruption of other volcanoes in the Cascade Range may pose a variety of health hazards, including blast, ashfalls, flooding, damage to public utilities, and possible psychosocial effects.

  20. Quality of health information on acute myocardial infarction and stroke in the world wide web.

    PubMed

    Bastos, Ana; Paiva, Dagmara; Azevedo, Ana

    2014-01-01

    Introdução: A informação sobre saúde disponível na Internet é de qualidade variável e frequentemente baixa. Esta questão é fundamental em doenças como as cardiovasculares em que a auto-gestão desempenha um papel importante. O objetivo deste estudo foi avaliar a qualidade dos sites portugueses como fonte de informação sobre enfarte agudo do miocárdio e acidente vascular cerebral.Material e Métodos: Utilizamos as expressões de pesquisa ‘enfarte miocardio’ e ‘acidente vascular cerebral’ no motor de busca Google® nos dias 5 e 7 de Abril de 2011, respetivamente, usando o Internet Explorer®. Os primeiros 200 URL que resultaram da pesquisa foram visitados de forma independente e foram selecionados sites de Portugal em língua portuguesa. Classificámos 121 sites de acordo com características estruturais, cobertura e validade da informação de acordo com itens previamente definidos, medidas de confiabilidade em geral de acordo com a Health on the Net Foundation e em relação aos tratamentos, utilizando o instrumento DISCERN (48 sites).Resultados: Os sites eram maioritariamente comerciais (49,5%), com parte do site dedicado a enfarte agudo do miocárdio/ acidente vascular cerebral (94,2%), com informações exclusivamente sobre factos médicos (59,5%) e apresentavam imagens, vídeos e animações para além do texto (60,3%). A confiabilidade dos sites foi baixa. Nenhum dos sites exibiu o selo da Health on the Net Foundation. Os sites de enfarte agudo do miocárdio/ acidente vascular cerebral diferiram na cobertura da informação. A validade da informação foi aceitável embora frequentemente incompleta.Conclusão: A qualidade da informação sobre enfarte agudo do miocárdio/ acidente vascular cerebral nos sites portugueses foi aceitável. A confiabilidade foi baixa o que pode comprometer a capacidade dos utilizadores em identificar conteúdos potencialmente mais credíveis.

  1. [Treatment of children with acute diarrheal disease. Knowledge and attitudes of the health personnel].

    PubMed

    Mota-Hernández, F; Zamora-Escudero, G

    1992-10-01

    Diarrheal diseases are still one of the most frequent causes of death due to dehydration in children; lack of information regarding the adequate treatment of diarrhea is the main cause. The results of an inquire sent to 620 physicians and nurses were analyzed to determine the knowledge and attitudes of the health care workers that reside in different diarrheal mortality areas in Mexico. The less professional experience time was correlated with more knowledge in etiology of diarrhea. More physicians than nurses had correct answers regarding the place of diarrheal diseases in child mortality and the correct use of antimicrobial, and other drugs and liquids to prevent and treat dehydration. Most workers did not know the inconvenience of hypertonic solutions to prevent dehydration and the importance of the oral solution flavor. This results suggest that nurses will, be included in clinical training by means of seminars in oral hydration therapy. Furthermore it seems convenient to increase the access to oral hydration solutions as well as the diffusion of its advantages.

  2. Estimating the acute health effects of coarse particulate matter accounting for exposure measurement error.

    PubMed

    Chang, Howard H; Peng, Roger D; Dominici, Francesca

    2011-10-01

    In air pollution epidemiology, there is a growing interest in estimating the health effects of coarse particulate matter (PM) with aerodynamic diameter between 2.5 and 10 μm. Coarse PM concentrations can exhibit considerable spatial heterogeneity because the particles travel shorter distances and do not remain suspended in the atmosphere for an extended period of time. In this paper, we develop a modeling approach for estimating the short-term effects of air pollution in time series analysis when the ambient concentrations vary spatially within the study region. Specifically, our approach quantifies the error in the exposure variable by characterizing, on any given day, the disagreement in ambient concentrations measured across monitoring stations. This is accomplished by viewing monitor-level measurements as error-prone repeated measurements of the unobserved population average exposure. Inference is carried out in a Bayesian framework to fully account for uncertainty in the estimation of model parameters. Finally, by using different exposure indicators, we investigate the sensitivity of the association between coarse PM and daily hospital admissions based on a recent national multisite time series analysis. Among Medicare enrollees from 59 US counties between the period 1999 and 2005, we find a consistent positive association between coarse PM and same-day admission for cardiovascular diseases.

  3. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints

    SciTech Connect

    Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B.; George, Kerry A.; Cucinotta, Francis A.

    2016-04-25

    The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE’s using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE’s are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (<10) are found for simple exchanges using a linear dose response model, however in the non-targeted effects model for fibroblast cells large RBE values (>10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE’s against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Finally, we discuss comparisons of the resulting model parameters to those used in the NASA radiation quality factor function.

  4. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints

    DOE PAGES

    Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B.; ...

    2016-04-25

    The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictionsmore » of the charge number and energy dependence of RBE’s using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE’s are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (<10) are found for simple exchanges using a linear dose response model, however in the non-targeted effects model for fibroblast cells large RBE values (>10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE’s against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Finally, we discuss comparisons of the resulting model parameters to those used in the NASA radiation quality factor function.« less

  5. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints

    PubMed Central

    Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B.; George, Kerry A.; Cucinotta, Francis A.

    2016-01-01

    The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE’s using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE’s are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (<10) are found for simple exchanges using a linear dose response model, however in the non-targeted effects model for fibroblast cells large RBE values (>10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE’s against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed. PMID:27111667

  6. Anatomy of an experimental two-link flexible manipulator under end-point control

    NASA Technical Reports Server (NTRS)

    Oakley, Celia M.; Cannon, Robert H., Jr.

    1990-01-01

    The design and experimental implementation of an end-point controller for two-link flexible manipulators are presented. The end-point controller is based on linear quadratic Gaussian (LQG) theory and is shown to exhibit significant improvements in trajectory tracking over a conventional controller design. To understand the behavior of the manipulator structure under end-point control, a strobe sequence illustrating the link deflections during a typical slew maneuver is included.

  7. Evaluating the impact of depression, anxiety & autonomic function on health related quality of life, vocational functioning and health care utilisation in acute coronary syndrome patients: the ADVENT study protocol

    PubMed Central

    2013-01-01

    Background Depression and anxiety are highly prevalent and co-morbid in acute coronary syndrome patients. Somatic and cognitive subtypes of depression and anxiety in acute coronary syndrome have been shown to be associated with mortality although their association with patient outcomes is unknown, as are the mechanisms that underpin these associations. We are conducting a prospective cohort study which aims to examine in acute coronary syndrome patients: (1) the role of somatic subtypes of depression and anxiety as predictors of health related quality of life outcomes; (2) how somatic subtypes of depression and anxiety relate to long term vocational functioning and healthcare utilisation; and (3) the role of the autonomic nervous system assessed by heart rate variability as a moderator of these associations. Methods Patients are being screened after index admission for acute coronary syndrome at a single, high volume centre, MonashHeart, Monash Health, Victoria, Australia. The inclusion criterion is all patients aged > 21 years old and fluent in English admitted to MonashHeart, Monash Health with a diagnosis of acute coronary syndrome. The primary outcome is mean health related quality of life (Short Form-36) Physical and Mental Health Summary scores at 12 and 24 months in subtypes with somatic symptoms of depression and anxiety. Depressive domains are assessed by the Beck Depression Inventory II and the Cardiac Depression Scale. Anxiety is measured using the Speilberger State-Trait Anxiety Inventory and the Crown Crisp Phobic Anxiety questionnaire. Secondary outcomes include clinical variables, healthcare service utilisation and vocational functioning. Discussion This manuscript presents the protocol for a prospective cohort study which will investigate the role of somatic subtypes of depression and anxiety as predictors of health related quality of life, long-term vocational functioning and health service use, and the role of the autonomic nervous system in

  8. Acute Health Effects Among Military Personnel Participating in the Cleanup of the Hebei Spirit Oil Spill, 2007, in Taean County, Korea

    PubMed Central

    Gwack, Jin; Lee, Ju Hyung; Kang, Young Ah; Chang, Kyu-jin; Lee, Moo Sik; Hong, Jee Young

    2012-01-01

    Objectives This study was conducted to investigate acute health effects and its related factors among military personnel participating in the cleanup of the 2007 Hebei Spirit oil spill accident in Taean county, Korea. Methods We collected data on acute symptoms during the cleanup and their predictors using a self-administered questionnaire to 2624 military personnel. Selfreported symptoms included six neurologic symptoms, five respiratory symptoms, two dermatologic symptoms, three ophthalmic symptoms, and three general symptoms. Independent variables were demographic factors (gender, age, education level, and rank), health behavioral factors (smoking history and usage of the personal protective equipment such as masks and gloves), and occupational history such as where and for how long individuals participated in cleanup. Results The duration of work days was significantly associated with 17 acute symptoms except for itchiness and red skin.Working in Taean county also increased the risk of most acute symptoms except headache and back pain. In regard to personal protective equipment, wearing masks was mainly related to the development of respiratory symptoms such as sore throat and wearing other protective equipment was related to the development of sore throat, back pain, headache, and cough. Military personnel younger than 25 years reported 4.66 times more hot flushing and 5.39 times more itchiness than those older than 25 years. Conclusion It should be emphasized that for early-stage cleanup the number of workers should be minimized, sufficient personal protective equipment with approved quality for blocking noxious gas should be supplied, and systematic health care for the workers should be provided. Health effects could be diminished by providing adequate education regarding the appropriate use of protective equipment, especially to nonprofessionals such as residents and volunteers. To make disaster response expeditious, a national and regional preparedness

  9. Impact of weighted composite compared to traditional composite endpoints for the design of randomized controlled trials.

    PubMed

    Bakal, Jeffrey A; Westerhout, Cynthia M; Armstrong, Paul W

    2015-12-01

    Composite endpoints are commonly used in cardiovascular clinical trials. When using a composite endpoint a subject is considered to have an event when the first component endpoint has occurred. The use of composite endpoints offers the ability to incorporate several clinically important endpoint events thereby augmenting the event rate and increasing statistical power for a given sample size. One assumption of the composite is that all component events are of equal clinical importance. This assumption is rarely achieved given the diversity of component endpoints included. One means of adjusting for this diversity is to adjust the outcomes using severity weights determined a priori. The use of a weighted endpoint also allows for the incorporation of multiple endpoints per patient. Although weighting the outcomes lowers the effective number of events, it offers additional information that reduces the variance of the estimate. We created a series of simulation studies to examine the effect on power as the individual components of a typical composite were changed. In one study, we noted that the weighted composite was able to offer discriminative power when the component outcomes were altered, while the traditional method was not. In the other study, we noted that the weighted composite offered a similar level of power to the traditional composite when the change was driven by the more severe endpoints.

  10. Predictors of Long‐term Clinical Endpoints in Patients With Refractory Angina

    PubMed Central

    Povsic, Thomas J.; Broderick, Samuel; Anstrom, Kevin J.; Shaw, Linda K.; Ohman, E. Magnus; Eisenstein, Eric L.; Smith, Peter K.; Alexander, John H.

    2015-01-01

    Background Clinical outcomes in patients with refractory angina (RA) are poorly characterized and variably described. Using the Duke Database for Cardiovascular Disease (DDCD), we explored characteristics that drive clinical endpoints in patients with class II to IV angina stabilized on medical therapy. Methods and Results We explored clinical endpoints and associated costs of patients who underwent catheterization at Duke University Medical Center from 1997 to 2010 for evaluation of coronary artery disease (CAD) and were found to have advanced CAD ineligible for additional revascularization, and were clinically stable for a minimum of 60 days. Of 77 257 cardiac catheterizations performed, 1908 patients met entry criteria. The 3‐year incidence of death; cardiac rehospitalization; and a composite of death, myocardial infarction, stroke, cardiac rehospitalization, and revascularization were 13.0%, 43.5%, and 52.2%, respectively. Predictors of mortality included age, ejection fraction (EF), low body mass index, multivessel CAD, low heart rate, diabetes, diastolic blood pressure, history of coronary artery bypass graft surgery, cigarette smoking, history of congestive heart failure (CHF), and race. Multivessel CAD, EF<45%, and history of CHF increased risk of mortality; angina class and prior revascularization did not. Total rehospitalization costs over a 3‐year period per patient were $10 185 (95% CI 8458, 11912) in 2012 US dollars. Conclusions Clinically stable patients with RA who are medically managed have a modest mortality, but a high incidence of hospitalization and resource use over 3 years. These findings point to the need for novel therapies aimed at symptom mitigation in this population and their potential impact on health care utilization and costs. PMID:25637344

  11. Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

  12. An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round.

    PubMed

    Ehling, G; Hecht, M; Heusener, A; Huesler, J; Gamer, A O; van Loveren, H; Maurer, Th; Riecke, K; Ullmann, L; Ulrich, P; Vandebriel, R; Vohr, H-W

    2005-08-15

    The original local lymph node assay (LLNA) is based on the use of radioactive labelling to measure cell proliferation. Other endpoints for the assessment of proliferation are also authorized by the OECD Guideline 429 provided there is appropriate scientific support, including full citations and description of the methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 2002.). Here, we describe the outcome of the second round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in nine laboratories in Europe. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight and cell counts were used to assess LN cell proliferation instead of [3H]TdR incorporation. In addition, the acute inflammatory skin reaction was measured by ear weight determination of circular biopsies of the ears to identify skin irritation properties of the test items. The statistical analysis was performed in the department of statistics at the university of Bern. Similar to the EC(3) values defined for the radioactive method, threshold values were calculated for the endpoints measured in this modification of the LLNA. It was concluded that all parameters measured have to be taken into consideration for the categorisation of compounds due to their sensitising potencies. Therefore, an assessment scheme has been developed which turned out to be of great importance to consistently assess sensitisation versus irritancy based on the data of the different parameters. In contrast to the radioactive method, irritants have been picked up by all the laboratories applying this assessment scheme.

  13. A retrospective study on acute health effects due to volcanic ash exposure during the eruption of Mount Etna (Sicily) in 2002

    PubMed Central

    2013-01-01

    Background Mount Etna, located in the eastern part of Sicily (Italy), is the highest and most active volcano in Europe. During the sustained eruption that occurred in October-November 2002 huge amounts of volcanic ash fell on a densely populated area south-east of Mount Etna in Catania province. The volcanic ash fall caused extensive damage to infrastructure utilities and distress in the exposed population. This retrospective study evaluates whether or not there was an association between ash fall and acute health effects in exposed local communities. Methods We collected the number and type of visits to the emergency department (ED) for diseases that could be related to volcanic ash exposure in public hospitals of the Province of Catania between October 20 and November 7, 2002. We compared the magnitude of differences in ED visits between the ash exposure period in 2002 and the same period of the previous year 2001. Results We observed a significant increase of ED visits for acute respiratory and cardiovascular diseases, and ocular disturbances during the ash exposure time period. Conclusions There was a positive association between exposure to volcanic ash from the 2002 eruption of Mount Etna and acute health effects in the Catania residents. This study documents the need for public health preparedness and response initiatives to protect nearby populations from exposure to ash fall from future eruptions of Mount Etna. PMID:23924394

  14. Long-term care and health information technology: opportunities and responsibilities for long-term and post-acute care providers.

    PubMed

    MacTaggart, Patricia; Thorpe, Jane Hyatt

    2013-01-01

    Long-term and post-acute care providers (LTPAC) need to understand the multiple aspects of health information technology (HIT) in the context of health systems transformation in order to be a viable participant. The issues with moving to HIT are not just technical and funding, but include legal and policy, technical and business operations, and very significantly, governance. There are many unanswered questions. However, changes in payment methodologies, service delivery models, consumer expectations, and regulatory requirements necessitate that LTPAC providers begin their journey.

  15. Responsiveness of endpoints in osteoporosis clinical trials--an update.

    PubMed

    Cranney, A; Welch, V; Tugwell, P; Wells, G; Adachi, J D; McGowan, J; Shea, B

    1999-01-01

    As an update of our earlier paper, published as part of the Outcome Measures in Rheumatology Clinical Trials (OMERACT 3) proceedings in 1996, we surveyed the types of outcomes incorporated in recent clinical trials. A literature search was conducted on MEDLINE and Current Contents, from January 1996 to March 1998, using the search strategy recommended by the Cochrane Collaboration for the identification of randomized controlled trials (RCT). Two independent reviewers selected trials according to inclusion criteria. The same reviewers extracted data on clinical and radiographic fractures, pain, quality of life, and bone mineral density (BMD). Seventy-four RCT conducted on bone loss in postmenopausal women were identified. Most trials incorporated biochemical markers and BMD as outcome measures. Fewer trials included vertebral fractures, pain, height, and quality of life. The responsiveness is presented in terms of the sample size needed per group to show a statistically significant difference. The most responsive outcomes were pain, BMD, and biochemical markers. The number needed to treat to prevent one vertebral fracture ranged from 13 to 54, depending on the intervention and population. Investigators should examine the characteristics of the patient population and the nature of the intervention in determining the sample size required to demonstrate a significant effect. The selection of endpoints should be based on their responsiveness, feasibility, and the importance of using standardized outcomes. Standardized outcomes greatly facilitate the synthesis of available information into systematic reviews by groups such as the Cochrane Collaboration.

  16. Staff nurse perceptions of the impact of mentalization-based therapy skills training when working with borderline personality disorder in acute mental health: a qualitative study.

    PubMed

    Warrender, D

    2015-10-01

    People diagnosed with borderline personality disorder (BPD) are highly prevalent in acute mental health wards, with staff nurses identifying a challenge in working with people who can be significantly distressed. This has contributed to a negative stereotype verging on stigmatization. Mentalization-based therapy (MBT) is a psychological therapy which has been shown to be of benefit to people with a diagnosis of BPD, yet it has been utilized and evaluated only in partial hospitalization and outpatient settings. Despite this, most people diagnosed with BPD will continue to be treated in generic inpatient settings such as acute mental health. Mentalization-based therapy skills training (MBT-S) is a new and cost-effective 2-day workshop aiming to provide generalist practitioners with MBT skills for use in generic settings. This study aimed to capture staff perceptions of the impact of MBT-S on their practice when working with people with a diagnosis of BPD in acute mental health. Through two focus groups, this study assessed the perceptions of nine staff nurses. An interpretive phenomenological approach was utilized in data analysis. Participants found the approach easy to grasp, improving of consistency between staff and flexible in its use in planned or 'off the cuff' discussions. MBT-S promoted empathy and humane responses to self-harm, impacted on participants ability to tolerate risk and went some way to turning the negative perception of BPD through changing the notion of patients as 'deliberately difficult'. Staff felt empowered and more confident in working with people with a diagnosis of BPD. The positive implication for practice was the ease in which the approach was adopted and participants perception of MBT-S as an empowering skill set which also contributed to attitudinal change. In acute mental health environments, which may not have the resources to provide long-term structured treatments to patients, MBT-S could be viewed as ideal as participants

  17. A clinical training unit for diarrhoea and acute respiratory infections: an intervention for primary health care physicians in Mexico.

    PubMed

    Bojalil, R; Guiscafré, H; Espinosa, P; Viniegra, L; Martínez, H; Palafox, M; Gutiérrez, G

    1999-01-01

    In Tlaxcala State, Mexico, we determined that 80% of children who died from diarrhoea or acute respiratory infections (ARI) received medical care before death; in more than 70% of the cases this care was provided by a private physician. Several strategies have been developed to improve physicians' primary health care practices but private practitioners have only rarely been included. The objective of the present study was to evaluate the impact of in-service training on the case management of diarrhoea and ARI among under-5-year-olds provided by private and public primary physicians. The training consisted of a five-day course of in-service practice during which physicians diagnosed and treated sick children attending a centre and conducted clinical discussions of cases under guidance. Each training course was limited to six physicians. Clinical performance was evaluated by observation before and after the courses. The evaluation of diarrhoea case management covered assessment of dehydration, hydration therapy, prescription of antimicrobial and other drugs, advice on diet, and counselling for mothers; that of ARI case management covered diagnosis, decisions on antimicrobial therapy, use of symptomatic drugs, and counselling for mothers. In general the performance of public physicians both before and after the intervention was better than that of private doctors. Most aspects of the case management of children with diarrhoea improved among both groups of physicians after the course; the proportion of private physicians who had five or six correct elements out of six increased from 14% to 37%: for public physicians the corresponding increase was from 53% to 73%. In ARI case management, decisions taken on antimicrobial therapy and symptomatic drug use improved in both groups; the proportion of private physicians with at least three correct elements out of four increased from 13% to 42%, while among public doctors the corresponding increase was from 43% to 78%. Hands

  18. Acute Physiological and Chronic Health Evaluation II Score and its Correlation with Three Surgical Strategies for Management of Ileal Perforations

    PubMed Central

    Munghate, Anand; Kumar, Ashwani; Mittal, Sushil; Singh, Harnam; Sharma, Jyoti; Yadav, Manish

    2015-01-01

    Introduction: Ileal perforation peritonitis is a common surgical emergency in the Indian subcontinent and in tropical countries. It is reported to constitute the fifth common cause of abdominal emergencies due to high incidence of enteric fever and tuberculosis in these management based on Acute Physiological and Chronic Health Evaluation II (APACHE II) score. Methods: The following study was conducted in the Department of General Surgery, Government Medical College, Patiala. A total of 57 patients were studied and divided in to Group I, II, and III. APACHE II score accessed and score between 10 and 19 were blindly randomized into three procedures primary closure, resection-anastomosis, and ileostomy. The outcome was compared. Results: Ileal perforations were most commonly observed in the third and fourth decade of life with male dominance. APACHE II score was accessed and out of total 57 patients, 6 patients had APACHE II score of 0–9, 48 patients had APACHE II score of 10–19, and 3 patients had APACHE II score of ≥20. In APACHE II score 10–19, 15 patients underwent primary closure, 16 patients underwent resection-anastomosis, and 17 patients underwent ileostomy. Discussion and Conclusion: Primary closure of perforation is advocated in patients with single, small perforation (<1 cm) with APACHE II score 10–19 irrespective of duration of perforation. Ileostomy is advocated in APACHE II score 10–19, where the terminal ileum is grossly inflamed with multiple perforations, large perforations (>1 cm), fecal peritonitis, matted bowel loops, intraoperative evidence of caseating lymph nodes, strictures, and an unhealthy gut due to edema. PMID:27512550

  19. A probabilistic assessment of health risks associated with short-term exposure to tropospheric ozone

    SciTech Connect

    Whitfield, R.G; Biller, W.F.; Jusko, M.J.; Keisler, J.M.

    1996-06-01

    The work described in this report is part of a larger risk assessment sponsored by the U.S. Environmental Protection Agency. Earlier efforts developed exposure-response relationships for acute health effects among populations engaged in heavy exertion. Those efforts also developed a probabilistic national ambient air quality standards exposure model and a general methodology for integrating probabilistic exposure-response relation- ships and exposure estimates to calculate overall risk results. Recently published data make it possible to model additional health endpoints (for exposure at moderate exertion), including hospital admissions. New air quality and exposure estimates for alternative national ambient air quality standards for ozone are combined with exposure-response models to produce the risk results for hospital admissions and acute health effects. Sample results explain the methodology and introduce risk output formats.

  20. A new respirometric endpoint-based biosensor to assess the relative toxicity of chemicals on immobilized human cells.

    PubMed

    Dragone, Roberto; Frazzoli, Chiara; Grappelli, Claudio; Campanella, Luigi

    2009-01-01

    Several functional and biochemical parameters have been proposed as biomarkers of effect of environmental pollutants. A rapid biosensor working with immobilized human U-937 cells was developed and applied to environmentally relevant chemicals with different structures and toxicological pathways, i.e. benzalkonium chloride, clofibric acid, diclofenac, mercury nitrate, ofloxacin, and sodium dodecyl sulphate. Respiration of cells was relied upon as a comprehensive biochemical effect for screening purposes. Analytical parameter (DeltappmO(2)) and toxicological index (respiratory inhibition, delta%) measured after 1h of exposure were utilized for dose-response relationship study. Results (toxicity rating scales based on delta(50)% and steepness) were compared with those obtained by the same approach previously optimized on Saccharomyces cerevisiae. The toxicity rating scale obtained by the biomarker based on human mitochondrial and cell metabolic activities compared well with previous scale obtained on yeast cells and with available in-vivo acute toxicity indexes; respiration was confirmed as toxicological endpoint reliably measurable by the biosensor.

  1. Statistical evaluation of surrogate endpoints with examples from cancer clinical trials.

    PubMed

    Buyse, Marc; Molenberghs, Geert; Paoletti, Xavier; Oba, Koji; Alonso, Ariel; Van der Elst, Wim; Burzykowski, Tomasz

    2016-01-01

    A surrogate endpoint is intended to replace a clinical endpoint for the evaluation of new treatments when it can be measured more cheaply, more conveniently, more frequently, or earlier than that clinical endpoint. A surrogate endpoint is expected to predict clinical benefit, harm, or lack of these. Besides the biological plausibility of a surrogate, a quantitative assessment of the strength of evidence for surrogacy requires the demonstration of the prognostic value of the surrogate for the clinical outcome, and evidence that treatment effects on the surrogate reliably predict treatment effects on the clinical outcome. We focus on these two conditions, and outline the statistical approaches that have been proposed to assess the extent to which these conditions are fulfilled. When data are available from a single trial, one can assess the "individual level association" between the surrogate and the true endpoint. When data are available from several trials, one can additionally assess the "trial level association" between the treatment effect on the surrogate and the treatment effect on the true endpoint. In the latter case, the "surrogate threshold effect" can be estimated as the minimum effect on the surrogate endpoint that predicts a statistically significant effect on the clinical endpoint. All these concepts are discussed in the context of randomized clinical trials in oncology, and illustrated with two meta-analyses in gastric cancer.

  2. Use of sublethal endpoints in sediment toxicity testing with the amphipod Hyalella azteca

    SciTech Connect

    Kemble, N.E.; Brunson, E.B.; Dwyer, F.J.; Ehrhardt, E.A.; Hardesty, D.K.; Haverland, P.S.; Ingersoll, C.G.

    1995-12-31

    ASTM and EPA standard methods for sediment toxicity tests with Hyalella azteca typically recommend use of lethality as the endpoint in a 10-d exposure. However, data from 10- to 28-d exposures with amphipods indicate sublethal endpoints (i.e., growth, sexual maturation, or reproduction) identify additional samples as toxic. The authors compared the frequency that lethal and sublethal endpoints identified a sediment sample as toxic in 14- and 28-d amphipod exposures. In the 14-d amphipod exposures, lethality identified 20% of the samples as toxic, and sublethal endpoints identified an additional 16% of the samples as toxic using sublethal endpoints only. Similarly, in the 28-d exposures, lethality identified 14% of the samples as toxic and sublethal endpoints identified an additional 18% of the samples as toxic. The authors are also currently evaluating Sediment Effect Concentrations (SECs) relative to both lethal and sublethal endpoints in H. azteca exposures. These SECs will be used to evaluate reliability in estimating toxicity of samples. Potential factors which may confound interpretation of sublethal endpoints in sediment tests include: (1) changes in sediment chemistry resulting from long-term storage or feeding (2) the influence of physical characteristics of sediment (grain size), and (3) effects of ammonia or hydrogen sulfide.

  3. 78 FR 46351 - Trial Designs and Endpoints for Liver Disease Secondary to Nonalcoholic Steatohepatitis; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ... HUMAN SERVICES Food and Drug Administration Trial Designs and Endpoints for Liver Disease Secondary to... Research in cosponsorship with the American Association for the Study of Liver Diseases (AASLD) is announcing a 2-day public workshop entitled ``Trial Designs and Endpoints for Liver Disease Secondary...

  4. A Few Endpoint Geodesic Restriction Estimates for Eigenfunctions

    NASA Astrophysics Data System (ADS)

    Chen, Xuehua; Sogge, Christopher D.

    2014-07-01

    We prove a couple of new endpoint geodesic restriction estimates for eigenfunctions. In the case of general 3-dimensional compact manifolds, after a TT* argument, simply by using the L 2-boundedness of the Hilbert transform on , we are able to improve the corresponding L 2-restriction bounds of Burq, Gérard and Tzvetkov (Duke Math J 138:445-486, 2007) and Hu (Forum Math 6:1021-1052, 2009). Also, in the case of 2-dimensional compact manifolds with nonpositive curvature, we obtain improved L 4-estimates for restrictions to geodesics, which, by Hölder's inequality and interpolation, implies improved L p -bounds for all exponents p ≥ 2. We do this by using oscillatory integral theorems of Hörmander (Ark Mat 11:1-11, 1973), Greenleaf and Seeger (J Reine Angew Math 455:35-56, 1994) and Phong and Stein (Int Math Res Notices 4:49-60, 1991), along with a simple geometric lemma (Lemma 3.2) about properties of the mixed-Hessian of the Riemannian distance function restricted to pairs of geodesics in Riemannian surfaces. We are also able to get further improvements beyond our new results in three dimensions under the assumption of constant nonpositive curvature by exploiting the fact that, in this case, there are many totally geodesic submanifolds.

  5. Is the tobacco control movement misrepresenting the acute cardiovascular health effects of secondhand smoke exposure? An analysis of the scientific evidence and commentary on the implications for tobacco control and public health practice

    PubMed Central

    Siegel, Michael

    2007-01-01

    While chronic exposure to secondhand smoke has been well recognized as a cause of heart disease in nonsmokers, there has been recent speculation about the potential acute cardiovascular effects of transient exposure to secondhand smoke among nonsmokers; in particular, the possibility that such exposure could increase the risk of acute myocardial infarction even in an otherwise healthy nonsmoker. This paper reviews the claims being made by a number of anti-smoking and public health groups regarding the acute cardiovascular effects of secondhand smoke exposure among otherwise healthy adults, analyzes the validity of these claims based on a review of the scientific evidence, and discusses the implications of the findings for tobacco control and public health practice. Based on the analysis, it appears that a large number of anti-smoking organizations are making inaccurate claims that a single, acute, transient exposure to secondhand smoke can cause severe and even fatal cardiovascular events in healthy nonsmokers. The dissemination of inaccurate information by anti-smoking groups to the public in support of smoking bans is unfortunate because it may harm the tobacco control movement by undermining its credibility, reputation, and effectiveness. Disseminating inaccurate information also represents a violation of basic ethical principles that are a core value of public health practice that cannot and should not be sacrificed, even for a noble end such as protecting nonsmokers from secondhand smoke exposure. How the tobacco control movement responds to this crisis of credibility will go a long way towards determining the future effectiveness of the movement and its ability to continue to save lives and protect the public's health. PMID:17927828

  6. Latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint.

    PubMed

    Hu, Chuanpu; Szapary, Philippe O; Mendelsohn, Alan M; Zhou, Honghui

    2014-08-01

    Informative exposure-response modeling of clinical endpoints is important in drug development. There has been much recent progress in latent variable modeling of ordered categorical endpoints, including the application of indirect response (IDR) models and accounting for residual correlations between multiple categorical endpoints. This manuscript describes a framework of latent-variable-based IDR models that facilitate easy simultaneous modeling of a continuous and a categorical clinical endpoint. The model was applied to data from two phase III clinical trials of subcutaneously administered ustekinumab for the treatment of psoriatic arthritis, where Psoriasis Area and Severity Index scores and 20, 50, and 70 % improvement in the American College of Rheumatology response criteria were used as efficacy endpoints. Visual predictive check and external validation showed reasonable parameter estimation precision and model performance.

  7. Prophylaxis of acute viral hepatitis by immune serum globulin, hepatitis B vaccine, and health education: a sixteen year study of Japan overseas cooperation volunteers.

    PubMed

    Ohara, H; Ebisawa, I; Naruto, H

    1997-01-01

    From 1978 to 1993 a study of acute viral hepatitis contracted by the Japan Overseas Cooperation Volunteers (JOCV) during their assignments in tropical and subtropical countries was conducted. Of 10,509 subjects in this study, 240 cases of acute viral hepatitis were confirmed (hepatitis A = 139, hepatitis B = 72, and non-A, non-B hepatitis = 29). The annual morbidity was 5.1% in 1978 and 4.9% in 1979, with hepatitis A accounting for 80% of the cases. However, it decreased significantly after the prophylactic inoculation with immune serum globulin (ISG) was started in 1980. A significant decrease of hepatitis B from 1.2% in 1980 to 0.1% in 1990 was also seen after vaccination was introduced for all volunteers in 1988. Health education concerning food and water sanitation, and providing general information on viral hepatitis, was also conducted throughout this period. These results indicate that acute viral hepatitis could be successfully prevented in the JOCV with a combination of ISG, hepatitis B vaccination, and health education.

  8. Utilizing electronic health records to predict acute kidney injury risk and outcomes: workgroup statements from the 15(th) ADQI Consensus Conference.

    PubMed

    Sutherland, Scott M; Chawla, Lakhmir S; Kane-Gill, Sandra L; Hsu, Raymond K; Kramer, Andrew A; Goldstein, Stuart L; Kellum, John A; Ronco, Claudio; Bagshaw, Sean M

    2016-01-01

    The data contained within the electronic health record (EHR) is "big" from the standpoint of volume, velocity, and variety. These circumstances and the pervasive trend towards EHR adoption have sparked interest in applying big data predictive analytic techniques to EHR data. Acute kidney injury (AKI) is a condition well suited to prediction and risk forecasting; not only does the consensus definition for AKI allow temporal anchoring of events, but no treatments exist once AKI develops, underscoring the importance of early identification and prevention. The Acute Dialysis Quality Initiative (ADQI) convened a group of key opinion leaders and stakeholders to consider how best to approach AKI research and care in the "Big Data" era. This manuscript addresses the core elements of AKI risk prediction and outlines potential pathways and processes. We describe AKI prediction targets, feature selection, model development, and data display.

  9. Risk factors of admission for acute colonic diverticulitis in a population-based cohort study: The North Trondelag Health Study, Norway

    PubMed Central

    Jamal Talabani, Aras; Lydersen, Stian; Ness-Jensen, Eivind; Endreseth, Birger Henning; Edna, Tom-Harald

    2016-01-01

    AIM To assess risk factors of hospital admission for acute colonic diverticulitis. METHODS The study was conducted as part of the second wave of the population-based North Trondelag Health Study (HUNT2), performed in North Trondelag County, Norway, 1995 to 1997. The study consisted of 42570 participants (65.1% from HUNT2) who were followed up from 1998 to 2012. Of these, 22436 (52.7%) were females. The cases were defined as those 358 participants admitted with acute colonic diverticulitis during follow-up. The remaining participants were used as controls. Univariable and multivariable Cox regression analyses was used for each sex separately after multiple imputation to calculate HR. RESULTS Multivariable Cox regression analyses showed that increasing age increased the risk of admission for acute colonic diverticulitis: Comparing with ages < 50 years, females with age 50-70 years had HR = 3.42, P < 0.001 and age > 70 years, HR = 6.19, P < 0.001. In males the corresponding values were HR = 1.85, P = 0.004 and 2.56, P < 0.001. In patients with obesity (body mass index ≥ 30) the HR = 2.06, P < 0.001 in females and HR = 2.58, P < 0.001 in males. In females, present (HR = 2.11, P < 0.001) or previous (HR = 1.65, P = 0.007) cigarette smoking increased the risk of admission. In males, breathlessness (HR = 2.57, P < 0.001) and living in rural areas (HR = 1.74, P = 0.007) increased the risk. Level of education, physical activity, constipation and type of bread eaten showed no association with admission for acute colonic diverticulitis. CONCLUSION The risk of hospital admission for acute colonic diverticulitis increased with increasing age, in obese individuals, in ever cigarette smoking females and in males living in rural areas. PMID:28082819

  10. A clinical training unit for diarrhoea and acute respiratory infections: an intervention for primary health care physicians in Mexico.

    PubMed Central

    Bojalil, R.; Guiscafré, H.; Espinosa, P.; Viniegra, L.; Martínez, H.; Palafox, M.; Gutiérrez, G.

    1999-01-01

    In Tlaxcala State, Mexico, we determined that 80% of children who died from diarrhoea or acute respiratory infections (ARI) received medical care before death; in more than 70% of the cases this care was provided by a private physician. Several strategies have been developed to improve physicians' primary health care practices but private practitioners have only rarely been included. The objective of the present study was to evaluate the impact of in-service training on the case management of diarrhoea and ARI among under-5-year-olds provided by private and public primary physicians. The training consisted of a five-day course of in-service practice during which physicians diagnosed and treated sick children attending a centre and conducted clinical discussions of cases under guidance. Each training course was limited to six physicians. Clinical performance was evaluated by observation before and after the courses. The evaluation of diarrhoea case management covered assessment of dehydration, hydration therapy, prescription of antimicrobial and other drugs, advice on diet, and counselling for mothers; that of ARI case management covered diagnosis, decisions on antimicrobial therapy, use of symptomatic drugs, and counselling for mothers. In general the performance of public physicians both before and after the intervention was better than that of private doctors. Most aspects of the case management of children with diarrhoea improved among both groups of physicians after the course; the proportion of private physicians who had five or six correct elements out of six increased from 14% to 37%: for public physicians the corresponding increase was from 53% to 73%. In ARI case management, decisions taken on antimicrobial therapy and symptomatic drug use improved in both groups; the proportion of private physicians with at least three correct elements out of four increased from 13% to 42%, while among public doctors the corresponding increase was from 43% to 78%. Hands

  11. Mastery and coping moderate the negative effect of acute and chronic stressors on mental health-related quality of life in HIV.

    PubMed

    Gibson, Katherine; Rueda, Sergio; Rourke, Sean B; Bekele, Tsegaye; Gardner, Sandra; Fenta, Haile; Hart, Trevor A

    2011-06-01

    Acute and chronic life stressors have a detrimental effect on the health of people living with HIV. Psychosocial resources such as mastery, coping, and social support may play a critical role in moderating the negative effects of stressors on health-related quality of life. A total of 758 participants provided baseline enrolment data on demographics (age, gender, ethnicity, sexual orientation, education, employment, income), clinical variables (CD4 counts, viral load, AIDS-defining condition, time since HIV diagnosis), psychosocial resources (mastery, coping, social support), life stressors (National Population Health Survey [NPHS] Stress Questionnaire), and health-related quality of life (SF-36). We performed hierarchical multivariate regression analyses to evaluate the potential moderating effects of psychosocial resources on the relationship between stressors and health-related quality of life. The top three stressors reported by participants were trying to take on too many things at once (51%), not having enough money to buy the things they needed (51%), and having something happen during childhood that scared them so much that they thought about it years later (42%). Life stressors were significantly and inversely associated with both physical and mental health-related quality of life. Mastery and maladaptive coping had significant moderating effects on mental health but not on physical health. These results suggest that developing interventions that improve mastery and reduce maladaptive coping may minimize the negative impact of life stressors on the mental health of people with HIV. They also highlight that it is important for clinicians to be mindful of the impact of life stressors on the health of patients living with HIV.

  12. End-points and clinical trial design in pulmonary arterial hypertension: have we made progress?

    PubMed

    Peacock, A J; Naeije, R; Galiè, N; Rubin, L

    2009-07-01

    There is enormous interest in the treatment of pulmonary arterial hypertension (PAH), so it is appropriate to consider the design of trials of new therapies and the end-points to be measured when trying to decide whether or not a therapy is effective. In May 2003, the first meeting devoted solely to the discussion of end-points and trial design in PAH was held in Gleneagles, UK. At that time, most of the randomised controlled trials in PAH had used 6-min walking distance and/or resting haemodynamics as their primary end-points. The present article considers the progress that has been made since 2003. It deals with aspects of clinical trial design (such as noninferiority, superiority and withdrawal trials), considers end-points used in previous and current studies (such as 6-min walking distance, time to clinical worsening, haemodynamics, imaging and plasma brain natriuretic peptide), and considers what end-points might be used in the future. The second end-points meeting was held in Turnberry, UK, in June 2007. It had a similar format to the first meeting. Much of what is presented here is a summary of the workshops from that meeting. An attempt has been made to both summarise the current state of end-points and trial design and suggest new ways in which they could be improved. The present article forms one of a series being published in the European Respiratory Journal on pulmonary hypertension.

  13. Mental- and physical-health effects of acute exposure to media images of the September 11, 2001, attacks and the Iraq War.

    PubMed

    Silver, Roxane Cohen; Holman, E Alison; Andersen, Judith Pizarro; Poulin, Michael; McIntosh, Daniel N; Gil-Rivas, Virginia

    2013-09-01

    Millions of people witnessed early, repeated television coverage of the September 11 (9/11), 2001, terrorist attacks and were subsequently exposed to graphic media images of the Iraq War. In the present study, we examined psychological- and physical-health impacts of exposure to these collective traumas. A U.S. national sample (N = 2,189) completed Web-based surveys 1 to 3 weeks after 9/11; a subsample (n = 1,322) also completed surveys at the initiation of the Iraq War. These surveys measured media exposure and acute stress responses. Posttraumatic stress symptoms related to 9/11 and physician-diagnosed health ailments were assessed annually for 3 years. Early 9/11- and Iraq War-related television exposure and frequency of exposure to war images predicted increased posttraumatic stress symptoms 2 to 3 years after 9/11. Exposure to 4 or more hr daily of early 9/11-related television and cumulative acute stress predicted increased incidence of health ailments 2 to 3 years later. These findings suggest that exposure to graphic media images may result in physical and psychological effects previously assumed to require direct trauma exposure.

  14. Effects of Educational Music Therapy on State Hope for Recovery in Acute Care Mental Health Inpatients: A Cluster-Randomized Effectiveness Study

    PubMed Central

    Silverman, Michael J.

    2016-01-01

    Background: There has been an increasing emphasis on recovery as the expectation for people with mental health disorders. Purpose: The purpose of this effectiveness study is to determine if group-based educational music therapy can immediately impact state hope for recovery in acute care mental health patients. Research questions included: will acute care mental health inpatients who participate in a single music therapy session have higher agency and pathway aspects of state hope for recovery than patients in a control condition? Will there be differences in state hope for recovery as a result of hope-oriented songwriting or lyric analysis interventions? Method: Participants (N = 169) were cluster randomized to one of three single-session conditions: lyric analysis, songwriting, or wait-list control. Results: There was no significant between-group difference. However, both music therapy conditions tended to have slightly higher mean pathway, agency, and total state hope scores than the control condition even within the temporal parameters of a single music therapy session. There was no between-group difference in the songwriting and lyric analysis interventions. Conclusion: Although not significant, results support that educational music therapy may impact state hope for recovery within the temporal parameters of a single session. The specific type of educational music therapy intervention did not affect results. Implications for practice, limitations, and suggestions for future research are provided. PMID:27774084

  15. Effects of Educational Music Therapy on State Hope for Recovery in Acute Care Mental Health Inpatients: A Cluster-Randomized Effectiveness Study.

    PubMed

    Silverman, Michael J

    2016-01-01

    Background: There has been an increasing emphasis on recovery as the expectation for people with mental health disorders. Purpose: The purpose of this effectiveness study is to determine if group-based educational music therapy can immediately impact state hope for recovery in acute care mental health patients. Research questions included: will acute care mental health inpatients who participate in a single music therapy session have higher agency and pathway aspects of state hope for recovery than patients in a control condition? Will there be differences in state hope for recovery as a result of hope-oriented songwriting or lyric analysis interventions? Method: Participants (N = 169) were cluster randomized to one of three single-session conditions: lyric analysis, songwriting, or wait-list control. Results: There was no significant between-group difference. However, both music therapy conditions tended to have slightly higher mean pathway, agency, and total state hope scores than the control condition even within the temporal parameters of a single music therapy session. There was no between-group difference in the songwriting and lyric analysis interventions. Conclusion: Although not significant, results support that educational music therapy may impact state hope for recovery within the temporal parameters of a single session. The specific type of educational music therapy intervention did not affect results. Implications for practice, limitations, and suggestions for future research are provided.

  16. Case-control study of severe life threatening asthma (SLTA) in adults: demographics, health care, and management of the acute attack

    PubMed Central

    Kolbe, J; Fergusson, W; Vamos, M; Garrett, J

    2000-01-01

    BACKGROUND—Severe life threatening asthma (SLTA) is important in its own right and as a proxy for asthma death. In order to target hospital based intervention strategies to those most likely to benefit, risk factors for SLTA among those admitted to hospital need to be identified. A case-control study was undertaken to determine whether, in comparison with patients admitted to hospital with acute asthma, those with SLTA have different sociodemographic and clinical characteristics, evidence of inadequate ongoing medical care, barriers to health care, or deficiencies in management of the acute attack.
METHODS—Seventy seven patients with SLTA were admitted to an intensive care unit (pH 7.17 (0.15), PaCO2 10.7 (5.0) kPa) and 239 matched controls (by date of index attack) with acute asthma were admitted to general medical wards. A questionnaire was administered 24-48 hours after admission.
RESULTS—The risk of SLTA in comparison with other patients admitted with acute asthma increased with age (odds ratio (OR) 1.04/year, 95% CI 1.01 to 1.07) and was less for women (OR 0.36, 95% CI 0.20to 0.68). These variables were controlled for in all subsequent analyses. There were no differences in other sociodemographic features. Cases were more likely to have experienced a previous SLTA (OR 2.04, 95% CI 1.20 to 3.45) and to have had a hospital admission in the last year (OR 1.86, 95% CI 1.09 to 3.18). There were no differences between cases and controls in terms of indicators of quality of ongoing asthma specific medical care, nor was there evidence of disproportionate barriers to health care. During the index attack cases had more severe asthma at the time of presentation, were less likely to have presented to general practitioners, and were more likely to have called an ambulance or presented to an emergency department. In terms of pharmacological management, those with SLTA were more likely to have been using oral theophylline (OR 2.14, 95% CI 1.35 to 3.68) and less

  17. Centralising acute stroke care and moving care to the community in a Danish health region: Challenges in implementing a stroke care reform.

    PubMed

    Douw, Karla; Nielsen, Camilla Palmhøj; Pedersen, Camilla Riis

    2015-08-01

    In May 2012, one of Denmark's five health care regions mandated a reform of stroke care. The purpose of the reform was to save costs, while at the same time improving quality of care. It included (1) centralisation of acute stroke treatment at specialised hospitals, (2) a reduced length of hospital stay, and (3) a shift from inpatient rehabilitation programmes to community-based rehabilitation programmes. Patients would benefit from a more integrated care pathway between hospital and municipality, being supported by early discharge teams at hospitals. A formal policy tool, consisting of a health care agreement between the region and municipalities, was used to implement the changes. The implementation was carried out in a top-down manner by a committee, in which the hospital sector--organised by regions--was better represented than the primary care sector-organised by municipalities. The idea of centralisation of acute care was supported by all stakeholders, but municipalities opposed the hospital-based early discharge teams as they perceived this to be interfering with their core tasks. Municipalities would have liked more influence on the design of the reform. Preliminary data suggest good quality of acute care. Cost savings have been achieved in the region by means of closure of beds and a reduction of hospital length of stay. The realisation of the objective of achieving integrated rehabilitation care between hospitals and municipalities has been less successful. It is likely that greater involvement of municipalities in the design phase and better representation of health care professionals in all phases would have led to more successful implementation of the reform.

  18. Sublethal Toxicity Endpoints of Heavy Metals to the Nematode Caenorhabditis elegans.

    PubMed

    Jiang, Ying; Chen, Jiandong; Wu, Yue; Wang, Qiang; Li, Huixin

    2016-01-01

    Caenorhabditis elegans, a free-living nematode, is commonly used as a model organism in ecotoxicological studies. The current literatures have provided useful insight into the relative sensitivity of several endpoints, but few direct comparisons of multiple endpoints under a common set of experimental conditions. The objective of this study was to determine appropriate sublethal endpoints to develop an ecotoxicity screening and monitoring system. C. elegans was applied to explore the sublethal toxicity of four heavy metals (copper, zinc, cadmium and chromium). Two physiological endpoints (growth and reproduction), three behavioral endpoints (head thrash frequency, body bend frequency and feeding) and two enzymatic endpoints (acetylcholine esterase [AChE] and superoxide dismutase [SOD]) were selected for the assessment of heavy metal toxicity. The squared correlation coefficients (R2) between the responses observed and fitted by Logit function were higher than 0.90 and the RMSE were lower than 0.10, indicating a good significance statistically. There was no significant difference among the half effect concentration (EC50) endpoints in physiological and behavioral effects of the four heavy metals, indicating similar sensitivity of physiological and behavioral effects. AChE enzyme was more sensitive to copper, zinc, and cadmium than to other physiological and behavioral effects, and SOD enzyme was most sensitive to chromium. The EC50 of copper, zinc, and cadmium, to the AChE enzyme in the nematodes were 0.68 mg/L, 2.76 mg/L, and 0.92 mg/L respectively and the EC50 of chromium to the SOD enzyme in the nematode was 1.58 mg/L. The results of this study showed that there was a good concentration-response relationship between all four heavy metals and the sublethal toxicity effects to C. elegans. Considering these sublethal endpoints in terms of simplicity, accuracy, repeatability and costs of the experiments, feeding is the relatively ideal sublethal toxicity endpoint of

  19. A Review of Clinical Trial Endpoints of Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension and How They Relate to Patient Outcomes in the United States.

    PubMed

    Divers, Christine; Platt, David; Wang, Edward; Lin, Jay; Lingohr-Smith, Melissa; Mathai, Stephen C

    2017-01-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are subgroups of pulmonary hypertension and are considered rare diseases. Understanding how endpoints of clinical trials (and patient registry studies) of patients with PAH and CTEPH are associated with patient outcomes is important in order to address the concerns of patients, health care providers, decision makers, and payers. The purpose of this review was to examine how endpoints used in clinical trials and patient registry studies are associated with outcomes of patients with PAH and CTEPH. A PubMed literature search was conducted to retrieve published studies, including randomized phase III clinical trials and observational studies, from years 2000 to May 2015 that evaluated the associations between change in 6-minute walking distance (6MWD), 6MWD thresholds, change in World Health Organization functional class (WHO-FC), and time to clinical worsening with outcomes of patients with PAH and CTEPH. Based on this review of published literature, a reduction in 6MWD as a criterion for PAH worsening, a deterioration in WHO-FC, and delay in the time to clinical worsening are clinically meaningful trial endpoints and are associated with outcomes of patients with PAH and CTEPH. Utilization and standardization of these endpoints will be useful for comparing interventions of clinical trials and therapies. Hospitalizations are frequent among patients with PAH and CTEPH, and total health care costs are high. From a U.S. payer perspective, clinical worsening is an important composite endpoint in that it includes hospitalization, which can be transformed into a preventative cost value associated with efficacious treatment of patients with PAH and CTEPH. In view of the greater number of medications available to treat PAH, the introduction of the first approved therapy to treat CTEPH, and the increasing use of combination pharmacotherapy, reliable prognostic markers of treatment

  20. The impact of telehealth monitoring on acute care hospitalization rates and emergency department visit rates for patients using home health skilled nursing care.

    PubMed

    Woods, Landace W; Snow, Susan W

    2013-01-01

    This article describes the design and results of a study to demonstrate the impact of telemonitoring on acute care hospitalization (ACH) and emergency department (ED) visit rates for a Medicare-certified home health agency (HHA). Sociodemographic characteristics did not significantly differ between patients in the baseline, control, and intervention groups. Patients in the telemonitoring group had a statistically lower rate of ACH and ED visit rates. Telemonitoring may be an effective strategy for HHAs to reduce hospitalization and ED visits for patients with cardiac and/or respiratory conditions.

  1. A Dynamical Modeling Approach for Analysis of Longitudinal Clinical Trials in the Presence of Missing Endpoints.

    PubMed

    Banks, H T; Hu, Shuhua; Rosenberg, Eric

    2017-01-01

    Randomized longitudinal clinical trials are the gold standard to evaluate the effectiveness of interventions among different patient treatment groups. However, analysis of such clinical trials becomes difficult in the presence of missing data, especially in the case where the study endpoints become difficult to measure because of subject dropout rates or/and the time to discontinue the assigned interventions are different among the patient groups. Here we report on using a validated mathematical model combined with an inverse problem approach to predict the values for the missing endpoints. A small randomized HIV clinical trial where endpoints for most of patients are missing is used to demonstrate this approach.

  2. Time-dependent endpoints as predictors of overall survival in multiple myeloma

    PubMed Central

    2013-01-01

    Background Supporting health care sector decisions using time-dependent endpoints (TDEs) such as time to progression (TTP), progression-free survival (PFS), and event-free survival (EFS) remains controversial. This study estimated the quantitative relationship between median TDE and median overall survival (OS) in multiple myeloma (MM) patients. Methods Studies (excluding allogeneic transplantation) published from 1970 to 2011 were systematically searched (PubMed). The nonparametric Spearman’s rank correlation coefficient measured the association between median TDE and OS. The quantitative relationship between TDEs and OS was estimated with a two-step approach to a simultaneous Tobit model. Results We identified 153 studies: 230 treatment arms, 22,696 patients and mean study duration of 3.8 years. Mean of median TDEs was 22.5 months and median OS was 39.1 months. Correlation coefficients of median TTP, PFS, and EFS with median OS were 0.51 (P = 0.003), 0.75 (P < 0.0001), and 0.84 (P < 0.0001), respectively. We estimate a 2.5 month (95% confidence interval, 1.7–3.2) increase in median OS for each additional month reported for median TDEs. There was no evidence that this relationship differed by type of surrogate. Conclusion TDEs predict OS in MM patients; this relationship may be valuable in clinical trial design, drug comparisons, and economic evaluation. PMID:23497363

  3. Determining significant endpoints for ecological risk analyses. 1997 annual progress report

    SciTech Connect

    Hinton, T.G.; Congdon, J.; Rowe, C.; Scott, D.; Bedford, J.; Whicker, F.W.

    1997-11-01

    'This report summarizes the first year''s progress of research funded under the Department of Energy''s Environmental Management Science Program. The research was initiated to better determine ecological risks from toxic and radioactive contaminants. More precisely, the research is designed to determine the relevancy of sublethal cellular damage to the performance of individuals and to identify characteristics of non-human populations exposed to chronic, low-level radiation, as is typically found on many DOE sites. The authors propose to establish a protocol to assess risks to non-human species at higher levels of biological organization by relating molecular damage to more relevant responses that reflect population health. They think that they can achieve this by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables, and by using novel biological dosimeters in controlled, manipulative dose/effects experiments. They believe that a scientifically defensible endpoint for measuring ecological risks can only be determined once its understood the extent to which molecular damage from contaminant exposure is detrimental at the individual and population levels of biological organization.'

  4. Phagocytosis in earthworms: An environmentally acceptable endpoint to assess immunotoxic potential of contaminated soils

    SciTech Connect

    Giggleman, M.A.; Fitzpatrick, L.C.; Goven, A.J.; Venables, B.J.; Callahan, C.A.

    1995-12-31

    Phagocytosis, a host-defense mechanism phylogenetically conserved throughout the animal kingdom, by earthworm (Lumbricus terrestris) coelomocytes has potential as a surrogate for vertebrates to be used as an environmentally acceptable endpoint to assess sublethal immunotoxic risks of contaminated soils to environmental (eg. higher wildlife) and public health. Coelomocytes can be exposed in vivo to complex contaminated parent soils by placing earthworms in situ at hazardous waste sites (HWS) or into soil samples and their dilutions with artificial soil (AS) in the laboratory, or in vitro to soil extracts and their fractionations. Here the authors report on phagocytosis by coelomocytes in earthworms exposed to pentachlorophenol (PCP) contaminated soils from a wood treatment HWS, PCP-spiked AS and PCP treated filter paper (FP). HWS soil was diluted to 25% with AS to a sublethal concentration (ca. 125 mg kg{sup {minus}1}) and earthworms exposed for 14d at 10 C under light conditions. AS was spiked at ca. 125 mg kg{sup {minus}1} PCP and earthworms were similarly exposed. Controls for both consisted of earthworms exposed to 100% AS. Earthworms were exposed to FP treated with a sublethal PCP concentration (15 {micro}g cm{sup {minus}2}) at 10 C under dark conditions for 96H. Controls were similarly exposed without PCP. Phagocytosis by coelomocytes in earthworms exposed to HWS soil, spiked AS and treated FP was suppressed 37, 41 and 29%, respectively. Results are discussed in terms of PCP body burdens and exposure protocols.

  5. Rare alleles within the CYP2E1 (MEOS system) could be associated with better short-term health outcome after acute methanol poisoning.

    PubMed

    Hubacek, Jaroslav A; Pelclova, Daniela; Seidl, Zdenek; Vaneckova, Manuela; Klempir, Jiri; Ruzicka, Evzen; Ridzon, Petr; Urban, Pavel; Fenclova, Zdenka; Petrik, Vit; Diblik, Pavel; Kuthan, Pavel; Miovsky, Michal; Janikova, Barbara; Adamkova, Vera; Zakharov, Sergey

    2015-02-01

    Genetic polymorphisms influence the metabolism of ethanol and methanol, but the potential effects of genetic predisposition on the clinical course, outcome and short-term health sequelae of acute methanol poisoning are unknown. To evaluate the role of the MEOS system in methanol poisoning, we analysed the effect of three polymorphisms (RsaI - rs2031920; PstI - rs3813867; insertion/deletion I/D) within the CYP2E1 enzyme (MEOS system) in 50 adult survivors of methanol poisoning and compared their genotype frequencies with 460 controls. The minor allele frequencies of all three polymorphisms were below 5% in both groups. We did not detect significant differences in the genotype frequencies between survivors of methanol poisoning and controls (p = 0.34 for the RsaI variant; p = 0.59 for the PstI variant and p = 0.21 for the I/D polymorphism). The carriers of at least one minor allele in the CYP2E1 gene had less severe clinical symptoms and better short-term outcome after acute poisoning. Variants within the CYP2E1 gene are likely not significant genetic determinants of acute methanol poisoning (if survivors are analysed), but they may influence the severity of methanol poisoning and its visual/central nervous system (CNS) outcome.

  6. Acute Alcohol Consumption and Secondary Psychopathic Traits Increase Ratings of the Attractiveness and Health of Ethnic Ingroup Faces but Not Outgroup Faces

    PubMed Central

    Mitchell, Ian J.; Gillespie, Steven M.; Leverton, Monica; Llewellyn, Victoria; Neale, Emily; Stevenson, Isobel

    2015-01-01

    Studies have consistently shown that both consumption of acute amounts of alcohol and elevated antisocial psychopathic traits are associated with an impaired ability for prepotent response inhibition. This may manifest as a reduced ability to inhibit prepotent race biased responses. Here, we tested the effects of acute alcohol consumption, and elevated antisocial psychopathic traits, on judgments of the attractiveness and health of ethnic ingroup and outgroup faces. In the first study, we show that following acute alcohol consumption, at a dose that is sufficient to result in impaired performance on tests of executive function, Caucasian participants judged White faces to be more attractive and healthier compared to when sober. However, this effect did not extend to Black faces. A similar effect was found in a second study involving sober Caucasian participants where secondary psychopathic traits were related to an intergroup bias in the ratings of attractiveness for White versus Black faces. These results are discussed in terms of a model which postulates that poor prefrontal functioning leads to increases in ingroup liking as a result of impaired abilities for prepotent response inhibition. PMID:25745403

  7. Health Risk Factors Associated with Acute Respiratory Illness Among U.S. Army Recruits Attending Basic Combat Training

    DTIC Science & Technology

    2012-06-11

    Respiratory Infections Acute respiratory infections (ARI) can involve the sinuses, pharynx (throat), tonsils, larynx (voice box), bronchi, and the lungs...respiratory tract infection (URTI) means the affected organs are primarily superior to the larynx and are generally self-limiting.20 Lower

  8. Israeli acute paralysis virus: epidemiology, pathogenesis and implications for honey bee health and Colony Collapse Disorder (CCD)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Israeli acute paralysis virus (IAPV) is a widespread RNA virus that was linked with honey bee Colony Collapse Disorder (CCD), the sudden and massive die-off of honey bee colonies in the U.S. in 2006-2007. Here we describe the transmission, prevalence and genetic diversity of IAPV, host transcripti...

  9. In-Hospital Mortality among Rural Medicare Patients with Acute Myocardial Infarction: The Influence of Demographics, Transfer, and Health Factors

    ERIC Educational Resources Information Center

    Muus, Kyle J.; Knudson, Alana D.; Klug, Marilyn G.; Wynne, Joshua

    2011-01-01

    Context/Purpose: Most rural hospitals can provide medical care to acute myocardial infarction (AMI) patients, but a need for advanced cardiac care requires timely transfer to a tertiary hospital. There is little information on AMI in-hospital mortality predictors among rural transfer patients. Methods: Cross-sectional retrospective analyses on…

  10. PREDICTING TOXICOLOGICAL ENDPOINTS OF CHEMICALS USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS)

    EPA Science Inventory

    Quantitative structure-activity relationships (QSARs) are being developed to predict the toxicological endpoints for untested chemicals similar in structure to chemicals that have known experimental toxicological data. Based on a very large number of predetermined descriptors, a...

  11. 78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-05

    ... as on scientific information that has become available to the Agency. We believe the revisions will... the Agency's current thinking on BE studies with pharmacokinetic endpoints for drug products...

  12. Health-Related Quality of Life Dynamics of HIV-positive South African Women up to ART Initiation: Evidence from the CAPRISA 002 Acute Infection Cohort Study

    PubMed Central

    Tomita, Andrew; Garrett, Nigel; Werner, Lise; Burns, Jonathan K.; Mpanza, Lindiwe; Mlisana, Koleka; van Loggerenberg, Francois; Karim, Salim S. Abdool

    2014-01-01

    Few studies have investigated the long-term dynamics in health-related quality of life (HRQoL) among HIV-positive persons from acute infection. From 2004, 160 women were enrolled into the CAPRISA 002 Acute Infection study at two sites in the province of KwaZulu-Natal and underwent 3–6 monthly HRQoL assessments using the functional assessment of HIV infection (FAHI) instrument. Overall and 5 sub-scale FAHI scores [physical well-being (PWB), emotional well-being (EWB), functional and global well-being (FGWB), social well-being (SWB) and cognitive functioning (CF)] were calculated up to antiretroviral therapy (ART) initiation and scores at enrollment were compared to the acute, early and established infection phases. Mixed-effects regression models adjusting for behavioral and clinical factors were applied to assess HRQoL trends and the proportion of women meeting minimally important differences was calculated. Our analyses revealed that overall/sub-scale scores improved over time, except from PWB and CF. A higher educational status, contraceptive use and a higher BMI were the strongest predictors of higher overall/sub-scale FAHI scores. CD4 count and HIV viral load were strongly associated with PWB and CF, but not overall FAHI and other sub-scales. Women newly diagnosed with acute HIV infection face profound HRQoL challenges. While early ART delivery may be important for PWB and CF, factors such as education, contraception provision and good nutritional status should be promoted to maximize HRQoL in HIV positive individuals. PMID:24368630

  13. Health-related quality of life dynamics of HIV-positive South African women up to ART initiation: evidence from the CAPRISA 002 acute infection cohort study.

    PubMed

    Tomita, Andrew; Garrett, Nigel; Werner, Lise; Burns, Jonathan K; Mpanza, Lindiwe; Mlisana, Koleka; van Loggerenberg, Francois; Abdool Karim, Salim S

    2014-06-01

    Few studies have investigated the long-term dynamics in health-related quality of life (HRQoL) among HIV-positive persons from acute infection. From 2004, 160 women were enrolled into the CAPRISA 002 Acute Infection study at two sites in the province of KwaZulu-Natal and underwent 3-6 monthly HRQoL assessments using the functional assessment of HIV infection (FAHI) instrument. Overall and 5 sub-scale FAHI scores [physical well-being (PWB), emotional well-being (EWB), functional and global well-being (FGWB), social well-being (SWB) and cognitive functioning (CF)] were calculated up to antiretroviral therapy (ART) initiation and scores at enrollment were compared to the acute, early and established infection phases. Mixed-effects regression models adjusting for behavioral and clinical factors were applied to assess HRQoL trends and the proportion of women meeting minimally important differences was calculated. Our analyses revealed that overall/sub-scale scores improved over time, except from PWB and CF. A higher educational status, contraceptive use and a higher BMI were the strongest predictors of higher overall/sub-scale FAHI scores. CD4 count and HIV viral load were strongly associated with PWB and CF, but not overall FAHI and other sub-scales. Women newly diagnosed with acute HIV infection face profound HRQoL challenges. While early ART delivery may be important for PWB and CF, factors such as education, contraception provision and good nutritional status should be promoted to maximize HRQoL in HIV positive individuals.

  14. Autonomous Sub-Pixel Satellite Track Endpoint Determination for Space Based Images

    SciTech Connect

    Simms, L M

    2011-03-07

    An algorithm for determining satellite track endpoints with sub-pixel resolution in spaced-based images is presented. The algorithm allows for significant curvature in the imaged track due to rotation of the spacecraft capturing the image. The motivation behind the subpixel endpoint determination is first presented, followed by a description of the methodology used. Results from running the algorithm on real ground-based and simulated spaced-based images are shown to highlight its effectiveness.

  15. 40 CFR Appendix A to Part 68 - Table of Toxic Endpoints

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....0011 75-78-5 Dimethyldichlorosilane 0.026 57-14-7 1,1-Dimethylhydrazine 0.012 106-89-8 Epichlorohydrin... Endpoints CAS No. Chemical name Toxic endpoint (mg/L) 107-02-8 Acrolein 0.0011 107-13-1 Acrylonitrile 0.076... Ammonia (anhydrous) 0.14 7664-41-7 Ammonia (conc 20% or greater) 0.14 7784-34-1 Arsenous trichloride...

  16. 40 CFR Appendix A to Part 68 - Table of Toxic Endpoints

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....0011 75-78-5 Dimethyldichlorosilane 0.026 57-14-7 1,1-Dimethylhydrazine 0.012 106-89-8 Epichlorohydrin... Endpoints CAS No. Chemical name Toxic endpoint (mg/L) 107-02-8 Acrolein 0.0011 107-13-1 Acrylonitrile 0.076... Ammonia (anhydrous) 0.14 7664-41-7 Ammonia (conc 20% or greater) 0.14 7784-34-1 Arsenous trichloride...

  17. Evaluation of three soil toxicity tests used to monitor acceptable endpoints

    SciTech Connect

    Brinkmann, M.; Stroo, H.; Leuschner, A.; Leuteritz, D.; Stromberg, M.; Brourman, M.

    1995-12-31

    Three terrestrial toxicity tests were used to evaluate the efficacy of biological treatment of creosote and pentachlorophenol impacted soils at a Superfund site. Microtox, 5-day lettuce seed, and 14-day earthworm toxicity tests were performed on 10 soil samples at the beginning and end of 3 months of land treatment. Secondary endpoints of root length and earthworm weight loss were also evaluated. EC50 and LC50 values were calculated using a Trimmed Logit Statistical Program and compared to toxicity of 10 background samples collected from the site. Results for initial soils demonstrated toxicity with three of the five endpoints. End treatment results showed no measurable toxicity using all endpoints. Toxicity testing results are critical for obtaining regulatory approval for the full-scale treatment system. Post treatment closure requirements for the site will be based on bioassay results. Evaluation of the three tests used showed the Microtox test to be the most sensitive to this type of toxicity. Lettuce seed germination results were the least sensitive of the three primary endpoints chosen. Of the secondary endpoint criteria, root length demonstrated reliable EC50 values and showed toxicity trends similar to Microtox and earthworm tests. The earthworm weight loss endpoint was not a useful toxicity measurement at 14 days.

  18. Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide

    PubMed Central

    McCurdy, Shannon R.; Kasamon, Yvette L.; Kanakry, Christopher G.; Bolaños-Meade, Javier; Tsai, Hua-Ling; Showel, Margaret M.; Kanakry, Jennifer A.; Symons, Heather J.; Gojo, Ivana; Smith, B. Douglas; Bettinotti, Maria P.; Matsui, William H.; Dezern, Amy E.; Huff, Carol Ann; Borrello, Ivan; Pratz, Keith W.; Gladstone, Douglas E.; Swinnen, Lode J.; Brodsky, Robert A.; Levis, Mark J.; Ambinder, Richard F.; Fuchs, Ephraim J.; Rosner, Gary L.; Jones, Richard J.; Luznik, Leo

    2017-01-01

    Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus-host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation. The median follow up was 4 (range, 0.02–11.4) years. Graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without grade III–IV acute graft-versus-host disease, chronic graft-versus-host disease requiring systemic treatment, relapse, or death. Chronic graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without moderate or severe chronic graft-versus-host disease, relapse, or death. One-year graft-versus-host disease-free, relapse-free survival and chronic graft-versus-host disease-free, relapse-free survival estimates were, respectively, 47% (95% CI: 41–55%) and 53% (95% CI: 46–61%) after myeloablative HLA-matched related, 42% (95% CI: 34–52%) and 52% (95% CI: 44–62%) after myeloablative HLA-matched unrelated, and 45% (95% CI: 40–50%) and 50% (95% CI: 45–55%) after non-myeloablative HLA-haploidentical donor transplantation. In multivariable models, there were no differences in graft-versus-host disease-free, or chronic graft-versus-host disease-free, relapse-free survival after either myeloablative HLA-matched unrelated or non-myeloablative HLA-haploidentical, compared with myeloablative HLA-matched related

  19. Factors influencing private health providers' technical quality of care for acute respiratory infections among under-five children in rural West Bengal, India.

    PubMed

    Chakraborty, Sarbani; Frick, Kevin

    2002-11-01

    In many developing countries, private health practitioners provide a significant portion of curative care for diseases which are of public health importance. Currently, health sector reform efforts in these countries are fostering increased participation of private providers in the delivery of health services, including those of public health importance. Guaranteeing good technical quality of care is critical to the process. However, little is known about private providers' technical quality of care (disease management practices) and the factors influencing these services. The purpose of this study was to contribute information on this topic. The study was conducted among private providers in rural West Bengal, India and focused on providers' disease management practices for acute respiratory infections (ARI) among under-five children. World Health Organization (WHO) guidelines for ARI case management were used as the expected standard of care. Observations of patient-provider encounters and interviews with the providers and mothers were the main sources of data. The study found that private health providers in rural West Bengal have inadequate technical quality of care. The problem was related both to low levels of performance (limited potential) and inconsistency in performance (within-provider variation). Limited potential for good technical quality for ARI among the providers was related to lack of knowledge (technical incompetence). One of the important factors influencing within-provider variation was patient load. Since rural private providers operate on a fee-for-service payment system, there are incentives related to seeing many patients. The study concluded that to bring about sustainable improvements in private providers' ARI disease management practices, training programs and interventions that improved compliance were necessary.

  20. A U.S. Partnership with India and Poland to Track Acute Chemical Releases to Serve Public Health

    PubMed Central

    Ruckart, Perri Zeitz; Orr, Maureen; Pałaszewska-Tkacz, Anna; Dewan, Aruna; Kapil, Vikas

    2009-01-01

    We describe a collaborative effort between the U.S., India, and Poland to track acute chemical releases during 2005–2007. In all three countries, fixed facility events were more common than transportation-related events; manufacturing and transportation/warehousing were the most frequently involved industries; and equipment failure and human error were the primary contributing factors. The most commonly released nonpetroleum substances were ammonia (India), carbon monoxide (U.S.) and mercury (Poland). More events in India (54%) resulted in victims compared with Poland (15%) and the U.S. (9%). The pilot program showed it is possible to successfully conduct international surveillance of acute hazardous substances releases with careful interpretation of the findings. PMID:19826549

  1. A hospital-level analysis of the work environment and workforce health indicators for registered nurses in Ontario's acute-care hospitals.

    PubMed

    Shamian, J; Kerr, M S; Laschinger, H K; Thomson, D

    2002-03-01

    The purpose of this study was to explore the relationship between hospital-level indicators of the work environment and aggregated indicators of health and well-being amongst registered nurses working in acute-care hospitals in Ontario, Canada. This ecological analysis used data from a self-reported survey instrument randomly allocated to nurses using a stratified sampling approach. Multivariable linear regression models were used to examine hospital-level associations for burnout, musculoskeletal pain, self-rated general health, and absence due to illness. The unit of analysis was the hospital (n = 160), with individual nurse responses (n = 6,609) aggregated within hospitals. After controlling for basic differences in nurse workforces, including mean age and education, higher (better) work-environment scores were found to be generally associated with higher health-indicator scores, while a larger proportion of full-time than part-time nurses was found to be associated with lower (poorer) health scores. This study may provide direction for policy-makers in coping with the recruitment and retention of nursing staff in light of the current nursing shortage.

  2. [Mental health care systems and provisions in the immediate and acute phase of the Great East Japan Earthquake: situational and support activities in Miyagi Prefecture].

    PubMed

    Matsumoto, Kazunori

    2014-01-01

    The Great East Japan Earthquake on March 11, 2011, which measured 9.0 on the Richter scale, was followed by a huge tsunami that caused catastrophic damage to the area extending from the Tohoku to Kanto regions. It was also accompanied by the meltdown of the Fukushima Daiichi Nuclear Power Station. Mental health service provisions were hit equally hard by the disaster, with a wide range of support and relief activities being implemented. This article reviews damage that was inflicted and support activities that were carried out in the mental health field in Miyagi Prefecture in the immediate aftermath and acute phase of the disaster, and also examines future challenges. Almost all mental health institutions in Miyagi Prefecture were affected by the disaster, and experienced difficulties such as feeding inpatients and securing necessary medication. Mental health institutions in the coastal area, in particular, were severely hit. Three hospitals-were seriously damaged by the tsunami, which forced them to make arrangements for the transfer of 300 inpatients. In the aftermath of the earthquake, it became difficult to access medical institutions, and confusion ensued regarding the provision of mental health services. Many municipalities in Miyagi Prefecture were seriously affected by the disaster, and information-gathering was crippled due to the disruption of communication and transport networks. Consequently, the administrative function regarding mental health service provisions was significantly impaired. Through official, private, and academic channels, volunteers in the field of mental health were sent to the affected areas in the immediate aftermath of the disaster. It was very difficult to coordinate these volunteers because of the confusion in gathering-information and in the chain of command for support activities. The number of support teams working in the affected areas peaked one to two months after the earthquake, but it became clear that continuous and long

  3. Gender Differences in the Trajectory of Recovery in Health Status Among Young Patients With Acute Myocardial Infarction: Results From the VIRGO Study

    PubMed Central

    Dreyer, Rachel P.; Wang, Yongfei; Strait, Kelly M.; Lorenze, Nancy P.; D’Onofrio, Gail; Bueno, Héctor; Lichtman, Judith H.; Spertus, John A.; Krumholz, Harlan M.

    2015-01-01

    Background Despite the excess risk of mortality in young women (≤55 years) following acute myocardial infarction (AMI), little is known about young women’s health status (symptoms, functioning, quality of life) during the first year of recovery after an AMI. We examined gender differences in health status over time from baseline to 12-months post AMI. Methods and Results A total of 3,501 AMI patients (67% women) aged 18-55 years were enrolled from 103 United States/24 Spanish hospitals. Data were obtained by medical record abstraction/patient interviews at baseline hospitalization, 1- and 12-months post AMI. Health status was measured by generic [Short Form-12 (SF-12), and disease specific [Seattle angina questionnaire (SAQ)] measures. We compared health status scores at all three time points, and utilized longitudinal linear mixed effects analyses to examine the independent effect of gender, adjusting for time and selected covariates. Women had significantly lower health status scores than men at each assessment (all P-values <0.0001). Following adjustment for time and all covariates, women had SF-12 physical/mental summary scores that were −0.96 (95% CI: −1.59, −0.32) and −2.36 points lower (95% CI: −2.99, −1.72) than men, as well as worse SAQ physical limitations (−2.44 points lower; 95% CI: −3.53, −1.34), more angina (−1.03 points lower; 95% CI: −1.98, −0.07), and poorer quality of life (−3.51 points lower; 95% CI: −4.80, −2.22) than men. Conclusions Although both genders recover similarly following AMI, women have poorer scores than men on all health status measures; a difference that persisted throughout the entire year after discharge. PMID:25862743

  4. Comparing three novel endpoints for developmental osteotoxicity in the embryonic stem cell test

    SciTech Connect

    Nieden, Nicole I. zur; Davis, Lesley A.; Rancourt, Derrick E.

    2010-09-01

    Birth defects belong to the most serious side effects of pharmaceutical compounds or environmental chemicals. In vivo, teratogens most often affect the normal development of bones, causing growth retardation, limb defects or craniofacial malformations. The embryonic stem cell test (EST) is one of the most promising models that allow the in vitro prediction of embryotoxicity, with one of its endpoints being bone tissue development. The present study was designed to describe three novel inexpensive endpoints to assess developmental osteotoxicity using the model compounds penicillin G (non-teratogenic), 5-fluorouracil (strong teratogen) and all-trans retinoic acid (bone teratogen). These three endpoints were: quantification of matrix incorporated calcium by (1) morphometric analysis and (2) measurement of calcium levels as well as (3) activity of alkaline phosphatase, an enzyme involved in matrix calcification. To evaluate our data, we have compared the concentration curves and resulting ID{sub 50}s of the new endpoints with mRNA expression for osteocalcin. Osteocalcin is an exclusive marker found only in mineralized tissues, is regulated upon compound treatment and reliably predicts the potential of a chemical entity acting as a bone teratogen. By comparing the new endpoints to quantitative expression of osteocalcin, which we previously identified as suitable to detect developmental osteotoxicity, we were ultimately able to illustrate IMAGE analysis and Ca{sup 2+} deposition assays as two reliable novel endpoints for the EST. This is of particular importance for routine industrial assessment of novel compounds as these two new endpoints may substitute previously used molecular read-out methods, which are often costly and time-consuming.

  5. Health-related Quality of Life (HR-QOL) and Chronic Health Conditions in Survivors of Childhood Acute Myeloid Leukemia (AML) with Down Syndrome (DS): A Report From the Children's Oncology Group.

    PubMed

    Schultz, Kris Ann P; Chen, Lu; Kunin-Batson, Alicia; Chen, Zhengjia; Woods, William G; Gamis, Alan; Kawashima, Toana; Oeffinger, Kevin C; Nicholson, H Stacy; Neglia, Joseph P

    2017-01-01

    Survival rates for children with Down syndrome (DS) and acute myeloid leukemia (AML) are high; however, little is known regarding the health-related quality of life (HR-QOL) of these survivors. Individuals who survived ≥5 years following diagnosis of childhood AML were invited to complete parent or patient-report surveys measuring HR-QOL and chronic health conditions. In total, 26 individuals with DS had a median age at diagnosis of 1.8 years (range, 0.77 to 10.9 y) and median age at interview of 15 years (range, 8.3 to 27.6 y). Participants with DS and AML were compared with AML survivors without DS whose caregiver completed a HR-QOL survey (CHQ-PF50). In total, 77% of survivors with DS reported ≥1 chronic health condition compared with 50% of AML survivors without DS (P=0.07). Mean physical and psychosocial QOL scores for children with DS and AML were statistically lower than the population mean, though not discrepant from AML survivors without DS. Although the overall prevalence of chronic health conditions in survivors with DS is higher than in survivors without DS, prior studies of children with DS have reported similarly high rates of chronic health conditions, suggesting that AML therapy may not substantially increase this risk.

  6. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  7. 2013 Space Radiation Standing Review Panel Status Review for: The Risk of Acute and Late Central Nervous System Effects from Radiation Exposure, The Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), The Risk Of Degenerative Tissue Or Other Health Effects From Radiation Exposure, and The Risk of Radiation Carcinogenesis

    NASA Technical Reports Server (NTRS)

    2014-01-01

    The Space Radiation Standing Review Panel (from here on referred to as the SRP) was impressed with the strong research program presented by the scientists and staff associated with NASA's Space Radiation Program Element and National Space Biomedical Research Institute (NSBRI). The presentations given on-site and the reports of ongoing research that were provided in advance indicated the potential Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS) and were extensively discussed by the SRP. This new data leads the SRP to recommend that a higher priority should be placed on research designed to identify and understand these risks at the mechanistic level. To support this effort the SRP feels that a shift of emphasis from Acute Radiation Syndromes (ARS) and carcinogenesis to CNS-related endpoints is justified at this point. However, these research efforts need to focus on mechanisms, should follow pace with advances in the field of CNS in general and should consider the specific comments and suggestions made by the SRP as outlined below. The SRP further recommends that the Space Radiation Program Element continue with its efforts to fill the vacant positions (Element Scientist, CNS Risk Discipline Lead) as soon as possible. The SRP also strongly recommends that NASA should continue the NASA Space Radiation Summer School. In addition to these broad recommendations, there are specific comments/recommendations noted for each risk, described in detail below.

  8. Knowledge and Awareness of Acute Human Immunodeficiency Virus Infection Among Mobile App-Using Men Who Have Sex With Men: A Missed Public Health Opportunity

    PubMed Central

    Siegler, Aaron J.; Sanchez, Travis; Sineath, R. Craig; Grey, Jeremy; Kahle, Erin; Sullivan, Patrick S.

    2015-01-01

    In a national online survey, we assessed awareness and knowledge of acute human immunodeficiency virus (HIV) infection manifestation among 1748 men who have sex with men (MSM). Only 39% of respondents were aware that acute HIV infection may be accompanied by symptoms. Education and increased access to acute HIV testing may facilitate MSM to appropriately seek acute HIV testing. PMID:26034766

  9. Acute toxicities of six manufactured nanomaterial suspensions to Daphnia magna

    NASA Astrophysics Data System (ADS)

    Zhu, Xiaoshan; Zhu, Lin; Chen, Yongsheng; Tian, Shengyan

    2009-01-01

    The rapid growth of nanotechnology is stimulating research on the potential environmental impacts of manufactured nanomaterials (MNMs). This paper summarizes a comprehensive study on the 48-h acute toxicity of water suspensions of six MNMs (i.e., ZnO, TiO2, Al2O3, C60, SWCNTs, and MWCNTs) to Daphnia magna, using immobilization and mortality as toxicological endpoints. The results show that the acute toxicities of all MNMs tested are dose dependent. The EC50 values for immobilization ranged from 0.622 mg/L (ZnO NPs) to 114.357 mg/L (Al2O3 NPs), while the LC50 values for mortality ranged from 1.511 mg/L (ZnO NPs) to 162.392 mg/L (Al2O3 NPs). In these tests, TiO2, Al2O3, and carbon-based nanomaterials were more toxic than their bulk counterparts. Moreover, D. magna were found to ingest nanomaterials from the test solutions through feeding behaviors, which indicates that the potential ecotoxicities and environmental health effects of these MNMs cannot be neglected.

  10. Development and pretesting of an electronic learning module to train health care professionals on the use of the Pediatric Respiratory Assessment Measure to assess acute asthma severity

    PubMed Central

    Lehr, Anab R; McKinney, Martha L; Gouin, Serge; Blais, Jean-Guy; Pusic, MV; Ducharme, Francine M

    2013-01-01

    BACKGROUND: Severity-specific guidelines based on the Pediatric Respiratory Assessment Measure (PRAM), a validated clinical score, reduce pediatric asthma hospitalization rates. OBJECTIVE: To develop, pretest the educational value of and revise an electronic learning module to train health care professionals on the use of the PRAM. METHODS: The respiratory efforts of 32 children with acute asthma were videotaped and pulmonary auscultation was recorded. A pilot module, composed of a tutorial and 18 clinical cases, was developed in French and English. Health care professionals completed the module and provided feedback. The performance of participants, case quality and difficulty, and learning curve were assessed using the Rasch test; quantitative and qualitative feedback served to revise the module. RESULTS: Seventy-two participants (19 physicians, 22 nurses, four respiratory therapists and 27 health care trainees) with a balanced distribution across self-declared expertise (26% beginner, 35% competent and 39% expert) were included. The accuracy of experts was superior to beginners (OR 1.79, 1.15 and 2.79, respectively). Overall performance significantly improved between the first and latter half of cases (P<0.001). Participants assessed the module to be clear (96%), relevant (98%), realistic (94%) and useful (99%) to learn the PRAM. The qualitative/quantitative analysis led to the deletion of three cases, modification of remaining cases to further enhance quality and reordering within three levels of difficulty. DISCUSSION: Using rigorous educational methods, an electronic module was developed to teach health care professionals on use of the PRAM score. Using the back-translation technique, both French and English versions were developed and validated simultaneously. The pilot module comprised a tutorial and three case-scenario sections, and was tested on a target audience of physicians, nurses, respiratory therapists and medical trainees. CONCLUSION: The final

  11. Latent variable indirect response modeling of categorical endpoints representing change from baseline.

    PubMed

    Hu, Chuanpu; Xu, Zhenhua; Mendelsohn, Alan M; Zhou, Honghui

    2013-02-01

    Accurate exposure-response modeling is important in drug development. Methods are still evolving in the use of mechanistic, e.g., indirect response (IDR) models to relate discrete endpoints, mostly of the ordered categorical form, to placebo/co-medication effect and drug exposure. When the discrete endpoint is derived using change-from-baseline measurements, a mechanistic exposure-response modeling approach requires adjustment to maintain appropriate interpretation. This manuscript describes a new modeling method that integrates a latent-variable representation of IDR models with standard logistic regression. The new method also extends to general link functions that cover probit regression or continuous clinical endpoint modeling. Compared to an earlier latent variable approach that constrained the baseline probability of response to be 0, placebo effect parameters in the new model formulation are more readily interpretable and can be separately estimated from placebo data, thus allowing convenient and robust model estimation. A general inherent connection of some latent variable representations with baseline-normalized standard IDR models is derived. For describing clinical response endpoints, Type I and Type III IDR models are shown to be equivalent, therefore there are only three identifiable IDR models. This approach was applied to data from two phase III clinical trials of intravenously administered golimumab for the treatment of rheumatoid arthritis, where 20, 50, and 70% improvement in the American College of Rheumatology disease severity criteria were used as efficacy endpoints. Likelihood profiling and visual predictive checks showed reasonable parameter estimation precision and model performance.

  12. Endpoint in plasma etch process using new modified w-multivariate charts and windowed regression

    NASA Astrophysics Data System (ADS)

    Zakour, Sihem Ben; Taleb, Hassen

    2017-02-01

    Endpoint detection is very important undertaking on the side of getting a good understanding and figuring out if a plasma etching process is done in the right way, especially if the etched area is very small (0.1%). It truly is a crucial part of supplying repeatable effects in every single wafer. When the film being etched has been completely cleared, the endpoint is reached. To ensure the desired device performance on the produced integrated circuit, the high optical emission spectroscopy (OES) sensor is employed. The huge number of gathered wavelengths (profiles) is then analyzed and pre-processed using a new proposed simple algorithm named Spectra peak selection (SPS) to select the important wavelengths, then we employ wavelet analysis (WA) to enhance the performance of detection by suppressing noise and redundant information. The selected and treated OES wavelengths are then used in modified multivariate control charts (MEWMA and Hotelling) for three statistics (mean, SD and CV) and windowed polynomial regression for mean. The employ of three aforementioned statistics is motivated by controlling mean shift, variance shift and their ratio (CV) if both mean and SD are not stable. The control charts show their performance in detecting endpoint especially W-mean Hotelling chart and the worst result is given by CV statistic. As the best detection of endpoint is given by the W-Hotelling mean statistic, this statistic will be used to construct a windowed wavelet Hotelling polynomial regression. This latter can only identify the window containing endpoint phenomenon.

  13. Treatment endpoints for resistant port wine stains with a 755 nm laser.

    PubMed

    Izikson, Leonid; Anderson, R Rox

    2009-03-01

    Laser therapy of port wine stains (PWS) resistant to pulsed dye laser is challenging and controversial. Based on the theory of selective photothermolysis, vessels in such lesions may be specifically targeted with the laser wavelength of 755 nm. There is much deeper penetration of the near-infrared light and it is difficult to visualize laser-induced changes within the deeper dermis. The recognition of an appropriate immediate endpoint response with this wavelength would be helpful. This is a clinical observations report. We present examples of an appropriate PWS tissue response endpoint based on our clinical observations in resistant PWS treated with a 755 nm laser at high fluences (40-100 J/cm(2)), 1.5-ms pulse duration, with dynamic cooling device (DCD) cooling. Mild-to-moderate PWS lightening was associated with the immediate endpoint of a transient gray color that gradually evolved into persistent deep purpura within several minutes. We also discuss the clinical endpoints that represent undertreatment and overtreatment of PWS. It is important to attain, and maintain, the correct endpoint when treating PWS with this deeply penetrating near-infrared laser at high fluences in order to (a) induce lesional lightening, and (b) avoid deep dermal burns that may produce scarring. Judicious use of the 755 nm laser can be beneficial for resistant PWS.

  14. The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial

    PubMed Central

    Massee, Laura A.; Ried, Karin; Pase, Matthew; Travica, Nikolaj; Yoganathan, Jaesshanth; Scholey, Andrew; Macpherson, Helen; Kennedy, Greg; Sali, Avni; Pipingas, Andrew

    2015-01-01

    Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered. PMID:26042037

  15. Acute effects of particulate matter on respiratory diseases, symptoms and functions:. epidemiological results of the Austrian Project on Health Effects of Particulate Matter (AUPHEP)

    NASA Astrophysics Data System (ADS)

    Neuberger, Manfred; Schimek, Michael G.; Horak, Friedrich; Moshammer, Hanns; Kundi, Michael; Frischer, Thomas; Gomiscek, Bostjan; Puxbaum, Hans; Hauck, Helger; Auphep-Team

    To examine hypotheses regarding health effects of particulate matter, we conducted time series studies in Austrian urban and rural areas. Of the pollutants measured, ambient PM 2.5 was most consistently associated with parameters of respiratory health. Time series studies applying semiparametric generalized additive models showed significant increases of respiratory hospital admissions (ICD 490-496) at age 65 and older. The early increase of 5.5% in Vienna at a lag of 2 days in males and of 5.6% per 10 μg/m 3 at a lag of 3 days in females was not observed in a nearby rural area. Another increase of respiratory admissions (mainly COPD) was observed after a lag of 10-11 days. A time series on a panel of 56 healthy preschool children showed a significant impact of the carbonaceous fraction of PM 2.5 on tidal breathing pattern assessed by inductive plethysmography. In repeated oscillometric measurements of respiratory resistance in 164 healthy elementary school children not only immediate responses to fine particulates were found but also latent ones, possibly indicating inflammatory changes in airways. It may be speculated that the improvements of urban air quality prevented measurable effects on respiratory mortality. More sensitive indicators, however, still show acute impairments of respiratory function and health in elderly and children which are associated with fine particulates and subfractions related to motor traffic.

  16. Does acute maternal stress in pregnancy affect infant health outcomes? Examination of a large cohort of infants born after the terrorist attacks of September 11, 2001

    PubMed Central

    Endara, Skye M; Ryan, Margaret AK; Sevick, Carter J; Conlin, Ava Marie S; Macera, Caroline A; Smith, Tyler C

    2009-01-01

    Background Infants in utero during the terrorist attacks of September 11, 2001 may have been negatively affected by maternal stress. Studies to date have produced contradictory results. Methods Data for this retrospective cohort study were obtained from the Department of Defense Birth and Infant Health Registry and included up to 164,743 infants born to active-duty military families. Infants were considered exposed if they were in utero on September 11, 2001, while the referent group included infants gestating in the same period in the preceding and following year (2000 and 2002). We investigated the association of this acute stress during pregnancy with the infant health outcomes of male:female sex ratio, birth defects, preterm birth, and growth deficiencies in utero and in infancy. Results No difference in sex ratio was observed between infants in utero in the first trimester of pregnancy on September 11, 2001 and infants in the referent population. Examination of the relationship between first-trimester exposure and birth defects also revealed no significant associations. In adjusted multivariable models, neither preterm birth nor growth deficiencies were significantly associated with the maternal exposure to the stress of September 11 during pregnancy. Conclusion The findings from this large population-based study suggest that women who were pregnant during the terrorist attacks of September 11, 2001 had no increased risk of adverse infant health outcomes. PMID:19619310

  17. Acute rheumatic fever and rheumatic heart disease--priorities in prevention, diagnosis and management. A report of the CSANZ Indigenous Cardiovascular Health Conference, Alice Springs 2011.

    PubMed

    Rémond, M G W; Wheaton, G R; Walsh, W F; Prior, D L; Maguire, G P

    2012-10-01

    Three priority areas in the prevention, diagnosis and management of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) were identified and discussed in detail: 1. Echocardiography and screening/diagnosis of RHD – Given the existing uncertainty it remains premature to advocate for or to incorporate echocardiographic screening for RHD into Australian clinical practice. Further research is currently being undertaken to evaluate the potential for echocardiography screening. 2. Secondary prophylaxis – Secondary prophylaxis (long acting benzathine penicillin injections) must be seen as a priority. Systems-based approaches are necessary with a focus on the development and evaluation of primary health care-based or led strategies incorporating effective health information management systems. Better/novel systems of delivery of prophylactic medications should be investigated. 3. Management of advanced RHD – National centres of excellence for the diagnosis, assessment and surgical management of RHD are required. Early referral for surgical input is necessary with multidisciplinary care and team-based decision making that includes patient, family, and local health providers. There is a need for a national RHD surgical register and research strategy for the assessment, intervention and long-term outcome of surgery and other interventions for RHD.

  18. Acute antimicrobial pesticide-related illnesses among workers in health-care facilities - California, Louisiana, Michigan, and Texas, 2002-2007.

    PubMed

    2010-05-14

    Antimicrobial pesticides (e.g., sterilizers, disinfectants, and sanitizers) are chemicals used to destroy or suppress the growth of harmful microorganisms on inanimate objects and surfaces. Health-care facilities use antimicrobial pesticides to prevent pathogen transmission from contaminated environmental surfaces. Occupational exposures to antimicrobial pesticides are known to cause adverse health effects. To assess the nature and frequency of such exposures in health-care settings, CDC analyzed data from pesticide poisoning surveillance programs in California, Louisiana, Michigan, and Texas (the only four states that regularly collect data on antimicrobial pesticide-related illness) for the period 2002-2007. This report summarizes the results of that analysis, which identified 401 cases of work-related illness associated with antimicrobial pesticide exposures in health-care facilities. Most cases were identified through workers compensation systems (61%) and occurred among females (82%) and persons aged 25-54 years (73%). The most frequent occupations reported were janitors/housekeepers (24%) and nursing/medical assistants (16%). The reported mechanism of injury usually was splashes/spills (51%). The eyes were the most common organ/system affected (55%); only 15% of the 265 persons who had exposures while handling antimicrobial pesticides reported using eye protection. Reported symptoms were mostly mild and temporary. One fatality due to acute asthma and subsequent cardiopulmonary collapse was identified. Health-care facilities should educate workers about antimicrobial pesticide hazards, promote the use of personal protective equipment (PPE) as appropriate, and implement effective risk communication strategies for antimicrobial pesticide use to prevent bystander exposure. Improved design of handling equipment might prevent handler and bystander exposure.

  19. Radiation-induced World Health Organization grade II meningiomas in young patients following prophylactic cranial irradiation for acute lymphoblastic leukemia in childhood. Three case reports.

    PubMed

    Oda, Keiko; Sato, Taku; Watanabe, Tadashi; Ichikawa, Masahiro; Ito, Eiji; Matsumoto, Yuka; Ando, Hitoshi; Sakuma, Jun; Kikuta, Atsushi; Hojo, Hiroshi; Saito, Kiyoshi

    2012-01-01

    Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation. We treated 3 young patients with World Health Organization grade II meningiomas who had previously received cranial irradiation for the treatment of childhood ALL: a cerebellopontine angle tumor in a 19-year-old woman, a petroclival tumor in a 28-year-old man, and a frontal parasagittal tumor in a 19-year-old woman. These cases were difficult to treat due to the aggressive and invasive biology of the tumors. Therefore, we recommend systematic cranial imaging and long follow-up periods for leukemia survivors to detect brain tumors before progression.

  20. Substance Use, Depression and Mental Health Functioning in Patients Seeking Acute Medical Care in an Inner-City ED

    PubMed Central

    Walton, Maureen A.; Barry, Kristin L.; Cunningham, Rebecca M.; Chermack, Stephen T.; Blow, Frederic C.

    2012-01-01

    The study investigated the behavioral health of a consecutive sample of 5,641 adult emergency department (ED) patients aged 19 through 60 presenting for medical care in a large, inner-city hospital emergency department. Twenty-three percent met criteria for major depression; average mental health functioning, as measured by the mental health component of the SF-12, was half of a standard deviation lower than in the general population; 15% met criteria for alcohol or drug abuse/dependence in the past year. Comorbidity was high. These behavioral health disorders may complicate treatment and diagnosis of the chief presenting complaint. These findings, coupled with the high rates of these disorders, suggest the importance of screening and either beginning appropriate treatment or offering appropriate referral for such disorders in ED settings. PMID:21086057

  1. FINE PARTICLES ARE MORE STRONGLY ASSOCIATED THAN COARSE PARTICLES WITH ACUTE REPIRATORY HEALTH EFFECTS IN SCHOOL CHILDREN

    EPA Science Inventory

    Numerous studies have reported associations between airborne particles and a range of respiratory outcomes from symptoms to mortality. Current attention has been focused on the characteristics of these particles responsible for the adverse health effects. We have reanalyzed three...

  2. Health care utilization for acute illnesses in an urban setting with a refugee population in Nairobi, Kenya: a cross-sectional survey

    PubMed Central

    2014-01-01

    Background Estimates place the number of refugees in Nairobi over 100,000. The constant movement of refugees between countries of origin, refugee camps, and Nairobi poses risk of introduction and transmission of communicable diseases into Kenya. We assessed the care-seeking behavior of residents of Eastleigh, a neighborhood in Nairobi with urban refugees. Methods During July and August 2010, we conducted a Health Utilization Survey in Section II of Eastleigh. We used a multistage random cluster sampling design to identify households for interview. A standard questionnaire on the household demographics, water and sanitation was administered to household caretakers. Separate questionnaires were administered to household members who had one or more of the illnesses of interest. Results Of 785 households targeted for interview, data were obtained from 673 (85.7%) households with 3,005 residents. Of the surveyed respondents, 290 (9.7%) individuals reported acute respiratory illness (ARI) in the previous 12 months, 222 (7.4%) reported fever in the preceding 2 weeks, and 54 (1.8%) reported having diarrhea in the 30 days prior to the survey. Children <5 years old had the highest frequency of all the illnesses surveyed: 17.1% (95% CI 12.2-21.9) reported ARI, 10.0% (95% CI 6.2-13.8) reported fever, and 6.9% (3.8-10.0) reported diarrhea during the time periods specified for each syndrome. Twenty-nine [7.5% (95% CI 4.3-10.7)] hospitalizations were reported among all age groups of those who sought care. Among participants who reported ≥1 illness, 330 (77.0%) sought some form of health care; most (174 [59.8%]) sought health care services from private health care providers. Fifty-five (18.9%) participants seeking healthcare services visited a pharmacy. Few residents of Eastleigh (38 [13.1%]) sought care at government-run facilities, and 24 (8.2%) sought care from a relative, a religious leader, or a health volunteer. Of those who did not seek any health care services (99 [23

  3. FluMob: Enabling Surveillance of Acute Respiratory Infections in Health-care Workers via Mobile Phones.

    PubMed

    Lwin, May Oo; Yung, Chee Fu; Yap, Peiling; Jayasundar, Karthikayen; Sheldenkar, Anita; Subasinghe, Kosala; Foo, Schubert; Jayasinghe, Udeepa Gayantha; Xu, Huarong; Chai, Siaw Ching; Kurlye, Ashwin; Chen, Jie; Ang, Brenda Sze Peng

    2017-01-01

    Singapore is a hotspot for emerging infectious diseases and faces a constant risk of pandemic outbreaks as a major travel and health hub for Southeast Asia. With an increasing penetration of smart phone usage in this region, Singapore's pandemic preparedness framework can be strengthened by applying a mobile-based approach to health surveillance and control, and improving upon existing ideas by addressing gaps, such as a lack of health communication. FluMob is a digitally integrated syndromic surveillance system designed to assist health authorities in obtaining real-time epidemiological and surveillance data from health-care workers (HCWs) within Singapore, by allowing them to report influenza incidence using smartphones. The system, integrating a fully responsive web-based interface and a mobile interface, is made available to HCW using various types of mobile devices and web browsers. Real-time data generated from FluMob will be complementary to current health-care- and laboratory-based systems. This paper describes the development of FluMob, as well as challenges faced in the creation of the system.

  4. FluMob: Enabling Surveillance of Acute Respiratory Infections in Health-care Workers via Mobile Phones

    PubMed Central

    Lwin, May Oo; Yung, Chee Fu; Yap, Peiling; Jayasundar, Karthikayen; Sheldenkar, Anita; Subasinghe, Kosala; Foo, Schubert; Jayasinghe, Udeepa Gayantha; Xu, Huarong; Chai, Siaw Ching; Kurlye, Ashwin; Chen, Jie; Ang, Brenda Sze Peng

    2017-01-01

    Singapore is a hotspot for emerging infectious diseases and faces a constant risk of pandemic outbreaks as a major travel and health hub for Southeast Asia. With an increasing penetration of smart phone usage in this region, Singapore’s pandemic preparedness framework can be strengthened by applying a mobile-based approach to health surveillance and control, and improving upon existing ideas by addressing gaps, such as a lack of health communication. FluMob is a digitally integrated syndromic surveillance system designed to assist health authorities in obtaining real-time epidemiological and surveillance data from health-care workers (HCWs) within Singapore, by allowing them to report influenza incidence using smartphones. The system, integrating a fully responsive web-based interface and a mobile interface, is made available to HCW using various types of mobile devices and web browsers. Real-time data generated from FluMob will be complementary to current health-care- and laboratory-based systems. This paper describes the development of FluMob, as well as challenges faced in the creation of the system. PMID:28367433

  5. Capitals diminished, denied, mustered and deployed. A qualitative longitudinal study of women's four year trajectories after acute health crisis, Burkina Faso

    PubMed Central

    Murray, Susan F.; Akoum, Mélanie S.; Storeng, Katerini T.

    2012-01-01

    Accumulating evidence indicates that health crises can play a key role in precipitating or exacerbating poverty. For women of reproductive age in low-income countries, the complications of pregnancy are a common cause of acute health crisis, yet investigation of longer-term dynamics set in motion by such events, and their interactions with other aspects of social life, is rare. This article presents findings from longitudinal qualitative research conducted in Burkina Faso over 2004–2010. Guided by an analytic focus on patterns of continuity and change, and drawing on recent discussions on the notion of ‘resilience’, and the concepts of ‘social capital’ and ‘bodily capital’, we explore the trajectories of 16 women in the aftermath of costly acute healthcare episodes. The synthesis of case studies shows that, in conditions of structural inequity and great insecurity, an individual's social capital ebbs and flow over time, resulting in a trajectory of multiple adaptations. Women's capacity to harness or exploit bodily capital in its various forms (beauty, youthfulness, physical strength, fertility) to some extent determines their ability to confront and overcome adversities. With this, they are able to further mobilise social capital without incurring excessive debt, or to access and accumulate significant new social capital. Temporary self-displacement, often to the parental home, is also used as a weapon of negotiation in intra-household conflict and to remind others of the value of one's productive and domestic labour. Conversely, diminished bodily capital due to the physiological impact of an obstetric event or its complications can lead to reduced opportunities, and to further disadvantage. PMID:23063215

  6. Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

    PubMed

    Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

    2016-04-01

    Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations.

  7. Sample size determination in group-sequential clinical trials with two co-primary endpoints.

    PubMed

    Asakura, Koko; Hamasaki, Toshimitsu; Sugimoto, Tomoyuki; Hayashi, Kenichi; Evans, Scott R; Sozu, Takashi

    2014-07-30

    We discuss sample size determination in group-sequential designs with two endpoints as co-primary. We derive the power and sample size within two decision-making frameworks. One is to claim the test intervention's benefit relative to control when superiority is achieved for the two endpoints at the same interim timepoint of the trial. The other is when superiority is achieved for the two endpoints at any interim timepoint, not necessarily simultaneously. We evaluate the behaviors of sample size and power with varying design elements and provide a real example to illustrate the proposed sample size methods. In addition, we discuss sample size recalculation based on observed data and evaluate the impact on the power and Type I error rate.

  8. The Feynman trajectories: determining the path of a protein using fixed-endpoint assays.

    PubMed

    Ketteler, Robin

    2010-03-01

    Richard Feynman postulated in 1948 that the path of an electron can be best described by the sum or functional integral of all possible trajectories rather than by the notion of a single, unique trajectory. As a consequence, the position of an electron does not harbor any information about the paths that contributed to this position. This observation constitutes a classical endpoint observation. The endpoint assay is the desired type of experiment for high-throughput screening applications, mainly because of limitations in data acquisition and handling. Quite contrary to electrons, it is possible to extract information about the path of a protein using endpoint assays, and these types of applications are reviewed in this article.

  9. Radiation acquisition and RBF neural network analysis on BOF end-point control

    NASA Astrophysics Data System (ADS)

    Zhao, Qi; Wen, Hong-yuan; Zhou, Mu-chun; Chen, Yan-ru

    2008-12-01

    There are some problems in Basic Oxygen Furnace (BOF) steelmaking end-point control technology at present. A new BOF end-point control model was designed, which was based on the character of carbon oxygen reaction in Basic Oxygen Furnace steelmaking process. The image capture and transformation system was established by Video for Windows (VFW) library function, which is a video software development package promoted by Microsoft Corporation. In this paper, the Radial Basic Function (RBF) neural network model was established by using the real-time acquisition information. The input parameters can acquire easily online and the output parameter is the end-point time, which can compare with the actual value conveniently. The experience results show that the predication result is ideal and the experiment results show the model can work well in the steelmaking adverse environment.

  10. Equivalency of risk for a modified health endpoint: a case from recreational water epidemiology studies

    EPA Science Inventory

    The United States Environmental Protection Agency (US EPA) and its predecessors have conducted three distinct series of epidemiological studies beginning in 1948 on the relationship between bathing water quality and swimmers' illnesses. Keeping pace with advances in microbial tec...

  11. The Developing Brain: A Largely Overlooked Health Endpoint in Risk Assessments for Synthetic Chemical Substances

    ERIC Educational Resources Information Center

    McElgunn, Barbara

    2010-01-01

    A large body of experimental animal research on the neurotoxic effects of certain environmental chemicals provides evidence of a cascade of neurobehavioural effects including learning deficits, hyperactivity, anxiety, depression, lack of motivation, increased aggressiveness, altered maternal care and bonding, and an over-reaction to small…

  12. Multiple endpoints for somatic mutations in humans provide complementary views for biodosimetry, genotoxicity, and health risks

    SciTech Connect

    Jensen, R.H.; Bigbee, W.L.; Langlois, R.G.

    1989-07-24

    There are now four somatic cell mutation assays that are being used to determine in vivo mutagenesis in humans. Each assay is identified by an acronym that specifies the protein in which mutations are determined: HPRT assay, GPA assay, HLA assay, and Hb assay. Potentially, each assay can be used for either of two important applications; biodosimetry or cancer risk estimation. Biodosimetry is a means for determining the amount of exposure of an individual to a toxic agent by measuring the biological effect on the individual who was exposed. Based on the observation that many toxic chemicals and ionizing radiation are mutagenic to cells in culture and also to animals, the somatic mutation assays also should serve as biodosimeters for exposure of humans to these genotoxic phenomena. These four somatic mutation assays should contribute to the possibility of estimating each individual's risk of developing cancer by monitoring for the presence of genotoxicity events similar to cancer initiation events or cancer promotion events on suppressor genes. 16 refs., 4 tabs.

  13. Acute Bronchitis

    MedlinePlus

    ... Health & Wellness > Health Professionals Lung Health & Wellness > Healthy Air (Indoor & Outdoor) Lung Health & Wellness > LUNG FORCE Updates Lung Health & Wellness > Quit Smoking Lung Health & ...

  14. Bayesian meta-analytical methods to incorporate multiple surrogate endpoints in drug development process.

    PubMed

    Bujkiewicz, Sylwia; Thompson, John R; Riley, Richard D; Abrams, Keith R

    2016-03-30

    A number of meta-analytical methods have been proposed that aim to evaluate surrogate endpoints. Bivariate meta-analytical methods can be used to predict the treatment effect for the final outcome from the treatment effect estimate measured on the surrogate endpoint while taking into account the uncertainty around the effect estimate for the surrogate endpoint. In this paper, extensions to multivariate models are developed aiming to include multiple surrogate endpoints with the potential benefit of reducing the uncertainty when making predictions. In this Bayesian multivariate meta-analytic framework, the between-study variability is modelled in a formulation of a product of normal univariate distributions. This formulation is particularly convenient for including multiple surrogate endpoints and flexible for modelling the outcomes which can be surrogate endpoints to the final outcome and potentially to one another. Two models are proposed, first, using an unstructured between-study covariance matrix by assuming the treatment effects on all outcomes are correlated and second, using a structured between-study covariance matrix by assuming treatment effects on some of the outcomes are conditionally independent. While the two models are developed for the summary data on a study level, the individual-level association is taken into account by the use of the Prentice's criteria (obtained from individual patient data) to inform the within study correlations in the models. The modelling techniques are investigated using an example in relapsing remitting multiple sclerosis where the disability worsening is the final outcome, while relapse rate and MRI lesions are potential surrogates to the disability progression.

  15. Effect of Pre-Fixation Delay and Freezing on Mink Testicular Endpoints for Environmental Research

    PubMed Central

    Spörndly-Nees, Ellinor; Ekstedt, Elisabeth; Magnusson, Ulf; Fakhrzadeh, Azadeh; Luengo Hendriks, Cris L.; Holm, Lena

    2015-01-01

    There is growing interest in using wild animals to monitor the real-life cocktail effect of environmental chemicals on male reproduction. However, practical difficulties, such as long distances to the laboratory, generally prolong the time between euthanisation and specimen handling. For instance, tissue fixation is often performed on frozen material or on material where deterioration has started, which may affect tissue morphology. This study examined the effect of pre-fixation delay and freezing on mink testicular endpoints in order to determine robust endpoints in suboptimally handled specimens. Sexually mature farmed mink (n=30) selected at culling were divided into six groups and subjected to different time intervals between euthanisation and fixation or freezing: 0 hours (fixed immediately post mortem), 6 hours, 18 hours, 30 hours, 42 hours, or frozen 6 hours post mortem and thawed overnight. Unaffected endpoints when pre-fixation storage was extended to 30 hours included: area and diameter of the seminiferous tubules, length and weight of the testes, and acrosomes marked with Gata-4. Epithelial height, Sertoli cells marked with Gata-4 and cell morphology were affected endpoints after 6 hours of storage. Freezing the tissue prior to fixation severely altered cell morphology and reduced testicular weight, tubular diameter and area. Morphological changes seen after 6 hours included shredded germ cells and excess cytoplasm in seminiferous tubular lumen, chromatin rearrangements and increased germ cell death. Extended delay before fixation and freezing affected many endpoints in the mink testicular tissue. Some of these endpoints may mimic chemically induced effects, which is important to consider when evaluating specimens from wild animals for environmental toxicity. PMID:25933113

  16. Multi-level assessment of chronic toxicity of estuarine sediments with the amphipod Gammarus locusta: II. Organism and population-level endpoints.

    PubMed

    Costa, Filipe O; Neuparth, Teresa; Correia, Ana D; Costa, Maria Helena

    2005-07-01

    This study aimed to test the performance of the amphipod Gammarus locusta (L.) in chronic sediment toxicity tests. It constitutes part of a multi-level assessment of chronic toxicity of estuarine sediments, integrating organism and population-level endpoints with biochemical markers responses. Here we account for organism and population-level effects, while biomarker responses were reported in a companion article. Five moderately contaminated sediments from Sado and Tagus estuaries were tested, comprising 3 muddy and 2 sandy sediments. These sediments either did not show acute toxicity or were diluted with control sediment as much as required to remove acute toxicity. Subsequent chronic tests consisted of 28-day exposures with survival, individual growth and reproductive traits as endpoints. Two of the muddy sediments induced higher growth rates in the amphipods, and improved reproductive traits. This was understood to be a consequence of the amount of organic matter in the sediment, which was nutritionally beneficial to the amphipods, while concurrently decreasing contaminant bioavailability. Biomarker responses did not reveal toxicant-induced stress in amphipods exposed to these sediments. One of the sandy sediments was acutely toxic at 50% dilution, but in contrast stimulated amphipod growth when diluted 75%. This was presumed to be an indication of a hormetic response. Finally the two remaining contaminated sediments showed pronounced chronic toxicity, affecting survival and reproduction. The sex ratio of survivors was highly biased towards females, and offspring production was severely impaired. The particulars of the responses of this amphipod were examined, as well as strengths versus limitations of the sediment test. This study illustrates the utility of this chronic test for toxicity assessment of contaminated estuarine sediments, with potential application all along Atlantic Europe.

  17. Review of the health effects of wildland fire smoke on wildland firefighters and the public.

    PubMed

    Adetona, Olorunfemi; Reinhardt, Timothy E; Domitrovich, Joe; Broyles, George; Adetona, Anna M; Kleinman, Michael T; Ottmar, Roger D; Naeher, Luke P

    2016-01-01

    Each year, the general public and wildland firefighters in the US are exposed to smoke from wildland fires. As part of an effort to characterize health risks of breathing this smoke, a review of the literature was conducted using five major databases, including PubMed and MEDLINE Web of Knowledge, to identify smoke components that present the highest hazard potential, the mechanisms of toxicity, review epidemiological studies for health effects and identify the current gap in knowledge on the health impacts of wildland fire smoke exposure. Respiratory events measured in time series studies as incidences of disease-caused mortality, hospital admissions, emergency room visits and symptoms in asthma and chronic obstructive pulmonary disease patients are the health effects that are most commonly associated with community level exposure to wildland fire smoke. A few recent studies have also determined associations between acute wildland fire smoke exposure and cardiovascular health end-points. These cardiopulmonary effects were mostly observed in association with ambient air concentrations of fine particulate matter (PM2.5). However, research on the health effects of this mixture is currently limited. The health effects of acute exposures beyond susceptible populations and the effects of chronic exposures experienced by the wildland firefighter are largely unknown. Longitudinal studies of wildland firefighters during and/or after the firefighting career could help elucidate some of the unknown health impacts of cumulative exposure to wildland fire smoke, establish occupational exposure limits and help determine the types of exposure controls that may be applicable to the occupation.

  18. Calculation of a velocity distribution from particle trajectory end-points.

    USGS Publications Warehouse

    Rasmussen, Lowell A.

    1983-01-01

    The longitudinal component of the velocity of a particle at or near a glacier surface is considered, its position as a function of time being termed its trajectory. Functional relationships are derived for obtaining the trajectory from the spatial distribution of velocity and for obtaining the velocity distribution from the trajectory. It is established that the trajectory end-points impose only an integral condition on the velocity distribution and that no individual point on the velocity distribution can be determined if only the end-points are known.-from Author

  19. Flexible stopping boundaries when changing primary endpoints after unblinded interim analyses.

    PubMed

    Chen, Liddy M; Ibrahim, Joseph G; Chu, Haitao

    2014-01-01

    It has been widely recognized that interim analyses of accumulating data in a clinical trial can inflate type I error. Different methods, from group sequential boundaries to flexible alpha spending functions, have been developed to control the overall type I error at prespecified level. These methods mainly apply to testing the same endpoint in multiple interim analyses. In this article, we consider a group sequential design with preplanned endpoint switching after unblinded interim analyses. We extend the alpha spending function method to group sequential stopping boundaries when the parameters can be different between interim, or between interim and final analyses.

  20. Acute Myeloid Leukemia (AML) (For Parents)

    MedlinePlus

    ... Your 1- to 2-Year-Old Acute Myeloid Leukemia (AML) KidsHealth > For Parents > Acute Myeloid Leukemia (AML) ... Treatment Coping en español Leucemia mieloide aguda About Leukemia Leukemia is a type of cancer that affects ...

  1. Effects of bifenthrin exposure in soil on whole-organism endpoints and biomarkers of earthworm Eisenia fetida.

    PubMed

    Li, Lingling; Yang, Da; Song, Yufang; Shi, Yi; Huang, Bin; Yan, Jun; Dong, Xinxin

    2017-02-01

    In this study, toxic effects of bifenthrin in soil on earthworms were evaluated by acute and chronic toxic endpoints combined with a set of biomarkers. Bifenthrin was moderately toxic in 72-h filter paper test and low toxic in 14-d soil test. The exposure of earthworms to bifenthrin-polluted soil for 8 weeks showed that cocoons were inhibited by high dose of bifenthrin, and larvae were stimulated by low dose but inhibited by high dose of bifenthrin. Furthermore, 28-d soil test on the responses of enzymes associated with antioxidation and detoxification in worms showed that peroxidase (POD) was stimulated by bifenthrin, superoxide dismutase (SOD) inhibited in the early period but stimulated in the later period, glutathione S- transferase (GST) inhibited in the later period, and ethoxyresorufin-O-deethylase (EROD) inhibited at day 3 but markedly stimulated at day 28 at high dose. The different responses of these indexes indicated that multi indexes should be jointly taken into account for comprehensive evaluation of the environmental risk of contaminants in soil.

  2. [Problematic substance abuse and history of suicidal behavior in female patients in an acute mental health service].

    PubMed

    Camino, Sebastián; Expósito, Ramiro; Rodante, Demián

    2016-07-01

    Current publications that analyze operational and epidemiologic variables in the Argentinian Mental Health System are scarce. Several international studies have found a correlation between substance abuse and suicidal behavior. However, to our knowledge, there are no local studies that verify this association, especially in hospitalized female patients. The aim of this study is to verify this association in a population of female patients hospitalized in a Mental Health Hospital between august 2007 and july 2013. The electronic database of the Emergency department of the "Braulio A. Moyano" Neuropsychiatric Hospital was used as secondary source. The correlation between problematic substance use and history of suicidal behavior was studied, according to the type of substance used, diagnosis and age of the sample. These results might allow the creation of hypotheses that may benefit the planning and clinical practice in mental health in the local area.

  3. Acute porphyric disorders.

    PubMed

    Moore, A W; Coke, J M

    2000-09-01

    Acute porphyrias are classified into 3 distinct groups of rare genetic disorders of metabolic enzyme biosynthesis. Acute porphyrias can significantly impact multiple organ systems, which often provides a challenge to the dentist presented with such a patient. A case of hereditary coproporphyria is reported in a patient with many of the classical signs and symptoms. The patient also had complex dental needs that required special medical and pharmacotherapeutic modifications. The acute porphyrias are reviewed by the authors with presentation of this challenging case. Recommendations for other dental health care professionals encountering these patients are then presented.

  4. Movement trajectory smoothness is not associated with the endpoint accuracy of rapid multi-joint arm movements in young and older adults.

    PubMed

    Poston, Brach; Van Gemmert, Arend W A; Sharma, Siddharth; Chakrabarti, Somesh; Zavaremi, Shahrzad H; Stelmach, George

    2013-06-01

    The minimum variance theory proposes that motor commands are corrupted by signal-dependent noise and smooth trajectories with low noise levels are selected to minimize endpoint error and endpoint variability. The purpose of the study was to determine the contribution of trajectory smoothness to the endpoint accuracy and endpoint variability of rapid multi-joint arm movements. Young and older adults performed arm movements (4 blocks of 25 trials) as fast and as accurately as possible to a target with the right (dominant) arm. Endpoint accuracy and endpoint variability along with trajectory smoothness and error were quantified for each block of trials. Endpoint error and endpoint variance were greater in older adults compared with young adults, but decreased at a similar rate with practice for the two age groups. The greater endpoint error and endpoint variance exhibited by older adults were primarily due to impairments in movement extent control and not movement direction control. The normalized jerk was similar for the two age groups, but was not strongly associated with endpoint error or endpoint variance for either group. However, endpoint variance was strongly associated with endpoint error for both the young and older adults. Finally, trajectory error was similar for both groups and was weakly associated with endpoint error for the older adults. The findings are not consistent with the predictions of the minimum variance theory, but support and extend previous observations that movement trajectories and endpoints are planned independently.

  5. Improvement in latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint in rheumatoid arthritis.

    PubMed

    Hu, Chuanpu; Zhou, Honghui

    2016-02-01

    Improving the quality of exposure-response modeling is important in clinical drug development. The general joint modeling of multiple endpoints is made possible in part by recent progress on the latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate, when modeling a continuous and a categorical clinical endpoint, the level of improvement achievable by joint modeling in the latent variable IDR modeling framework through the sharing of model parameters for the individual endpoints, guided by the appropriate representation of drug and placebo mechanism. This was illustrated with data from two phase III clinical trials of intravenously administered mAb X for the treatment of rheumatoid arthritis, with the 28-joint disease activity score (DAS28) and 20, 50, and 70% improvement in the American College of Rheumatology (ACR20, ACR50, and ACR70) disease severity criteria were used as efficacy endpoints. The joint modeling framework led to a parsimonious final model with reasonable performance, evaluated by visual predictive check. The results showed that, compared with the more common approach of separately modeling the endpoints, it is possible for the joint model to be more parsimonious and yet better describe the individual endpoints. In particular, the joint model may better describe one endpoint through subject-specific random effects that would not have been estimable from data of this endpoint alone.

  6. SEMICONDUCTOR TECHNOLOGY A signal processing method for the friction-based endpoint detection system of a CMP process

    NASA Astrophysics Data System (ADS)

    Chi, Xu; Dongming, Guo; Zhuji, Jin; Renke, Kang

    2010-12-01

    A signal processing method for the friction-based endpoint detection system of a chemical mechanical polishing (CMP) process is presented. The signal process method uses the wavelet threshold denoising method to reduce the noise contained in the measured original signal, extracts the Kalman filter innovation from the denoised signal as the feature signal, and judges the CMP endpoint based on the feature of the Kalman filter innovation sequence during the CMP process. Applying the signal processing method, the endpoint detection experiments of the Cu CMP process were carried out. The results show that the signal processing method can judge the endpoint of the Cu CMP process.

  7. Estimating the spatial distribution of acute undifferentiated fever (AUF) and associated risk factors using emergency call data in India. A symptom-based approach for public health surveillance.

    PubMed

    Kauhl, Boris; Pilot, Eva; Rao, Ramana; Gruebner, Oliver; Schweikart, Jürgen; Krafft, Thomas

    2015-01-01

    The System for Early-warning based on Emergency Data (SEED) is a pilot project to evaluate the use of emergency call data with the main complaint acute undifferentiated fever (AUF) for syndromic surveillance in India. While spatio-temporal methods provide signals to detect potential disease outbreaks, additional information about socio-ecological exposure factors and the main population at risk is necessary for evidence-based public health interventions and future preparedness strategies. The goal of this study is to investigate whether a spatial epidemiological analysis at the ecological level provides information on urban-rural inequalities, socio-ecological exposure factors and the main population at risk for AUF. Our results displayed higher risks in rural areas with strong local variation. Household industries and proximity to forests were the main socio-ecological exposure factors and scheduled tribes were the main population at risk for AUF. These results provide additional information for syndromic surveillance and could be used for evidence-based public health interventions and future preparedness strategies.

  8. An estimate of the cost of acute health effects from food- and water-borne marine pathogens and toxins in the USA.

    PubMed

    Ralston, Erin P; Kite-Powell, Hauke; Beet, Andrew

    2011-12-01

    Large and growing segments of the United States population consume seafood or engage in marine recreation. These activities provide significant benefits but also bring risk of exposure to marine-borne illness. To manage these risks, it is important to understand the incidence and cost of marine-borne disease. We review the literature and surveillance/monitoring data to determine the annual incidence of disease and health consequences due to marine-borne pathogens from seafood consumption and beach recreation in the USA. Using this data, we employ a cost-of-illness model to estimate economic impacts. Our results suggest that health consequences due to marine-borne pathogens in the USA have annual costs on the order of US$900 million. This includes US$350 million due to pathogens and marine toxins specifically identified as causing food-borne disease, an estimated US$300 million due to seafood-borne disease with unknown etiology, US$30 million from direct exposure to the Vibrio species, and US$300 million due to gastrointestinal illness from beach recreation. Although there is considerable uncertainty about the degree of underreporting of certain pathogen-specific acute marine-related illnesses, the conservative assumptions we have used in constructing our estimate suggest that it should be considered a lower bound on true costs.

  9. [Good practice in occupational health services--Certification of stroke as an accident at work. Need for secondary prevention in people returning to work after acute cerebrovascular events].

    PubMed

    Marcinkiewicz, Andrzej; Walusiak-Skorupa, Jolanta

    2015-01-01

    The classification of an acute vascular episode, both heart infarct and stroke, as an accident at work poses difficulties not only for post accidental teams, but also to occupational health professionals, experts and judges at labor and social insurance courts. This article presents the case of a 41-year-old office worker, whose job involved client services. While attending a very aggressive customer she developed solid stress that resulted in symptoms of the central nervous system (headache, speech disturbances). During her hospitalisation at the neurological unit ischemic stroke with transient mixed type aphasia was diagnosed. Magnetic resonance imaging (MRI) scan of the head revealed subacute ischemia. After an analysis of the accident circumstances, the employer's post accidental team decided that ischemic stroke had been an accident at work, because it was a sudden incident due to an external cause inducing work-related traumatic stroke. As a primary cause tough stress and emotional strain due to the situation developed while attending the customer were acknowledged. During control medical check up after 5 months the patient was found to be fit for work, so she could return to work. However, it should be noted that such a check up examination of subjects returning to work after stroke must be holistic, including the evaluation of job predispositions and health education aimed at secondary prevention of heart and vascular diseases with special reference to their risk factors.

  10. Acute phase reaction and acute phase proteins*

    PubMed Central

    Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.

    2005-01-01

    A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. PMID:16252337

  11. Association between health information, use of protective devices and occurrence of acute health problems in the Prestige oil spill clean-up in Asturias and Cantabria (Spain): a cross-sectional study

    PubMed Central

    Carrasco, José Miguel; Lope, Virginia; Pérez-Gómez, Beatriz; Aragonés, Nuria; Suárez, Berta; López-Abente, Gonzalo; Rodríguez-Artalejo, Fernando; Pollán, Marina

    2006-01-01

    Background This paper examines the association between use of protective devices, frequency of acute health problems and health-protection information received by participants engaged in the Prestige oil spill clean-up in Asturias and Cantabria, Spain. Methods We studied 133 seamen, 135 bird cleaners, 266 volunteers and 265 paid workers selected by random sampling, stratified by type of worker and number of working days. Information was collected by telephone interview conducted in June 2003. The association of interest was summarized, using odds ratios (OR) obtained from logistic regression. Results Health-protection briefing was associated with use of protective devices and clothing. Uninformed subjects registered a significant excess risk of itchy eyes (OR:2.89; 95%CI:1.21–6.90), nausea/vomiting/dizziness (OR:2.25; 95%CI:1.17–4.32) and throat and respiratory problems (OR:2.30; 95%CI:1.15–4.61). There was a noteworthy significant excess risk of headaches (OR:3.86: 95%CI:1.74–8.54) and respiratory problems (OR:2.43; 95%CI:1.02–5.79) among uninformed paid workers. Seamen, the group most exposed to the fuel-oil, were the worst informed and registered the highest frequency of toxicological problems. Conclusion Proper health-protection briefing was associated with greater use of protective devices and lower frequency of health problems. Among seamen, however, the results indicate poorer dissemination of information and the need of specific guidelines for removing fuel-oil at sea. PMID:16390547

  12. Acute otitis media and acute bacterial sinusitis.

    PubMed

    Wald, Ellen R

    2011-05-01

    Acute otitis media and acute bacterial sinusitis are 2 of the most common indications for antimicrobial agents in children. Together, they are responsible for billions of dollars of health care expenditures. The pathogenesis of the 2 conditions is identical. In the majority of children with each condition, a preceding viral upper respiratory tract infection predisposes to the development of the acute bacterial complication. It has been shown that viral upper respiratory tract infection predisposes to the development of acute otitis media in 37% of cases. Currently, precise microbiologic diagnosis of acute otitis media and acute bacterial sinusitis requires performance of tympanocentesis in the former and sinus aspiration in the latter. The identification of a virus from the nasopharynx in either case does not obviate the need for antimicrobial therapy. Furthermore, nasal and nasopharyngeal swabs are not useful in predicting the results of culture of the middle ear or paranasal sinus. However, it is possible that a combination of information regarding nasopharyngeal colonization with bacteria and infection with specific viruses may inform treatment decisions in the future.

  13. ECOLOGICAL ENDPOINT MODELING FOR TMDLS: EFFECTS OF SEDIMENT ON FISH POPULATIONS

    EPA Science Inventory

    Sediment is one of the primary stressors of concern for Total Maximum Daily Loads (TMDLs) for streams, and often it is a concern because of its impact on ecological endpoints. A modeling approach relating sediment to stream fish population dynamics is presented. Equations are d...

  14. Selecting surrogate endpoints for estimating pesticide effects on avian reproductive success

    EPA Science Inventory

    A Markov chain nest productivity model (MCnest) has been developed for projecting the effects of a specific pesticide-use scenario on the annual reproductive success of avian species of concern. A critical element in MCnest is the use of surrogate endpoints, defined as measured ...

  15. EFFECTS OF COPPER ON COMMUNITY, FUNCTIONAL, AND BEHAVIORAL ENDPOINTS IN AN ARTIFICIAL STREAM STUDY

    EPA Science Inventory

    A study of the effects of copper on biota and behavioral endpoints was carried out at the U.S. EPA's Experimental Stream Facility (ESF), Milford OH. The objective of the study was to identify relationships between structural (macrobenthos and periphyton indices), functional (inte...

  16. Shape and Steepness of Toxicological Dose-Response Relationships of Continuous Endpoints

    EPA Science Inventory

    A re-analysis of a large number of historical dose-response data for continuous endpoints indicates that an exponential or a Hill model with four parameters both adequately describe toxicological dose-responses. The four parameters relate to the background response, the potency o...

  17. Development of a Computer Model for Prediction of PCB Degradation Endpoints

    SciTech Connect

    Just, E.M.; Klasson, T.

    1999-12-07

    Several researchers have demonstrated the transformation if polychlorinated biphenyls (PCBs) by both aerobic and anaerobic bacteria. This transformation, or conversion, is characteristic and often dependent on PCB congener structure and in addition, dictates the products or endpoints. Since transformation is linked to microbial activities, bioremediation has been hailed as a possible solution for PCB-contaminated soils and sediments, and several demonstration activities have verified laboratory results. This paper presents results from mathematical modeling of PCB transformation as a means of predicting possible endpoints of bioremediation. Since transformation can be influenced by both starting composition of the PCBs and microbial activity, this paper systematically evaluates several of the most common transformation patterns. The predicted data are also compared with experimental results. For example, the correlation between laboratory-observed and predicted endpoint data was, in some cases, as good as 0.98 (perfect correlation = 1.0). In addition to predicting chemical endpoints, the possible human effects of the PCBs are discussed through the use of documented dioxin-like toxicity and accumulation in humans before and after transformation.

  18. Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints.

    PubMed

    Bujkiewicz, Sylwia; Thompson, John R; Spata, Enti; Abrams, Keith R

    2015-08-13

    We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta-analytical methods are implemented using illustrative examples in relapsing-remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions.

  19. Predictive Signatures from ToxCast Data for Chronic, Developmental and Reproductive Toxicity Endpoints

    EPA Science Inventory

    The EPA ToxCast program is using in vitro assay data and chemical descriptors to build predictive models for in vivo toxicity endpoints. In vitro assays measure activity of chemicals against molecular targets such as enzymes and receptors (measured in cell-free and cell-based sys...

  20. Detecting Blending End-Point Using Mean Squares Successive Difference Test and Near-Infrared Spectroscopy.

    PubMed

    Khorasani, Milad; Amigo, José M; Bertelsen, Poul; Van Den Berg, Frans; Rantanen, Jukka

    2015-08-01

    An algorithm based on mean squares successive difference test applied to near-infrared and principal component analysis scores was developed to monitor and determine the blending profile and to assess the end-point in the statistical stabile phase. Model formulations consisting of an active compound (acetylsalicylic acid), together with microcrystalline cellulose and two grades of calcium carbonate with dramatically different particle shapes, were prepared. The formulation comprising angular-shaped calcium carbonate reached blending end-point slower when compared with the formulation comprising equant-shaped calcium carbonate. Utilizing the ring shear test, this distinction in end-point could be related to the difference in flowability of the formulations. On the basis of the two model formulations, a design of experiments was conducted to characterize the blending process by studying the effect of CaCO3 grades and fill level of the bin on blending end-point. Calcium carbonate grades, fill level, and their interaction were shown to have a significant impact on the blending process.

  1. Developing ecosystem services-based assessment endpoints for determining ecological risks to estuarine environments

    EPA Science Inventory

    Current U.S. EPA ecological risk assessment (ERA) guidance defines an assessment endpoint (AE) as an explicit expression of the environmental value that is to be protected, and recommends that AEs are selected based on ecological relevance, susceptibility to known or potential st...

  2. LIFE CYCLE IMPACT ASSESSMENT WORKSHOP SUMMARY - MIDPOINTS VERSUS ENDPOINTS: THE SACRIFICES AND BENEFITS

    EPA Science Inventory

    On 5/25-26/2000 in Brighton, England, the third international workshop was held under the umbrella of UNEP addressing issues in Life Cycle Impact Assessment (LCIA). The workshop provided a forum for experts to discuss midpoint vs. endpoint modeling. Midpoints are considered to be...

  3. 77 FR 49447 - Endpoints for Clinical Trials in Kidney Transplantation; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... HUMAN SERVICES Food and Drug Administration Endpoints for Clinical Trials in Kidney Transplantation... trials of drugs and therapeutic biologics in kidney transplantation. This public workshop is intended to... evaluate patient and allograft outcome in clinical trials of kidney transplantation. The meeting...

  4. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    DTIC Science & Technology

    2013-10-01

    Study Endpoint and Label Development Team, and FDA Division of Anesthesia, Analgesia and Rheumatology Products, in order to establish discrete...Team, and FDA Division of Anesthesia, Analgesia and Rheumatology Products, in order to establish discrete guidelines and produce a publication

  5. Plasma creatinine results derived from an endpoint modification of the Jaffé method.

    PubMed

    Schurman, S J; Perlman, S A; Chamizo, W

    1998-06-01

    For values in the normal pediatric range, endpoint modifications of the Jaffé method for measuring plasma creatinine (PCr) yield higher results than other commonly used techniques. In an effort to evaluate the Olympus AU5000 endpoint method used by the large reference laboratory to which many of our patients are directed by their third-party payor, we compared results with a kinetic Jaffé technique using paired samples from the same specimens. In 46 samples, the kinetic method measured Pcr at < or =0.8 mg/dl, whereas the endpoint technique PCr was higher by 0.1 mg/dl in 6 (13%), 0.2 mg/dl in 23 (50%), and 0.3 mg/dl in 16 (35%) samples (P<0.0001). The combination of these higher values and the same reported normal range for all children ages 2-12 years (0.3-1.0 mg/dl) and 13-17 years (0.7-1.4 mg/dl) makes interpretation of Olympus AU5000 endpoint method results difficult, particularly for younger children. The results reinforce the need for each laboratory to provide comprehensive age- and sex-adjusted normal PCr ranges.

  6. 76 FR 51993 - Draft Guidance for Industry on Standards for Clinical Trial Imaging Endpoints; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... standardization of imaging procedures when an important imaging endpoint is used in a clinical trial of a... outlines the major considerations for standardization of image acquisition, image interpretation methods... of image acquisition and interpretation standardization, a medical practice standard and a...

  7. Coulometric Titration of Ethylenediaminetetraacetate (EDTA) with Spectrophotometric Endpoint Detection: An Experiment for the Instrumental Analysis Laboratory

    ERIC Educational Resources Information Center

    Williams, Kathryn R.; Young, Vaneica Y.; Killian, Benjamin J.

    2011-01-01

    Ethylenediaminetetraacetate (EDTA) is commonly used as an anticoagulant in blood-collection procedures. In this experiment for the instrumental analysis laboratory, students determine the quantity of EDTA in commercial collection tubes by coulometric titration with electrolytically generated Cu[superscript 2+]. The endpoint is detected…

  8. 77 FR 46444 - Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics (GREAT); Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-03

    ..., pediatric and adult inflammatory bowel disease, and parenteral nutrition-associated liver disease. DATES... liver disease is to discuss endpoints and their measurement for clinical trials in which parenteral nutrition-induced liver disease is either an efficacy or safety outcome measure. Particpation In the...

  9. Can joint sound assess soft and hard endpoints of the Lachman test?: A preliminary study.

    PubMed

    Hattori, Koji; Ogawa, Munehiro; Tanaka, Kazunori; Matsuya, Ayako; Uematsu, Kota; Tanaka, Yasuhito

    2016-05-12

    The Lachman test is considered to be a reliable physical examination for anterior cruciate ligament (ACL) injury. Patients with a damaged ACL demonstrate a soft endpoint feeling. However, examiners judge the soft and hard endpoints subjectively. The purpose of our study was to confirm objective performance of the Lachman test using joint auscultation. Human and porcine knee joints were examined. Knee joint sound during the Lachman test (Lachman sound) was analyzed by fast Fourier transformation. As quantitative indices of Lachman sound, the peak sound as the maximum relative amplitude (acoustic pressure) and its frequency were used. The mean Lachman peak sound for healthy volunteer knees was 86.9 ± 12.9 Hz in frequency and -40 ± 2.5 dB in acoustic pressure. The mean Lachman peak sound for intact porcine knees was 84.1 ± 9.4 Hz and -40.5 ± 1.7 dB. Porcine knees with ACL deficiency had a soft endpoint feeling during the Lachman test. The Lachman peak sounds of porcine knees with ACL deficiency were dispersed into four distinct groups, with center frequencies of around 40, 160, 450, and 1600. The Lachman peak sound was capable of assessing soft and hard endpoints of the Lachman test objectively.

  10. Recent Developments in Whole Sediment Toxicity Identification Evaluations: Innovations in Manipulations and Endpoints

    EPA Science Inventory

    Whole sediment Toxicity Identification Evaluation (TIE) methods were developed primarily in the late 1990s and early 2000s in research programs dedicated to developing manipulations and endpoints to characterize and identify causes of toxicity to benthic freshwater and marine org...

  11. A health-care system perspective on implementing genomic medicine: pediatric acute lymphoblastic leukemia as a paradigm.

    PubMed

    Evans, W E; Crews, K R; Pui, C-H

    2013-08-01

    The promise of genomic medicine has received great attention over the past decade, projecting how genomics will soon guide the prevention, diagnosis, and treatment of human diseases. However, this evolution has been slower than forecast, even where evidence is often strong (e.g., pharmacogenomics). Reasons include the requirement for institutional resources and the need for the will to push beyond barriers impeding health-care changes. Here, we illustrate how genomics has been deployed to advance the treatment of childhood leukemia.

  12. Embryotoxicity assessment of developmental neurotoxicants using a neuronal endpoint in the embryonic stem cell test.

    PubMed

    Baek, Dae Hyun; Kim, Tae Gyun; Lim, Hwa Kyung; Kang, Jin Wook; Seong, Su Kyoung; Choi, Seung Eun; Lim, So Yun; Park, Sung Hee; Nam, Bong-hyun; Kim, Eun Hee; Kim, Mun Sin; Park, Kui Lea

    2012-08-01

    The embryonic stem cell test (EST) is a validated in vitro embryotoxicity test; however, as the inhibition of cardiac differentiation alone is used as a differentiation endpoint in the EST, it may not be a useful test to screen embryotoxic chemicals that affect the differentiation of noncardiac tissues. Previously, methylmercury (MeHg), cadmium and arsenic compounds, which are heavy metals that induce developmental neurotoxicity in vivo, were misclassified as nonembryotoxic with the EST. The aim of this study was to improve the EST to correctly screen such developmental neurotoxicants. We developed a neuronal endpoint (Tuj-1 ID₅₀) using flow cytometry analysis of Tuj-1-positive cells to screen developmental neurotoxicants (MeHg, valproic acid, sodium arsenate and sodium arsenite) correctly using an adherent monoculture differentiation method. Using Tuj-1 ID₅₀ in the EST instead of cardiac ID₅₀, all of the tested chemicals were classified as embryotoxic, while the negative controls were correctly classified as nonembryotoxic. To support the validity of Tuj-1 ID₅₀) , we compared the results from two experimenters who independently tested MeHg using our modified EST. An additional neuronal endpoint (MAP2 ID₅₀), obtained by analyzing the relative quantity of MAP2 mRNA, was used to classify the same chemicals. There were no significant differences in the three endpoint values of the two experimenters or in the classification results, except for isoniazid. In conclusion, our results indicate that Tuj-1 ID₅₀ can be used as a surrogate endpoint of the traditional EST to screen developmental neurotoxicants correctly and it can also be applied to other chemicals.

  13. Linaclotide: Promising IBS-C Efficacy in an Era of Provisional Study Endpoints

    PubMed Central

    Sayuk, Gregory S.

    2013-01-01

    Recent disappointing developments in the pharmacotherapy of irritable bowel syndrome (IBS) have not dampened the enthusiasm surrounding linaclotide, a novel guanylate cyclase-C agonist for the management of constipation-predominant IBS (IBS-C). Two recent phase 3 studies reporting on a single, daily dose of linaclotide are presented in this issue of the American Journal of Gastroenterology. Importantly, these studies are the first to examine a provisional Food and Drug Administration (FDA) combined response endpoint for IBS-C, which mandates improvements of both abdominal pain and defecatory symptoms. Potential limitations of this FDA endpoint relate to a lack of inclusion of other potentially important IBS symptoms and an inability to directly compare findings with other recent IBS-C trials. Both studies successfully reached this endpoint in approximately one-third of study subjects, resulting in numbers needed to treat (NNT) of five to eight, to achieve an FDA responder. Individual symptom responses to linaclotide were seen in nearly 50% of participants, and potential explanations for these discrepancies when compared with the FDA endpoint are offered. Adequate relief measures also were assessed and, with NNTs of 3.4–6.8, compared favorably with other contemporary IBS-C studies. Overall, both linaclotide trials found the medication to be safe in terms of serious adverse events, though the secretagogue mechanism of action led to diarrhea in approximately one in five subjects. Together, these studies inspire several other important questions regarding linaclotide, including its role in the management of IBS-C relative to existing treatment options, such as lubiprostone. Greater clinical use of linaclotide will reveal whether the observed responses measured with the FDA provisional endpoint will translate into real-world experiences of improvement in IBS patients. “ In seeking absolute truth we aim at the unattainable and must be content with broken portions

  14. Linaclotide: promising IBS-C efficacy in an era of provisional study endpoints.

    PubMed

    Sayuk, Gregory S

    2012-11-01

    Recent disappointing developments in the pharmacotherapy of irritable bowel syndrome (IBS) have not dampened the enthusiasm surrounding linaclotide, a novel guanylate cyclase-C agonist for the management of constipation-predominant IBS (IBS-C). Two recent phase 3 studies reporting on a single, daily dose of linaclotide are presented in this issue of the American Journal of Gastroenterology. Importantly, these studies are the first to examine a provisional Food and Drug Administration (FDA) combined response endpoint for IBS-C, which mandates improvements of both abdominal pain and defecatory symptoms. Potential limitations of this FDA endpoint relate to a lack of inclusion of other potentially important IBS symptoms and an inability to directly compare findings with other recent IBS-C trials. Both studies successfully reached this endpoint in approximately one-third of study subjects, resulting in numbers needed to treat (NNT) of five to eight, to achieve an FDA responder. Individual symptom responses to linaclotide were seen in nearly 50% of participants, and potential explanations for these discrepancies when compared with the FDA endpoint are offered. Adequate relief measures also were assessed and, with NNTs of 3.4-6.8, compared favorably with other contemporary IBS-C studies. Overall, both linaclotide trials found the medication to be safe in terms of serious adverse events, though the secretagogue mechanism of action led to diarrhea in approximately one in five subjects. Together, these studies inspire several other important questions regarding linaclotide, including its role in the management of IBS-C relative to existing treatment options, such as lubiprostone. Greater clinical use of linaclotide will reveal whether the observed responses measured with the FDA provisional endpoint will translate into real-world experiences of improvement in IBS patients.

  15. The barriers to and enablers of providing reasonably adjusted health services to people with intellectual disabilities in acute hospitals: evidence from a mixed-methods study

    PubMed Central

    Tuffrey-Wijne, Irene; Goulding, Lucy; Giatras, Nikoletta; Abraham, Elisabeth; Gillard, Steve; White, Sarah; Edwards, Christine; Hollins, Sheila

    2014-01-01

    Objective To identify the factors that promote and compromise the implementation of reasonably adjusted healthcare services for patients with intellectual disabilities in acute National Health Service (NHS) hospitals. Design A mixed-methods study involving interviews, questionnaires and participant observation (July 2011–March 2013). Setting Six acute NHS hospital trusts in England. Methods Reasonable adjustments for people with intellectual disabilities were identified through the literature. Data were collected on implementation and staff understanding of these adjustments. Results Data collected included staff questionnaires (n=990), staff interviews (n=68), interviews with adults with intellectual disabilities (n=33), questionnaires (n=88) and interviews (n=37) with carers of patients with intellectual disabilities, and expert panel discussions (n=42). Hospital strategies that supported implementation of reasonable adjustments did not reliably translate into consistent provision of such adjustments. Good practice often depended on the knowledge, understanding and flexibility of individual staff and teams, leading to the delivery of reasonable adjustments being haphazard throughout the organisation. Major barriers included: lack of effective systems for identifying and flagging patients with intellectual disabilities, lack of staff understanding of the reasonable adjustments that may be needed, lack of clear lines of responsibility and accountability for implementing reasonable adjustments, and lack of allocation of additional funding and resources. Key enablers were the Intellectual Disability Liaison Nurse and the ward manager. Conclusions The evidence suggests that ward culture, staff attitudes and staff knowledge are crucial in ensuring that hospital services are accessible to vulnerable patients. The authors suggest that flagging the need for specific reasonable adjustments, rather than the vulnerable condition itself, may address some of the barriers

  16. Seasonal variation in the acute effect of particulate air pollution on mortality in the China Air Pollution and Health Effects Study (CAPES)

    PubMed Central

    Chen, Renjie; Peng, Roger D.; Meng, Xia; Zhou, Zhijun; Chen, Bingheng; Kan, Haidong

    2013-01-01

    Epidemiological findings concerning the seasonal variation in the acute effect of particulate matter (PM) are inconsistent. We investigated the seasonality in the association between PM with an aerodynamic diameter of less than 10 μm (PM10) and daily mortality in 17 Chinese cities. We fitted the “main” time-series model after adjustment for time-varying confounders using smooth functions with natural splines. We established a “seasonal” model to obtain the season-specific effect estimates of PM10, and a “harmonic” model to show the seasonal pattern that allows PM10 effects to vary smoothly with the day in a year. At the national level, a 10 μg/m3 increase in the two-day moving average concentrations (lag 01) of PM10 was associated with 0.45% [95% posterior interval (PI), 0.15% to 0.76%], 0.17% (95% PI, −0.09% to 0.43%), 0.55% (95% PI, 0.15% to 0.96%) and 0.25% (95%PI, −0.05% to 0.56%) increases in total mortality for winter, spring, summer and fall, respectively. For the smoothly-varying plots of seasonality, we identified a two-peak pattern in winter and summer. The observed seasonal pattern was generally insensitive to model specifications. Our analyses suggest that the acute effect of particulate air pollution could vary by seasons with the largest effect in winter and summer in China. To our knowledge, this is the first multicity study in developing countries to analyze the seasonal variations of PM-related health effects. PMID:23500824

  17. Factors driving customers to seek health care from pharmacies for acute respiratory illness and treatment recommendations from drug sellers in Dhaka city, Bangladesh

    PubMed Central

    Chowdhury, Fahmida; Sturm-Ramirez, Katharine; Mamun, Abdullah Al; Iuliano, A Danielle; Bhuiyan, Mejbah Uddin; Chisti, Mohammod Jobayer; Ahmed, Makhdum; Haider, Sabbir; Rahman, Mahmudur; Azziz-Baumgartner, Eduardo

    2017-01-01

    Background Pharmacies in Bangladesh serve as an important source of health service. A survey in Dhaka reported that 48% of respondents with symptoms of acute respiratory illness (ARI) identified local pharmacies as their first point of care. This study explores the factors driving urban customers to seek health care from pharmacies for ARI, their treatment adherence, and outcome. Methods A cross-sectional study was conducted among 100 selected pharmacies within Dhaka from June to December 2012. Study participants were patients or patients’ relatives aged >18 years seeking care for ARI from pharmacies without prescription. Structured interviews were conducted with customers after they sought health service from drug sellers and again over phone 5 days postinterview to discuss treatment adherence and outcome. Results We interviewed 302 customers patronizing 76 pharmacies; 186 (62%) sought care for themselves and 116 (38%) sought care for a sick relative. Most customers (215; 71%) were males. The majority (90%) of customers sought care from the study pharmacy as their first point of care, while 18 (6%) had previously sought care from another pharmacy and 11 (4%) from a physician for their illness episodes. The most frequently reported reasons for seeking care from pharmacies were ease of access to pharmacies (86%), lower cost (46%), availability of medicine (33%), knowing the drug seller (20%), and convenient hours of operation (19%). The most commonly recommended drugs were acetaminophen dispensed in 76% (228) of visits, antihistamine in 69% (208), and antibiotics in 42% (126). On follow-up, most (86%) of the customers had recovered and 12% had sought further treatment. Conclusion People with ARI preferred to seek care at pharmacies rather than clinics because these pharmacies were more accessible and provided prompt treatment and medicine with no service charge. We recommend raising awareness among drug sellers on proper dispensing practices and enforcement of

  18. Reducing sample sizes in two-stage phase II cancer trials by using continuous tumour shrinkage end-points.

    PubMed

    Wason, James M S; Mander, Adrian P; Eisen, Tim G

    2011-05-01

    Reducing the number of patients required for a clinical trial is important for shortening development time. Phase II cancer trials assess the tumour-shrinking effect of a novel compound through a binary end-point formed from the percentage change in total lesion diameter. We compare single-arm two-stage designs which use the binary end-point to those which directly use the continuous end-point. Using the continuous end-point results in lower expected and maximum sample sizes. For larger trials the reduction is around 37%. This assumes that the dichotomisation point of the continuous end-point is chosen to give the best sample size, with the trial design using the binary end-point performing even worse otherwise. We consider a previous trial designed using a Simon two-stage design and show that if the continuous end-point had been used, the expected and maximum sample sizes of the trial would be reduced by around 50%. Using the continuous end-point in a two-stage cancer trial results in large sample size reductions. The methods discussed in this paper work best when the number of complete responses is low, as is true in several types of cancer. We discuss what could be done if this is not the case.

  19. Predicting frequent hospital admission risk in Singapore: a retrospective cohort study to investigate the impact of comorbidities, acute illness burden and social determinants of health

    PubMed Central

    Liu, Nan; Wang, Sijia; Thumboo, Julian; Ong, Marcus Eng Hock; Lee, Kheng Hock

    2016-01-01

    Objectives To evaluate the impact of comorbidities, acute illness burden and social determinants of health on predicting the risk of frequent hospital admissions. Design Multivariable logistic regression was used to associate the predictive variables extracted from electronic health records and frequent hospital admission risk. The model's performance of our predictive model was evaluated using a 10-fold cross-validation. Setting A single tertiary hospital in Singapore. Participants All adult patients admitted to the hospital between 1 January 2013 and 31 May 2014 (n=25 244). Main outcome measure Frequent hospital admissions, defined as 3 or more inpatient admissions within 12 months of discharge. Area under the receiver operating characteristic curve (AUC) of the predictive model, and the sensitivity, specificity and positive predictive values for various cut-offs. Results 4322 patients (17.1%) met the primary outcome. 11 variables were observed as significant predictors and included in the final regression model. The strongest independent predictor was treatment with antidepressants in the past 1 year (adjusted OR 2.51, 95% CI 2.26 to 2.78). Other notable predictors include requiring dialysis and treatment with intravenous furosemide during the index admission. The predictive model achieved an AUC of 0.84 (95% CI 0.83 to 0.85) for predicting frequent hospital admission risk, with a sensitivity of 73.9% (95% CI 72.6% to 75.2%), specificity of 79.1% (78.5% to 79.6%) and positive predictive value of 42.2% (95% CI 41.1% to 43.3%) at the cut-off of 0.235. Conclusions We have identified several predictors for assessing the risk of frequent hospital admissions that achieved high discriminative model performance. Further research is necessary using an external validation cohort. PMID:27742630

  20. Sex Differences in the Treatment and Outcome of Korean Patients With Acute Myocardial Infarction Using the Korean National Health Insurance Claims Database

    PubMed Central

    Hong, Jae-Seok; Kang, Hee-Chung

    2015-01-01

    Abstract Evidence showing higher acute myocardial infarction (AMI) mortality rates among female compared with male inpatients has stimulated interest in whether this disparity is the result of biological factors or differences in the provision of healthcare services. We investigated the impact of sex on in-hospital mortality rates due to AMI, and evaluated the contribution of differences in the delivery of optimal medical services for AMI. We retrospectively constructed a dataset of 85,329 new patients admitted to Korean hospitals with AMI between 2003 and 2007 from the Korea National Health Insurance Claims Database. We used the claims database to provide information about treatment after admission or death for each patient. Proportionally more female than male patients aged 65 years or older had complications; however, proportionally fewer female patients underwent invasive procedures. Female patients had a higher in-hospital mortality rate than males (21.2% vs 14.6%, odds ratio [OR] 1.58, 95% confidence interval [CI] 1.52–1.64). The probability of death within 30 days after admission remained higher for females than males after adjusting for demographic characteristics and severity (OR 1.08, 95% CI 1.04–1.13). After additionally adjusting for invasive and medical management, the probability of death within 30 days did not differ between males and females (OR 1.04, 95% CI 0.99–1.08). A similar trend was revealed by an additional analysis of patients according to younger (<65 years) and older (≥65 years) age groups. The higher in-hospital mortality rates after AMI in Korean female patients was associated with a lower procedure rate. Evidence indicating that AMI symptoms differ according to sex highlights the need for health policies and public education programs that raise awareness of sex-related differences in early AMI symptoms to increase the incidence of appropriate early treatment in females. PMID:26334894

  1. Development and implementation of a participative intervention to improve the psychosocial work environment and mental health in an acute care hospital

    PubMed Central

    Bourbonnais, R; Brisson, C; Vinet, A; Vézina, M; Lower, A

    2006-01-01

    Objectives To describe the development and implementation phases of a participative intervention aimed at reducing four theory grounded and empirically supported adverse psychosocial work factors (high psychological demands, low decision latitude, low social support, and low reward), and their mental health effects. Methods The intervention was realised among 500 care providers in an acute care hospital. A prior risk evaluation was performed, using a quantitative approach, to determine the prevalence of adverse psychosocial work factors and of psychological distress in the hospital compared to an appropriate reference population. In addition, a qualitative approach included observation in the care units, interviews with key informants, and collaborative work with an intervention team (IT) including all stakeholders. Results The prior risk evaluation showed a high prevalence of adverse psychosocial factors and psychological distress among care providers compared to a representative sample of workers from the general population. Psychosocial variables at work associated with psychological distress in the prior risk evaluation were high psychological demands (prevalence ratio (PR) = 2.27), low social support from supervisors and co‐workers (PR = 1.35), low reward (PR = 2.92), and effort‐reward imbalance (PR = 2.65). These results showed the empirical relevance of an intervention on the four selected adverse psychosocial factors among care providers. Qualitative methods permitted the identification of 56 adverse conditions and of their solutions. Targets of intervention were related to team work and team spirit, staffing processes, work organisation, training, communication, and ergonomy. Conclusion This study adds to the scarce literature describing the development and implementation of preventive intervention aimed at reducing psychosocial factors at work and their health effects. Even if adverse conditions in the psychosocial environment and

  2. Endpoint temperature prediction of molten steel in RH using improved case-based reasoning

    NASA Astrophysics Data System (ADS)

    Feng, Kai; Wang, Hong-bing; Xu, An-jun; He, Dong-feng

    2013-12-01

    An improved case-based reasoning (CBR) method was proposed to predict the endpoint temperature of molten steel in Ruhrstahl Heraeus (RH) process. Firstly, production data were analyzed by multiple linear regressions and a pairwise comparison matrix in analytic hierarchy process (AHP) was determined by this linear regression's coefficient. The weights of various influencing factors were obtained by AHP. Secondly, the dividable principles of case base including "0-1" and "breakpoint" were proposed, and the case base was divided into several homogeneous parts. Finally, the improved CBR was compared with ordinary CBR, which is based on the even weight and the single base. The results show that the improved CBR has a higher hit rate for predicting the endpoint temperature of molten steel in RH.

  3. Fabrication of spintronic devices: etching endpoint detection by resistance measurement for magnetic tunnel junctions

    NASA Astrophysics Data System (ADS)

    Pong, Philip W. T.; Schmoueli, Moshe; Egelhoff, William F., Jr.

    2007-09-01

    Magnetic tunnel junctions (MTJs) have received tremendous interest since the discovery of substantial room temperature tunneling magnetoresistance (TMR) due to spin-dependent tunneling, and have been intensively investigated for applications in next-generation memory devices, hard disk drives, and magnetic sensors. In the fabrication of MTJs, etching is needed to remove the top cap layers, upper magnetic layers, and the middle oxide layer in order to form a tunneling junction. In view of this, we have devised an innovative, simple, low-cost endpoint detection method for fabricating MTJs. In this method, the endpoint is detected by measurement of the sheet resistance of the MTJ stack. Only a multimeter is needed in this method, hence it provides a simple low-cost alternative for spintronic device researchers to explore the research field of magnetic tunnel junctions. This technique is also of great use in other kinds of metallic stack etching experiments.

  4. A Speech Endpoint Detection Algorithm Based on BP Neural Network and Multiple Features

    NASA Astrophysics Data System (ADS)

    Shi, Yong-Qiang; Li, Ru-Wei; Zhang, Shuang; Wang, Shuai; Yi, Xiao-Qun

    Focusing on a sharp decline in the performance of endpoint detection algorithm in a complicated noise environment, a new speech endpoint detection method based on BPNN (back propagation neural network) and multiple features is presented. Firstly, maximum of short-time autocorrelation function and spectrum variance of speech signals are extracted respectively. Secondly, these feature vectors as the input of BP neural network are trained and modeled and then the Genetic Algorithm is used to optimize the BP Neural Network. Finally, the signal's type is determined according to the output of Neural Network. The experiments show that the correct rate of this proposed algorithm is improved, because this method has better robustness and adaptability than algorithm based on maximum of short-time autocorrelation function or spectrum variance.

  5. Outcomes-Based CV Imaging Research Endpoints and Trial Design: From Pixels to Patient Satisfaction.

    PubMed

    Fordyce, Christopher B; Douglas, Pamela S

    2017-03-01

    The categories and quality of evidence documenting the value of noninvasive cardiovascular imaging have evolved substantially over the last several decades. From an initial emphasis on the diagnostic accuracy of various imaging modalities, cardiovascular imaging has matured into an outcomes-based field that now provides evidence on adverse events, safety, cost, and patient quality-of-life endpoints, and does so in the setting of large randomized trials. This review aims to highlight types of outcomes endpoints, including updating the hierarchy of evidence for diagnostic imaging as first proposed by Fryback and Thornbury, and critically reviewing their application in the current cardiovascular imaging evidence base. We describe the range of data categories generated to date for the various imaging modalities, and indicate how this provides insights into contemporary study design and future directions in cardiovascular imaging outcomes research.

  6. Coulometric trace determination of water by using Karl Fischer reagent and potentiometric end-point detection.

    PubMed

    Cedergren, A

    1974-06-01

    A new approach to the determination of water via the Karl Fischer reaction is described. Iodine is coulometrically generated and the end-point corresponding to a slight excess of iodine, is detected potentiometrically with a non-polarized platinum electrode. Samples of 1-500 mul containing 0.05-200 mug of water were analysed with a standard deviation of 0.015 mug in the range 0.05-20 mug of H(2)O. A specially constructed electrolysis cell was used in combination with an LKB 16300 Coulometric Analyzer and the time for a complete analysis was 1-4 min, depending on sample size. The reagent composition has been optimized in order to enhance the rate of the main reaction and to minimize the extent of side-reactions. Decreasing the temperature reduced the extent of side-reactions. The displacement of end-point potential on dilution was studied and a correction is discussed.

  7. Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative.

    PubMed

    Lansky, Alexandra J; Messé, Steven R; Brickman, Adam M; Dwyer, Michael; van der Worp, H Bart; Lazar, Ronald M; Pietras, Cody G; Abrams, Kevin J; McFadden, Eugene; Petersen, Nils H; Browndyke, Jeffrey; Prendergast, Bernard; Ng, Vivian G; Cutlip, Donald E; Kapadia, Samir; Krucoff, Mitchell W; Linke, Axel; Moy, Claudia Scala; Schofer, Joachim; van Es, Gerrit-Anne; Virmani, Renu; Popma, Jeffrey; Parides, Michael K; Kodali, Susheel; Bilello, Michel; Zivadinov, Robert; Akar, Joseph; Furie, Karen L; Gress, Daryl; Voros, Szilard; Moses, Jeffrey; Greer, David; Forrest, John K; Holmes, David; Kappetein, Arie P; Mack, Michael; Baumbach, Andreas

    2017-02-14

    Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

  8. Establishing Good Practices for Exposure–Response Analysis of Clinical Endpoints in Drug Development

    PubMed Central

    Overgaard, RV; Ingwersen, SH; Tornøe, CW

    2015-01-01

    This tutorial aims at promoting good practices for exposure–response (E-R) analyses of clinical endpoints in drug development. The focus is on practical aspects of E-R analyses to assist modeling scientists with a process of performing such analyses in a consistent manner across individuals and projects and tailored to typical clinical drug development decisions. This includes general considerations for planning, conducting, and visualizing E-R analyses, and how these are linked to key questions. PMID:26535157

  9. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    DTIC Science & Technology

    2015-10-01

    Award Number: W81XWH-11-1-0639 TITLE: Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval PRINCIPAL...Clinical Trials and Drug Approval 5b. GRANT NUMBER PC100563 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT NUMBER Ethan Basch...meet regulatory requirements for drug approval and labeling. The primary aim of this award is to conduct an observational longitudinal study in men

  10. Muscle Synergies Heavily Influence the Neural Control of Arm Endpoint Stiffness and Energy Consumption

    PubMed Central

    Inouye, Joshua M.; Valero-Cuevas, Francisco J.

    2016-01-01

    Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies—correlated muscle activations—to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption—when available—can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the

  11. Muscle Synergies Heavily Influence the Neural Control of Arm Endpoint Stiffness and Energy Consumption.

    PubMed

    Inouye, Joshua M; Valero-Cuevas, Francisco J

    2016-02-01

    Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies--correlated muscle activations--to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption--when available--can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the mechanisms

  12. Energy metabolism and biotransformation as endpoints to pre-screen hepatotoxicity using a liver spheroid model

    SciTech Connect

    Xu Jinsheng . E-mail: jinsheng.xu@uwe.ac.uk; Purcell, Wendy M.

    2006-10-15

    The current study investigated liver spheroid culture as an in vitro model to evaluate the endpoints relevant to the status of energy metabolism and biotransformation after exposure to test toxicants. Mature rat liver spheroids were exposed to diclofenac, galactosamine, isoniazid, paracetamol, m-dinitrobenzene (m-DNB) and 3-nitroaniline (3-NA) for 24 h. Pyruvate uptake, galactose biotransformation, lactate release and glucose secretion were evaluated after exposure. The results showed that pyruvate uptake and lactate release by mature liver spheroids in culture were maintained at a relatively stable level. These endpoints, together with glucose secretion and galactose biotransformation, were related to and could reflect the status of energy metabolism and biotransformation in hepatocytes. After exposure, all of the test agents significantly reduced glucose secretion, which was shown to be the most sensitive endpoint of those evaluated. Diclofenac, isoniazid, paracetamol and galactosamine reduced lactate release (P < 0.01), but m-DNB increased lactate release (P < 0.01). Diclofenac, isoniazid and paracetamol also reduced pyruvate uptake (P < 0.01), while galactosamine had little discernible effect. Diclofenac, galactosamine, paracetamol and m-DNB also reduced galactose biotransformation (P < 0.01), by contrast, isoniazid did not. The metabolite of m-DNB, 3-NA, which served as a negative control, did not cause significant changes in lactate release, pyruvate uptake or galactose biotransformation. It is concluded that pyruvate uptake, galactose biotransformation, lactate release and glucose secretion can be used as endpoints for evaluating the status of energy metabolism and biotransformation after exposure to test agents using the liver spheroid model to pre-screen hepatotoxicity.

  13. Acute Exposure to Particulate Matter (PM) Alters Physiologic and Toxicologic Endpoints in a Rat Model of Heart Failure

    EPA Science Inventory

    Human exposure to ambient PM from fossil-fuel emissions is linked to cardiovascular disease and death. This association strengthens in people with preexisting cardiopulmonary diseases—especially heart failure (HF). We previously examined the effects of PM on HF by exposing Sponta...

  14. Optimisation of infection prevention and control in acute health care by use of behaviour change: a systematic review.

    PubMed

    Edwards, Rachel; Charani, Esmita; Sevdalis, Nick; Alexandrou, Banos; Sibley, Eleanor; Mullett, David; Loveday, Heather P; Drumright, Lydia N; Holmes, Alison

    2012-04-01

    Changes in the behaviour of health-care workers (HCWs) are required to improve adherence to infection prevention and control (IPC) guidelines. Despite heavy investment in strategies to change behaviour, effectiveness has not been adequately assessed. We did a systematic review to assess the effectiveness and sustainability of interventions to change IPC behaviour and assessed exploratory literature for barriers to and facilitators of behaviour change. 21 studies published from 1999 to 2011 met our inclusion criteria: seven intervention studies and 14 exploratory studies. Of the intervention studies none explicitly incorporated psychological theory and only two contained elements of social marketing in the design, although five addressed sustainability. All elicited behaviour change, reduction in infection risk, or both. The exploratory studies identified social and cultural factors that affect the IPC behaviour of HCWs. To improve the standard of research and broaden the evidence base, we recommend that quality criteria are added to existing systematic review guidelines to enable the inclusion of qualitative research and to ensure robust design, implementation, and reporting of interventions.

  15. Differences in end-point force trajectories elicited by electrical stimulation of individual human calf muscles

    PubMed Central

    Giordano, S B; Segal, R L; Abelew, T A

    2009-01-01

    The purpose of this study was to investigate the end-point force trajectories of the fibularis longus (FIB), lateral gastrocnemius (LG) and medial gastrocnemius (MG) muscles. Most information about individual muscle function has come from studies which use models based on electromyographic (EMG) recordings. In this study (N=20 subjects) we used electrical stimulation (20Hz) to elicit activity in individual muscles, recorded the end-point forces at the foot and verified the selectivity of stimulation by using magnetic resonance imaging. Unexpectedly, no significant differences were found between LG and MG force directions. Stimulation of LG and MG resulted in downward and medial or lateral forces depending on the subject. We found FIB end-point forces to be significantly different than those of LG and MG. In all subjects, stimulation of FIB resulted in downward and lateral forces. Based on our results, we suggest that there are multiple factors determining when and whether LG or MG will produce a medial or lateral force and FIB consistently plays a significant role in eversion/abduction and plantarflexion. We suggest that the inter-subject variability we found is not simply an artifact of experimental or technical error but is functionally relevant and should be addressed in future studies and models. PMID:20095454

  16. A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

    PubMed

    Low, Ariana; Kok, Si Ling; Khong, Yuet Mei; Chan, Sui Yung; Gokhale, Rajeev

    2015-11-01

    No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs.

  17. Effects of the polycyclic musk HHCB on individual- and population-level endpoints in Potamopyrgus antipodarum.

    PubMed

    Pedersen, Signe; Selck, Henriette; Salvito, Daniel; Forbes, Valery

    2009-05-01

    Although the polycyclic musk 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[gamma]-2-benzopyran (HHCB) is frequently detected in aquatic sediments, very little is known about its effects on sediment-feeding organisms. Effects of sediment-associated HHCB on growth, feeding rate, survival and reproduction in the gastropod Potamopyrgus antipodarum were measured in the laboratory. Snails were exposed to six nominal HHCB concentrations: 0, 0.1, 1, 10, 30 and 100microg g(-1) dry weight (dw) sediment. Adult survival and growth were not affected by HHCB. However, juvenile growth and survival, reproduction, time to first reproduction and adult feeding rate were more sensitive endpoints and declined with increasing HHCB concentration. Individual-level endpoints for P. antipodarum were integrated into a population model to investigate the effects of HHCB on population growth rate. Under otherwise favorable laboratory conditions, population growth rate was slightly (by ca. 2%), but not significantly, reduced with increasing HHCB exposure concentration. Model simulations were performed to explore the consequences of HHCB exposure under more ecologically realistic conditions (i.e., survival and reproduction of unexposed snails were markedly reduced relative to the laboratory). The results suggest that despite detectable effects of HHCB on individual-level endpoints measured in the laboratory, impacts on population dynamics of this deposit feeder are not likely to occur at environmentally relevant exposure concentrations.

  18. Scientific and societal considerations in selecting assessment endpoints for environmental decision making.

    PubMed

    Strange, Elizabeth M; Lipton, Joshua; Beltman, Douglas; Snyder, Blaine D

    2002-03-08

    It is sometimes argued that, from an ecological point of view, population-, community-, and ecosystem-level endpoints are more relevant than individual-level endpoints for assessing the risks posed by human activities to the sustainability of natural resources. Yet society values amenities provided by natural resources that are not necessarily evaluated or protected by assessment tools that focus on higher levels of biological organization. For example, human-caused stressors can adversely affect recreational opportunities that are valued by society even in the absence of detectable population-level reductions in biota. If protective measures are not initiated until effects at higher levels of biological organization are apparent, natural resources that are ecologically important or highly valued by the public may not be adequately protected. Thus, environmental decision makers should consider both scientific and societal factors in selecting endpoints for ecological risk assessments. At the same time, it is important to clearly distinguish the role of scientists, which is to evaluate ecological effects, from the role of policy makers, which is to determine how to address the uncertainty in scientific assessment in making environmental decisions and to judge what effects are adverse based on societal values and policy goals.

  19. Superiority inferences on individual endpoints following noninferiority testing in clinical trials.

    PubMed

    Logan, Brent R; Tamhane, Ajit C

    2008-10-01

    We consider the problem of drawing superiority inferences on individual endpoints following non-inferiority testing. Röhmel et al. (2006) pointed out this as an important problem which had not been addressed by the previous procedures that only tested for global superiority. Röhmel et al. objected to incorporating the non-inferiority tests in the assessment of the global superiority test by exploiting the relationship between the two, since the results of the latter test then depend on the non-inferiority margins specified for the former test. We argue that this is justified, besides the fact that it enhances the power of the global superiority test. We provide a closed testing formulation which generalizes the three-step procedure proposed by Röhmel et al. for two endpoints. For the global superiority test, Röhmel et al. suggest using the Läuter (1996) test which is modified to make it monotone. The resulting test not only is complicated to use, but the modification does not readily extend to more than two endpoints, and it is less powerful in general than several of its competitors. This is verified in a simulation study. Instead, we suggest applying the one-sided likelihood ratio test used by Perlman and Wu (2004) or the union-intersection t(max) test used by Tamhane and Logan (2004).

  20. Pediatric phase I trial design using maximum target inhibition as the primary endpoint.

    PubMed

    Meany, Holly; Balis, Frank M; Aikin, Alberta; Whitcomb, Patricia; Murphy, Robert F; Steinberg, Seth M; Widemann, Brigitte C; Fox, Elizabeth

    2010-06-16

    The extent to which a drug inhibits a target responsible for a therapeutic effect is a more rational primary endpoint for dose-finding studies of more selective anticancer drugs than the conventional endpoint of dose-limiting toxicity (DLT) used for cytotoxic agents. An adaptive phase I trial design incorporating maximum target inhibition as the primary endpoint was developed to define the optimal dose of talabostat, a dipeptidyl peptidase (DPP) inhibitor, in children with relapsed or refractory solid tumors. The relationship between dose and effect (percent inhibition of serum DPP-4) was assessed using a maximum effect model. Maximum target inhibition was defined as greater than 90% DPP-4 inhibition in five or more of six patients 24 hours post-dose. If DLT was to occur, the trial would adapt to a traditional phase I design with a more conservative dose escalation. At the 600 microg/m(2) dose level, serum DPP-4 inhibition at 24 hours was 85%. No talabostat-related DLT occurred. The maximum effect model predicted that 1200 microg/m(2) of talabostat would maximally inhibit DPP-4. This adaptive trial design appears to be feasible, safe, and efficient and warrants further evaluation for development of molecularly targeted agents.

  1. Sensitivity Enhancement of RF Plasma Etch Endpoint Detection With K-means Cluster Analysis

    NASA Astrophysics Data System (ADS)

    Lee, Honyoung; Jang, Haegyu; Lee, Hak-Seung; Chae, Heeyeop

    2015-09-01

    Plasma etching process is the core process in semiconductor fabrication, and the etching endpoint detection is one of the essential FDC (Fault Detection and Classification) for yield management and mass production. In general, Optical emission spectrocopy (OES) has been used to detect endpoint because OES can be a non-invasive and real-time plasma monitoring tool. In OES, the trend of a few sensitive wavelengths is traced. However, in case of small-open area etch endpoint detection (ex. contact etch), it is at the boundary of the detection limit because of weak signal intensities of reaction reactants and products. Furthemore, the various materials covering the wafer such as photoresist, dielectric materials, and metals make the analysis of OES signals complicated. In this study, full spectra of optical emission signals were collected and the data were analyzed by a data-mining approach, modified K-means cluster analysis. The K-means cluster analysis is modified suitably to analyze a thousand of wavelength variables from OES. This technique can improve the sensitivity of EPD for small area oxide layer etching processes: about 1.0% oxide area. This technique is expected to be applied to various plasma monitoring applications including fault detections as well as EPD. Plasma Etch, EPD, K-means Cluster Analysis.

  2. End-point impedance measurements across dominant and nondominant hands and robotic assistance with directional damping.

    PubMed

    Erden, Mustafa Suphi; Billard, Aude

    2015-06-01

    The goal of this paper is to perform end-point impedance measurements across dominant and nondominant hands while doing airbrush painting and to use the results for developing a robotic assistance scheme. We study airbrush painting because it resembles in many ways manual welding, a standard industrial task. The experiments are performed with the 7 degrees of freedom KUKA lightweight robot arm. The robot is controlled in admittance using a force sensor attached at the end-point, so as to act as a free-mass and be passively guided by the human. For impedance measurements, a set of nine subjects perform 12 repetitions of airbrush painting, drawing a straight-line on a cartoon horizontally placed on a table, while passively moving the airbrush mounted on the robot's end-point. We measure hand impedance during the painting task by generating sudden and brief external forces with the robot. The results show that on average the dominant hand displays larger impedance than the nondominant in the directions perpendicular to the painting line. We find the most significant difference in the damping values in these directions. Based on this observation, we develop a "directional damping" scheme for robotic assistance and conduct a pilot study with 12 subjects to contrast airbrush painting with and without robotic assistance. Results show significant improvement in precision with both dominant and nondominant hands when using robotic assistance.

  3. Resummation of Large Endpoint Corrections to Color-Octet J/psi Photoproduction

    SciTech Connect

    Sean Fleming; Adam K. Leibovich; Thomas Mehen

    2006-07-27

    An unresolved problem in J/{psi} phenomenology is a systematic understanding of the differential photoproduction cross section, d{sigma}/dz [{gamma} + p {yields} J/{psi} + X], where z = E{sub {psi}}/E{sub {gamma}} in the proton rest frame. In the non-relativistic QCD (NRQCD) factorization formalism, fixed-order perturbative calculations of color-octet mechanisms suffer from large perturbative and nonperturbative corrections that grow rapidly in the endpoint region, z {yields} 1. In this paper, NRQCD and soft collinear effective theory are combined to resum these large corrections to the color-octet photoproduction cross section. We derive a factorization theorem for the endpoint differential cross section involving the parton distribution function and the color-octet J/{psi} shape functions. A one loop matching calculation explicitly confirms our factorization theorem at next-to-leading order. Large perturbative corrections are resummed using the renormalization group. The calculation of the color-octet contribution to d{sigma}/dz is in qualitative agreement with data. Quantitative tests of the universality of color-octet matrix elements require improved knowledge of shape functions entering these calculations as well as resummation of the color-singlet contribution which accounts for much of the total cross section and also peaks near the endpoint.

  4. Combining SVM and flame radiation to forecast BOF end-point

    NASA Astrophysics Data System (ADS)

    Wen, Hongyuan; Zhao, Qi; Xu, Lingfei; Zhou, Munchun; Chen, Yanru

    2009-05-01

    Because of complex reactions in Basic Oxygen Furnace (BOF) for steelmaking, the main end-point control methods of steelmaking have insurmountable difficulties. Aiming at these problems, a support vector machine (SVM) method for forecasting the BOF steelmaking end-point is presented based on flame radiation information. The basis is that the furnace flame is the performance of the carbon oxygen reaction, because the carbon oxygen reaction is the major reaction in the steelmaking furnace. The system can acquire spectrum and image data quickly in the steelmaking adverse environment. The structure of SVM and the multilayer feed-ward neural network are similar, but SVM model could overcome the inherent defects of the latter. The model is trained and forecasted by using SVM and some appropriate variables of light and image characteristic information. The model training process follows the structure risk minimum (SRM) criterion and the design parameter can be adjusted automatically according to the sampled data in the training process. Experimental results indicate that the prediction precision of the SVM model and the executive time both meet the requirements of end-point judgment online.

  5. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    MedlinePlus

    ... 1- to 2-Year-Old Acute Lymphoblastic Leukemia (ALL) KidsHealth > For Parents > Acute Lymphoblastic Leukemia (ALL) Print A A A What's in this article? ... child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood ...

  6. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    MedlinePlus

    ... 1- to 2-Year-Old Acute Lymphoblastic Leukemia (ALL) KidsHealth > For Parents > Acute Lymphoblastic Leukemia (ALL) A A A What's in this article? About ... child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood ...

  7. EXPOSURE DOMAINS: ROLE OF TIMING, PATTERN AND MAGNITUDE OF EXPOSURE ON HEALTH RISKS

    EPA Science Inventory

    Environmental health risk assessment may be broadly separated into assessment of risks from exposures to agents affecting health endpoints for which it may be presumed there is no dose threshold, and to agents affecting endpoints that more likely have a dose threshold. For hea...

  8. Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 2: endpoint definitions: A consensus document from the Mitral Valve Academic Research Consortium.

    PubMed

    Stone, Gregg W; Adams, David H; Abraham, William T; Kappetein, Arie Pieter; Généreux, Philippe; Vranckx, Pascal; Mehran, Roxana; Kuck, Karl-Heinz; Leon, Martin B; Piazza, Nicolo; Head, Stuart J; Filippatos, Gerasimos; Vahanian, Alec S

    2015-08-01

    Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous aetiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodelling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of trans- catheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.

  9. Idaho National Laboratory Test Area North: Application of Endpoints to Guide Adaptive Remediation at a Complex Site: INL Test Area North: Application of Endpoints

    SciTech Connect

    Lee, M. Hope; Truex, Mike; Freshley, Mark; Wellman, Dawn

    2016-09-01

    Complex sites are defined as those with difficult subsurface access, deep and/or thick zones of contamination, large areal extent, subsurface heterogeneities that limit the effectiveness of remediation, or where long-term remedies are needed to address contamination (e.g., because of long-term sources or large extent). The Test Area North at the Idaho National Laboratory, developed for nuclear fuel operations and heavy metal manufacturing, is used as a case study. Liquid wastes and sludge from experimental facilities were disposed in an injection well, which contaminated the subsurface aquifer located deep within fractured basalt. The wastes included organic, inorganic, and low-level radioactive constituents, with the focus of this case study on trichloroethylene. The site is used as an example of a systems-based framework that provides a structured approach to regulatory processes established for remediation under existing regulations. The framework is intended to facilitate remedy decisions and implementation at complex sites where restoration may be uncertain, require long timeframes, or involve use of adaptive management approaches. The framework facilitates site, regulator, and stakeholder interactions during the remedial planning and implementation process by using a conceptual model description as a technical foundation for decisions, identifying endpoints, which are interim remediation targets or intermediate decision points on the path to an ultimate end, and maintaining protectiveness during the remediation process. At the Test Area North, using a structured approach to implementing concepts in the endpoint framework, a three-component remedy is largely functioning as intended and is projected to meet remedial action objectives by 2095 as required. The remedy approach is being adjusted as new data become available. The framework provides a structured process for evaluating and adjusting the remediation approach, allowing site owners, regulators, and

  10. Automatic Identification of the Repolarization Endpoint by Computing the Dominant T-wave on a Reduced Number of Leads

    PubMed Central

    Giuliani, C.; Agostinelli, A.; Di Nardo, F.; Fioretti, S.; Burattini, L.

    2016-01-01

    Electrocardiographic (ECG) T-wave endpoint (Tend) identification suffers lack of reliability due to the presence of noise and variability among leads. Tend identification can be improved by using global repolarization waveforms obtained by combining several leads. The dominant T-wave (DTW) is a global repolarization waveform that proved to improve Tend identification when computed using the 15 (I to III, aVr, aVl, aVf, V1 to V6, X, Y, Z) leads usually available in clinics, of which only 8 (I, II, V1 to V6) are independent. The aim of the present study was to evaluate if the 8 independent leads are sufficient to obtain a DTW which allows a reliable Tend identification. To this aim Tend measures automatically identified from 15-dependent-lead DTWs of 46 control healthy subjects (CHS) and 103 acute myocardial infarction patients (AMIP) were compared with those obtained from 8-independent-lead DTWs. Results indicate that Tend distributions have not statistically different median values (CHS: 340 ms vs. 340 ms, respectively; AMIP: 325 ms vs. 320 ms, respectively), besides being strongly correlated (CHS: ρ=0.97, AMIP: 0.88; P<10-27). Thus, measuring Tend from the 15-dependent-lead DTWs is statistically equivalent to measuring Tend from the 8-independent-lead DTWs. In conclusion, for the clinical purpose of automatic Tend identification from DTW, the 8 independent leads can be used without a statistically significant loss of accuracy but with a significant decrement of computational effort. The lead dependence of 7 out of 15 leads does not introduce a significant bias in the Tend determination from 15 dependent lead DTWs. PMID:27347218

  11. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials

    PubMed Central

    Hoemann, Caroline; Kandel, Rita; Roberts, Sally; Saris, Daniel B.F.; Creemers, Laura; Mainil-Varlet, Pierre; Méthot, Stephane; Hollander, Anthony P.; Buschmann, Michael D.

    2011-01-01

    Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character. PMID:26069577

  12. Comparative study on health care utilization and hospital outcomes of severe acute exacerbation of chronic obstructive pulmonary disease managed by pulmonologists vs internists

    PubMed Central

    Pothirat, Chaicharn; Liwsrisakun, Chalerm; Bumroongkit, Chaiwat; Deesomchok, Athavudh; Theerakittikul, Theerakorn; Limsukon, Atikun

    2015-01-01

    Background Care for many chronic health conditions is delivered by both specialists and generalists. Differences in patients’ quality of care and management between generalists and specialists have been well documented for asthma, whereas a few studies for COPD reported no differences. Objective The objective of this study is to compare consistency with Global initiative for chronic Obstructive Lung Disease guidelines, as well as rate, health care utilization, and hospital outcomes of severe acute exacerbation (AE) of COPD patients managed by pulmonologists and internists. Materials and methods This is a 12-month prospective, comparative observational study among 208 COPD patients who were regularly managed by pulmonologists (Group A) and internists (Group B). Clinical data, health care utilization, and hospital outcomes of the two groups were statistically compared. Results Out of 208 enrolled patients, 137 (Group A) and 71 (Group B) were managed by pulmonologists and internists, respectively. Pharmacological treatment corresponding to disease severity stages between the two groups was not statistically different. Group A received care consistent with guidelines in terms of annual influenza vaccination (31.4% vs 9.9%, P<0.001) and pulmonary rehabilitation (24.1% vs 0%, P<0.001) greater than Group B. Group A had reduced rates (12.4% vs 23.9%, P=0.033) and numbers of severe AE (0.20±0.63 person-years vs 0.41±0.80 person-years, P=0.029). Among patients with severe AE requiring mechanical ventilation, Group A had reduced mechanical ventilator duration (1.5 [1–7] days vs 5 [3–29] days, P=0.005), hospital length of stay (3.5 [1–20] days vs 16 [6–29] days, P=0.012), and total hospital cost ($863 [247–2,496] vs $2,095 [763–6,792], P=0.049) as compared with Group B. Conclusion This study demonstrated that pulmonologists followed national COPD guidelines more closely than internists. The rates and frequencies of severe AE were significantly lower in patients

  13. BRIDGING FROM CLINICAL ENDPOINTS TO ESTIMATES OF TREATMENT VALUE FOR EXTERNAL DECISION MAKERS

    PubMed Central

    ZHU, C.W.; LEIBMAN, C.; TOWNSEND, R.; MCLAUGHLIN, T.; SCARMEAS, N.; ALBERT, M.; BRANDT, J.; BLACKER, D.; SANO, M.; STERN, Y.

    2009-01-01

    Aim While clinical endpoints provide important information on the efficacy of treatment in controlled conditions, they often are not relevant to decision makers trying to gauge the potential economic impact or value of new treatments. Therefore, it is often necessary to translate changes in cognition, function or behavior into changes in cost or other measures, which can be problematic if not conducted in a transparent manner. The Dependence Scale (DS), which measures the level of assistance a patient requires due to AD-related deficits, may provide a useful measure of the impact of AD progression in a way that is relevant to patients, providers and payers, by linking clinical endpoints to estimates of cost effectiveness or value. The aim of this analysis was to test the association of the DS to clinical endpoints and AD-related costs. Method The relationship between DS score and other endpoints was explored using the Predictors Study, a large, multi-center cohort of patients with probable AD followed annually for four years. Enrollment required a modified Mini-Mental State Examination (mMMS) score ≥30, equivalent to a score of approximately ≥16 on the MMSE. DS summated scores (range: 0–15) were compared to measures of cognition (MMSE), function (Blessed Dementia Rating Scale, BDRS, 0–17), behavior, extrapyramidal symptoms (EPS), and psychotic symptoms (illusions, delusions or hallucinations). Also, estimates for total cost (sum of direct medical cost, direct non-medical cost, and cost of informal caregivers’ time) were compared to DS scores. Results For the 172 patients in the analysis, mean baseline scores were: DS: 5.2 (SD: 2.0), MMSE: 23.0 (SD: 3.5), BDRS: 2.9 (SD: 1.3), EPS: 10.8%, behavior: 28.9% psychotic symptoms: 21.1%. After 4 years, mean scores were: DS: 8.9 (SD: 2.9), MMSE: 17.2 (SD: 4.7), BDRS: 5.2 (SD: 1.4), EPS: 37.5%, behavior: 60.0%, psychotic symptoms: 46.7%. At baseline, DS scores were significantly correlated with MMSE (r=−0.299, p<0

  14. Representing and Retrieving Patients' Falls Risk Factors and Risk for Falls among Adults in Acute Care through the Electronic Health Record

    ERIC Educational Resources Information Center

    Pfaff, Jann

    2013-01-01

    Defining fall risk factors and predicting fall risk status among patients in acute care has been a topic of research for decades. With increasing pressure on hospitals to provide quality care and prevent hospital-acquired conditions, the search for effective fall prevention interventions continues. Hundreds of risk factors for falls in acute care…

  15. A logrank test-based method for sizing clinical trials with two co-primary time-to-event endpoints.

    PubMed

    Sugimoto, Tomoyuki; Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R

    2013-07-01

    We discuss sample size determination for clinical trials evaluating the joint effects of an intervention on two potentially correlated co-primary time-to-event endpoints. For illustration, we consider the most common case, a comparison of two randomized groups, and use typical copula families to model the bivariate endpoints. A correlation structure of the bivariate logrank statistic is specified to account for the correlation among the endpoints, although the between-group comparison is performed using the univariate logrank statistic. We propose methods to calculate the required sample size to compare the two groups and evaluate the performance of the methods and the behavior of required sample sizes via simulation.

  16. C-reactive protein point-of-care testing and antibiotic prescribing for acute respiratory tract infections in rural primary health centres of North Ethiopia: a cross-sectional study

    PubMed Central

    Yebyo, Henock; Medhanyie, Araya Abrha; Spigt, Mark; Hopstaken, Rogier

    2016-01-01

    Unjustified antibiotic prescribing for acute upper respiratory infections (URTIs) is probably more common in poor-resource settings where physicians are scarce. Introducing C-reactive protein (CRP) point-of-care testing in such settings could reduce the misuse of antibiotics, which could avert antibiotic resistance. However, information useful for the applicability of CRP test in resource-limited settings is lacking. This study aimed to elicit the frequency of antibiotic prescribing and distribution of CRP levels in remote, rural settings in Ethiopia. We included 414 patients with acute URTIs from four health centres. Health professionals recorded the clinical features of the patients, but the laboratory professionals measured the CRP levels of all patients at the point of care. The most prominent respiratory causes for consultation were acute URTIs combined (44.4%), and lower respiratory tract infections—pneumonia (29.71%) and acute bronchitis (25.84%). The CRP distribution was <20 mg/l, 20–99 mg/l and 100 mg/l or more in 66.6%, 27.9% and 5.5% of the patients, respectively. The CRP levels were significantly different among these clinical diagnoses (X2=114.3, P<0.001, d.f.=4). A wide range of antibiotics was administered for 87.8% of the patients, regardless of the diagnostic or prognostic nature of their diseases. Antibiotic prescribing for acute URTIs in the rural areas of Ethiopia is unduly high, with high proportions of mild, self-limiting illness, mostly URTIs. Implementation of CRP point-of-care testing in such resource-constrained settings, with low- or middle-grade healthcare professionals, could help reconcile the inappropriate use of antibiotics by withholding from patients who do not benefit from antibiotic treatment. PMID:26769226

  17. Evaluation of multiple mechanism-based toxicity endpoints in primary cultured human hepatocytes for the identification of drugs with clinical hepatotoxicity: Results from 152 marketed drugs with known liver injury profiles.

    PubMed

    Zhang, Jie; Doshi, Utkarsh; Suzuki, Ayako; Chang, Ching-Wei; Borlak, Jürgen; Li, Albert P; Tong, Weida

    2016-08-05

    We report here the results of a collaborative research program to develop a robust and reliable in vitro system to allow an accurate definition of the drug-induced liver injury (DILI) potential of new drug entities during drug development. The in vitro hepatotoxic potential of 152 drugs with known DILI profiles were evaluated in primary cultured human hepatocytes with four mechanistically-relevant endpoints: cellular ATP depletion, reactive oxygen species (ROS), glutathione (GSH) depletion, and caspase activation for apoptosis. The drugs, 80 in the testing set and 72 in the validation set, were classified based on serious clinical/regulatory outcomes as defined by reported acute liver failure, black-box warning, and/or withdrawal. The drugs were further sub-categorized for dominant types of liver injury. Logistic regression models were performed to calculate the area under the receiver operating characteristics curve (AUROC) and to evaluate the prediction potential of the selected endpoints for serious clinical/regulatory outcomes. The ROS/ATP ratio was found to yield an excellent AUROC in both the testing (0.8989, P < 0.0001) and validation set (0.8545, P < 0.0001), and was found to distinguish drugs associated with severe from non-severe DILI cases (p < 0.0001). The results suggest that evaluation of drugs in primary human hepatocytes using the ROS/ATP ratio endpoint may aid the definition of their potential to cause severe DILI.

  18. [Emergence of new pneumonia: besides severe acute respiratory syndrome].

    PubMed

    Mangiarotti, P; Pozzi, E

    2006-10-01

    Important epidemiological modifications have been registered in respiratory infections, both in immunocompetent and immunocompromised hosts. Pathogens with modified antibiotic susceptibility patterns have emerged, which display an increased antibiotic resistance, such as S. pneumoniae, S. aureus, H. influenzae. This trait has a strong impact on the therapeutic choices, particularly when an empiric antibiotic treatment is selected. The prevalence of bacterial species showing non-susceptibility to the most common prescribed antibiotics (betalactams, macrolides etc.) follows a different geographic distribution. Some pathogens have acquired a new epidemiological role in patients affected with immune deficiencies: among them P. carinii and other bacterial, fungal and viral pathogens. The emergence of new, previously unknown, species, has been registered, both bacteria (C. pneumoniae) and viruses (Metapneumovirus, Hantavirus etc.). Such aspects must be considered in the diagnosis of respiratory infections, which should include diagnostic tests for the identification of such pathogens. Among the new respiratory infections severe acute respiratory syndrome (SARS) has quickly become a health care emergency, so that efforts have been made to identify the aetiological agent as well as the main epidemiological and clinical characteristics of the disease. Avian influenza has raised great interest immediately after the first cases of human infection caused by the avian virus, especially after the outbreaks in Asian countries and in the Netherlands. A crucial step in containing infection is the prevention of the disease; efforts are directed toward this endpoint.

  19. Rationale and design of a randomized controlled trial evaluating Community Health Worker (CHW) based interventions for the secondary prevention of acute coronary syndromes in India (SPREAD)

    PubMed Central

    Kamath, Deepak Y; Xavier, Denis; Gupta, Rajeev; Devereaux, P.J.; Sigamani, Alben; Hussain, Tanvir; Umesh, Sowmya; Xavier, Freeda; Girish, Preeti; George, Nisha; Thomas, Tinku; Chidambaram, N.; Joshi, Rajnish; Pais, Prem; Yusuf, Salim

    2014-01-01

    Background There is a need to evaluate & implement cost-effective strategies to improve adherence to treatments in Coronary Heart Disease (CHD). There are no studies from Low Middle Income Countries (LMICs) evaluating trained Community Health Worker (CHW) based interventions for the secondary prevention of CHD. Methods We designed a hospital-based, open randomized trial of CHW based interventions versus standard care. Patients after an Acute Coronary Syndrome (ACS) were randomized to an intervention group (a CHW based intervention package, comprising education tools to enhance self-care and adherence, and regular follow-up by the CHW) or to standard care for 12 months during which study outcomes were recorded. The CHWs were trained over a period of 6 months. The primary outcome measure was medication adherence. The secondary outcomes were differences in adherence to lifestyle modification, physiological parameters (BP, body weight, BMI, heart rate, lipids) and major adverse cardiovascular events. Results We recruited 806 patients stabilized after an ACS from 14 hospitals in 13 Indian cities. The mean age was 56.4 (+/−11.32) and 17.2% were females. A high prevalence of risk factors -hypertension (43.4%), diabetes (31.9%), tobacco consumption (35.4%) and inadequate physical activity (70.5%) were documented. A little over half had ST elevation myocardial infarction (STEMI, 53.7%) and 46.3% had non-ST elevation myocardial infarction (NSTEMI) or unstable angina. Conclusion The CHW interventions and training for SPREAD have been developed and adapted for local use. The results and experience of this study will be important to counter the burden of Cardiovascular Diseases (CVD) in LMICs. PMID:25440797

  20. Evaluation of a Medical and Mental Health Unit compared with standard care for older people whose emergency admission to an acute general hospital is complicated by concurrent 'confusion': a controlled clinical trial. Acronym: TEAM: Trial of an Elderly Acute care Medical and mental health unit

    PubMed Central

    2011-01-01

    Background Patients with delirium and dementia admitted to general hospitals have poor outcomes, and their carers report poor experiences. We developed an acute geriatric medical ward into a specialist Medical and Mental Health Unit over an eighteen month period. Additional specialist mental health staff were employed, other staff were trained in the 'person-centred' dementia care approach, a programme of meaningful activity was devised, the environment adapted to the needs of people with cognitive impairment, and attention given to communication with family carers. We hypothesise that patients managed on this ward will have better outcomes than those receiving standard care, and that such care will be cost-effective. Methods/design We will perform a controlled clinical trial comparing in-patient management on a specialist Medical and Mental Health Unit with standard care. Study participants are patients over the age of 65, admitted as an emergency to a single general hospital, and identified on the Acute Medical Admissions Unit as being 'confused'. Sample size is 300 per group. The evaluation design has been adapted to accommodate pressures on bed management and patient flows. If beds are available on the specialist Unit, the clinical service allocates patients at random between the Unit and standard care on general or geriatric medical wards. Once admitted, randomised patients and their carers are invited to take part in a follow up study, and baseline data are collected. Quality of care and patient experience are assessed in a non-participant observer study. Outcomes are ascertained at a follow up home visit 90 days after randomisation, by a researcher blind to allocation. The primary outcome is days spent at home (for those admitted from home), or days spent in the same care home (if admitted from a care home). Secondary outcomes include mortality, institutionalisation, resource use, and scaled outcome measures, including quality of life, cognitive function

  1. [Detection of endpoint for segmentation between consonants and vowels in aphasia rehabilitation software based on artificial intelligence scheduling].

    PubMed

    Deng, Xingjuan; Chen, Ji; Shuai, Jie

    2009-08-01

    For the purpose of improving the efficiency of aphasia rehabilitation training, artificial intelligence-scheduling function is added in the aphasia rehabilitation software, and the software's performance is improved. With the characteristics of aphasia patient's voice as well as with the need of artificial intelligence-scheduling functions under consideration, the present authors have designed a set of endpoint detection algorithm. It determines the reference endpoints, then extracts every word and ensures the reasonable segmentation points between consonants and vowels, using the reference endpoints. The results of experiments show that the algorithm is able to attain the objects of detection at a higher accuracy rate. Therefore, it is applicable to the detection of endpoint on aphasia-patient's voice.

  2. Does bisphenol A induce superfeminization in Marisa cornuarietis? Part I: intra- and inter-laboratory variability in test endpoints.

    PubMed

    Forbes, Valery E; Selck, Henriette; Palmqvist, Annemette; Aufderheide, John; Warbritton, Ryan; Pounds, Nadine; Thompson, Roy; van der Hoeven, Nelly; Caspers, Norbert

    2007-03-01

    It has been claimed that bisphenol A (BPA) induces superfeminization in the freshwater gastropod, Marisa cornuarietis. To explore the reproducibility of prior work, here we present results from a three-laboratory study, the objectives of which were to determine the mean and variability in test endpoints (i.e., adult fecundity, egg hatchability, and juvenile growth) under baseline conditions and to identify the sources of variability. A major source of variability for all of the measured endpoints was due to differences within and among individuals. With few exceptions, variability among laboratories and among replicate tanks within laboratories contributed little to the observed variability in endpoints. The results highlight the importance of obtaining basic knowledge of husbandry requirements and baseline information on life-history traits of potential test species prior to designing toxicity test protocols. Understanding of the levels and sources of endpoint variability is essential so that statistically robust and ecologically relevant tests of chemicals can be conducted.

  3. End-point control of a two-link manipulator with a very flexible forearm - Issues and experiments

    NASA Technical Reports Server (NTRS)

    Oakley, Celia M.; Cannon, Robert H., Jr.

    1989-01-01

    For mechanical manipulators, a logical sensor location is at the manipulator end-point where tasks are performed. Unfortunately, when bending flexibility exists between an end-point sensor and a joint actuator, stability and performance are achieved only through sophisticated control design. Some of the issues involved in utilizing end-point sensing for two-link flexible manipulators are addressed. A modeling technique that properly represents the foreshortening of a flexible link undergoing deflections is presented. In order to realize fully the advantages of the assumed-modes modeling method, mode shapes are selected that allow a low-order model to be used effectively for simulation and control purposes. A nonlinear controller, incorporating state feedback and a constant-gain extended Kalman filter driven by end-point measurements, is designed and compared to a conventional proportional-plus-derivative controller that uses collocated sensors. Results from implementing these controllers on the experimental Stanford multilink flexible manipulator are given.

  4. Guidance for Using Non-Definitive Endpoints in Evaluating Risks to Listed and Non-listed Animal Species

    EPA Pesticide Factsheets

    Ensure consistency among OPP scientists in the use of non-definitive toxicity endpoints for terrestrial and aquatic animals when conducting ecological risk assessments for pesticides and federally listed and non-listed species.

  5. What is Normal? A Characterization of the Values and Variabilty in Reproductive Endpoints of the Fathead Minnow, Pimephales promelas

    EPA Science Inventory

    Jensen et al. investigated aspects of the normal reproductive biology of the fathead minnow (FHM, P. promelas), and subsequent studies have generated a large amount of additional reproductive data for endpoints such as plasma steroid hormone and vitellogenin concentrations, spa...

  6. Communication and care in an acute cancer center: the effects of patients' willingness to communicate about health, health-care environment perceptions, and health status on information seeking, participation in care practices, and satisfaction.

    PubMed

    Wright, Kevin B; Frey, Lawrence R

    2008-07-01

    This study investigated the role of willingness to communicate about health (WTCH) among older patients in a state-of-the-art cancer center. Specifically, relationships were examined between patients' WTCH and their information seeking, perceptions of coping activities the center offered, and satisfaction with the center. The study also explored how those relationships may be mediated by patients' perceptions of the health-care environment and their health status. The results indicated that WTCH may play an important role in predicting information-seeking behaviors, perceived helpfulness of center-sponsored activities, and overall satisfaction with care received at the center. Evidence also was found that perceptions of the health-care environment mediated cancer patients' WTCH. The implications of these findings for communication theory and application, as well as limitations and future directions for research, are discussed.

  7. Deriving sulfamethoxazole dissipation endpoints in pasture soils using first order and biphasic kinetic models.

    PubMed

    Srinivasan, Prakash; Sarmah, Ajit K; Rohan, Maheswaran

    2014-08-01

    Single first-order (SFO) kinetic model is often used to derive the dissipation endpoints of an organic chemical in soil. This model is used due to its simplicity and requirement by regulatory agencies. However, using the SFO model for all types of decay pattern could lead to under- or overestimation of dissipation endpoints when the deviation from first-order is significant. In this study the performance of three biphasic kinetic models - bi-exponential decay (BEXP), first-order double exponential decay (FODED), and first-order two-compartment (FOTC) models was evaluated using dissipation datasets of sulfamethoxazole (SMO) antibiotic in three different soils under varying concentration, depth, temperature, and sterile conditions. Corresponding 50% (DT50) and 90% (DT90) dissipation times for the antibiotics were numerically obtained and compared against those obtained using the SFO model. The fit of each model to the measured values was evaluated based on an array of statistical measures such as coefficient of determination (R(2)adj), root mean square error (RMSE), chi-square (χ(2)) test at 1% significance, Bayesian Information Criteria (BIC) and % model error. Box-whisker residual plots were also used to compare the performance of each model to the measured datasets. The antibiotic dissipation was successfully predicted by all four models. However, the nonlinear biphasic models improved the goodness-of-fit parameters for all datasets. Deviations from datasets were also often less evident with the biphasic models. The fits of FOTC and FODED models for SMO dissipation datasets were identical in most cases, and were found to be superior to the BEXP model. Among the biphasic models, the FOTC model was found to be the most suitable for obtaining the endpoints and could provide a mechanistic explanation for SMO dissipation in the soils.

  8. Use of behavioral endpoints to determine protective concentrations of the insecticide fonofos for bluegill (Lepomis macrochirus)

    USGS Publications Warehouse

    Fairchild, J.F.; Little, E.E.

    1999-01-01

    This research compared the results of laboratory and mesocosm studies to determine the effectiveness of using behavioral measures of sublethal exposure to define environmental concentration ranges that are protective of free-ranging populations of bluegill (Lepomis macrochirus) exposed to the organophophate insecticide fonofos. Thirty-day laboratory chronic studies were conducted to determine the relative sensitivity of standard (e.g. survival and growth) and non-standard behavioral (e.g. swimming capacity, feeding efficiency, and aggression) endpoints in predicting concentrations of fonofos protective of bluegill growth and survival. The lowest observable effect concentration (LOECs) for the standard measures of survival and growth was 5.6 ??g/L. Two behavioral endpoints were of similar sensitivity to the standard measures: swimming capacity, LOEC of 5.6 ??g/L; and prey strike frequency, LOEC of 5.6 ??g/L. However, aggressive interactions were ten-fold more sensitive than swimming or feeding behavior with a LOEC occurring at 0.6 ??g/L. Lab results were compared to an aquatic mesocosm study which exposed adult and juvenile bluegill to a 9.41 ??g/L concentration of fonofos. The dissipation half-life of fonofos was 5 days in 0.1 hectare aquatic mesocosms. Significant mortality among caged bluegill occurred within 4 days of exposure at 9.41 ??g/L. However, the 9.41 ??g/L concentration of fonofos had no statistically significant effects on survival, growth, reproduction, or total biomass of free-ranging populations of bluegill. We conclude from these studies that laboratory data can accurately estimate concentrations that are lethal in the field and that the use of behavioral endpoints can provide ecologically relevant, yet conservative estimates of concentrations that are protective of field populations.

  9. Comparing toxicity endpoints on Lecane quadridentata (Rotifera: Monogononta) exposed to two anticholinesterases pesticides.

    PubMed

    Pérez-Legaspi, Ignacio Alejandro; Quintanar, J Luis; Rico-Martínez, Roberto

    2012-09-01

    Toxicity tests were performed on the freshwater rotifer Lecane quadridentata exposed to the pesticides carbaryl and methyl parathion (lethal, sublethal, and chronic) to compare the sensitivity between different endpoints: (a) 48-h mortality; (b) 30-min in vivo inhibition of esterase activity; (c) 5-day inhibition of the instantaneous growth rate. The emphasis of this work was to find the most appropriate endpoint to evaluate the toxicity of these pesticides in view of their sensitivity, duration, and ecological relevance. The comparison between the three toxicity tests show that the 5-day chronic tests have the lowest EC50 (2.22 and 6.6 mg/L), lowest-observed-effect concentration (2.5 and 2.5 mg/L), and no-observed-effect concentration (1.0 and 1.2 mg/L) values for carbaryl and methyl parathion, respectively. This indicates that the estimate of the instantaneous rate of natural increase r is the most sensitive endpoint regarding the toxicity of these pesticides. This sensitivity might be due to the effect on reducing the growth potential form the first generation on. Lethal and sublethal tests are closely related, suggesting that the immediate effect after inhibition of esterases is death. In general, the sensitivity of L. quadridentata is similar to other species of rotifers exposed to methyl parathion. Therefore, the 5-day chronic toxicity test with the freshwater rotifer L. quadridentata should be considered a good candidate to evaluate the effect of anticholinesterase pesticides, due to its high sensitivity and ecological relevance.

  10. Determination of Endpoint Energy and Bremsstrahlung Spectra for High-Energy Radiation-Therapy Beams

    NASA Astrophysics Data System (ADS)

    Landry, Danny Joe

    Few attempts have been made to experimentally determine thick-target bremsstrahlung spectra of megavoltage therapy beams. For spectral studies using the Compton scattering technique, sodium iodine (NaI) detectors with relatively poor energy resolution have been used. Other experimental techniques for determining spectra are generally not suited for a clinical environment with the inherent time and space constraints. To gather more spectral information than previously obtained in the region near the endpoint energy, the use of a high-resolution intrinsic-germanium (Ge) detector was proposed. A response function matrix was determined from experimentally obtained pulse height distributions on the multichannel analyzer. The distributions were for nine various monoenergetic sources between 280 adn 1525 keV. The response function was used to convert the measured pulse height distributions to photon flux spectra using an iterative approximation technique with a computer. Photon flux spectra from the Sagittaire Linear Accelerator were obtained at average-electron endpoint energies of 15, 20, and 25 MeV. Two spectra were measured at the 25 MeV setting; one spectrum was measured along the central axis and one spectrum at 4(DEGREES) off axis. Photon spectra were also obtained for a Van de Graaff generator at the nominal endpoint energies of 2.2, 2.35, and 2.5 MeV. The results for both the linac and the Van de Graaff generator were compared with theoretical spectra and previously measured spectra where available. Also, photon spectra from a Theratron-80 (('60)Co) unit were determined for three field sizes and for a 10 x 10 cm. field with a lucite tray or a 45(DEGREES) wedge in the beam. The resulting spectra were compared to previously measured ('60)Co spectra.

  11. Control of end-point forces of a multijoint limb by functional neuromuscular stimulation.

    PubMed

    Lan, N; Crago, P E; Chizeck, H J

    1991-10-01

    A multivariable feedback controller was designed and tested for regulating the magnitude and orientation of the force vector at the end point of a multijoint limb in contact with an isometric load. The force vector was produced by electrical stimulation of muscles. To achieve arbitrary control of end-point force magnitude and orientation, two coupling issues must be dealt with by the control system. First, there is a geometric coupling between the end-point force vector and joint torques. The amplitude and orientation of the force vector depend on the limb geometry. Second, torques at two joints may be coupled due to activation of muscles that cross them (biarticular coupling). To eliminate the geometric coupling, a transformation of controller error from the Cartesian space to the joint space was employed. A multivariable proportional-plus-integral (PI) control law was used to calculate muscle activation based on the transformed controller error. Centralized and decentralized controls were investigated for decoupling the effects of biarticular muscles. The results obtained from cat experiments showed that the magnitude and orientation of the end-point forces of the cat hindlimb could be regulated by this controller. In the presence of strong biarticular coupling, centralized control yielded better performance than decentralized control during transient responses. Both control strategies could decouple the biarticular muscle at steady state. When no biarticular coupling was present, centralized control sometimes performed worse than decentralized control. This is the first step in the simultaneous control of multiple joints by functional neuromuscular stimulation (FNS). The controller has broad potential applications in FNS neural prostheses.

  12. Multisite Comparison of Anti-Human Immunodeficiency Virus Microbicide Activity in Explant Assays Using a Novel Endpoint Analysis ▿ †

    PubMed Central

    Richardson-Harman, Nicola; Lackman-Smith, Carol; Fletcher, Patricia S.; Anton, Peter A.; Bremer, James W.; Dezzutti, Charlene S.; Elliott, Julie; Grivel, Jean-Charles; Guenthner, Patricia; Gupta, Phalguni; Jones, Maureen; Lurain, Nell S.; Margolis, Leonid B.; Mohan, Swarna; Ratner, Deena; Reichelderfer, Patricia; Roberts, Paula; Shattock, Robin J.; Cummins, James E.

    2009-01-01

    Microbicide candidates with promising in vitro activity are often advanced for evaluations using human primary tissue explants relevant to the in vivo mucosal transmission of human immunodeficiency virus type 1 (HIV-1), such as tonsil, cervical, or rectal tissue. To compare virus growth or the anti-HIV-1 efficacies of candidate microbicides in tissue explants, a novel soft-endpoint method was evaluated to provide a single, objective measurement of virus growth. The applicability of the soft endpoint is shown across several different ex vivo tissue types, with the method performed in different laboratories, and for a candidate microbicide (PRO 2000). The soft-endpoint method was compared to several other endpoint methods, including (i) the growth of virus on specific days after infection, (ii) the area under the virus growth curve, and (iii) the slope of the virus growth curve. Virus growth at the assay soft endpoint was compared between laboratories, methods, and experimental conditions, using nonparametric statistical analyses. Intra-assay variability determinations using the coefficient of variation demonstrated higher variability for virus growth in rectal explants. Significant virus inhibition by PRO 2000 and significant differences in the growth of certain primary HIV-1 isolates were observed by the majority of laboratories. These studies indicate that different laboratories can provide consistent measurements of anti-HIV-1 microbicide efficacy when (i) the soft endpoint or another standardized endpoint is used, (ii) drugs and/or virus reagents are centrally sourced, and (iii) the same explant tissue type and method are used. Application of the soft-endpoint method reduces the inherent variability in comparisons of preclinical assays used for microbicide development. PMID:19726602

  13. Multisite comparison of anti-human immunodeficiency virus microbicide activity in explant assays using a novel endpoint analysis.

    PubMed

    Richardson-Harman, Nicola; Lackman-Smith, Carol; Fletcher, Patricia S; Anton, Peter A; Bremer, James W; Dezzutti, Charlene S; Elliott, Julie; Grivel, Jean-Charles; Guenthner, Patricia; Gupta, Phalguni; Jones, Maureen; Lurain, Nell S; Margolis, Leonid B; Mohan, Swarna; Ratner, Deena; Reichelderfer, Patricia; Roberts, Paula; Shattock, Robin J; Cummins, James E

    2009-11-01

    Microbicide candidates with promising in vitro activity are often advanced for evaluations using human primary tissue explants relevant to the in vivo mucosal transmission of human immunodeficiency virus type 1 (HIV-1), such as tonsil, cervical, or rectal tissue. To compare virus growth or the anti-HIV-1 efficacies of candidate microbicides in tissue explants, a novel soft-endpoint method was evaluated to provide a single, objective measurement of virus growth. The applicability of the soft endpoint is shown across several different ex vivo tissue types, with the method performed in different laboratories, and for a candidate microbicide (PRO 2000). The soft-endpoint method was compared to several other endpoint methods, including (i) the growth of virus on specific days after infection, (ii) the area under the virus growth curve, and (iii) the slope of the virus growth curve. Virus growth at the assay soft endpoint was compared between laboratories, methods, and experimental conditions, using nonparametric statistical analyses. Intra-assay variability determinations using the coefficient of variation demonstrated higher variability for virus growth in rectal explants. Significant virus inhibition by PRO 2000 and significant differences in the growth of certain primary HIV-1 isolates were observed by the majority of laboratories. These studies indicate that different laboratories can provide consistent measurements of anti-HIV-1 microbicide efficacy when (i) the soft endpoint or another standardized endpoint is used, (ii) drugs and/or virus reagents are centrally sourced, and (iii) the same explant tissue type and method are used. Application of the soft-endpoint method reduces the inherent variability in comparisons of preclinical assays used for microbicide development.

  14. Sensitivity, variability, and recovery of functional and structural endpoints of an aquatic community exposed to herbicides.

    PubMed

    Knauer, Katja; Hommen, Udo

    2012-04-01

    A mesocosm study with three photosystem-II inhibitors and an equipotent mixture was performed to address the value of functional and structural endpoints in evaluating the impact of herbicides on aquatic systems. The herbicides atrazine, diuron, and isoproturon were dosed in the ratio of their relative potencies as HC30 for the single substance treatments and as 1/3 HC30 for the mixture treatment to obtain comparable effect concentrations. To investigate the effects of the three herbicides and their mixture on photosynthesis of the whole system, the physical-chemical parameters pH, dissolved oxygen, and conductivity were monitored. To address effects on photosynthesis more specifically, the photosynthetic efficiency of phytoplankton and three submersed macrophytes (Elodea canadensis, Myriophyllum spicatum, and Potamogeton lucens) were investigated applying in vivo chlorophyll fluorescence as an indicator for their activity. As a structural endpoint, the species abundance and community structure of the phytoplankton community was determined. Effects were continuously monitored over a five week period of constant exposure, and during a 3 month post-exposure period. The sensitivity, expressed as maximum effect during constant exposure, was higher for the structural parameters (total and single species abundances and PRC) than for the functional parameters. The mean coefficient of variation (CV) for the physical-chemical parameters was below 10%, for the photosynthesis measurement of the phytoplankton and macrophytes below 10 and 30%, respectively. Structural parameters, however, yielded higher variability with mean CVs for phytoplankton abundance data and single sensitive species reaching up to 96%. Effects on the phytoplankton photosynthesis measured via in vivo chlorophyll fluorescence were constant during the exposure period; whereas macrophytes recovered quickly from photosynthesis inhibition despite constant exposure. Effects on total system photosynthesis

  15. An Application of Endpoint Detection to Bivariate Data in Tau-Path Order.

    PubMed

    Sampath, Srinath; Verducci, Joseph S

    2014-08-01

    The Fligner and Verducci (1988) multistage model for rankings is modified to create the moving average maximum likelihood estimator (MAMLE), a locally smooth estimator that measures stage-wise agreement between two long ranked lists, and provides a stopping rule for the detection of the endpoint of agreement. An application of this MAMLE stopping rule to bivariate data set in tau-path order (Yu, Verducci and Blower (2011)) is discussed. Data from the National Cancer Institute measuring associations between gene expression and compound potency are studied using this application, providing insights into the length of the relationship between the variables.

  16. Application of molecular endpoints in early life stage salmonid environmental biomonitoring.

    PubMed

    Marlatt, Vicki L; Sherrard, Ryan; Kennedy, Chris J; Elphick, James R; Martyniuk, Christopher J

    2016-04-01

    Molecular endpoints can enhance existing whole animal bioassays by more fully characterizing the biological impacts of aquatic pollutants. Laboratory and field studies were used to examine the utility of adopting molecular endpoints for a well-developed in situ early life stage (eyed embryo to onset of swim-up fry) salmonid bioassay to improve diagnostic assessments of water quality in the field. Coastal cutthroat trout (Oncorhynchus clarki clarki) were exposed in the laboratory to the model metal (zinc, 40μg/L) and the polycyclic aromatic hydrocarbon (pyrene, 100μg/L) in water to examine the resulting early life stage salmonid responses. In situ field exposures and bioassays were conducted in parallel to evaluate the water quality of three urban streams in British Columbia (two sites with anthropogenic inputs and one reference site). The endpoints measured in swim-up fry included survival, deformities, growth (weight and length), vitellogenin (vtg) and metallothionein (Mt) protein levels, and hepatic gene expression (e.g., metallothioneins [mta and mtb], endocrine biomarkers [vtg and estrogen receptors, esr] and xenobiotic-metabolizing enzymes [cytochrome P450 1A3, cyp1a3 and glutathione transferases, gstk]). No effects were observed in the zinc treatment, however exposure of swim-up fry to pyrene resulted in decreased survival, deformities and increased estrogen receptor alpha (er1) mRNA levels. In the field exposures, xenobiotic-metabolizing enzymes (cyp1a3, gstk) and zinc transporter (zntBigM103) mRNA were significantly increased in swim-up fry deployed at the sites with more anthropogenic inputs compared to the reference site. Cluster analysis revealed that gene expression profiles in individuals from the streams receiving anthropogenic inputs were more similar to each other than to the reference site. Collectively, the results obtained in this study suggest that molecular endpoints may be useful, and potentially more sensitive, indicators of site

  17. Optimal Futility Interim Design: A Predictive Probability of Success Approach with Time-to-Event Endpoint.

    PubMed

    Tang, Zhongwen

    2015-01-01

    An analytical way to compute predictive probability of success (PPOS) together with credible interval at interim analysis (IA) is developed for big clinical trials with time-to-event endpoints. The method takes account of the fixed data up to IA, the amount of uncertainty in future data, and uncertainty about parameters. Predictive power is a special type of PPOS. The result is confirmed by simulation. An optimal design is proposed by finding optimal combination of analysis time and futility cutoff based on some PPOS criteria.

  18. Prognostic factors versus markers of response to treatment versus surrogate endpoints: Three different concepts.

    PubMed

    Sormani, Maria Pia

    2017-03-01

    Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments.

  19. Comparison of adequate relief with symptom, global, and responder endpoints in linaclotide phase 3 trials in IBS-C

    PubMed Central

    Camilleri, Michael; Lembo, Anthony J; Lavins, Bernard J; MacDougall, James E; Carson, Robyn T; Williams, Valerie SL; Nelson, Lauren M; Shiff, Steven J; Currie, Mark G; Kurtz, Caroline B

    2015-01-01

    Background Optimal clinical trial endpoints for irritable bowel syndrome with constipation (IBS-C) are uncertain. Objective The objective of this article is to compare adequate relief (AR) to abdominal/bowel symptoms, global endpoints, and FDA and EMA responder criteria; and to use AR as an anchor to assess clinically meaningful change (CMC) in IBS-C symptoms. Methods Using pooled 12-week data from two phase 3 linaclotide clinical trials, daily abdominal/bowel symptoms and weekly global assessments were correlated with AR. Symptom CMC thresholds were estimated using AR as an anchor. Agreement between AR and FDA/EMA responder criteria was assessed. Results Correlations of AR with percentage change in abdominal symptoms, bowel symptoms, and global endpoints ranged from 0.48–0.54, 0.32–0.39, and 0.61–0.71, respectively. Using AR as an anchor, CMC thresholds were 29% improvement in abdominal pain, 29% improvement in abdominal discomfort, and 0.7/week increase in CSBMs, similar to thresholds for IBS-C responder endpoints recommended by the FDA and EMA. There was considerable agreement of weekly responder rates between AR and the FDA and EMA endpoints (on average, 70%–76% and 71%–82% of weeks with agreement, respectively). Conclusions AR bridges IBS-C clinical trials, putting into perspective the disparate primary endpoints recommended by professional societies and regulatory authorities, and allowing researchers, practitioners, and regulators to compare trial results. PMID:25653859

  20. A convenient formula for sample size calculations in clinical trials with multiple co-primary continuous endpoints.

    PubMed

    Sugimoto, Tomoyuki; Sozu, Takashi; Hamasaki, Toshimitsu

    2012-01-01

    The clinical efficacy of a new treatment may often be better evaluated by two or more co-primary endpoints. Recently, in pharmaceutical drug development, there has been increasing discussion regarding establishing statistically significant favorable results on more than one endpoint in comparisons between treatments, which is referred to as a problem of multiple co-primary endpoints. Several methods have been proposed for calculating the sample size required to design a trial with multiple co-primary correlated endpoints. However, because these methods require users to have considerable mathematical sophistication and knowledge of programming techniques, their application and spread may be restricted in practice. To improve the convenience of these methods, in this paper, we provide a useful formula with accompanying numerical tables for sample size calculations to design clinical trials with two treatments, where the efficacy of a new treatment is demonstrated on continuous co-primary endpoints. In addition, we provide some examples to illustrate the sample size calculations made using the formula. Using the formula and the tables, which can be read according to the patterns of correlations and effect size ratios expected in multiple co-primary endpoints, makes it convenient to evaluate the required sample size promptly.

  1. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology.

    PubMed

    Palevsky, Paul M; Molitoris, Bruce A; Okusa, Mark D; Levin, Adeera; Waikar, Sushrut S; Wald, Ron; Chertow, Glenn M; Murray, Patrick T; Parikh, Chirag R; Shaw, Andrew D; Go, Alan S; Faubel, Sarah G; Kellum, John A; Chinchilli, Vernon M; Liu, Kathleen D; Cheung, Alfred K; Weisbord, Steven D; Chawla, Lakhmir S; Kaufman, James S; Devarajan, Prasad; Toto, Robert M; Hsu, Chi-yuan; Greene, Tom; Mehta, Ravindra L; Stokes, John B; Thompson, Aliza M; Thompson, B Taylor; Westenfelder, Christof S; Tumlin, James A; Warnock, David G; Shah, Sudhir V; Xie, Yining; Duggan, Emily G; Kimmel, Paul L; Star, Robert A

    2012-05-01

    Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.

  2. Scenario-targeted toxicity assessment through multiple endpoint bioassays in a soil posing unacceptable environmental risk according to regulatory screening values.

    PubMed

    Rodriguez-Ruiz, A; Etxebarria, J; Boatti, L; Marigómez, I

    2015-09-01

    Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

  3. Heart failure therapeutics on the basis of a biased ligand of the angiotensin-2 type 1 receptor. Rationale and design of the BLAST-AHF study (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure).

    PubMed

    Felker, G Michael; Butler, Javed; Collins, Sean P; Cotter, Gad; Davison, Beth A; Ezekowitz, Justin A; Filippatos, Gerasimos; Levy, Phillip D; Metra, Marco; Ponikowski, Piotr; Soergel, David G; Teerlink, John R; Violin, Jonathan D; Voors, Adriaan A; Pang, Peter S

    2015-03-01

    The BLAST-AHF (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure) study is designed to test the efficacy and safety of TRV027, a novel biased ligand of the angiotensin-2 type 1 receptor, in patients with acute heart failure (AHF). AHF remains a major public health problem, and no currently-available therapies have been shown to favorably affect outcomes. TRV027 is a novel biased ligand of the angiotensin-2 type 1 receptor that antagonizes angiotensin-stimulated G-protein activation while stimulating β-arrestin. In animal models, these effects reduce afterload while increasing cardiac performance and maintaining stroke volume. In initial human studies, TRV027 appears to be hemodynamically active primarily in patients with activation of the renin-angiotensin-aldosterone system, a potentially attractive profile for an AHF therapeutic. BLAST-AHF is an international prospective, randomized, phase IIb, dose-ranging study that will randomize up to 500 AHF patients with systolic blood pressure ≥120 mm Hg and ≤200 mm Hg within 24 h of initial presentation to 1 of 3 doses of intravenous TRV027 (1, 5, or 25 mg/h) or matching placebo (1:1:1:1) for at least 48 h and up to 96 h. The primary endpoint is a composite of 5 clinical endpoints (dyspnea, worsening heart failure, length of hospital stay, 30-day rehospitalization, and 30-day mortality) combined using an average z-score. Secondary endpoints will include the assessment of dyspnea and change in amino-terminal pro-B-type natriuretic peptide. The BLAST-AHF study will assess the efficacy and safety of a novel biased ligand of the angiotensin-2 type 1 receptor in AHF.

  4. EXTRAPOLATING ACUTE MORTALITY OF AMPELISCA ABDITA TO POPULATION RISK USING A POPULATION MODEL AND MONITORING DATA

    EPA Science Inventory

    Ten-day acute mortality of the benthic amphipod, Ampelisca abdita, is used in a number of regulatory, research, and monitoring programs to evaluate chemical contamination of marine sediments. Although this endpoint has proven to be valuable for characterizing the relative toxicit...

  5. Hairy black holes and the endpoint of AdS4 charged superradiance

    NASA Astrophysics Data System (ADS)

    Dias, Óscar J. C.; Masachs, Ramon

    2017-02-01

    We construct hairy black hole solutions that merge with the anti-de Sitter (AdS4) Reissner-Nordström black hole at the onset of superradiance. These hairy black holes have, for a given mass and charge, higher entropy than the corresponding AdS4-Reissner-Nordström black hole. Therefore, they are natural candidates for the endpoint of the charged superradiant instability. On the other hand, hairy black holes never dominate the canonical and grand-canonical ensembles. The zero-horizon radius of the hairy black holes is a soliton (i.e. a boson star under a gauge transformation). We construct our solutions perturbatively, for small mass and charge, so that the properties of hairy black holes can be used to testify and compare with the endpoint of initial value simulations. We further discuss the near-horizon scalar condensation instability which is also present in global AdS4-Reissner-Nordström black holes. We highlight the different nature of the near-horizon and superradiant instabilities and that hairy black holes ultimately exist because of the non-linear instability of AdS.

  6. Using an Ecosystem Approach to complement protection schemes based on organism-level endpoints.

    PubMed

    Bradshaw, Clare; Kapustka, Lawrence; Barnthouse, Lawrence; Brown, Justin; Ciffroy, Philippe; Forbes, Valery; Geras'kin, Stanislav; Kautsky, Ulrik; Bréchignac, François

    2014-10-01

    Radiation protection goals for ecological resources are focussed on ecological structures and functions at population-, community-, and ecosystem-levels. The current approach to radiation safety for non-human biota relies on organism-level endpoints, and as such is not aligned with the stated overarching protection goals of international agencies. Exposure to stressors can trigger non-linear changes in ecosystem structure and function that cannot be predicted from effects on individual organisms. From the ecological sciences, we know that important interactive dynamics related to such emergent properties determine the flows of goods and services in ecological systems that human societies rely upon. A previous Task Group of the IUR (International Union of Radioecology) has presented the rationale for adding an Ecosystem Approach to the suite of tools available to manage radiation safety. In this paper, we summarize the arguments for an Ecosystem Approach and identify next steps and challenges ahead pertaining to developing and implementing a practical Ecosystem Approach to complement organism-level endpoints currently used in radiation safety.

  7. General description of electromagnetic radiation processes based on instantaneous charge acceleration in ''endpoints''

    SciTech Connect

    James, Clancy W.; Falcke, Heino; Huege, Tim; Ludwig, Marianne

    2011-11-15

    We present a methodology for calculating the electromagnetic radiation from accelerated charged particles. Our formulation - the 'endpoint formulation' - combines numerous results developed in the literature in relation to radiation arising from particle acceleration using a complete, and completely general, treatment. We do this by describing particle motion via a series of discrete, instantaneous acceleration events, or 'endpoints', with each such event being treated as a source of emission. This method implicitly allows for particle creation and destruction, and is suited to direct numerical implementation in either the time or frequency domains. In this paper we demonstrate the complete generality of our method for calculating the radiated field from charged particle acceleration, and show how it reduces to the classical named radiation processes such as synchrotron, Tamm's description of Vavilov-Cherenkov, and transition radiation under appropriate limits. Using this formulation, we are immediately able to answer outstanding questions regarding the phenomenology of radio emission from ultra-high-energy particle interactions in both the earth's atmosphere and the moon. In particular, our formulation makes it apparent that the dominant emission component of the Askaryan effect (coherent radio-wave radiation from high-energy particle cascades in dense media) comes from coherent 'bremsstrahlung' from particle acceleration, rather than coherent Vavilov-Cherenkov radiation.

  8. Contaminant effect endpoints in terrestrial vertebrates at and above the individual level

    USGS Publications Warehouse

    Rattner, B.A.; Cohen, J.B.; Golden, N.H.; Albers, P.H.; Heinz, G.H.; Ohlendorf, H.M.

    2000-01-01

    Use of biochemical, physiological, anatomical, reproductive and behavioral characteristics of wild terrestrial vertebrates to assess contaminant exposure and effects has become commonplace over the past 3 decades. At the level of the individual organism, response patterns have been associated with and sometimes causally linked to contaminant exposure. However, such responses at the organismal level are rarely associated with or causally linked to effects at the population level. Although the ultimate goal of ecotoxicology is the protection of populations, communities, and ecosystems, most of the existing science and regulatory legislation focus on the level of the individual. Consequently, much of this overview concentrates on contaminant effects at the organismal level, with some extrapolation to higher-level effects. In this chapter, we review the state of the science for the evaluation of biotic end-points used to assess contaminant exposure and effects at or above the level of the individual. In addition, we describe extant contaminant concentration thresholds, guidelines, or standards (toxicant criteria) in environmental matrices (e.g., water, soil, sediment, foods) that have been developed to protect wild terrestrial vertebrates. Suggestions are provided to develop and embellish the use and value of such endpoints and criteria for extrapolation of effects to higher levels of biological organization. Increasing focus on populations, communities, and ecosystems is needed to develop biologically meaningful regulatory guidelines that will protect natural resources.

  9. Evaluation and QSAR modeling on multiple endpoints of estrogen activity based on different bioassays.

    PubMed

    Liu, Huanxiang; Papa, Ester; Gramatica, Paola

    2008-02-01

    There is a great need for an effective means of rapidly assessing endocrine-disrupting activity, especially estrogen-simulating activity, due to the large number of chemicals that have serious adverse effects on the environment. Many approaches using a variety of biological screening assays are used to identify endocrine disrupting chemicals. The present investigation analyzes the consistency and peculiarity of information from different experimental assays collected from a literature survey, by studying the correlation of the different endpoints. In addition, the activity values of more widely used selected bioassays have been combined by principle components analysis (PCA) to build one cumulative endpoint, the estrogen activity index (EAI), for priority setting to identify chemicals most likely possessing estrogen activity for early entry into screening. This index was then modeled using only a few theoretical molecular descriptors. The constructed MLR-QSAR model has been statistically validated for its predictive power, and can be proposed as a preliminary evaluative method to screen/prioritize estrogens according to their integrated estrogen activity, just starting from molecular structure.

  10. Challenges to the Therapeutic Pipeline for Irritable Bowel Syndrome: Endpoints and Regulatory Hurdles

    PubMed Central

    Camilleri, Michael; Chang, Lin

    2008-01-01

    Recent advances in our understanding of basic neuroenteric mechanisms and the role of effectors and transmitters in the brain-gut axis have provided opportunities to develop new therapeutic agents for irritable bowel syndrome (IBS). Furthermore, human pharmacodynamic studies utilizing transit, colonic or rectal sensitivity, and brain imaging have been useful in determining therapeutic efficacy (particularly for drugs that act on motor function). This review provides an overview of medications that have not yet been approved for treatment of patients with IBS, yet have shown promise in phase IIB trials. These include drugs that act on the serotonin receptor and transporter system, antidepressants, norepinephrine reuptake inhibitors, opioids, cholecystokinin antagonists, neurokinin-antagonists, chloride channel activators, guanylate cyclase C agonists, atypical benzodiazepines, probiotics and antibiotics. The changing landscape in the regulatory approval process has impacted the development of IBS drugs. Guidance documents from regulatory agencies in Europe and the United States have focused on patients’ reported outcomes and associated quality of life. After a decade of experience with different endpoints that have generated some data on psychometric validation and unprecedented information about responsiveness of the binary or global endpoints to drug therapy, it is necessary to pursue further validation studies before or during pivotal phase IIB or III trials. The hope of providing relief to patients should galvanize all parties to achieve these goals. PMID:18848833

  11. The sleep apnea cardiovascular endpoints (SAVE) trial: Rationale and start-up phase.

    PubMed

    McEvoy, R Doug; Anderson, Craig S; Antic, Nick A; Chen, Baoyuan; He, Quanying; Heeley, Emma; Huang, Shaoguang; Huang, Yining; Wang, Jiguang; Zhong, Nanshan

    2010-09-01

    THE SLEEP APNEA CARDIOVASCULAR ENDPOINTS (SAVE) STUDY (CLINICAL TRIALS REGISTRATION NUMBER: NCT00738170) is an academic initiated and conducted, multinational, open, blinded endpoint, randomised controlled trial designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the incidence of serious cardiovascular events in patients with established cardiovascular disease. The answer to this question is of major importance to populations undergoing ageing and lifestyle changes all over the world. The SAVE study brings together respiratory, sleep and cardiovascular clinician-scientists in a unique interdisciplinary collaborative effort with industry sponsors to conduct the largest and most ambitious clinical trial yet conducted in the field of sleep apnea, with a global recruitment target of 5000 patients. Following its launch in Australia and China in late 2008, SAVE has now entered a phase of international expansion with new recruitment networks being established in New Zealand, India and Latin America. This article describes the rationale for the SAVE study, the considerations behind its design, and progress thus far in establishing the recruitment network. The report emphasises the important role that Chinese sleep and cardiovascular investigators have played in the start-up phase of this landmark international project.

  12. One-stage and two-stage designs for phase II clinical trials with survival endpoints.

    PubMed

    Whitehead, John

    2014-09-28

    This work is motivated by trials in rapidly lethal cancers or cancers for which measuring shrinkage of tumours is infeasible. In either case, traditional phase II designs focussing on tumour response are unsuitable. Usually, tumour response is considered as a substitute for the more relevant but longer-term endpoint of death. In rapidly lethal cancers such as pancreatic cancer, there is no need to use a surrogate, as the definitive endpoint is (sadly) available so soon. In uveal cancer, there is no counterpart to tumour response, and so, mortality is the only realistic response available. Cytostatic cancer treatments do not seek to kill tumours, but to mitigate their effects. Trials of such therapy might also be based on survival times to death or progression, rather than on tumour shrinkage. Phase II oncology trials are often conducted with all study patients receiving the experimental therapy, and this approach is considered here. Simple extensions of one-stage and two-stage designs based on binary responses are presented. Outcomes based on survival past a small number of landmark times are considered: here, the case of three such times is explored in examples. This approach allows exact calculations to be made for both design and analysis purposes. Simulations presented here show that calculations based on normal approximations can lead to loss of power when sample sizes are small. Two-stage versions of the procedure are also suggested.

  13. Patient-specific dosimetric endpoints based treatment plan quality control in radiotherapy.

    PubMed

    Song, Ting; Staub, David; Chen, Mingli; Lu, Weiguo; Tian, Zhen; Jia, Xun; Li, Yongbao; Zhou, Linghong; Jiang, Steve B; Gu, Xuejun

    2015-11-07

    In intensity modulated radiotherapy (IMRT), the optimal plan for each patient is specific due to unique patient anatomy. To achieve such a plan, patient-specific dosimetric goals reflecting each patient's unique anatomy should be defined and adopted in the treatment planning procedure for plan quality control. This study is to develop such a personalized treatment plan quality control tool by predicting patient-specific dosimetric endpoints (DEs). The incorporation of patient specific DEs is realized by a multi-OAR geometry-dosimetry model, capable of predicting optimal DEs based on the individual patient's geometry. The overall quality of a treatment plan is then judged with a numerical treatment plan quality indicator and characterized as optimal or suboptimal. Taking advantage of clinically available prostate volumetric modulated arc therapy (VMAT) treatment plans, we built and evaluated our proposed plan quality control tool. Using our developed tool, six of twenty evaluated plans were identified as sub-optimal plans. After plan re-optimization, these suboptimal plans achieved better OAR dose sparing without sacrificing the PTV coverage, and the dosimetric endpoints of the re-optimized plans agreed well with the model predicted values, which validate the predictability of the proposed tool. In conclusion, the developed tool is able to accurately predict optimally achievable DEs of multiple OARs, identify suboptimal plans, and guide plan optimization. It is a useful tool for achieving patient-specific treatment plan quality control.

  14. Patient-specific dosimetric endpoints based treatment plan quality control in radiotherapy

    NASA Astrophysics Data System (ADS)

    Song, Ting; Staub, David; Chen, Mingli; Lu, Weiguo; Tian, Zhen; Jia, Xun; Li, Yongbao; Zhou, Linghong; Jiang, Steve B.; Gu, Xuejun

    2015-11-01

    In intensity modulated radiotherapy (IMRT), the optimal plan for each patient is specific due to unique patient anatomy. To achieve such a plan, patient-specific dosimetric goals reflecting each patient’s unique anatomy should be defined and adopted in the treatment planning procedure for plan quality control. This study is to develop such a personalized treatment plan quality control tool by predicting patient-specific dosimetric endpoints (DEs). The incorporation of patient specific DEs is realized by a multi-OAR geometry-dosimetry model, capable of predicting optimal DEs based on the individual patient’s geometry. The overall quality of a treatment plan is then judged with a numerical treatment plan quality indicator and characterized as optimal or suboptimal. Taking advantage of clinically available prostate volumetric modulated arc therapy (VMAT) treatment plans, we built and evaluated our proposed plan quality control tool. Using our developed tool, six of twenty evaluated plans were identified as sub-optimal plans. After plan re-optimization, these suboptimal plans achieved better OAR dose sparing without sacrificing the PTV coverage, and the dosimetric endpoints of the re-optimized plans agreed well with the model predicted values, which validate the predictability of the proposed tool. In conclusion, the developed tool is able to accurately predict optimally achievable DEs of multiple OARs, identify suboptimal plans, and guide plan optimization. It is a useful tool for achieving patient-specific treatment plan quality control.

  15. Medical expenses in treating acute esophageal variceal bleeding

    PubMed Central

    Liu, Chueh-Ling; Wu, Cheng-Kun; Shi, Hon-Yi; Tai, Wei-Chen; Liang, Chih-Ming; Yang, Shih-Cheng; Wu, Keng-Liang; Chiu, Yi-Chun; Chuah, Seng-Kee

    2016-01-01

    Abstract Acute variceal bleeding in patients with cirrhosis is related to high mortality and medical expenses. The purpose of present studies was to analyze the medical expenses in treating acute esophageal variceal bleeding among patients with cirrhosis and potential influencing clinical factors. A total of 151,863 patients with cirrhosis with International Classification of Diseases-9 codes 456.0 and 456.20 were analyzed from the Taiwan National Health Insurance Research Database from January 1, 1996 to December 31, 2010. Time intervals were divided into three phases for analysis as T1 (1996–2000), T2 (2001–2005), and T3 (2006–2010). The endpoints were prevalence, length of hospital stay, medical expenses, and mortality rate. Our results showed that more patients were <65 years (75.6%) and of male sex (78.5%). Patients were mostly from teaching hospitals (90.8%) with high hospital volume (50.9%) and high doctor service load (51.1%). The prevalence of acute esophageal variceal bleeding and mean length of hospital stay decreased over the years (P < 0.001), but the overall medical expenses increased (P < 0.001). Multiple regression analysis showed that older age, female sex, Charlson comorbidity index (CCI) score >1, patients from teaching hospitals, and medium to high or very high patient numbers were independent factors for longer hospital stay and higher medical expenses. Aged patients, female sex, increased CCI score, and low doctor service volume were independent factors for both in-hospital and 5-year mortality. Patients from teaching hospitals and medium to high or very high service volume hospitals were independent factors for in-hospital mortality, but not 5-year mortality. Medical expenses in treating acute esophageal variceal bleeding increased despite the decreased prevalence rate and length of hospital stay in Taiwan. Aged patients, female sex, patients with increased CCI score from teaching hospitals, and medium to high or very high

  16. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

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