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Sample records for cap-88 dose risk

  1. Modeling Considerations for Ingestion Pathway Dose Calculations Using CAP88.

    Science.gov (United States)

    Stuenkel, David

    2017-04-01

    The CAP88-PC computer model was developed by the U.S. Environmental Protection Agency to demonstrate compliance under the National Emission Standards for Hazardous Air Pollutants (NESHAPS). The program combines atmospheric transport models with the terrestrial food chain models in the U.S. Nuclear Regulatory Commission Regulatory Guide 1.109 to compute the radionuclide concentrations in the air, on ground surfaces and plants, and the concentrations in food to estimate the dose to individuals living in the area around a facility emitting radionuclides into the atmosphere. CAP88 allows the user to select the size of the assessment area and the receptor locations used to calculate the radionuclide concentrations in non-leafy vegetables, leafy vegetables, milk, and meat consumed by the receptors. Depending on the food scenario selected and the type of calculation ("Population" or "Individual") chosen, the annual effective dose from ingestion can depend on both the size of the assessment area and the location of the receptors. Illustrative examples demonstrate the effect of the choice of these input parameters on the annual effective dose from ingestion. An understanding of the model used in CAP88 and the differences between "Population" and "Individual" run types will enable the CAP88 user to better model the ingestion dose.

  2. NESHAP Area-Specific Dose-Release Factors for Potential Onsite Member-of-the-Public Locations at SRS using CAP88-PC Version 4.0

    Energy Technology Data Exchange (ETDEWEB)

    Trimor, P. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-08-09

    The Environmental Protection Agency (EPA) requires the use of the computer model CAP88-PC to estimate the total effective doses (TED) for demonstrating compliance with 40 CFR 61, Subpart H (EPA 2006), the National Emission Standards for Hazardous Air Pollutants (NESHAP) regulations. As such, CAP88 Version 4.0 was used to calculate the receptor dose due to routine atmospheric releases at the Savannah River Site (SRS). For estimation, NESHAP dose-release factors (DRFs) have been supplied to Environmental Compliance and Area Closure Projects (EC&ACP) for many years. DRFs represent the dose to a maximum receptor exposed to 1 Ci of a specified radionuclide being released into the atmosphere. They are periodically updated to include changes in the CAP88 version, input parameter values, site meteorology, and location of the maximally exposed individual (MEI). In this report, the DRFs were calculated for potential radionuclide atmospheric releases from 13 SRS release points. The three potential onsite MEI locations to be evaluated are B-Area, Three Rivers Landfill (TRL), and Savannah River Ecology Lab Conference Center (SRELCC) with TRL’s onsite workers considered as members-of-the-public, and the potential future constructions of dormitories at SRELCC and Barracks at B-Area. Each MEI location was evaluated at a specified compass sector with different area to receptor distances and was conducted for both ground-level and elevated release points. The analysis makes use of area-specific meteorological data (Viner 2014). The resulting DRFs are compared to the 2014 NESHAP offsite MEI DRFs for three operational areas; A-Area, H-Area, and COS for a release rate of 1 Ci of tritium oxide at 0 ft. elevation. CAP88 was executed again using the 2016 NESHAP MEI release rates for 0 and 61 m stack heights to determine the radionuclide dose at TRL from the center-of-site (COS).

  3. NESHAP Dose-Release Factor Isopleths for Five Source-to-Receptor Distances from the Center of Site and H-Area for all Compass Sectors at SRS using CAP88-PC Version 4.0

    Energy Technology Data Exchange (ETDEWEB)

    Trimor, P. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-08-09

    The Environmental Protection Agency (EPA) requires the use of the computer model CAP88-PC to estimate the total effective doses (TED) for demonstrating compliance with 40 CFR 61, Subpart H (EPA 2006), the National Emission Standards for Hazardous Air Pollutants (NESHAP) regulations. As such, CAP88 Version 4.0 was used to calculate the receptor dose due to routine atmospheric releases at the Savannah River Site (SRS). For estimation, NESHAP dose-release factors (DRFs) have been supplied to Environmental Compliance and Area Closure Projects (EC&ACP) for many years. DRFs represent the dose to a maximum receptor exposed to 1 Ci of a specified radionuclide being released into the atmosphere. They are periodically updated to include changes in the CAP88 version, input parameter values, site meteorology, and location of the maximally exposed individual (MEI). This report presents the DRFs of tritium oxide released at two onsite locations, center-of-site (COS) and H-Area, at 0 ft. elevation to maximally exposed individuals (MEIs) located 1000, 3000, 6000, 9000, and 12000 meters from the release areas for 16 compass sectors. The analysis makes use of area-specific meteorological data (Viner 2014).

  4. The comparison of CAP88-PC version 2.0 versus CAP88-PC version 1.0

    Energy Technology Data Exchange (ETDEWEB)

    Yakubovich, B.A.; Klee, K.O.; Palmer, C.R.; Spotts, P.B.

    1997-12-01

    40 CFR Part 61 (Subpart H of the NESHAP) requires DOE facilities to use approved sampling procedures, computer models, or other approved procedures when calculating Effective Dose Equivalent (EDE) values to members of the public. Currently version 1.0 of the approved computer model CAP88-PC is used to calculate EDE values. The DOE has upgraded the CAP88-PC software to version 2.0. This version provides simplified data entry, better printing characteristics, the use of a mouse, and other features. The DOE has developed and released version 2.0 for testing and comment. This new software is a WINDOWS based application that offers a new graphical user interface with new utilities for preparing and managing population and weather data, and several new decay chains. The program also allows the user to view results before printing. This document describes a test that confirmed CAP88-PC version 2.0 generates results comparable to the original version of the CAP88-PC program.

  5. Population Files for use with CAP88 at Los Alamos

    Energy Technology Data Exchange (ETDEWEB)

    McNaughton, Michael W [Los Alamos National Laboratory; Brock, Burgandy R [Los Alamos National Laboratory

    2012-07-10

    CAP88 (Clean Air Act Assessment Package 1988) is a computer model developed for the US Environmental Protection Agency to assess the potential dose from radionuclide emissions to air and to demonstrate compliance with the Clean Air Act. It has options to calculate either individual doses, in units of mrem, or a collective dose, also called population dose, in units of person-rem. To calculate the collective dose, CAP88 uses a population file such as LANL.pop, that lists the number of people in each sector (N, NNE, NE, etc.) as a function of distance (1 to 2 km, etc.) out to a maximum radius of 80 km. Early population files are described in the Los Alamos National Laboratory (LANL) Environmental Reports for 1985 (page 14) and subsequent years. LA-13469-MS describes a population file based on the 1990 census. These files have been updated several times, most recently in 2006 for CAP88 version 3. The 2006 version used the US census for 2000. The present paper describes the 2012 updates, using the 2010 census.

  6. Comparison of CAP88 and MCNP for Overhead Gamma-emitting Plumes

    Energy Technology Data Exchange (ETDEWEB)

    Mcnaughton, Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gillis, Jessica Mcdonnel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); McClory, Aysha Reede [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Whicker, Jeffrey Jay [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Fuehne, David Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-08

    The purpose of this paper is to use the Monte Carlo N-Particle Code (MCNP) to investigate the dose from gamma-emitting radionuclides such as Carbon-11 when a plume passes overhead. MCNP results are compared with results from the EPA program, CAP88. In some cases, typically near the source during stable conditions, the CAP88 results are less than the MCNP results. However, in the case of a receptor 800 m from a source at the Los Alamos Neutron Science Center (LANSCE), the CAP88 result is greater than the MCNP result.

  7. Comparison of U.S. Environmental Protection Agency's CAP88 PC Versions 3.0 and 4.0.

    Science.gov (United States)

    Jannik, Tim; Farfan, Eduardo B; Dixon, Ken; Newton, Joseph; Sailors, Christopher; Johnson, Levi; Moore, Kelsey; Stahman, Richard

    2015-08-01

    The Savannah River National Laboratory (SRNL) with the assistance of Georgia Regents University, completed a comparison of the U.S. Environmental Protection Agency's (U.S. EPA) environmental dosimetry code CAP88 PC V3.0 with the recently developed V4.0. CAP88 is a set of computer programs and databases used for estimation of dose and risk from radionuclide emissions to air. At the U.S. Department of Energy's Savannah River Site, CAP88 is used by SRNL for determining compliance with U.S. EPA's National Emission Standards for Hazardous Air Pollutants (40 CFR 61, Subpart H) regulations. Using standardized input parameters, individual runs were conducted for each radionuclide within its corresponding database. Some radioactive decay constants, human usage parameters, and dose coefficients changed between the two versions, directly causing a proportional change in the total effective dose. A detailed summary for select radionuclides of concern at the Savannah River Site (60Co, 137Cs, 3H, 129I, 239Pu, and 90Sr) is provided. In general, the total effective doses will decrease for alpha/beta emitters because of reduced inhalation and ingestion rates in V4.0. However, for gamma emitters, such as 60Co and 137Cs, the total effective doses will increase because of changes U.S. EPA made in the external ground shine calculations.

  8. Assessment of radionuclide databases in CAP88 mainframe version 1.0 and Windows-based version 3.0.

    Science.gov (United States)

    LaBone, Elizabeth D; Farfán, Eduardo B; Lee, Patricia L; Jannik, G Timothy; Donnelly, Elizabeth H; Foley, Trevor Q

    2009-09-01

    In this study the radionuclide databases for two versions of the Clean Air Act Assessment Package-1988 (CAP88) computer model were assessed in detail. CAP88 estimates radiation dose and the risk of health effects to human populations from radionuclide emissions to air. This program is used by several U.S. Department of Energy (DOE) facilities to comply with National Emission Standards for Hazardous Air Pollutants regulations. CAP88 Mainframe, referred to as version 1.0 on the U.S. Environmental Protection Agency Web site (http://www.epa.gov/radiation/assessment/CAP88/), was the very first CAP88 version released in 1988. Some DOE facilities including the Savannah River Site still employ this version (1.0) while others use the more user-friendly personal computer Windows-based version 3.0 released in December 2007. Version 1.0 uses the program RADRISK based on International Commission on Radiological Protection Publication 30 as its radionuclide database. Version 3.0 uses half-life, dose, and risk factor values based on Federal Guidance Report 13. Differences in these values could cause different results for the same input exposure data (same scenario), depending on which version of CAP88 is used. Consequently, the differences between the two versions are being assessed in detail at Savannah River National Laboratory. The version 1.0 and 3.0 database files contain 496 and 838 radionuclides, respectively, and though one would expect the newer version to include all the 496 radionuclides, 35 radionuclides are listed in version 1.0 that are not included in version 3.0. The majority of these has either extremely short or long half-lives or is no longer in production; however, some of the short-lived radionuclides might produce progeny of great interest at DOE sites. In addition, 122 radionuclides were found to have different half-lives in the two versions, with 21 over 3 percent different and 12 over 10 percent different.

  9. ASSESSMENT OF RADIONUCLIDES DATABASES IN CAP88 MAINFRAME VERSION 1.0 AND WINDOWS-BASED VERSION 3.0

    Energy Technology Data Exchange (ETDEWEB)

    Farfan, E.; Lee, P.; Jannik, T.; Donnelly, E.

    2008-09-16

    In this study the radionuclide databases for two versions of the Clean Air Act Assessment Package-1988 (CAP88) computer model were assessed in detail. CAP88 estimates radiation dose and the risk of health effects to human populations from radionuclide emissions to air. This program is used by several Department of Energy (DOE) facilities to comply with National Emission Standards for Hazardous Air Pollutants (NESHAP) regulations. CAP88 Mainframe, referred to as Version 1.0 on the Environmental Protection Agency (EPA) website (http://www.epa.gov/radiation/assessment/CAP88/), was the very first CAP88 version released in 1988. Some DOE facilities including the Savannah River Site still employ this version (1.0) while others use the more user-friendly personal computer Windows-based Version 3.0 released in December 2007. Version 1.0 uses the program RADRISK based on International Commission on Radiological Protection (ICRP) Publication 30 as its radionuclide database. Version 3.0 uses half-life, dose and risk factor values based on Federal Guidance Report 13. Differences in these values could cause different results for the same input exposure data (same scenario), depending on which version of CAP88 is used. Consequently, the differences between the two versions are being assessed in detail at Savannah River National Laboratory. The version 1.0 and 3.0 database files contain 496 and 838 radionuclides, respectively, and though one would expect the newer version to include all the 496 radionuclides, thirty-five radionuclides are listed in version 1.0 that are not included in version 3.0. The majority of these has either extremely short or long half-lives or is no longer in production; however, some of the short-lived radionuclides might produce progeny of great interest at DOE sites. In addition, one hundred and twenty-two radionuclides were found to have different half-lives in the two versions, with 21 over 3 percent different and 12 over 10 percent different.

  10. Validation test for CAP88 predictions of tritium dispersion at Los Alamos National Laboratory.

    Science.gov (United States)

    Michelotti, Erika; Green, Andrew; Whicker, Jeffrey; Eisele, William; Fuehne, David; McNaughton, Michael

    2013-08-01

    Gaussian plume models, such as CAP88, are used regularly for estimating downwind concentrations from stack emissions. At many facilities, the U.S. Environmental Protection Agency (U.S. EPA) requires that CAP88 be used to demonstrate compliance with air quality regulations for public protection from emissions of radionuclides. Gaussian plume models have the advantage of being relatively simple and their use pragmatic; however, these models are based on simplifying assumptions and generally they are not capable of incorporating dynamic meteorological conditions or complex topography. These limitations encourage validation tests to understand the capabilities and limitations of the model for the specific application. Los Alamos National Laboratory (LANL) has complex topography but is required to use CAP88 for compliance with the Clean Air Act Subpart H. The purpose of this study was to test the accuracy of the CAP88 predictions against ambient air measurements using released tritium as a tracer. Stack emissions of tritium from two LANL stacks were measured and the dispersion modeled with CAP88 using local meteorology. Ambient air measurements of tritium were made at various distances and directions from the stacks. Model predictions and ambient air measurements were compared over the course of a full year's data. Comparative results were consistent with other studies and showed the CAP88 predictions of downwind tritium concentrations were on average about three times higher than those measured, and the accuracy of the model predictions were generally more consistent for annual averages than for bi-weekly data.

  11. Radiation doses and risks from internal emitters

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, John [Health Protection Agency, Radiation Protection Division, CRCE, Chilton, Didcot, Oxon OX11 0RQ (United Kingdom); Day, Philip [School of Chemistry, University of Manchester, Manchester M13 9PL (United Kingdom)], E-mail: john.harrison@hpa.org.uk, E-mail: philip.day@manchester.ac.uk

    2008-06-01

    This review updates material prepared for the UK Government Committee Examining Radiation Risks from Internal Emitters (CERRIE) and also refers to the new recommendations of the International Commission on Radiological Protection (ICRP) and other recent developments. Two conclusions from CERRIE were that ICRP should clarify and elaborate its advice on the use of its dose quantities, equivalent and effective dose, and that more attention should be paid to uncertainties in dose and risk estimates and their implications. The new ICRP recommendations provide explanations of the calculation and intended purpose of the protection quantities, but further advice on their use would be helpful. The new recommendations refer to the importance of understanding uncertainties in estimates of dose and risk, although methods for doing this are not suggested. Dose coefficients (Sv per Bq intake) for the inhalation or ingestion of radionuclides are published as reference values without uncertainty. The primary purpose of equivalent and effective dose is to enable the summation of doses from different radionuclides and from external sources for comparison with dose limits, constraints and reference levels that relate to stochastic risks of whole-body radiation exposure. Doses are calculated using defined biokinetic and dosimetric models, including reference anatomical data for the organs and tissues of the human body. Radiation weighting factors are used to adjust for the different effectiveness of different radiation types, per unit absorbed dose (Gy), in causing stochastic effects at low doses and dose rates. Tissue weighting factors are used to take account of the contribution of individual organs and tissues to overall detriment from cancer and hereditary effects, providing a simple set of rounded values chosen on the basis of age- and sex-averaged values of relative detriment. While the definition of absorbed dose has the scientific rigour required of a basic physical quantity

  12. Recommendations for Insulin Dose Calculator Risk Management

    Science.gov (United States)

    2014-01-01

    Several studies have shown the usefulness of an automated insulin dose bolus advisor (BA) in achieving improved glycemic control for insulin-using diabetes patients. Although regulatory agencies have approved several BAs over the past decades, these devices are not standardized in their approach to dosage calculation and include many features that may introduce risk to patients. Moreover, there is no single standard of care for diabetes worldwide and no guidance documents for BAs, specifically. Given the emerging and more stringent regulations on software used in medical devices, the approval process is becoming more difficult for manufacturers to navigate, with some manufacturers opting to remove BAs from their products altogether. A comprehensive literature search was performed, including publications discussing: diabetes BA use and benefit, infusion pump safety and regulation, regulatory submissions, novel BAs, and recommendations for regulation and risk management of BAs. Also included were country-specific and international guidance documents for medical device, infusion pump, medical software, and mobile medical application risk management and regulation. No definitive worldwide guidance exists regarding risk management requirements for BAs, specifically. However, local and international guidance documents for medical devices, infusion pumps, and medical device software offer guidance that can be applied to this technology. In addition, risk management exercises that are algorithm-specific can help prepare manufacturers for regulatory submissions. This article discusses key issues relevant to BA use and safety, and recommends risk management activities incorporating current research and guidance. PMID:24876550

  13. Evaluation of effective dose and excess lifetime cancer risk from ...

    African Journals Online (AJOL)

    Evaluation of effective dose and excess lifetime cancer risk from indoor and outdoor gamma dose rate of university of Port Harcourt Teaching Hospital, ... In addition, the excess lifetime cancer risk (ELCR) calculated for indoor exposure ranges ...

  14. Low doses of radiation reduce risks in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Mitchel, R.E.J. [Atomic Energy of Canada Ltd., Chalk River, Ontario (Canada)

    2004-05-01

    The 'Linear No Threshold' hypothesis, used in all radiation protection practices, assumes that all doses, no matter how low, increase risk. The protective effects of adaptive responses to radiation, shown to exist in lower organisms and in human and other mammalian cells, are inconsistent with this hypothesis. An in vivo test of the hypothesis in mice showed that a 100-mGy dose of {gamma}-radiation protected the mice by increasing latency for acute myeloid leukemia initiated by a subsequent large dose. A similar result was observed in cancer prone mice, where a 10-mGy adapting exposure prior to a large acute dose increased latency for lymphomas without altering frequency. Increasing the adapting dose to 100-mGy eliminated the protective effect. In the cancer prone mice, a 10-mGy dose alone, without a subsequent high dose, increased latency for spontaneous osteosarcomas and lymphomas without altering frequency. Increasing the dose to 100-mGy decreased latency for spontaneous osteosarcomas but still increased latency for lymphomas, indicating that this higher dose was in a transition zone between reduced and increased risk, and that the transition dose from protective to detrimental effects is tumor type specific. In genetically normal fetal mice, prior low doses also protected against radiation induced teratogenic effects. In genetically normal adult male mice, high doses induce mutations in sperm stem cells, detectable as heritable mutations in the offspring of these mice. A prior 100 mGy dose protected the male mice from induction of these heritable mutations by the large dose. We conclude that adaptive responses are induced by low doses in normal or cancer prone mice, and that these responses can reduce the risk of cancer, teratogenesis and heritable mutations. At low doses in vivo, the relationship between dose and risk is not linear, and low doses can reduce risk. (author)

  15. Model Averaging Software for Dichotomous Dose Response Risk Estimation

    Directory of Open Access Journals (Sweden)

    Matthew W. Wheeler

    2008-02-01

    Full Text Available Model averaging has been shown to be a useful method for incorporating model uncertainty in quantitative risk estimation. In certain circumstances this technique is computationally complex, requiring sophisticated software to carry out the computation. We introduce software that implements model averaging for risk assessment based upon dichotomous dose-response data. This software, which we call Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD, fits the quantal response models, which are also used in the US Environmental Protection Agency benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates. The software fulfills a need for risk assessors, allowing them to go beyond one single model in their risk assessments based on quantal data by focusing on a set of models that describes the experimental data.

  16. Radiation Dose Risk and Diagnostic Benefit in Imaging Investigations

    CERN Document Server

    Dobrescu, Lidia

    2015-01-01

    The paper presents many facets of medical imaging investigations radiological risks. The total volume of prescribed medical investigations proves a serious lack in monitoring and tracking of the cumulative radiation doses in many health services. Modern radiological investigations equipment is continuously reducing the total dose of radiation due to improved technologies, so a decrease in per caput dose can be noticed, but the increasing number of investigations has determined a net increase of the annual collective dose. High doses of radiation are cumulated from Computed Tomography investigations. An integrated system for radiation safety of the patients investigated by radiological imaging methods, based on smart cards and Public Key Infrastructure allow radiation absorbed dose data storage.

  17. Radiation Dose-Response Relationships and Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Daniel J.

    2005-07-05

    The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is also the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of

  18. Correlation between effective dose and radiological risk: general concepts*

    Science.gov (United States)

    Costa, Paulo Roberto; Yoshimura, Elisabeth Mateus; Nersissian, Denise Yanikian; Melo, Camila Souza

    2016-01-01

    The present review aims to offer an educational approach related to the limitations in the use of the effective dose mgnitude as a tool for the quantification of doses resulting from diagnostic applications of ionizing radiation. We present a critical analysis of the quantities accepted and currently used for dosimetric evaluation in diagnostic imaging procedures, based on studies published in the literature. It is highlighted the use of these quantities to evaluate the risk attributed to the procedure and to calculate the effective dose, as well as to determine its correct use and interpretation. PMID:27403018

  19. Correlation between effective dose and radiological risk: general concepts

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Paulo Roberto; Yoshimura, Elisabeth Mateus; Nersissian, Denise Yanikian; Melo, Camila Souza, E-mail: pcosta@if.usp.br [Universidade de Sao Paulo (IF/USP), Sao Paulo, SP (Brazil). Instituto de Fisica

    2016-05-15

    The present review aims to offer an educational approach related to the limitations in the use of the effective dose magnitude as a tool for the quantification of doses resulting from diagnostic applications of ionizing radiation. We present a critical analysis of the quantities accepted and currently used for dosimetric evaluation in diagnostic imaging procedures, based on studies published in the literature. It is highlighted the use of these quantities to evaluate the risk attributed to the procedure and to calculate the effective dose, as well as to determine its correct use and interpretation. (author)

  20. Dose-effect relationships, epidemiological analysis and the derivation of low dose risk

    Energy Technology Data Exchange (ETDEWEB)

    Leenhouts, H P [Bennekom (Netherlands); Chadwick, K H, E-mail: kennethhchadwick@aol.com [Cowan Head, Kendal (United Kingdom)

    2011-03-01

    This paper expands on our recent comments in a letter to this journal about the analysis of epidemiological studies and the determination of low dose RBE of low LET radiation (Chadwick and Leenhouts 2009 J. Radiol. Prot. 29 445-7). Using the assumption that radiation induced cancer arises from a somatic mutation (Chadwick and Leenhouts 2011 J. Radiol. Prot. 31 41-8) a model equation is derived to describe cancer induction as a function of dose. The model is described briefly, evidence is provided in support of it, and it is applied to a set of experimental animal data. The results are compared with a linear fit to the data as has often been done in epidemiological studies. The article presents arguments to support several related messages which are relevant to epidemiological analysis, the derivation of low dose risk and the weighting factor of sparsely ionising radiations. The messages are: (a) cancer incidence following acute exposure should, in principle, be fitted to a linear-quadratic curve with cell killing using all the data available; (b) the acute data are dominated by the quadratic component of dose; (c) the linear fit of any acute data will essentially be dependent on the quadratic component and will be unrelated to the effectiveness of the radiation at low doses; consequently, (d) the method used by ICRP to derive low dose risk from the atomic bomb survivor data means that it is unrelated to the effectiveness of the hard gamma radiation at low radiation doses; (e) the low dose risk value should, therefore, not be used as if it were representative for hard gamma rays to argue for an increased weighting factor for tritium and soft x-rays even though there are mechanistic reasons to expect this; (f) epidemiological studies of chronically exposed populations supported by appropriate cellular radiobiological studies have the best chance of revealing different RBE values for different sparsely ionising radiations.

  1. Dose evaluation of organs at risk (OAR) cervical cancer using dose volume histogram (DVH) on brachytherapy

    Science.gov (United States)

    Arif Wibowo, R.; Haris, Bambang; Inganatul Islamiyah, dan

    2017-05-01

    Brachytherapy is one way to cure cervical cancer. It works by placing a radioactive source near the tumor. However, there are some healthy tissues or organs at risk (OAR) such as bladder and rectum which received radiation also. This study aims to evaluate the radiation dose of the bladder and rectum. There were 12 total radiation dose data of the bladder and rectum obtained from patients’ brachytherapy. The dose of cervix for all patients was 6 Gy. Two-dimensional calculation of the radiation dose was based on the International Commission on Radiation Units and Measurements (ICRU) points or called DICRU while the 3-dimensional calculation derived from Dose Volume Histogram (DVH) on a volume of 2 cc (D2cc). The radiation dose of bladder and rectum from both methods were analysed using independent t test. The mean DICRU of bladder was 4.33730 Gy and its D2cc was4.78090 Gy. DICRU and D2cc bladder did not differ significantly (p = 0.144). The mean DICRU of rectum was 3.57980 Gy and 4.58670 Gy for D2cc. The mean DICRU of rectum differed significantly from D2cc of rectum (p = 0.000). The three-dimensional method radiation dose of the bladder and rectum was higher than the two-dimensional method with ratios 1.10227 for bladder and 1.28127 for rectum. The radiation dose of the bladder and rectum was still below the tolerance dose. Two-dimensional calculation of the bladder and rectum dose was lower than three-dimension which was more accurate due to its calculation at the whole volume of the organs.

  2. Cancer risk from low doses of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Auvinen, A.

    1997-06-01

    The aim of the study was to estimate cancer risk from small doses of ionizing radiation from various sources, including both external and internal exposure. The types of radiation included alpha, gamma, and neutron radiation. A nationwide follow-up study covering the years up to 1992 revealed no significant association between fallout from the Chernobyl accident and incidence of childhood leukemia. An excess of eight cases or more per year could be excluded. However, some indication of an increase was evident in the most heavily affected areas. Furthermore, the risk estimates were in accordance with those reported from Hiroshima and Nagasaki, although the confidence intervals were wide. (282 refs.).

  3. CANCER RISKS ATTRIBUTABLE TO LOW DOSES OF IONIZING RADIATION - ASSESSING WHAT WE REALLY KNOW?

    Science.gov (United States)

    Cancer Risks Attributable to Low Doses of Ionizing Radiation - What Do We Really Know?AbstractHigh doses of ionizing radiation clearly produce deleterious consequences in humans including, but not exclusively, cancer induction. At very low radiation doses the situatio...

  4. Dose and risk evaluation in digital mammography using computer modeling

    Energy Technology Data Exchange (ETDEWEB)

    Correa, Samanda Cristine Arruda; Souza, Edmilson Monteiro de, E-mail: scorrea@nuclear.ufrj.b, E-mail: emonteiro@nuclear.ufrj.b [Centro Universitario Estadual da Zona Oeste (CCMAT/UEZO), Rio de Janeiro, RJ (Brazil); Silva, Humberto de Oliveira, E-mail: hbetorj@gmail.co [Universidade Federal do Rio de Janeiro IF/UFRJ, RJ (Brazil). Inst. de Fisica; Silva, Ademir Xavier da; Lopes, Ricardo Tadeu; Magalhaes, Sarah Braga, E-mail: ademir@nuclear.ufrj.b, E-mail: ricardo@lin.ufrj.b, E-mail: smagalhaes@nuclear.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (COPPE/UFRJ), RJ (Brazil). Programa de Engenharia Nuclear

    2010-07-01

    Digital mammography has been introduced in several countries in the last years. The new technology requires new optimising methods considering for instance the increased possibility of changing the absorbed dose, mainly in modern mammographic systems that allow the operator to choose the beam quality by varying the tube voltage, and filter and target materials. In this work, the Monte Carlo code MCNPX is used in order to investigate how the average glandular dose vary with tube voltage (23-32 kV) and anode-filter combination (Mo-Mo,Mo-Rh and Rh-Rh) in digital mammographic examinations. Furthermore, the risk of breast cancer incidence attributable to mammography exams was estimated using the Biological Effects of Ionizing Radiations (BEIR) VII Committee Report. The results show that the risk of breast cancer incidence in women younger than 30 years of age tends to decrease significantly using Rh-Rh anode-filter combination and higher tube voltage. For women older than 50 years of age the variation of tube voltage, and anode-filter combination did not influence the risk values considerably. (author)

  5. Low Dose Radiation Cancer Risks: Epidemiological and Toxicological Models

    Energy Technology Data Exchange (ETDEWEB)

    David G. Hoel, PhD

    2012-04-19

    The basic purpose of this one year research grant was to extend the two stage clonal expansion model (TSCE) of carcinogenesis to exposures other than the usual single acute exposure. The two-stage clonal expansion model of carcinogenesis incorporates the biological process of carcinogenesis, which involves two mutations and the clonal proliferation of the intermediate cells, in a stochastic, mathematical way. The current TSCE model serves a general purpose of acute exposure models but requires numerical computation of both the survival and hazard functions. The primary objective of this research project was to develop the analytical expressions for the survival function and the hazard function of the occurrence of the first cancer cell for acute, continuous and multiple exposure cases within the framework of the piece-wise constant parameter two-stage clonal expansion model of carcinogenesis. For acute exposure and multiple exposures of acute series, it is either only allowed to have the first mutation rate vary with the dose, or to have all the parameters be dose dependent; for multiple exposures of continuous exposures, all the parameters are allowed to vary with the dose. With these analytical functions, it becomes easy to evaluate the risks of cancer and allows one to deal with the various exposure patterns in cancer risk assessment. A second objective was to apply the TSCE model with varing continuous exposures from the cancer studies of inhaled plutonium in beagle dogs. Using step functions to estimate the retention functions of the pulmonary exposure of plutonium the multiple exposure versions of the TSCE model was to be used to estimate the beagle dog lung cancer risks. The mathematical equations of the multiple exposure versions of the TSCE model were developed. A draft manuscript which is attached provides the results of this mathematical work. The application work using the beagle dog data from plutonium exposure has not been completed due to the fact

  6. Lung cancer risk at low doses of alpha particles.

    Science.gov (United States)

    Hofmann, W; Katz, R; Zhang, C X

    1986-10-01

    A survey of inhabitant exposures arising from the inhalation of 222Rn and 220Rn progeny, and lung cancer mortality has been carried out in two adjacent areas in Guangdong Province, People's Republic of China, designated as the "high background" and the "control" area. Annual exposure rates are 0.38 working level months (WLM) per year in the high background, and 0.16 WLM/yr in the control area. In 14 yr of continuous study, from 1970 to 1983, age-adjusted mortality rates were found to be 2.7 per 10(5) living persons of all ages in the high background area, and 2.9 per 10(5) living persons in the control area. From this data, we conclude that we are unable to determine excess lung cancers over the normal fluctuations below a cumulative exposure of 15 WLM. This conclusion is supported by lung cancer mortality data from Austrian and Finnish high-background areas. A theoretical analysis of epidemiological data on human lung cancer incidence from inhaled 222Rn and 220Rn progeny, which takes into account cell killing as competitive with malignant transformation, leads to the evaluation of a risk factor which is either a linear-exponential or a quadratic-exponential function of the alpha-particle dose. Animal lung cancer data and theoretical considerations can be supplied to support either hypothesis. Thus we conclude that at our current stage of knowledge both the linear-exponential and the quadratic-exponential extrapolation to low doses seem to be equally acceptable for Rn-induced lung cancer risk, possibly suggesting a linear-quadratic transformation function with an exponential cell-killing term, or the influence of risk-modifying factors such as repair or proliferation stimuli.

  7. Toxicity risk of non-target organs at risk receiving low-dose radiation: case report

    Directory of Open Access Journals (Sweden)

    Chen Yu-Jen

    2009-12-01

    Full Text Available Abstract The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT, a new image-guided intensity modulated radiotherapy (IMRT, delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy.

  8. Cardiovascular risks associated with low dose ionizing particle radiation.

    Directory of Open Access Journals (Sweden)

    Xinhua Yan

    Full Text Available Previous epidemiologic data demonstrate that cardiovascular (CV morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1H; 0.5 Gy, 1 GeV and iron ion ((56Fe; 0.15 Gy, 1GeV/nucleon irradiation with and without an acute myocardial ischemia (AMI event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  9. Risk of solid cancer in low dose-rate radiation epidemiological studies and the dose-rate effectiveness factor.

    Science.gov (United States)

    Shore, Roy; Walsh, Linda; Azizova, Tamara; Rühm, Werner

    2017-10-01

    Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy(-1)) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta-analyses that included only cohorts in which the mean dose was radiation exposure. The LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the

  10. The effect of dose heterogeneity on radiation risk in medical imaging.

    Science.gov (United States)

    Samei, Ehsan; Li, Xiang; Chen, Baiyu; Reiman, Robert

    2013-06-01

    The current estimations of risk associated with medical imaging procedures rely on assessing the organ dose via direct measurements or simulation. The dose to each organ is assumed to be homogeneous. To take into account the differences in radiation sensitivities, the mean organ doses are weighted by a corresponding tissue-weighting coefficients provided by ICRP to calculate the effective dose, which has been used as a surrogate of radiation risk. However, those coefficients were derived under the assumption of a homogeneous dose distribution within each organ. That assumption is significantly violated in most medical-imaging procedures. In helical chest CT, for example, superficial organs (e.g. breasts) demonstrate a heterogeneous dose distribution, whereas organs on the peripheries of the irradiation field (e.g. liver) might possess a discontinuous dose profile. Projection radiography and mammography involve an even higher level of organ dose heterogeneity spanning up to two orders of magnitude. As such, mean dose or point measured dose values do not reflect the maximum energy deposited per unit volume of the organ. In this paper, the magnitude of the dose heterogeneity in both CT and projection X-ray imaging was reported, using Monte Carlo methods. The lung dose demonstrated factors of 1.7 and 2.2 difference between the mean and maximum dose for chest CT and radiography, respectively. The corresponding values for the liver were 1.9 and 3.5. For mammography and breast tomosynthesis, the difference between mean glandular dose and maximum glandular dose was 3.1. Risk models based on the mean dose were found to provide a reasonable reflection of cancer risk. However, for leukaemia, they were found to significantly under-represent the risk when the organ dose distribution is heterogeneous. A systematic study is needed to develop a risk model for heterogeneous dose distributions.

  11. Metrics, Dose, and Dose Concept: The Need for a Proper Dose Concept in the Risk Assessment of Nanoparticles

    Directory of Open Access Journals (Sweden)

    Myrtill Simkó

    2014-04-01

    Full Text Available In order to calculate the dose for nanoparticles (NP, (i relevant information about the dose metrics and (ii a proper dose concept are crucial. Since the appropriate metrics for NP toxicity are yet to be elaborated, a general dose calculation model for nanomaterials is not available. Here we propose how to develop a dose assessment model for NP in analogy to the radiation protection dose calculation, introducing the so-called “deposited and the equivalent dose”. As a dose metric we propose the total deposited NP surface area (SA, which has been shown frequently to determine toxicological responses e.g. of lung tissue. The deposited NP dose is proportional to the total surface area of deposited NP per tissue mass, and takes into account primary and agglomerated NP. By using several weighting factors the equivalent dose additionally takes into account various physico-chemical properties of the NP which are influencing the biological responses. These weighting factors consider the specific surface area, the surface textures, the zeta-potential as a measure for surface charge, the particle morphology such as the shape and the length-to-diameter ratio (aspect ratio, the band gap energy levels of metal and metal oxide NP, and the particle dissolution rate. Furthermore, we discuss how these weighting factors influence the equivalent dose of the deposited NP.

  12. Re-distribution of brachytherapy dose using a differential dose prescription adapted to risk of local failure in low-risk prostate cancer patients

    DEFF Research Database (Denmark)

    Rylander, Susanne; Polders, Daniel; Steggerda, Marcel J;

    2015-01-01

    . The median D10% and D30% to the urethra significantly decreased by 9Gy and 11Gy, respectively and for bladder neck by 18Gy and 15Gy, respectively. The median rectal D2.0cm(3) had a significant decrease of4Gy, while the median rectal D0.1cm(3) showed an increase of 1Gy. CONCLUSIONS: Our risk adaptive target......- and dose prescription concept of prescribing a lower dose to the whole gland and an escalated dose to the GTV using LDR-BT seed planning was technically feasible and resulted in a significant dose-reduction to urethra and bladder neck....

  13. Molecular mechanisms linking high dose medroxyprogesterone with HIV-1 risk.

    Directory of Open Access Journals (Sweden)

    Susan C Irvin

    Full Text Available Epidemiological studies suggest that medroxyprogesterone acetate (MPA may increase the risk of HIV-1. The current studies were designed to identify potential underlying biological mechanisms.Human vaginal epithelial (VK2/E6E7, peripheral blood mononuclear (PBMC, and polarized endometrial (HEC-1-A cells were treated with a range of concentrations of MPA (0.015-150 μg/ml and the impact on gene expression, protein secretion, and HIV infection was evaluated.Treatment of VK2/E6E7 cells with high doses (>15 μg/ml] of MPA significantly upregulated proinflammatory cytokines, which resulted in a significant increase in HIV p24 levels secreted by latently infected U1 cells following exposure to culture supernatants harvested from MPA compared to mock-treated cells. MPA also increased syndecan expression by VK2/E6E7 cells and cells treated with 15 μg/ml of MPA bound and transferred more HIV-1 to T cells compared to mock-treated cells. Moreover, MPA treatment of epithelial cells and PBMC significantly decreased cell proliferation resulting in disruption of the epithelial barrier and decreased cytokine responses to phytohaemagglutinin, respectively.We identified several molecular mechanisms that could contribute to an association between DMPA and HIV including proinflammatory cytokine and chemokine responses that could activate the HIV promoter and recruit immune targets, increased expression of syndecans to facilitate the transfer of virus from epithelial to immune cells and decreased cell proliferation. The latter could impede the ability to maintain an effective epithelial barrier and adversely impact immune cell function. However, these responses were observed primarily following exposure to high (15-150 μg/ml MPA concentrations. Clinical correlation is needed to determine whether the prolonged MPA exposure associated with contraception activates these mechanisms in vivo.

  14. Molecular mechanisms linking high dose medroxyprogesterone with HIV-1 risk.

    Science.gov (United States)

    Irvin, Susan C; Herold, Betsy C

    2015-01-01

    Epidemiological studies suggest that medroxyprogesterone acetate (MPA) may increase the risk of HIV-1. The current studies were designed to identify potential underlying biological mechanisms. Human vaginal epithelial (VK2/E6E7), peripheral blood mononuclear (PBMC), and polarized endometrial (HEC-1-A) cells were treated with a range of concentrations of MPA (0.015-150 μg/ml) and the impact on gene expression, protein secretion, and HIV infection was evaluated. Treatment of VK2/E6E7 cells with high doses (>15 μg/ml] of MPA significantly upregulated proinflammatory cytokines, which resulted in a significant increase in HIV p24 levels secreted by latently infected U1 cells following exposure to culture supernatants harvested from MPA compared to mock-treated cells. MPA also increased syndecan expression by VK2/E6E7 cells and cells treated with 15 μg/ml of MPA bound and transferred more HIV-1 to T cells compared to mock-treated cells. Moreover, MPA treatment of epithelial cells and PBMC significantly decreased cell proliferation resulting in disruption of the epithelial barrier and decreased cytokine responses to phytohaemagglutinin, respectively. We identified several molecular mechanisms that could contribute to an association between DMPA and HIV including proinflammatory cytokine and chemokine responses that could activate the HIV promoter and recruit immune targets, increased expression of syndecans to facilitate the transfer of virus from epithelial to immune cells and decreased cell proliferation. The latter could impede the ability to maintain an effective epithelial barrier and adversely impact immune cell function. However, these responses were observed primarily following exposure to high (15-150 μg/ml) MPA concentrations. Clinical correlation is needed to determine whether the prolonged MPA exposure associated with contraception activates these mechanisms in vivo.

  15. A method to adjust radiation dose-response relationships for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane Lindegaard; Vogelius, Ivan R

    2012-01-01

    Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

  16. Radiation Doses and Associated Risk From the Fukushima Nuclear Accident.

    Science.gov (United States)

    Ishikawa, Tetsuo

    2017-03-01

    The magnitude of dose due to the Fukushima Daiichi Accident was estimated by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2013 report published in April 2014. Following this, the UNSCEAR white paper, which comprises a digest of new information for the 2013 Fukushima report, was published in October 2015. Another comprehensive report on radiation dose due to the accident is the International Atomic Energy Agency (IAEA) report on the Fukushima Daiichi Accident published in August 2015. Although the UNSCEAR and IAEA publications well summarize doses received by residents, they review only literature published before the end of December 2014 and the end of March 2015, respectively. However, some studies on dose estimation have been published since then. In addition, the UNSCEAR 2013 report states it was likely that some overestimation had been introduced generally by the methodology used by the Committee. For example, effects of decontamination were not considered in the lifetime external dose estimated. Decontamination is in progress for most living areas in Fukushima Prefecture, which could reduce long-term external dose to residents. This article mainly reviews recent English language articles that may add new information to the UNSCEAR and IAEA publications. Generally, recent articles suggest lower doses than those presented by the UNSCEAR 2013 report.

  17. Radiation Leukemogenesis: Applying Basic Science of Epidemiological Estimates of Low Dose Risks and Dose-Rate Effects

    Energy Technology Data Exchange (ETDEWEB)

    Hoel, D. G.

    1998-11-01

    The next stage of work has been to examine more closely the A-bomb leukemia data which provides the underpinnings of the risk estimation of CML in the above mentioned manuscript. The paper by Hoel and Li (Health Physics 75:241-50) shows how the linear-quadratic model has basic non-linearities at the low dose region for the leukemias including CML. Pierce et. al., (Radiation Research 123:275-84) have developed distributions for the uncertainty in the estimated exposures of the A-bomb cohort. Kellerer, et. al., (Radiation and Environmental Biophysics 36:73-83) has further considered possible errors in the estimated neutron values and with changing RBE values with dose and has hypothesized that the tumor response due to gamma may not be linear. We have incorporated his neutron model and have constricted new A-bomb doses based on his model adjustments. The Hoel and Li dose response analysis has also been applied using the Kellerer neutron dose adjustments for the leukemias. Finally, both Pierce's dose uncertainties and Kellerer neutron adjustments are combined as well as the varying RBE with dose as suggested by Rossi and Zaider and used for leukemia dose-response analysis. First the results of Hoel and Li showing a significantly improved fit of the linear-quadratic dose response by the inclusion of a threshold (i.e. low-dose nonlinearity) persisted. This work has been complete for both solid tumor as well as leukemia for both mortality as well as incidence data. The results are given in the manuscript described below which has been submitted to Health Physics.

  18. Towards individualized dose constraints: Adjusting the QUANTEC radiation pneumonitis model for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane L; Vogelius, Ivan R.; Farr, Katherina P.

    2014-01-01

    Background. Understanding the dose-response of the lung in order to minimize the risk of radiation pneumonitis (RP) is critical for optimization of lung cancer radiotherapy. We propose a method to combine the dose-response relationship for RP in the landmark QUANTEC paper with known clinical risk......-only QUANTEC model and the model including risk factors. Subdistribution cumulative incidence functions were compared for patients with high/low-risk predictions from the two models, and concordance indices (c-indices) for the prediction of RP were calculated. Results. The reference dose- response relationship...... factors, in order to enable individual risk prediction. The approach is validated in an independent dataset. Material and methods. The prevalence of risk factors in the patient populations underlying the QUANTEC analysis was estimated, and a previously published method to adjust dose...

  19. Equivalent dose, effective dose and risk assessment from panoramic radiography to the critical organs of head and neck region

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Bong Hae; Nah, Kyung Soo [Dept. of Dental Radiology, College of Dentistry, Pusan National University, Pusan (Korea, Republic of); Lee, Ae Ryeon [Dept. of Pediatric Dentistry, College of Dentistry, Pusan National University, Pusan (Korea, Republic of)

    1995-08-15

    The purpose of this study was to evaluate the equivalent and effective dose, and estimate radiation risk to the critical organs of head and neck region from the use of adult and child mode in panoramic radiography. The results were as follows. 1. The salivary glands showed the highest equivalent and effective dose in adult and child mode. The equivalent and effective dose in adult mode were 837 {mu}Sv and 20.93 {mu}Sv, those in child mode were 462 {mu}Sv and 11.54 {mu}Sv, respectively. 2. Total effective doses to the critical head and neck organs were estimated 34.2l {mu}Sv in adult mode, 20.14 {mu}Sv in child mode. From these data, the probabilities of stochastic effect from adult and child mode were 2.50xl0{sup -6} and 1.47x10{sup -6} 3. The other remainder showed the greatest risk of fatal cancer. The risk estimate were 4.5 and 2.7 fatal malignancies in adult and child mode from million examinations. The bone marrow and thyroid gland showed about 0.1 fatal cancer in adult. and child mode from these examinations.

  20. Health risks associated with low dose diagnostic or therapeutic radiation exposures

    Energy Technology Data Exchange (ETDEWEB)

    Boreham, D.R. [McMaster Univ., Dept. of Medical Physics and Applied Radiation Sciences, Hamilton, Ontario (Canada)

    2007-07-01

    The health risks to humans associated with exposure to low doses of ionizing radiation have been extrapolated from effects observed at high doses, dose rates, and mixed radiation qualities using a linear no threshold model. Based on this approach, it has been argued that human exposure to low doses of diagnostics X-rays and gamma-rays increase an individual's risk of developing cancer throughout their life-time. Also, repeated medical diagnostic procedures involving low dose exposures will have an additive effect and consequently further increase health risk. The specific aim of this seminar will be to address the relative risk associated with diagnostic X-rays from CT scans and gamma-rays from positron emission tomography (PET) scans. Objectives of the talk will include: 1) Defining low dose exposures at a cellular level and relate that to diagnostic or therapeutic exposures, 2) Describing modern tools in molecular cytogenetics to estimate radiation exposure and assess radiation risk, 3) Identifying the different cellular mechanisms that influence radiation risk at high and low dose exposures and relate that to individual radiation risk. (author)

  1. Changes in biomarkers from space radiation may reflect dose not risk

    Science.gov (United States)

    Brooks, Antone L.; Lei, Xingye C.; Rithidech, Kanokporn

    This presentation evaluates differences between radiation biomarkers of dose and risk and demonstrates the consequential problems associated with using biomarkers to do risk calculations following radiation exposures to the complex radiation environment found in deep space. Dose is a physical quantity, while risk is a biological quantity. Dose does not predict risk. This manuscript discusses species sensitivity factors, tissue weighting factors, and radiation quality factors derived from relative biological effectiveness (RBE). These factors are used to modify dose to make it a better predictor of risk. At low doses, where it is not possible to measure changes in risk, biomarkers have been used incorrectly as an intermediate step in predicting risk. Examples of biomarkers that do not predict risk are reviewed. Species sensitivity factors were evaluated using the Syrian hamster and the Wistar rat. Although the frequency of chromosome damage is very similar in these two species, the Wistar rat is very sensitive to radiation-induced lung cancer while the Syrian hamster is very resistant. To illustrate problems involved in using tissue weighting factors, rat trachea and deep lung tissues were compared. The similar level of chromosome damage observed in these two tissues would predict that the risk for cancer induction would be the same. However, even though large numbers of deep lung tumors result from inhaled radon, under the same exposure conditions there has never been a tracheal tumor observed. Finally, the Relative Biological Effectiveness (RBE) used to generate "quality factors" that convert exposure and dose from different types of radiation to a single measure of risk, is discussed. Important risk comparisons are done at very low doses, where the response to the reference radiation has been shown to either increase or decrease as a function of dose. Thus, the RBE and the subsequent risk predicted is more dependent on the background response of the endpoint and

  2. Dose-response modeling : Evaluation, application, and development of procedures for benchmark dose analysis in health risk assessment of chemical substances

    OpenAIRE

    Sand, Salomon

    2005-01-01

    In this thesis, dose-response modeling and procedures for benchmark dose (BMD) analysis in health risk assessment of chemical substances have been investigated. The BMD method has been proposed as an alternative to the NOAEL (no-observedadverse- effect-level) approach in health risk assessment of non-genotoxic agents. According to the BMD concept, a dose-response model is fitted to data and the BMD is defined as the dose causing a predetermined change in response. A lowe...

  3. Variability of a peripheral dose among various linac geometries for second cancer risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Joosten, A; Bochud, F; Baechler, S; Moeckli, R [University Institute for Radiation Physics, CHUV and University of Lausanne, Grand-Pre 1, CH-1007 Lausanne (Switzerland); Levi, F [Cancer Epidemiology Unit and Cancer Registries of Vaud and Neuchatel, Institute of Social and Preventive Medecine (IUMSP) and University of Lausanne, CHUV-Falaises 1, CH-1011 Lausanne (Switzerland); Mirimanoff, R-O, E-mail: raphael.moeckli@chuv.ch [Radio-Oncology Department, CHUV and University of Lausanne, Bugnon 21, CH-1011 Lausanne (Switzerland)

    2011-08-21

    Second cancer risk assessment for radiotherapy is controversial due to the large uncertainties of the dose-response relationship. This could be improved by a better assessment of the peripheral doses to healthy organs in future epidemiological studies. In this framework, we developed a simple Monte Carlo (MC) model of the Siemens Primus 6 MV linac for both open and wedged fields that we then validated with dose profiles measured in a water tank up to 30 cm from the central axis. The differences between the measured and calculated doses were comparable to other more complex MC models and never exceeded 50%. We then compared our simple MC model with the peripheral dose profiles of five different linacs with different collimation systems. We found that the peripheral dose between two linacs could differ up to a factor of 9 for small fields (5 x 5 cm{sup 2}) and up to a factor of 10 for wedged fields. Considering that an uncertainty of 50% in dose estimation could be acceptable in the context of risk assessment, the MC model can be used as a generic model for large open fields ({>=}10 x 10 cm{sup 2}) only. The uncertainties in peripheral doses should be considered in future epidemiological studies when designing the width of the dose bins to stratify the risk as a function of the dose.

  4. Cancer incidence after retinoblastoma - Radiation dose and sarcoma risk

    NARCIS (Netherlands)

    Wong, FL; Boice, JD; Abramson, DH; Tarone, RE; Kleinerman, RA; Stovall, M; Goldman, MB; Seddon, JM; Tarbell, N; Fraumeni, JF; Li, FP

    1997-01-01

    Context.-There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy. Objective.-To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development. De

  5. Do changes in biomarkers from space radiation reflect dose or risk?

    Science.gov (United States)

    Brooks, A.

    The space environment is made up of many different kinds of radiation so that the proper use of biomarkers is essential to estimate radiation risk. This presentation will evaluate differences between biomarkers of dose and risk and demonstrate why they should not be confused following radiation exposures in deep space. Dose is a physical quantity, while risk is a biological quantity. Many examples exist w ereh dose or changes in biomarkers of dose are inappropriately used as predictors of risk. Without information on the biology of the system, the biomarkers of dose provide little help in predicting risk in tissues or radiation exposure types where no excess risk can be demonstrated. Many of these biomarkers of dose only reflect changes in radiation dose or exposure. However, these markers are often incorrectly used to predict risk. For example, exposure of the trachea or of the deep lung to high-LET alpha particles results in similar changes in the biomarker chromosome damage in these two tissues. Such an observation would predict that the risk for cancer induction would be similar in these two tissues. It has been noted , however, that there has never been a tracheal tumor observed in rats that inhaled radon, but with the same exposure, large numbers of tumors were produced in the deep lung. The biology of the different tissues is the major determinant of the risk rather than the radiation dose. Recognition of this fact has resulted in the generation of tissue weighting factors for use in radiation protection. When tissue weighting factors are used the values derived are still called "dose". It is important to recognize that tissue specific observations have been corrected to reflect risk, and therefore should no longer be viewed as dose. The relative biological effectiveness (RBE) is also used to estimate radiation risk. The use of biomarkers to derive RBE is a difficult since it involves the use of a biological response to a standard low-LET reference radiation

  6. Dose dense (CEOP-14) vs dose dense and rituximab (CEOP-14 +R) in high-risk diffuse large cell lymphoma.

    Science.gov (United States)

    Avilés, Agustin; Nambo, María J; Neri, Natividad; Cleto, Sergio; Castañeda, Claudia; Huerta-Guzmàn, Judith; Murillo, Edgar; Contreras, Margarita; Talavera, Alejandra; González, Martha

    2007-01-01

    To assess efficacy and toxicity of rituximab and dose chemotherapy in high-risk diffuse large cell lymphoma, we conducted a controlled clinical trial to assess efficacy and toxicity of a dose-dense regimen CEOP- 14 (cyclophosphamide, epirubicin, vincristine, and prednisone every 14 d) compared to CEOP-14 plus rituximab. One hundred and ninety-six patients were randomized to received CEOP-rituximab (cyclophosphamide 1500 mg/m2, epirubicin 120 mg/m2, vincristine, and prednisone at standard dose and rituximab at 375 mg/m2) compared with the same chemotherapy administered every 14 d (CEOP-14). In an intent-to-treat analysis all patients were available for efficacy and toxicity. Complete response in CEOP-14 was observed in 73 cases (74%) and in 75 patients (76%) in the CEOP-R regimen (76%) (p = 0.8). With a median follow-up of 53.4 mo, median has not been reached in time to tumor-progression (TTP) and overall survival (OS). Actuarial curves at 5 yr showed that TTP and OS in patients treated with CEOP-R were 74% and 67%, respectively, that were not statistical different when compared to CEOP-14, 72% and 65%, respectively (p = 0.8). Acute toxicity was mild and well tolerated. The use of a dense-dose regimen is useful and well tolerated in patients with very high risk diffuse large cell lymphoma. The addition of rituximab did not improve outcome in these setting of patients.

  7. Appropriate Use of Effective Dose in Radiation Protection and Risk Assessment.

    Science.gov (United States)

    Fisher, Darrell R; Fahey, Frederic H

    2017-08-01

    Effective dose was introduced by the ICRP for the single, over-arching purpose of setting limits for radiation protection. Effective dose is a derived quantity or mathematical construct and not a physical, measurable quantity. The formula for calculating effective dose to a reference model incorporates terms to account for all radiation types, organ and tissue radiosensitivities, population groups, and multiple biological endpoints. The properties and appropriate applications of effective dose are not well understood by many within and outside the health physics profession; no other quantity in radiation protection has been more confusing or misunderstood. According to ICRP Publication 103, effective dose is to be used for "prospective dose assessment for planning and optimization in radiological protection, and retrospective demonstration of compliance for regulatory purposes." In practice, effective dose has been applied incorrectly to predict cancer risk among exposed persons. The concept of effective dose applies generally to reference models only and not to individual subjects. While conceived to represent a measure of cancer risk or heritable detrimental effects, effective dose is not predictive of future cancer risk. The formula for calculating effective dose incorporates committee-selected weighting factors for radiation quality and organ sensitivity; however, the organ weighting factors are averaged across all ages and both genders and thus do not apply to any specific individual or radiosensitive subpopulations such as children and young women. Further, it is not appropriate to apply effective dose to individual medical patients because patient-specific parameters may vary substantially from the assumptions used in generalized models. Also, effective dose is not applicable to therapeutic uses of radiation, as its mathematical underpinnings pertain only to observed late (stochastic) effects of radiation exposure and do not account for short-term adverse

  8. Comparison of Vocal Vibration-Dose Measures for Potential-Damage Risk Criteria

    Science.gov (United States)

    Titze, Ingo R.; Hunter, Eric J.

    2015-01-01

    Purpose: School-teachers have become a benchmark population for the study of occupational voice use. A decade of vibration-dose studies on the teacher population allows a comparison to be made between specific dose measures for eventual assessment of damage risk. Method: Vibration dosimetry is reformulated with the inclusion of collision stress.…

  9. Patient doses and radiation risks in film-screen mammography in Finland

    Energy Technology Data Exchange (ETDEWEB)

    Servomaa, A.; Parviainen, T.; Komppa, T. [Finnish Centre for Radiation and Nuclear Safety (STUK), Helsinki (Finland)

    1995-12-31

    Screen-film mamography is the most sensitive method for the early detection of breast cancer. Breast doses in mamography should be measured for several reasons, especially for the evaluation of patient risk in a screening programme, but also for the assessment and comparison of imaging techniques and equipment performance. In this study, the factors affecting patient doses were assessed by making performance and patient dose measurements; about 50 mammographic units used for screening were included in the study. The lifetime risk as a function of age at exposure was calculated using the average glandular dose, the relative risk model shown in the BEIR V report, and the breast cancer mortality in Finland. The mean surface dose of a 4.5 cm thick phantom was 6.3 mGy, and the mean glandular dose 1.0 mGy. Analysis of the surface dose with respect to film optical density, relative speed of film processing, sensitivity of image receptors, and antiscatter grid showed that the mean surface dose could be decreased by more than 50%. For the screened age group of 50 to 59 years, the risk of exposure-induced death (REID) of breast cancer is about 1.4 x 10{sup -6} mSv{sup -1}, and the average loss of life expectancy due to the radiation-induced breast cancer deaths (LLE/REID) is about 9.5 years. (Author).

  10. [Risk and prevention of gastrointestinal complications due to low-dose aspirin and other antiplatelet agents].

    Science.gov (United States)

    Bretagne, Jean-François

    2008-09-15

    Upper and lower gastrointestinal (GI) haemorrhages are the main complications associated with low-dose aspirin or anti-thrombotic drugs. In France, low-dose aspirin or anti-thrombotic agents use has been found in 30% of upper GI and 40% of lower GI bleeding episodes. Main causes of GI bleeding with low-dose aspirin are gastroduodenal peptic ulcer and colonic diverticulosis. Recent cohort studies have shown that the relative risk of GI bleeding with low-dose aspirin was comprised between 2 and 4 and the absolute risk comprised between 1 per 100 and 1 per 1000 aspirin users per year. Main risk factors for upper GI bleeding with low-dose aspirin are concomitant antiplatelet agents, anticoagulants, non steroidal anti-inflammatory drugs or steroids use, and recent history of complicated or non-complicated gastroduodenal ulcer. Helicobacter pylori infection increases the risk for upper GI bleeding with low-dose aspirin, but infection should be searched and treated only in patients with peptic ulcer. Despite eradication of H. pylori in the latter patients, gastroprotection with PPI is strongly recommended. In patients presenting with peptic ulcer bleeding with low-dose aspirin, aspirin should be continued in association with PPI rather than replaced with clopidogrel. Discontinuation of low-dose aspirin which exposes to increased cardiovascular complications and mortality should be avoided, even in cases of peptic ulcer bleeding.

  11. Towards individualized dose constraints: Adjusting the QUANTEC radiation pneumonitis model for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane L; Vogelius, Ivan R.; Farr, Katherina P.;

    2014-01-01

    Background. Understanding the dose-response of the lung in order to minimize the risk of radiation pneumonitis (RP) is critical for optimization of lung cancer radiotherapy. We propose a method to combine the dose-response relationship for RP in the landmark QUANTEC paper with known clinical risk...... factors, in order to enable individual risk prediction. The approach is validated in an independent dataset. Material and methods. The prevalence of risk factors in the patient populations underlying the QUANTEC analysis was estimated, and a previously published method to adjust dose......-response relationships for clinical risk factors was employed. Effect size estimates (odds ratios) for risk factors were drawn from a recently published meta-analysis. Baseline values for D50 and γ50 were found. The method was tested in an independent dataset (103 patients), comparing the predictive power of the dose......-only QUANTEC model and the model including risk factors. Subdistribution cumulative incidence functions were compared for patients with high/low-risk predictions from the two models, and concordance indices (c-indices) for the prediction of RP were calculated. Results. The reference dose- response relationship...

  12. Radiation dose, reproductive history, and breast cancer risk among Japanese A-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Land, C.E. [National Cancer Institute, Bethesda, MD (United States)

    1992-06-01

    Excess risk of female breast cancer is among the most comprehensively documented late effects of exposure to substantial doses of ionizing radiation, based on studies of medically irradiated populations and the survivors of the A-bombings of Hiroshima and Nagasaki. This study looks at the interaction of dose with epidemiological factors like age at first full-term pregnancy and family history of breast cancer, most closely associated with risk in epidemiological studies of non-irradiatied populations. 1 fig., 2 tabs.

  13. Risk of a second malignant neoplasm after cancer in childhood treated with radiotherapy: correlation with the integral dose

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, F.; Rubino, C.; Guerin, S.; de Vathaire, F. [National Institute of Public Health and Medical Research (INSERM) Unit 605, Institut Gustave-Roussy, Villejuif (France); Diallo, I.; Samand, A. [National Institute of Public Health and Medical Research (INSERM) Unit 605, Institut Gustave-Roussy, Villejuif, (France); Medical Physics and Radiotherapy Departments, Institut Gustave-Roussy, Villejuif (France); Hawkins, M. [Centre for Childhood Cancer Survivor Studies, University of Birmingham, Birmingham (United Kingdom); Oberlin, O. [Paediatrics Department, Institut Gustave-Roussy, Villejuif (France); Lefkopoulos, D. [Medical Physics and Radiotherapy Departments, Institut Gustave-Roussy, Villejuif (France)

    2006-07-01

    In the cohort, among patients who had received radiotherapy, only those who had received the highest integral dose had a higher risk. Among the other patients, including 80% of the variability of the integral dose, no increased risk was evidenced. Thus, the integral dose in the study cannot be considered as a good predictor of later risk. (N.C.)

  14. Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model.

    Science.gov (United States)

    Dropkin, Greg

    2016-11-24

    Analyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour. GAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 - 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy. For all solid cancer incidence, RR estimated from 0 - 100 mGy and 0 - 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 - 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort. Non-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.

  15. Estimated Risk Level of Unified Stereotactic Body Radiation Therapy Dose Tolerance Limits for Spinal Cord.

    Science.gov (United States)

    Grimm, Jimm; Sahgal, Arjun; Soltys, Scott G; Luxton, Gary; Patel, Ashish; Herbert, Scott; Xue, Jinyu; Ma, Lijun; Yorke, Ellen; Adler, John R; Gibbs, Iris C

    2016-04-01

    A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose-volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2-3Gy fractions and 3 patients developed treatment-related myelopathy. These dose-volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of ≤1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of ≤3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation.

  16. Cumulative Doses of T-Cell Depleting Antibody and Cancer Risk after Kidney Transplantation.

    Directory of Open Access Journals (Sweden)

    Jenny H C Chen

    Full Text Available T-cell depleting antibody is associated with an increased risk of cancer after kidney transplantation, but a dose-dependent relationship has not been established. This study aimed to determine the association between cumulative doses of T-cell depleting antibody and the risk of cancer after kidney transplantation. Using data from the Australian and New Zealand Dialysis and Transplant Registry between 1997-2012, we assessed the risk of incident cancer and cumulative doses of T-cell depleting antibody using adjusted Cox regression models. Of the 503 kidney transplant recipients with 2835 person-years of follow-up, 276 (55%, 209 (41% and 18 (4% patients received T-cell depleting antibody for induction, rejection or induction and rejection respectively. The overall cancer incidence rate was 1,118 cancers per 100,000 patient-years, with 975, 1093 and 1377 cancers per 100,000 patient-years among those who had received 1-5 doses, 6-10 doses and >10 doses, respectively. There was no association between cumulative doses of T cell depleting antibody and risk of incident cancer (1-5: referent, 6-10: adjusted hazard ratio (HR 1.19, 95%CI 0.48-2.95, >10: HR 1.42, 95%CI 0.50-4.02, p = 0.801. This lack of association is contradictory to our hypothesis and is likely attributed to the low event rates resulting in insufficient power to detect significant differences.

  17. ANDROS: A code for Assessment of Nuclide Doses and Risks with Option Selection

    Energy Technology Data Exchange (ETDEWEB)

    Begovich, C.L.; Sjoreen, A.L.; Ohr, S.Y.; Chester, R.O.

    1986-11-01

    ANDROS (Assessment of Nuclide Doses and Risks with Option Selection) is a computer code written to compute doses and health effects from atmospheric releases of radionuclides. ANDROS has been designed as an integral part of the CRRIS (Computerized Radiological Risk Investigation System). ANDROS reads air concentrations and environmental concentrations of radionuclides to produce tables of specified doses and health effects to selected organs via selected pathways (e.g., ingestion or air immersion). The calculation may be done for an individual at a specific location or for the population of the whole assessment grid. The user may request tables of specific effects for every assessment grid location. Along with the radionuclide concentrations, the code requires radionuclide decay data, dose and risk factors, and location-specific data, all of which are available within the CRRIS. This document is a user manual for ANDROS and presents the methodology used in this code.

  18. Beyond dose assessment: using risk with full disclosure of uncertainty in public and scientific communication.

    Science.gov (United States)

    Hoffman, F Owen; Kocher, David C; Apostoaei, A Iulian

    2011-11-01

    Evaluations of radiation exposures of workers and the public traditionally focus on assessments of radiation dose, especially annual dose, without explicitly evaluating the health risk associated with those exposures, principally the risk of radiation-induced cancer. When dose is the endpoint of an assessment, opportunities to communicate the significance of exposures are limited to comparisons with dose criteria in regulations, doses due to natural background or medical x-rays, and doses above which a statistically significant increase of disease has been observed in epidemiologic studies. Risk assessment generally addresses the chance (probability) that specific diseases might be induced by past, present, or future exposure. The risk of cancer per unit dose will vary depending on gender, age, exposure type (acute or chronic), and radiation type. It is not uncommon to find that two individuals with the same effective dose will have substantially different risks. Risk assessment has shown, for example, that: (a) medical exposures to computed tomography scans have become a leading source of future risk to the general population, and that the risk would be increased above recently published estimates if the incidence of skin cancer and the increased risk from exposure to x-rays compared with high-energy photons were taken into account; (b) indoor radon is a significant contributor to the baseline risk of lung cancer, particularly among people who have never smoked; and (c) members of the public who were exposed in childhood to I in fallout from atmospheric nuclear weapons tests and were diagnosed with thyroid cancer later in life would frequently meet criteria established for federal compensation of cancers experienced by energy workers and military participants at atmospheric weapons tests. Risk estimation also enables comparisons of impacts of exposures to radiation and chemical carcinogens and other hazards to life and health. Communication of risk with

  19. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

    Science.gov (United States)

    Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

    2014-05-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

  20. Thyroid doses and risk to paediatric patients undergoing neck CT examinations

    Energy Technology Data Exchange (ETDEWEB)

    Spampinato, Maria Vittoria; Tipnis, Sameer; Huda, Walter [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Tavernier, Joshua [Medical University of South Carolina, College of Medicine, Charleston, SC (United States)

    2015-07-15

    To estimate thyroid doses and cancer risk for paediatric patients undergoing neck computed tomography (CT). We used average CTDI{sub vol} (mGy) values from 75 paediatric neck CT examinations to estimate thyroid dose in a mathematical anthropomorphic phantom (ImPACT Patient CT Dosimetry Calculator). Patient dose was estimated by modelling the neck as mass equivalent water cylinder. A patient size correction factor was obtained using published relative dose data as a function of water cylinder size. Additional correction factors included scan length and radiation intensity variation secondary to tube-current modulation. The mean water cylinder diameter that modelled the neck was 14 ± 3.5 cm. The mathematical anthropomorphic phantom has a 16.5-cm neck, and for a constant CT exposure, would have thyroid doses that are 13-17 % lower than the average paediatric patient. CTDI{sub vol} was independent of age and sex. The average thyroid doses were 31 ± 18 mGy (males) and 34 ± 15 mGy (females). Thyroid cancer incidence risk was highest for infant females (0.2 %), lowest for teenage males (0.01 %). Estimated absorbed thyroid doses in paediatric neck CT did not significantly vary with age and gender. However, the corresponding thyroid cancer risk is determined by gender and age. (orig.)

  1. Noninvasive non Doses Method for Risk Stratification of Breast Diseases

    Directory of Open Access Journals (Sweden)

    I. A. Apollonova

    2014-01-01

    Full Text Available The article concerns a relevant issue that is a development of noninvasive method for screening diagnostics and risk stratification of breast diseases. The developed method and its embodiment use both the analysis of onco-epidemiologic tests and the iridoglyphical research.Widely used onco-epidemiologic tests only reflect the patient’s subjective perception of her own life history and sickness. Therefore to confirm the revealed factors, modern objective and safe methods are necessary.Iridoglyphical research may be considered as one of those methods, since it allows us to reveal changes in iris’ zones in real time. As these zones are functionally linked with intern organs and systems, in this case mammary glands, changes of iris’ zones may be used to assess risk groups for mammary gland disorders.The article presents results of research conducted using a prototype of the hardwaresoftware complex to provide screening diagnostics and risk stratification of mammary gland disorders.Research has been conducted using verified materials, provided by the Biomedical Engineering Faculty and the Scientific Biometry Research and Development Centre of Bauman Moscow State Technical University, the City of Moscow’s GUZ Clinical and Diagnostic Centre N°4 of the Western Administrative District and the First Mammology (Breast Care Centre of the Russian Federation’s Ministry of Health and Social Development.The information, obtained as a result of onco-epidemiological tests and iridoglyphical research, was used to develop a procedure of quantitative diagnostics aimed to assess mammary gland cancer risk groups. The procedure is based on Bayes conditional probability.The task of quantitative diagnostics may be formally divided into the differential assessment of three states. The first, D1, is the norm, which corresponds to the population group with a lack of risk factors or changes of the mammary glands. The second, D2, is the population group

  2. Radiation dose measurement and risk estimation for paediatric patients undergoing micturating cystourethrography.

    Science.gov (United States)

    Sulieman, A; Theodorou, K; Vlychou, M; Topaltzikis, T; Kanavou, D; Fezoulidis, I; Kappas, C

    2007-09-01

    Micturating cystourethrography (MCU) is considered to be the gold-standard method used to detect and grade vesicoureteric reflux (VUR) and show urethral and bladder abnormalities. It accounts for 30-50% of all fluoroscopic examinations in children. Therefore, it is crucial to define and optimize the radiation dose received by a child during MCU examination, taking into account that children have a higher risk of developing radiation-induced cancer than adults. This study aims to quantify and evaluate, by means of thermoluminescence dosimetry (TLD), the radiation dose to the newborn and paediatric populations undergoing MCU using fluoroscopic imaging. Evaluation of entrance surface dose (ESD), organ and surface dose to specific radiosensitive organs was carried out. Furthermore, the surface dose to the co-patient, i.e. individuals helping in the support, care and comfort of the children during the examination, was evaluated in order to estimate the level of risk. 52 patients with mean age of 0.36 years who had undergone MCU using digital fluoroscopy were studied. ESD, surface doses to thyroid, testes/ovaries and co-patients were measured with TLDs. MCU with digital equipment and fluoroscopy-captured image technique can reduce the radiation dose by approximately 50% while still obtaining the necessary diagnostic information. Radiographic exposures were made in cases of the presence of reflux or of the difficulty in evaluating a finding. The radiation surface doses to the thyroid and testes are relatively low, whereas the radiation dose to the co-patient is negligible. The risks associated with MCU for patients and co-patients are negligible. The results of this study provide baseline data to establish reference dose levels for MCU examination in very young patients.

  3. Automation of PCXMC and ImPACT for NASA Astronaut Medical Imaging Dose and Risk Tracking

    Science.gov (United States)

    Bahadori, Amir; Picco, Charles; Flores-McLaughlin, John; Shavers, Mark; Semones, Edward

    2011-01-01

    To automate astronaut organ and effective dose calculations from occupational X-ray and computed tomography (CT) examinations incorporating PCXMC and ImPACT tools and to estimate the associated lifetime cancer risk per the National Council on Radiation Protection & Measurements (NCRP) using MATLAB(R). Methods: NASA follows guidance from the NCRP on its operational radiation safety program for astronauts. NCRP Report 142 recommends that astronauts be informed of the cancer risks from reported exposures to ionizing radiation from medical imaging. MATLAB(R) code was written to retrieve exam parameters for medical imaging procedures from a NASA database, calculate associated dose and risk, and return results to the database, using the Microsoft .NET Framework. This code interfaces with the PCXMC executable and emulates the ImPACT Excel spreadsheet to calculate organ doses from X-rays and CTs, respectively, eliminating the need to utilize the PCXMC graphical user interface (except for a few special cases) and the ImPACT spreadsheet. Results: Using MATLAB(R) code to interface with PCXMC and replicate ImPACT dose calculation allowed for rapid evaluation of multiple medical imaging exams. The user inputs the exam parameter data into the database and runs the code. Based on the imaging modality and input parameters, the organ doses are calculated. Output files are created for record, and organ doses, effective dose, and cancer risks associated with each exam are written to the database. Annual and post-flight exposure reports, which are used by the flight surgeon to brief the astronaut, are generated from the database. Conclusions: Automating PCXMC and ImPACT for evaluation of NASA astronaut medical imaging radiation procedures allowed for a traceable and rapid method for tracking projected cancer risks associated with over 12,000 exposures. This code will be used to evaluate future medical radiation exposures, and can easily be modified to accommodate changes to the risk

  4. Computation of thyroid doses and carcinogenic radiation risks to patients undergoing neck CT examinations.

    Science.gov (United States)

    Huda, Walter; Spampinato, Maria V; Tipnis, Sameer V; Magill, Dennise

    2013-10-01

    The aim of the study was to investigate how differences in patient anatomy and CT technical factors in neck CT impact on thyroid doses and the corresponding carcinogenic risks. The CTDIvol and dose-length product used in 11 consecutive neck CT studies, as well as data on automatic exposure control (AEC) tube current variation(s) from the image DICOM header, were recorded. For each CT image that included the thyroid, the mass equivalent water cylinder was estimated based on the patient cross-sectional area and average relative attenuation coefficient (Hounsfield unit, HU). Patient thyroid doses were estimated by accounting for radiation intensity at the location of the patient's thyroid, patient size and the scan length. Thyroid doses were used to estimate thyroid cancer risks as a function of patient demographics using risk factors in BEIR VII. The length of the thyroid glands ranged from 21 to 54 mm with an average length of 42 ± 12 mm. Water cylinder diameters corresponding to the central slice through the patient thyroid ranged from 18 to 32 cm with a mean of 25 ± 5 cm. The average CTDIvol (32-cm phantom) used to perform these scans was 26 ± 6 mGy, but the use of an AEC increased the tube current by an average of 44 % at the thyroid mid-point. Thyroid doses ranged from 29 to 80 mGy, with an average of 55 ± 19 mGy. A 20-y-old female receiving the highest thyroid dose of 80 mGy would have a thyroid cancer risk of nearly 0.1 %, but radiation risks decreased very rapidly with increasing patient age. The key factors that affect thyroid doses in neck CT examinations are the radiation intensity at the thyroid location and the size of the patient. The corresponding patient thyroid cancer risk is markedly influenced by patient sex and age.

  5. Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate cancer risk

    DEFF Research Database (Denmark)

    Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael

    2016-01-01

    Purpose Increasing evidence suggests that aspirin use may protect against prostate cancer. In a nationwide case–control study, using Danish high-quality registry data, we evaluated the association between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs......) and the risk of prostate cancer. Methods We identified 35,600 patients (cases) with histologically verified prostate cancer during 2000–2012. Cases were matched to 177,992 population controls on age and residence by risk-set sampling. Aspirin and nonaspirin NSAID exposure was defined by type, estimated dose......, duration, and consistency of use. We used conditional logistic regression to estimate odds ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer associated with low-dose aspirin (75–150 mg) or nonaspirin NSAID use, adjusted for potential confounders. Results Use of low-dose aspirin...

  6. Low-dose aspirin use and the risk of ovarian cancer in Denmark

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kjaer, S K; Olsen, J H;

    2015-01-01

    BACKGROUND: A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low......-dose aspirin and the risk of ovarian cancer. PATIENTS AND METHODS: We identified all patients in the Danish Cancer Registry aged 30-84 years old with a histologically verified first diagnosis of epithelial ovarian cancer during 2000-2011. Each patient was sex- and age-matched to 15 population controls using...... risk-set sampling. Prescription use, comorbidity, reproductive history, and demographic characteristics data were obtained from nationwide registries. The use of low-dose (75-150 mg) aspirin was defined according to the dose as well as the duration and consistency of use. Conditional logistic...

  7. Benchmark dose profiles for joint-action continuous data in quantitative risk assessment.

    Science.gov (United States)

    Deutsch, Roland C; Piegorsch, Walter W

    2013-09-01

    Benchmark analysis is a widely used tool in biomedical and environmental risk assessment. Therein, estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a prespecified benchmark response (BMR) is well understood for the case of an adverse response to a single stimulus. For cases where two agents are studied in tandem, however, the benchmark approach is far less developed. This paper demonstrates how the benchmark modeling paradigm can be expanded from the single-agent setting to joint-action, two-agent studies. Focus is on continuous response outcomes. Extending the single-exposure setting, representations of risk are based on a joint-action dose-response model involving both agents. Based on such a model, the concept of a benchmark profile-a two-dimensional analog of the single-dose BMD at which both agents achieve the specified BMR-is defined for use in quantitative risk characterization and assessment.

  8. Intake risk and dose evaluation methods for workers in radiochemistry labs of a medical cyclotron facility.

    Science.gov (United States)

    Calandrino, Riccardo; del Vecchio, Antonella; Savi, Annarita; Todde, Sergio; Belloli, Sara

    2009-10-01

    The aim of this paper is to evaluate the risks and doses for the internal contamination of the radiochemistry staff in a high workload medical cyclotron facility. The doses from internal contamination derive from the inhalation of radioactive gas leakage from the cells by personnel involved in the synthesis processes and are calculated from urine sample measurements. Various models are considered for the calculation of the effective committed dose from the analysis of these urine samples, and the results are compared with data obtained from local environmental measurement of the radioactivity released inside the lab.

  9. [Fetus radiation doses from nuclear medicine and radiology diagnostic procedures. Potential risks and radiation protection instructions].

    Science.gov (United States)

    Markou, Pavlos

    2007-01-01

    Although in pregnancy it is strongly recommended to avoid diagnostic nuclear medicine and radiology procedures, in cases of clinical necessity or when pregnancy is not known to the physician, these diagnostic procedures are to be applied. In such cases, counseling based on accurate information and comprehensive discussion about the risks of radiation exposure to the fetus should follow. In this article, estimations of the absorbed radiation doses due to nuclear medicine and radiology diagnostic procedures during the pregnancy and their possible risk effects to the fetus are examined and then discussed. Stochastic and detrimental effects are evaluated with respect to other risk factors and related to the fetus absorbed radiation dose and to the post-conception age. The possible termination of a pregnancy, due to radiation exposure is discussed. Special radiation protection instructions are given for radiation exposures in cases of possible, confirmed or unknown pregnancies. It is concluded that nuclear medicine and radiology diagnostic procedures, if not repeated during the pregnancy, are rarely an indication for the termination of pregnancy, because the dose received by the fetus is expected to be less than 100 mSv, which indicates the threshold dose for having deterministic effects. Therefore, the risk for the fetus due to these diagnostic procedures is low. However, stochastic effects are still possible but will be minimized if the radiation absorbed dose to the fetus is kept as low as possible.

  10. Benchmark dose profiles for joint-action quantal data in quantitative risk assessment.

    Science.gov (United States)

    Deutsch, Roland C; Piegorsch, Walter W

    2012-12-01

    Benchmark analysis is a widely used tool in public health risk analysis. Therein, estimation of minimum exposure levels, called Benchmark Doses (BMDs), that induce a prespecified Benchmark Response (BMR) is well understood for the case of an adverse response to a single stimulus. For cases where two agents are studied in tandem, however, the benchmark approach is far less developed. This article demonstrates how the benchmark modeling paradigm can be expanded from the single-dose setting to joint-action, two-agent studies. Focus is on response outcomes expressed as proportions. Extending the single-exposure setting, representations of risk are based on a joint-action dose-response model involving both agents. Based on such a model, the concept of a benchmark profile (BMP) - a two-dimensional analog of the single-dose BMD at which both agents achieve the specified BMR - is defined for use in quantitative risk characterization and assessment. The resulting, joint, low-dose guidelines can improve public health planning and risk regulation when dealing with low-level exposures to combinations of hazardous agents.

  11. Radiation dose and radiation risk to foetuses and newborns during X-ray examinations

    Energy Technology Data Exchange (ETDEWEB)

    Kettunen, A. [Oulu Univ. (Finland)

    2004-05-01

    The purpose of this study is to determine the way in which the demands set by degree 423/2000 by the Ministry of Social Affairs and Health are fulfilled with respect to the most radiosensitive groups, the foetus and the child, by estimating the radiation dose and radiation risk to the foetus from x-ray examinations of an expectant mother's pelvic region, finding out the practice involved in preventing doses to embryos and foetuses and assessing dose practices in cases where an embryo or foetus is or shall be exposed, and by estimating radiation dose and risk due to the radiation received by a new-born being treated in a paediatric intensive care unit. No statistics are available in Finland to indicate how many x-ray examinations of the pelvic region and lower abdomen are made to pregnant patients or to show the dose and risk to the foetus due these examinations. In order to find out the practices in radiological departments concerning the pelvic x-ray examination of fertile woman and the number of foetuses exposed, a questionnaire was sent to all radiation safety officers responsible for the safe use of radiation (n = 290). A total of 173 questionnaires were returned. This study recorded the technique and Dose-Area Product of 118 chest examinations of newborns in paediatric intensive care units. Entrance surface doses and effective doses were calculated separately to each newborn. Based on the patient records, the number of all x-ray examinations during the study was calculated and the effective doses were estimated retrospectively to each child. The radiation risk was estimated both for the foetuses and for the newborns. According to this study, it is rare in Finland to expose a pregnant woman to radiation. On the other hand, with the exception of pelvimetry examinations, there are no compiled statistics concerning the number of pelvic x-ray examinations of a pregnant woman. There was no common practice on how to exclude the possibility of pregnancy. The dose

  12. Cancer risk assessment: Optimizing human health through linear dose-response models.

    Science.gov (United States)

    Calabrese, Edward J; Shamoun, Dima Yazji; Hanekamp, Jaap C

    2015-07-01

    This paper proposes that generic cancer risk assessments be based on the integration of the Linear Non-Threshold (LNT) and hormetic dose-responses since optimal hormetic beneficial responses are estimated to occur at the dose associated with a 10(-4) risk level based on the use of a LNT model as applied to animal cancer studies. The adoption of the 10(-4) risk estimate provides a theoretical and practical integration of two competing risk assessment models whose predictions cannot be validated in human population studies or with standard chronic animal bioassay data. This model-integration reveals both substantial protection of the population from cancer effects (i.e. functional utility of the LNT model) while offering the possibility of significant reductions in cancer incidence should the hormetic dose-response model predictions be correct. The dose yielding the 10(-4) cancer risk therefore yields the optimized toxicologically based "regulatory sweet spot". Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Radiation therapy for stage IIA and IIB testicular seminoma: peripheral dose calculations and risk assessments

    Science.gov (United States)

    Mazonakis, Michalis; Berris, Theocharris; Lyraraki, Efrossyni; Damilakis, John

    2015-03-01

    This study was conducted to calculate the peripheral dose to critical structures and assess the radiation risks from modern radiotherapy for stage IIA/IIB testicular seminoma. A Monte Carlo code was used for treatment simulation on a computational phantom representing an average adult. The initial treatment phase involved anteroposterior and posteroanaterior modified dog-leg fields exposing para-aortic and ipsilateral iliac lymph nodes followed by a cone-down phase for nodal mass irradiation. Peripheral doses were calculated using different modified dog-leg field dimensions and an extended conventional dog-leg portal. The risk models of the BEIR-VII report and ICRP-103 were combined with dosimetric calculations to estimate the probability of developing stochastic effects. Radiotherapy for stage IIA seminoma with a target dose of 30 Gy resulted in a range of 23.0-603.7 mGy to non-targeted peripheral tissues and organs. The corresponding range for treatment of stage IIB disease to a cumulative dose of 36 Gy was 24.2-633.9 mGy. A dose variation of less than 13% was found by altering the field dimensions. Radiotherapy with the conventional instead of the modern modified dog-leg field increased the peripheral dose up to 8.2 times. The calculated heart doses of 589.0-632.9 mGy may increase the risk for developing cardiovascular diseases whereas the testicular dose of more than 231.9 mGy may lead to a temporary infertility. The probability of birth abnormalities in the offspring of cancer survivors was below 0.13% which is much lower than the spontaneous mutation rate. Abdominoplevic irradiation may increase the lifetime intrinsic risk for the induction of secondary malignancies by 0.6-3.9% depending upon the site of interest, patient’s age and tumor dose. Radiotherapy for stage IIA/IIB seminoma with restricted fields and low doses is associated with an increased morbidity. These data may allow the definition of a risk-adapted follow-up scheme for long

  14. Genetic radiation risks: a neglected topic in the low dose debate

    Science.gov (United States)

    2016-01-01

    Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (Abomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down’s syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about

  15. Burden of upper gastrointestinal symptoms in patients receiving low-dose acetylsalicylic acid for cardiovascular risk management

    DEFF Research Database (Denmark)

    Bytzer, Peter; Pratt, Stephen; Elkin, Eric

    2013-01-01

    Continuous low-dose acetylsalicylic acid (aspirin; ASA) is a mainstay of cardiovascular (CV) risk management. It is well established, however, that troublesome upper gastrointestinal (GI) symptoms are commonly experienced among low-dose ASA users.......Continuous low-dose acetylsalicylic acid (aspirin; ASA) is a mainstay of cardiovascular (CV) risk management. It is well established, however, that troublesome upper gastrointestinal (GI) symptoms are commonly experienced among low-dose ASA users....

  16. Intestinal biospy in children with coeliac disease; a Swedish national study of radiation dose and risk

    Energy Technology Data Exchange (ETDEWEB)

    Persliden, J.; Pettersson, H.B.L. [Linkoeping Univ. (Sweden). Dept. of Radiation Physics; Faelth-Magnusson, K. [University of Linkoeping (Sweden). Faculty of Health Sciences

    1995-12-31

    In paediatric patients, fluoroscopy is used to monitor intestinal biopsies obtained for the diagnosis of coeliac disease. The radiation dose to the child is dependent on the equipment, the sedation of the patient and the experience of the operator. This study presents patient measurements from a national study in Sweden. The cancer excess lifetime mortality risk (CELMR) and the loss of life expectancy (LLE) are calculated for this patient group. TLD measurements were performed by dosemeters at 40 Swedish paediatric departments performing these biopsies. Information was received on sedation techniques, equipment used and fluoroscopy duration. An exponential curve fit was applied to the entrance and exit dose values and this dose distribution was integrated to get the integral dose. From this the mean absorbed dose in the irradiated volume was calculated. The mean and the median of the mean absorbed dose in the irradiated volume to the children was found to be 1.3 mGy (range 0.05-17.5 mGy) and 0.56 mGy respectively. The mean value of the entrance surface dose was 3.0 mGy (range 0.10-27.1 mGy) and the median was 1.4 mGy. The annual collective dose was calculated to 3.3 man Gy, based on 2500 biopsies per year. Variation in doses was found to depend on, e.g. the age of the equipment, focus to patient distance, sedation and operator experience. With this knowledge of doses received by the children in the diagnosis of coeliac disease, CELMR was found to be 0.5 per 25000 biopsies and LLE was 18 years. Recommendations are given on the proper choice of equipment for the reduction of fluoroscopy doses in pediatric radiology. (Author).

  17. Esophageal Dose Tolerance to Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors for Late Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Stephans, Kevin L., E-mail: stephak@ccf.org [Department of Radiation Oncology, Cleveland Clinic, Taussig Cancer Center, Cleveland, Ohio (United States); Djemil, Toufik [Department of Radiation Oncology, Cleveland Clinic, Taussig Cancer Center, Cleveland, Ohio (United States); Diaconu, Claudiu [Cleveland Clinic Learner College of Medicine, Cleveland, Ohio (United States); Reddy, Chandana A.; Xia, Ping; Woody, Neil M.; Greskovich, John [Department of Radiation Oncology, Cleveland Clinic, Taussig Cancer Center, Cleveland, Ohio (United States); Makkar, Vinit [Department of Medical Oncology, Cleveland Clinic, Taussig Cancer Center, Cleveland, Ohio (United States); Videtic, Gregory M.M. [Department of Radiation Oncology, Cleveland Clinic, Taussig Cancer Center, Cleveland, Ohio (United States)

    2014-09-01

    Purpose: To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). Methods and Materials: This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. Results: The median esophageal point dose and 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Conclusions: Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy

  18. Overview of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

    Science.gov (United States)

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

    Solar particle events (SPEs) pose the risk of acute radiation sickness (ARS) to astronauts be-cause organ doses from large SPEs may reach critical levels during extra vehicular activities (EVAs) or lightly shielded spacecraft. NASA has developed an organ dose projection model of Baryon transport code (BRYNTRN) with an output data processing module of SUMDOSE, and a probabilistic model of acute radiation risk (ARR). BRYNTRN code operation requires extensive input preparation, and the risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, these response models can be connected easily and correctly to BRYNTRN in a user-friendly way. The GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations direc-torate (MOD), and space biophysics researchers. Assessment of astronauts' organ doses and ARS from the exposure to historically large SPEs is in support of mission design and opera-tion planning to avoid ARS and stay within the current NASA short-term dose limits. The ARRBOD GUI will serve as a proof-of-concept for future integration of other risk projection models for human space applications. We present an overview of the ARRBOD GUI prod-uct, which is a new self-contained product, for the major components of the overall system, subsystem interconnections, and external interfaces.

  19. Mechanisms of Enhanced Cell Killing at Low Doses: Implications for Radiation Risk

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Peter J. Johnston; Dr. George D. Wilson

    2003-10-15

    We have shown that cell lethality actually measured after exposure to low-doses of low-LET radiation, is markedly enhanced relative to the cell lethality previously expected by extrapolation of the high-dose cell-killing response. Net cancer risk is a balance between cell transformation and cell kill and such enhanced lethality may more than compensate for transformation at low radiation doses over a least the first 10 cGy of low-LET exposure. This would lead to a non-linear, threshold, dose-risk relationship. Therefore our data imply the possibility that the adverse effects of small radiation doses (<10 cGy) could be overestimated in specific cases. It is now important to research the mechanisms underlying the phenomenon of low-dose hypersensitivity to cell killing, in order to determine whether this can be generalized to safely allow an increase in radiation exposure limits. This would have major cost-reduction implications for the whole EM program.

  20. Risk Factors for Upper GI Damage in Low-Dose Aspirin Users and the Interaction Between H. pylori Infection and Low-Dose Aspirin Use.

    Science.gov (United States)

    Iijima, Katsunori; Shimosegawa, Tooru

    2015-01-01

    Nowadays, low-dose aspirin is widely administered at low dose as an antithrombotic drug for the prevention of cerebrovascular and cardiovascular diseases. However, aspirin, even at a low dose, can induce varying degrees of gastroduodenal mucosal injury (erosion, ulcer, ulcer bleeding). Hence, co-prescription of proton pump inhibitors with low-dose aspirin is recommended for those at high risk for adverse gastroduodenal events. At present, a history of peptic ulcer, especially that of complicated ulcer, is the most important risk factor for low-dose aspirin-associated gastroduodenal adverse events. Additionally, concomitant use of non-steroidal anti-inflammatory drugs including COX-2 selective inhibitors, anti-platelet agents, anti-coagulants, and oral corticosteroid is recognized to increase the risk for adverse gastroduodenal events in low-dose aspirin users. H. pylori infection could also be associated with the increased risk for adverse gastroduodenal events in low-dose aspirin users, especially in patients with histories of peptic ulcers. Therefore, eradication therapy for such patients can prevent ulcer recurrence. However, the efficacy of eradication therapy on low-dose aspirin-related gastroduodenal lesions in unselected H. pylori-positive lowdose aspirin users without histories of peptic ulcers remains to be clarified.

  1. A Biodosimeter for Multiparametric Determination of Radiation Dose, Radiation Quality, and Radiation Risk

    Science.gov (United States)

    Richmond, Robert; Cruz, Angela; Jansen, Heather; Bors, Karen

    2003-01-01

    Predicting risk of human cancer following exposure of an individual or a population to ionizing radiation is challenging. To an approximation, this is because uncertainties of uniform absorption of dose and the uniform processing of dose-related damage at the cellular level within a complex set of biological variables degrade the confidence of predicting the delayed expression of cancer as a relatively rare event. Cellular biodosimeters that simultaneously report: 1) the quantity of absorbed dose after exposure to ionizing radiation, 2) the quality of radiation delivering that dose, and 3) the risk of developing cancer by the cells absorbing that dose would therefore be useful. An approach to such a multiparametric biodosimeter will be reported. This is the demonstration of a dose responsive field effect of enhanced expression of keratin 18 (K18) in cultures of human mammary epithelial cells irradiated with cesium-1 37 gamma-rays. Dose response of enhanced K18 expression was experimentally extended over a range of 30 to 90 cGy for cells evaluated at mid-log phase. K18 has been reported to be a marker for tumor staging and for apoptosis, and thereby serves as an example of a potential marker for cancer risk, where the reality of such predictive value would require additional experimental development. Since observed radiogenic increase in expression of K18 is a field effect, ie., chronically present in all cells of the irradiated population, it may be hypothesized that K18 expression in specific cells absorbing particulate irradiation, such as the high-LET-producing atomic nuclei of space radiation, will report on both the single-cell distributions of those particles amongst cells within the exposed population, and that the relatively high dose per cell delivered by densely ionizing tracks of those intersecting particles will lead to cell-specific high-expression levels of K18, thereby providing analytical end points that may be used to resolve both the quantity and

  2. A dose rate model predicting radon-induced lung cancer risk in rats

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, W.; Lettner, H. (Salzburg Univ. (Austria). Div. of Biophysics); Crawford-Brown, D.J. (North Carolina Univ., Chapel Hill, NC (United States). Dept. of Environmental Sciences and Engineering)

    1992-01-01

    The laboratory rat has been used in inhalation studies as a surrogate to estimate human lung cancer risk following exposure to ambient radon progeny. Deposition, mucociliary clearance and dosimetry for the inhalation of radon progeny in the rat lung have been simulated for a variety of inhalation conditions. A state-vector model for radiation carcinogenesis has then been applied to predict the carcinogenic risk in the rat lung for different doses and dose rates. The model is based on the concepts of initiation and promotion, with the irradiation acting both to damage intercellular structures and to change the state of cells surrounding an initiated cell. Predicted lung cancer incidences show fair agreement with the experimental data. Consistent with the experimental evidence is the inverse dose rate effect observed for intermediate cumulative exposures. (author).

  3. Concord grape juice polyphenols and cardiovascular risk factors: dose-response relationships

    Science.gov (United States)

    Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship ...

  4. Estimates of Radiation Doses and Cancer Risk from Food Intake in Korea.

    Science.gov (United States)

    Moon, Eun-Kyeong; Ha, Wi-Ho; Seo, Songwon; Jin, Young Woo; Jeong, Kyu Hwan; Yoon, Hae-Jung; Kim, Hyoung-Soo; Hwang, Myung-Sil; Choi, Hoon; Lee, Won Jin

    2016-01-01

    The aim of this study was to estimate internal radiation doses and lifetime cancer risk from food ingestion. Radiation doses from food intake were calculated using the Korea National Health and Nutrition Examination Survey and the measured radioactivity of (134)Cs, (137)Cs, and (131)I from the Ministry of Food and Drug Safety in Korea. Total number of measured data was 8,496 (3,643 for agricultural products, 644 for livestock products, 43 for milk products, 3,193 for marine products, and 973 for processed food). Cancer risk was calculated by multiplying the estimated committed effective dose and the detriment adjusted nominal risk coefficients recommended by the International Commission on Radiation Protection. The lifetime committed effective doses from the daily diet are ranged 2.957-3.710 mSv. Excess lifetime cancer risks are 14.4-18.1, 0.4-0.5, and 1.8-2.3 per 100,000 for all solid cancers combined, thyroid cancer, and leukemia, respectively.

  5. Impact of acquired immunity and dose-dependent probability of illness on quantitative microbial risk assessment

    NARCIS (Netherlands)

    Havelaar, A. H.; Swart, A. N.

    2014-01-01

    Dose-response models in microbial risk assessment consider two steps in the process ultimately leading to illness: from exposure to (asymptomatic) infection, and from infection to (symptomatic) illness. Most data and theoretical approaches are available for the exposure-infection step; the infection

  6. Physical activity and cancer risk: dose-response and cancer, all sites and site-specific.

    Science.gov (United States)

    Thune, I; Furberg, A S

    2001-06-01

    The association between physical activity and overall and site-specific cancer risk is elaborated in relation to whether any observed dose-response association between physical activity and cancer can be interpreted in terms of how much physical activity (type, intensity, duration, frequency) is needed to influence site- and gender-specific cancer risk. Observational studies were reviewed that have examined the independent effect of the volume of occupational physical activity (OPA) and/or leisure time physical activity (LPA) on overall and site-specific cancer risk. The evidence of cohort and case-control studies suggests that both leisure time and occupational physical activity protect against overall cancer risk, with a graded dose-response association suggested in both sexes. Confounding effects such as diet, body weight, and parity are often included as a covariate in the analyses, with little influence on the observed associations. A crude graded inverse dose-response association was observed between physical activity and colon cancer in 48 studies including 40,674 colon/colorectal cancer cases for both sexes. A dose-response effect of physical activity on colon cancer risk was especially observed, when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed as MET-hours per week. An observed inverse association with a dose-response relationship between physical activity and breast cancer was also identified in the majority of the 41 studies including 108,031 breast cancer cases. The dose-response relationship was in particular observed in case-control studies and supported by observations in cohort studies when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed by MET-hours per week. This association between physical activity and breast cancer risk is possibly dependent on age at exposure, age at diagnosis, menopausal status and other effect

  7. Radiation dose and cancer risk from pediatric CT examinations on 64-slice CT: A phantom study

    Energy Technology Data Exchange (ETDEWEB)

    Feng Shiting [Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Law, Martin Wai-Ming [Department of Clinical Oncology, Queen Mary Hospital (Hong Kong); Huang Bingsheng [Department of Diagnostic Radiology, University of Hong Kong (Hong Kong); Ng, Sherry [Department of Clinical Oncology, Queen Mary Hospital (Hong Kong); Li Ziping; Meng Quanfei [Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Khong, Pek-Lan, E-mail: plkhong@hkucc.hku.hk [Department of Diagnostic Radiology, University of Hong Kong (Hong Kong)

    2010-11-15

    Objective: To measure the radiation dose from CT scans in an anthropomorphic phantom using a 64-slice MDCT, and to estimate the associated cancer risk. Materials and methods: Organ doses were measured with a 5-year-old phantom and thermoluminescent dosimeters. Four protocols; head CT, thorax CT, abdomen CT and pelvis CT were studied. Cancer risks, in the form of lifetime attributable risk (LAR) of cancer incidence, were estimated by linear extrapolation using the organ radiation doses and the LAR data. Results: The effective doses for head, thorax, abdomen and pelvis CT, were 0.7 mSv, 3.5 mSv, 3.0 mSv, 1.3 mSv respectively. The organs with the highest dose were; for head CT, salivary gland (22.33 mGy); for thorax CT, breast (7.89 mGy); for abdomen CT, colon (6.62 mGy); for pelvis CT, bladder (4.28 mGy). The corresponding LARs for boys and girls were 0.015-0.053% and 0.034-0.155% respectively. The organs with highest LARs were; for head CT, thyroid gland (0.003% for boys, 0.015% for girls); for thorax CT, lung for boys (0.014%) and breast for girls (0.069%); for abdomen CT, colon for boys (0.017%) and lung for girls (0.016%); for pelvis CT, bladder for both boys and girls (0.008%). Conclusion: The effective doses from these common pediatric CT examinations ranged from 0.7 mSv to 3.5 mSv and the associated lifetime cancer risks were found to be up to 0.16%, with some organs of higher radiosensitivity including breast, thyroid gland, colon and lungs.

  8. Youth suicide attempts and the dose-response relationship to parental risk factors: a population-based study

    DEFF Research Database (Denmark)

    Christiansen, E; Goldney, R D; Beautrai, A L;

    2011-01-01

    illness and low level of income were all significant independent risk factors for offspring's suicide attempts. CONCLUSIONS: Knowledge of the effect of multiple risk factors on the likelihood of suicide attempts in children and adolescents is important for risk assessment. Dose-response effects......BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk...... to each case and a link to the offspring's biological parents was established. RESULTS: There was a dose-response relationship between the number of exposures and the risk of suicide attempts, with the increased risk seeming to be a multiplicative effect. Parental suicide, suicide attempt, psychiatric...

  9. Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Blumberg

    2015-12-01

    Full Text Available Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD, blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages.

  10. Dose-to-dose variations with single packages of counterfeit medicines and adulterated dietary supplements as a potential source of false negatives and inaccurate health risk assessments.

    Science.gov (United States)

    Venhuis, B J; Zwaagstra, M E; Keizers, P H J; de Kaste, D

    2014-02-01

    In this report, we show three examples of how the variability in dose units in single packages of counterfeit medicines and adulterated dietary supplements may contribute to a false negative screening result and inaccurate health risk assessments. We describe a counterfeit Viagra 100mg blister pack and a box of an instant coffee both containing dose units with and without an active pharmaceutical ingredient (API). We also describe a purportedly herbal slimming product with capsules that mutually differed in API and impurities. The adulterated dietary supplements contained sibutramine, benzyl-sibutramine, N-desmethyl-sibutramine (DMS), N,N-didesmethyl-sibutramine (DDMS) and several other related impurities. Counterfeit medicines and adulterated dietary supplements are a health risk because their quality is unreliable. Health risks are even greater when such unreliability extends to fundamental differences between dose units in one package. Because dose-to-dose variability for these products is unpredictable, the confidence interval of a sample size is unknown. Consequently, the analyses of a selection of dose units may not be representative for the package. In the worst case, counterfeit or unauthorised medicines are not recognised as such or a health risk is not identified. In order to reduce erroneous results particular care should be taken when analysing a composite of dose units, when finding no API in a dietary supplement and when finding conformity in a suspect counterfeit medicine. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Estimation of effective dose and lifetime attributable risk from multiple head CT scans in ventriculoperitoneal shunted children

    Energy Technology Data Exchange (ETDEWEB)

    Aw-Zoretic, J., E-mail: Jaw@luriechildrens.org [Department of Medical Imaging, Ann and Robert H. Lurie Children' s Hospital of Chicago, Chicago, IL (United States); Seth, D.; Katzman, G.; Sammet, S. [Department of Radiology, University of Chicago, Chicago, IL (United States)

    2014-10-15

    Purpose: The purpose of this review is to determine the averaged effective dose and lifetime attributable risk factor from multiple head computed tomography (CT) dose data on children with ventriculoperitoneal shunts (VPS). Method and materials: A total of 422 paediatric head CT exams were found between October 2008 and January 2011 and retrospectively reviewed. The CT dose data was weighted with the latest IRCP 103 conversion factor to obtain the effective dose per study and the averaged effective dose was calculated. Estimates of the lifetime attributable risk were also calculated from the averaged effective dose using a conversion factor from the latest BEIR VII report. Results: Our study found the highest effective doses in neonates and the lowest effective doses were observed in the 10–18 years age group. We estimated a 0.007% potential increase risk in neonates and 0.001% potential increased risk in teenagers over the base risk. Conclusion: Multiple head CTs in children equates to a slight potential increase risk in lifetime attributable risk over the baseline risk for cancer, slightly higher in neonates relative to teenagers. The potential risks versus clinical benefit must be assessed.

  12. Critical appraisal of a fixed combination of esomeprazole and low dose aspirin in risk reduction

    Directory of Open Access Journals (Sweden)

    Ravi Vachhani

    2010-06-01

    Full Text Available Ravi Vachhani1, Doumit Bouhaidar1, Alvin Zfass1, Bimaljit Sandhu1, Ali Nawras21Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298–0341, USA; 2Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Toledo Medical Center, Toledo, Ohio 43606-3390, USAAbstract: Low dose aspirin (≤325 mg is routinely used for primary and secondary prophylaxis of cardiovascular and cerebrovascular events. The use of low dose aspirin is associated with two-to four-fold greater risk of symptomatic or complicated peptic ulcers. Risk factors associated with low dose aspirin induced gastrointestinal toxicity includes prior history of ulcer or upper gastrointestinal (GI bleeding, concomitant use of other nonsteroidal anti-inflammatory drugs, corticosteroid or warfarin, dual antiplatelet therapy, Helicobacter pylori (H. pylori infection, and advanced age. Esomeprazole, like other proton pump inhibitors (PPIs is very effective in decreasing the risk of aspirin induced gastrointestinal toxicity. Although evidence to support esomeprazole or other PPIs for primary prophylaxis in aspirin induced gastrointestinal toxicity is limited, its role in secondary prophylaxis is well established.Keywords: esomeprazole, proton pump inhibitors, low dose aspirin, gastrointestinal toxicity, gastrointestinal bleeding

  13. Analysis of dose and risk associated with the use of backscatter vans

    Energy Technology Data Exchange (ETDEWEB)

    Correa, Samanda C.A.; Aquino, Josilto O., E-mail: scorrea@cnen.gov.b, E-mail: josilto@cnen.gov.b [Comissao Nacional de Energia Nuclear (DIAPI/CGMI/CNEN), Rio de Janeiro, RJ (Brazil). Coordenacao Geral de Instalacoes Medicas e Industriais. Div. de Aplicacoes Industriais; Souza, Edmilson M., E-mail: emonteiro@nuclear.ufrj.b [Centro Universitario Estadual da Zona Oeste (CAPI/UEZO), Rio de Janeiro, RJ (Brazil); Silva, Ademir X., E-mail: ademir@con.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (PEN/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear

    2011-07-01

    In recent years, imaging technology using radiation has been gaining in importance for the screening of persons for security reasons and in order to detect contraband. And currently, new X-ray detection technologies have been introduced such as the Backscatter Van. The Backscatter Van is used in port and border security, force protection, urban surveillance, and other critical security applications in order to seize drugs, explosives, and more. The system is mobile, affordable and the faster, more effective, and less expensive than any mobile screening solution in the marketplace. However, although the application of this equipment in the national security area is indeed relevant, its use has caused a great deal of controversy, especially with regard to the doses absorbed and to the cancer induction risk associated with these exposures. The aim of this study is to use the Monte Carlo MCNPX code and the male adult voxel (MAX) and female adult voxel (FAX) phantoms, to evaluate the absorbed dose, effective dose and cancer induction risk values associated with the exposures of individuals submitted to Backscatter Van. The effective dose values were calculated as recommended by the new ICRP 103 and the cancer induction risk values were estimated through the BEIR VII document. (author)

  14. [Method of ecological risk assessment for risk pollutants under short-term and high dose exposure in water pollution accident].

    Science.gov (United States)

    Lei, Bing-Li; Sun, Yan-Feng; Liu, Qian; Yu, Zhi-Qiang; Zeng, Xiang-Ying

    2011-11-01

    In recent years, water pollution accidents resulting in acute aquatic ecological risk and security issues become a research focus. However, in our country, the surface water quality standards and drinking water health standards were used to determine the safety of waters or not in pollution incidents due to lacking safety effect threshold or risk value for protection of aquatic life. In foreign countries, although predicted no effect concentration (PNEC) or risk value (R) of pollutants were provided for protection of aquatic organisms, the PNECs or risk values were derived based on long-term exposure toxicity data NOECs (no observed effect concentrations) and lack of short-term exposure risk or threshold values. For the short-term and high dose exposure in pollution incident, ecological risk assessment methods were discussed according to the procedures of the conventional ecological risk assessment and the water quality criteria establishment of the U.S. EPA for the protection of aquatic organisms in short-term exposure, and had a case study. At the same time, we provide some suggestions for the establishment of ecological risk assessment system in water pollution incidents.

  15. Effective dose and cancer risk in PET/CT exams; Dose efetiva e risco de cancer em exames de PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Gabriella M.; Sa, Lidia Vasconcellos de, E-mail: montezano@ird.gov.br, E-mail: Iidia@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2013-07-01

    Due to the use of radiopharmaceutical positron-emitting in PET exam and realization of tomography by x-ray transmission in CT examination, an increase of dose with hybrid PET/CT technology is expected. However, differences of doses have been reported in many countries for the same type of procedure. It is expected that the dose is an influent parameter to standardize the protocols of PET/CT. This study aimed to estimate the effective doses and absorbed in 65 patients submitted to oncological Protocol in a nuclear medicine clinic in Rio de Janeiro, considering the risk of induction of cancer from the scan. The CT exam-related doses were estimated with a simulator of PMMA and simulated on the lmPACT resistance, which for program effective dose, were considered the weight factors of the lCRP 103. The PET exam doses were estimated by multiplying the activity administered to the patient with the ICRP dose 80 factors. The radiological risk for cancer incidence were estimated according to the ICRP 103. The results showed that the effective dose from CT exam is responsible for 70% of the effective total in a PET/CT scan. values of effective dose for the PET/CT exam reached average values of up to 25 mSv leading to a risk of 2, 57 x 10{sup -4}. Considering that in staging of oncological diseases at least four tests are performed annually, the total risk comes to 1,03x 10{sup -3}.

  16. The Quality of General Movements after Treatment with Low-Dose Dexamethasone in Preterm Infants at Risk of Bronchopulmonary Dysplasia

    NARCIS (Netherlands)

    Hitzert, Marrit M.; Roescher, Annemiek M.; Bos, Arend F.

    2014-01-01

    Background: High-dose dexamethasone (DXM) treatment of preterms at risk of bronchopulmonary dysplasia leads to a deterioration in quality of their general movements (GMs). It is unknown whether low-dose DXM affects GM quality similarly. Objectives: To assess the effect of low-dose DXM treatment on t

  17. Dose to the Developing Dentition During Therapeutic Irradiation: Organ at Risk Determination and Clinical Implications

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Reid F., E-mail: Reid.Thompson@uphs.upenn.edu [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Schneider, Ralf A., E-mail: ralf.schneider@psi.ch [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Albertini, Francesca; Lomax, Antony J.; Ares, Carmen; Goitein, Gudrun [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Hug, Eugen B. [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); ProCure Therapy Centers, New York, New York (United States)

    2013-05-01

    Purpose: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. Methods and Materials: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions for a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. Results: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. Conclusions: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the

  18. Alanine aminotransferase and risk of the metabolic syndrome: a linear dose-response relationship.

    Directory of Open Access Journals (Sweden)

    Setor K Kunutsor

    Full Text Available BACKGROUND: Elevated baseline circulating alanine aminotransferase (ALT level has been demonstrated to be associated with an increased risk of the metabolic syndrome (MetS, but the nature of the dose-response relationship is uncertain. METHODS: We performed a systematic review and meta-analysis of published prospective cohort studies to characterize in detail the nature of the dose-response relationship between baseline ALT level and risk of incident MetS in the general population. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science up to December 2013. Prospective studies in which investigators reported relative risks (RRs of MetS for 3 or more categories of ALT levels were eligible. A potential nonlinear relationship between ALT levels and MetS was examined using restricted cubic splines. RESULTS: Of the 489 studies reviewed, relevant data were available on 29,815 non-overlapping participants comprising 2,125 incident MetS events from five prospective cohort studies. There was evidence of a linear association (P for nonlinearity=0.38 between ALT level and risk of MetS, characterised by a graded increase in MetS risk at ALT levels 6-40 U/L. The risk of MetS increased by 14% for every 5 U/L increment in circulating ALT level (95% CI: 12-17%. Evidence was lacking of heterogeneity and publication bias among the contributing studies. CONCLUSIONS: Baseline ALT level is associated with risk of the MetS in a linear dose-response manner. Studies are needed to determine whether the association represents a causal relationship.

  19. Breastfeeding Mode and Risk of Breast Cancer: A Dose-Response Meta-Analysis.

    Science.gov (United States)

    Unar-Munguía, Mishel; Torres-Mejía, Gabriela; Colchero, M Arantxa; González de Cosío, Teresita

    2017-05-01

    Breastfeeding reduces women's risk of breast cancer. Since exclusive breastfeeding has a stronger hormonal effect, it could theoretically result in a greater reduction in breast cancer risk than any breastfeeding mode. No meta-analysis has examined breast cancer risk by breastfeeding mode. Research aim: The authors conducted a meta-analysis for breast cancer risk in parous women who breastfed exclusively or in any mode versus parous women who formula fed their infants, and they estimated the summary dose-response association by the accumulated duration of any breastfeeding mode. A systematic review of studies published between 2005 and 2015 analyzing breastfeeding and breast cancer risk in women was conducted in PubMed and EBSCOhost. A meta-analysis ( n = 65 studies) with fixed effects (or random effects, if heterogeneity existed) was carried out stratified by breastfeeding mode and menopausal and parity status. A summary dose-response association was estimated using the generalized least-squares method. The summary relative risk (SRR) for breast cancer in parous women who breastfed exclusively was 0.72, 95% confidence interval (CI) [0.58, 0.90], versus parous women who had never breastfed. For parous women who breastfed in any mode, the SRR was lower in both premenopausal women (0.86, 95% CI [0.80, 0.93]) and postmenopausal women (0.89, 95% CI [0.83, 0.95]). There was no heterogeneity or publication bias. There is weak evidence of a difference between exclusive and any breastfeeding mode ( p = .08). The summary dose-response curve was nonlinear ( p < .001). Exclusive breastfeeding among parous women reduces the risk of breast cancer compared with parous women who do not breastfeed exclusively.

  20. Perception of radiation dose and potential risks of computed tomography in emergency department medical personnel

    Science.gov (United States)

    Lee, Jin Hee; Kim, Kyuseok; Lee, Kyoung Ho; Kim, Kwang Pyo; Kim, Yu Jin; Park, Chanjong; Kang, Changwoo; Lee, Soo Hoon; Jeong, Jin Hee; Rhee, Joong Eui

    2015-01-01

    Objective Use of computed tomography (CT) continues to increase, but the relatively high radiation doses associated with CT have raised health concerns such as future risk of cancer. We investigated the level of awareness regarding radiation doses and possible risks associated with CT in medical personnel (MP). Methods This study was conducted from April to May 2012 and included physicians and nurses who worked in the emergency department of 17 training hospitals. The questionnaire included measurement of the effect of CT or radiography on health using a 10-point numerical rating scale, estimation of the radiation dose of one abdominal CT scan compared with one chest radiograph, and perception of the increased lifetime risk of cancer associated with CT. Results A total of 354 MP participated in this study: 142 nurses, 87 interns, 86 residents, and 39 specialists. Interns were less aware of the effects of CT or radiography on health than other physicians or nurses (mean±SD of 4.8±2.7, 5.9±2.7, 6.1±2.7, and 6.0±2.2 for interns, residents, specialists, and nurses, respectively; P<0.05). There was a significant difference in knowledge about the relative radiation dose of one abdominal CT scan compared with one chest radiograph between physicians and nurses (48.6% vs. 28.9% for physicians vs. nurses, P<0.05). MP perceived an increased risk of cancer from radiation associated with CT. Conclusion MP perceive the risk of radiation associated with CT, but their level of knowledge seems to be insufficient.

  1. Chronic low-dose exposure in the Techa River cohort. Risk of mortality from circulatory diseases

    Energy Technology Data Exchange (ETDEWEB)

    Krestinina, Lyudmila Yurievna; Epifanova, Svetlana; Silkin, Stanislav; Mikryukova, Lyudmila; Degteva, Marina; Shagina, Natalia; Akleyev, Alexander [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation)

    2013-03-15

    The aim of the present study was to analyze the mortality from circulatory diseases for about 30,000 members of the Techa River cohort over the period 1950-2003, and to investigate how these rates depend on radiation doses. This population received both external and internal exposures from {sup 90}Sr, {sup 89}Sr, {sup 137}Cs, and other uranium fission products as a result of waterborne releases from the Mayak nuclear facility in the Southern Urals region of the Russian Federation. The analysis included individualized estimates of the total (external plus internal) absorbed dose in muscle calculated based on the Techa River Dosimetry System 2009. The cohort-average dose to muscle tissue was 35 mGy, and the maximum dose was 510 mGy. Between 1950 and 2003, 7,595 deaths from circulatory diseases were registered among cohort members with 901,563 person years at risk. Mortality rates in the cohort were analyzed using a simple parametric excess relative risk (ERR) model. For all circulatory diseases, the estimated excess relative risk per 100 mGy with a 15-year lag period was 3.6 % with a 95 % confidence interval of 0.2-7.5 %, and for ischemic heart disease it was 5.6 % with a 95 % confidence interval of 0.1-11.9 %. A linear ERR model provided the best fit. Analyses with a lag period shorter than 15 years from the beginning of exposure did not reveal any significant risk of mortality from either all circulatory diseases or ischemic heart disease. There was no evidence of an increased mortality risk from cerebrovascular disease (p > 0.5). These results should be regarded as preliminary, since they will be updated after adjustment for smoking and alcohol consumption. (orig.)

  2. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2011-01-01

    Prenatal exposure to antiepileptic drugs is associated with a greater risk of major congenital malformations, but there is inadequate information on the comparative teratogenicity of individual antiepileptic drugs and the association with dose. We aimed to establish the risks of major congenital...... malformations after monotherapy exposure to four major antiepileptic drugs at different doses....

  3. Bright-light intervention induces a dose-dependent increase in striatal response to risk in healthy volunteers

    DEFF Research Database (Denmark)

    Macoveanu, Julian; Fisher, Patrick M; Madsen, Martin K

    2016-01-01

    -light intervention led to a dose-dependent increase in risk-taking in the LA/LA group relative to the non-LA/LA group. Further, bright-light intervention enhanced risk-related activity in ventral striatum and head of caudate nucleus in proportion with the individual bright-light dose. The augmentation effect...

  4. Non-targeted effects of ionising radiation—Implications for low dose risk

    DEFF Research Database (Denmark)

    Kadhim, Munira; Salomaa, Sisko; Wright, Eric

    2013-01-01

    Non-DNA targeted effects of ionising radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects...... with respect to systemic (human health) consequences at low and intermediate doses of ionising radiation. Other outstanding questions include links between the different non-targeted responses and the variations in response observed between individuals and cell lines, possibly a function of genetic background......) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. © 2012 Elsevier B.V. All rights reserved....

  5. High-dose anti-histamine use and risk factors in children with urticaria

    Science.gov (United States)

    Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

    2016-01-01

    Aim The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. Material and Methods The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. Results The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=−0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (purticaria. Conclusion The requirement of high-dose H1-antihistamines was higher with children’s increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines. PMID:28123332

  6. Evolving Adjustments to External (Gamma) Slope Factors for CERCLA Risk and Dose Assessments - 12290

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Stuart [U.S. Environmental Protection Agency (United States)

    2012-07-01

    To model the external exposure pathway in risk and dose assessments of radioactive contamination at Superfund sites, the U.S. Environmental Protection Agency (EPA) uses slope factors (SFs), also known as risk coefficients, and dose conversion factors (DCFs). Without any adjustment these external radiation exposure pathways effectively assumes that an individual is exposed to a source geometry that is effectively an infinite slab. The concept of an 'infinite slab' means that the thickness of the contaminated zone and its aerial extent are so large that it behaves as if it were infinite in its physical dimensions. EPA has been making increasingly complex adjustments to account for the extent of the contamination and its corresponding radiation field to provide more accurate risk and dose assessment modeling when using its calculators. In most instances, the more accurate modeling results derived from these gamma adjustments are less conservative. The notable exception are for some radionuclides in rooms with contaminated walls, ceiling, and floors, and the receptor is in location of the room with the highest amount of radiation exposure, usually the corner of small rooms and the center of large conference rooms. (authors)

  7. Radiation dose assessments to support evaluations of radiological control levels for recycling or reuse of materials and equipment

    Energy Technology Data Exchange (ETDEWEB)

    Hill, R.L.; Aaberg, R.L.; Baker, D.A.; Kennedy, W.E. Jr.

    1995-07-01

    Pacific Northwest Laboratory is providing Environmental Protection Support and Assistance to the USDOE, Office of Environmental Guidance. Air, Water, and Radiation Division. As part of this effort, PNL is collecting data and conducting technical evaluations to support DOE analyses of the feasibility of developing radiological control levels for recycling or reuse of metals, concrete, or equipment containing residual radioactive contamination from DOE operations. The radiological control levels will be risk-based, as developed through a radiation exposure scenario and pathway analysis. The analysis will include evaluation of relevant radionuclides, potential mechanisms of exposure, and both health and non-health-related impacts. The main objective of this report is to develop a methodology for establishing radiological control levels for recycle or reuse. This report provides the results of the radiation exposure scenario and pathway analyses for 42 key radionuclides generated during DOE operations that may be contained in metals or equipment considered for either recycling or reuse. The scenarios and information developed by the IAEA. Application of Exemption Principles to the Recycle and Reuse of Materials from Nuclear Facilities, are used as the initial basis for this study. The analyses were performed for both selected worker populations at metal smelters and for the public downwind of a smelter facility. Doses to the public downwind were estimated using the US (EPA) CAP88-PC computer code with generic data on atmospheric dispersion and population density. Potential non-health-related effects of residual activity on electronics and on film were also analyzed.

  8. Half-dose gadoxetic acid-enhanced liver magnetic resonance imaging in patients at risk for nephrogenic systemic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kyoung Doo [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Kim, Seong Hyun, E-mail: kshyun@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Lee, Jisun; Kang, Kyung A. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Kim, Joungyoun; Yoo, Heejin [Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 135-710 (Korea, Republic of)

    2015-03-15

    Highlights: •Half dose of gadoxetic acid achieved more than 75% enhancement degree of a standard dose. •No significant difference was observed in enhancement quality between half-dose and standard-dose MRIs for all upper abdominal organs. •Liver MRI using half-dose gadoxetic acid at 3-T can be a feasible alternative for standard-dose MRI in patients at risk for NSF. -- Abstract: Purpose: To evaluate the feasibility of half-dose gadoxetic acid (0.0125 mmol/kg) for liver MRI at 3-T compared to standard-dose (0.025 mmol/kg) in patients at risk for nephrogenic systemic fibrosis (NSF). Materials and methods: Forty patients who underwent both half-dose and standard-dose gadoxetic acid-enhanced MRIs were included. Contrast enhancement index (CEI) was calculated for liver, aorta, pancreas and kidney. Two observers independently rated and performed a one-to-one direct comparison of enhancement quality for both groups. Results: Liver CEIs were not significantly different on arterial phase between the two groups but CEIs of standard-dose MRIs were greater than half-dose MRIs on other phases (P < 0.001). CEIs were not significantly different on arterial phase for the aorta or on any phases for the pancreas. Kidney CEIs of standard-dose MRIs were greater than half-dose MRIs on all phases (P < 0.05). Enhancement quality of both groups was diagnostic and did not significantly differ for any organs. In one-to-one direct comparisons of enhancement quality, equal ratings were given in 87.5% (35/40) of cases by observer 1 and 85.0% (34/40) by observer 2. Conclusion: Liver MRI using half-dose gadoxetic acid at 3-T can be a feasible alternative for standard-dose MRI in patients at risk for NSF.

  9. Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term Survivors of Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kleinerman, Ruth A., E-mail: kleinerr@mail.nih.gov [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Rockville, Maryland (United States); Smith, Susan A. [Department of Radiation Physics, University of Texas M D Anderson Cancer Center, Houston, Texas (United States); Holowaty, Eric [Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario (Canada); Hall, Per [Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm (Sweden); Pukkala, Eero [Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki (Finland); Vaalavirta, Leila [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Stovall, Marilyn; Weathers, Rita [Department of Radiation Physics, University of Texas M D Anderson Cancer Center, Houston, Texas (United States); Gilbert, Ethel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Rockville, Maryland (United States); Aleman, Berthe M.P. [Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam (Netherlands); Kaijser, Magnus [Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Andersson, Michael [Department of Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Storm, Hans [Cancer Prevention and Documentation, Danish Cancer Society, Copenhagen (Denmark); Joensuu, Heikki [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Lynch, Charles F. [Department of Epidemiology, University of Iowa, Iowa City, Iowa (United States); and others

    2013-08-01

    Purpose: To assess the dose–response relationship for stomach cancer after radiation therapy for cervical cancer. Methods and Materials: We conducted a nested, matched case–control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63 Gy, range 0.12-6.3). Results: More than 90% of women received radiation therapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses ≥5 Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, P{sub trend}=.047) compared with nonirradiated women. A highly significant radiation dose–response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (P{sub trend}=.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (P{sub trend}=.23). Conclusions: Our findings show for the first time a significant linear dose–response relationship for risk of stomach cancer in long-term survivors of cervical cancer.

  10. Cardiovascular risk factors in children after repeat doses of antenatal glucocorticoids: an RCT.

    Science.gov (United States)

    McKinlay, Christopher J D; Cutfield, Wayne S; Battin, Malcolm R; Dalziel, Stuart R; Crowther, Caroline A; Harding, Jane E

    2015-02-01

    Treatment of women at risk for preterm birth with repeat doses of glucocorticoids reduces neonatal morbidity but could have adverse long-term effects on cardiometabolic health in offspring. We assessed whether exposure to repeat antenatal betamethasone increased risk factors for later cardiometabolic disease in children whose mothers participated in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids. Women were randomized to betamethasone or placebo treatment, ≥ 7 days after an initial course of glucocorticoids, repeated each week that they remained at risk for preterm birth at children were assessed at 6 to 8 years' corrected age for body composition, insulin sensitivity, ambulatory blood pressure, and renal function. Of 320 eligible childhood survivors, 258 were studied (81%; 123 repeat betamethasone group; 135 placebo [single course] group). Children exposed to repeat antenatal betamethasone and those exposed to placebo had similar total fat mass (geometric mean ratio 0.98, 95% confidence interval [CI] 0.78 to 1.23), minimal model insulin sensitivity (geometric mean ratio 0.89, 95% CI 0.74 to 1.08), 24-hour ambulatory blood pressure (mean difference systolic 0 mm Hg, 95% CI -2 to 2; diastolic 0 mm Hg, 95% CI -1 to 1), and estimated glomerular filtration rate (mean difference 1.2 mL/min/1.73 m(2), 95% CI -3.2 to 5.6). Exposure to repeat doses of antenatal betamethasone compared with a single course of glucocorticoids does not increase risk factors for cardiometabolic disease at early school age. Copyright © 2015 by the American Academy of Pediatrics.

  11. "The Dose Makes the Poison": Informing Consumers About the Scientific Risk Assessment of Food Additives.

    Science.gov (United States)

    Bearth, Angela; Cousin, Marie-Eve; Siegrist, Michael

    2016-01-01

    Intensive risk assessment is required before the approval of food additives. During this process, based on the toxicological principle of "the dose makes the poison,ˮ maximum usage doses are assessed. However, most consumers are not aware of these efforts to ensure the safety of food additives and are therefore sceptical, even though food additives bring certain benefits to consumers. This study investigated the effect of a short video, which explains the scientific risk assessment and regulation of food additives, on consumers' perceptions and acceptance of food additives. The primary goal of this study was to inform consumers and enable them to construct their own risk-benefit assessment and make informed decisions about food additives. The secondary goal was to investigate whether people have different perceptions of food additives of artificial (i.e., aspartame) or natural origin (i.e., steviolglycoside). To attain these research goals, an online experiment was conducted on 185 Swiss consumers. Participants were randomly assigned to either the experimental group, which was shown a video about the scientific risk assessment of food additives, or the control group, which was shown a video about a topic irrelevant to the study. After watching the video, the respondents knew significantly more, expressed more positive thoughts and feelings, had less risk perception, and more acceptance than prior to watching the video. Thus, it appears that informing consumers about complex food safety topics, such as the scientific risk assessment of food additives, is possible, and using a carefully developed information video is a successful strategy for informing consumers.

  12. Evaluation of risk of nephrotoxicity with high dose, extended-interval colistin administration

    Directory of Open Access Journals (Sweden)

    Arun Dewan

    2014-01-01

    Full Text Available Aim: The aim was to evaluate the risk of nephrotoxicity with high-dose, extended-interval regimen of colistin administration in critical ill patients. Materials and Methods: This prospective study was conducted on patients suffering from sepsis due to Gram-negative infection susceptible only to colistin. The dosing schedule for colistin was 9 million units stat followed by 4.5 million units at 12 hourly interval (adjusted as per body weight and renal functions. The serum creatinine and creatinine clearance were estimated at the start of therapy and daily during therapy. Results: Thirty-one patients suffering ventilator associated pneumonia (61.29%, blood stream infections (29.03% and urinary tract infections (9.67% due to Gram-negative multiple drug resistance organisms were assessed. Most commonly isolated organism were Acinetobacter baumannii (54.83%, Klebsiella pneumonia (16.12% and Pseudomonas (29.03%. Five patients (16.12% developed acute kidney injury within 4-5 days of start of therapy and returned to baseline after 6 days with no patient requiring renal replacement therapy or discontinuation of colistin. Conclusion: Our study showed that high-dose, extended-interval colistin can be given to critically ill patients without any significant risk of nephrotoxicity.

  13. Organ doses, effective doses, and risk indices in adult CT: Comparison of four types of reference phantoms across different examination protocols

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Yakun; Li Xiang; Paul Segars, W.; Samei, Ehsan [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 and Carl E. Ravin Advanced Imaging Laboratories, Duke University, Durham, North Carolina 27705 (United States); Carl E. Ravin Advanced Imaging Laboratories, Duke University, Durham, North Carolina 27705 and Department of Radiology, Duke University, Durham, North Carolina 27705 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Carl E. Ravin Advanced Imaging Laboratories, Duke University, Durham, North Carolina 27705 (United States) and Department of Radiology, Duke University, Durham, North Carolina 27705 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Carl E. Ravin Advanced Imaging Laboratories, Duke University, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University, Durham, North Carolina 27705 (United States) and Departments of Physics, Biomedical Engineering, and Electrical and Computer Engineering, Duke University, Durham, North Carolina 27705 (United States)

    2012-06-15

    Purpose: Radiation exposure from computed tomography (CT) to the public has increased the concern among radiation protection professionals. Being able to accurately assess the radiation dose patients receive during CT procedures is a crucial step in the management of CT dose. Currently, various computational anthropomorphic phantoms are used to assess radiation dose by different research groups. It is desirable to better understand how the dose results are affected by different choices of phantoms. In this study, the authors assessed the uncertainties in CT dose and risk estimation associated with different types of computational phantoms for a selected group of representative CT protocols. Methods: Routinely used CT examinations were categorized into ten body and three neurological examination categories. Organ doses, effective doses, risk indices, and conversion coefficients to effective dose and risk index (k and q factors, respectively) were estimated for these examinations for a clinical CT system (LightSpeed VCT, GE Healthcare). Four methods were used, each employing a different type of reference phantoms. The first and second methods employed a Monte Carlo program previously developed and validated in our laboratory. In the first method, the reference male and female extended cardiac-torso (XCAT) phantoms were used, which were initially created from the Visible Human data and later adjusted to match organ masses defined in ICRP publication 89. In the second method, the reference male and female phantoms described in ICRP publication 110 were used, which were initially developed from tomographic data of two patients and later modified to match ICRP 89 organ masses. The third method employed a commercial dosimetry spreadsheet (ImPACT group, London, England) with its own hermaphrodite stylized phantom. In the fourth method, another widely used dosimetry spreadsheet (CT-Expo, Medizinische Hochschule, Hannover, Germany) was employed together with its associated

  14. Evaluation of excess life time cancer risk from gamma dose rates in Jhelum valley

    Directory of Open Access Journals (Sweden)

    Muhammad Rafique

    2014-01-01

    Full Text Available Human beings are continuously exposed to the radiations coming from outside and inside their bodies. Outside and inside radiations are coming from ground, building materials, food, air, the universe and even elements within human own bodies. According to UNSCEAR 2000 report, background radiations deliver an average effective dose of 2.4 mSv per person worldwide. Sustained exposure from high background radiation levels may pose substantial health threats to general public. In the current study we are presenting the results of ambient outdoor gamma dose rates measured for Jhelum valley of the state of Azad Kashmir. This study has been carried out by using Ludlum micrometer-19 which is an active and portable detector. Effects of different parameters of interest on the measured values of gamma dose rates have been investigated. For the region under investigation, minimum and maximum indoor gamma dose rates were found as 610 ± 4.05 μGy·y−1 and 1372 ± 2.7 μGy·y−1, respectively, whilst minimum and maximum outdoor gamma dose rates were found as 495 ± 4.49 μGy·y−1 and 1296 ± 2.78 μGy·y−1, respectively. Overall arithmetic mean (A.M and geometric mean (G.M values of gamma dose rates for indoor and outdoor measurements were found as 940 ± 3.26 μGy·y−1, 892 ± 3.35 μGy·y−1 and 928 ± 3.28 μGy·y−1, 880 ± 3.37 μGy·y−1 respectively. Excess life time cancer risk (ELCR for indoor exposure ranges from 1.057 × 10−3 to 2.377 × 10−3 with an average value of 1.629 × 10−3. For outdoor exposure, ELCR varies from 0.352 × 10−3 to 0.792 × 10−3 with mean value of 0.543 × 10−3. Average values of indoor gamma doses were found to be greater than the world population-weighted average for indoor gamma dose rates (780 μGy·y−1 or 89 nGy h−1.

  15. Information about radiation dose and risks in connection with radiological examinations: what patients would like to know.

    Science.gov (United States)

    Ukkola, Leila; Oikarinen, Heljä; Henner, Anja; Honkanen, Hilkka; Haapea, Marianne; Tervonen, Osmo

    2016-02-01

    To find out patients' wishes for the content and sources of the information concerning radiological procedures. A questionnaire providing quantitative and qualitative data was prepared. It comprised general information, dose and risks of radiation, and source of information. Two tables demonstrating different options to indicate the dose or risks were also provided. Patients could give one or many votes. Altogether, 147 patients (18-85 years) were interviewed after different radiological examinations using these devices. 95% (139/147) of the patients wished for dose and risk information. Symbols (78/182 votes) and verbal scale (56/182) were preferred to reveal the dose, while verbal (83/164) and numerical scale (55/164) on the risk of fatal cancer were preferred to indicate the risks. Wishes concerning the course, options and purpose of the examination were also expressed. Prescriber (3.9 on a scale 1-5), information letter (3.8) and radiographer (3.3) were the preferred sources. Patients aged 66-85 years were reluctant to choose electronic channels. Apart from general information, patients wish for dose and risk information in connection with radiological examinations. The majority preferred symbols to indicate dose and verbal scales to indicate risks, and the preferred source of information was the prescriber or information letter. • 95% of patients expect information on the dose and risks of radiation. • Symbols and verbal scale are preferred to indicate the dose. • Verbal and numerical scales are preferred to indicate fatal cancer risk. • Patients expect information on course, options and purpose of examination. • Prescriber, information letter and radiographer are popular sources of the overall information.

  16. Information about radiation dose and risks in connection with radiological examinations: what patients would like to know

    Energy Technology Data Exchange (ETDEWEB)

    Ukkola, Leila; Oikarinen, Heljae; Haapea, Marianne; Tervonen, Osmo [Oulu University Hospital, Department of Diagnostic Radiology, POB 50, Oulu (Finland); Henner, Anja; Honkanen, Hilkka [Oulu University of Applied Sciences, Oulu (Finland)

    2016-02-15

    To find out patients' wishes for the content and sources of the information concerning radiological procedures. A questionnaire providing quantitative and qualitative data was prepared. It comprised general information, dose and risks of radiation, and source of information. Two tables demonstrating different options to indicate the dose or risks were also provided. Patients could give one or many votes. Altogether, 147 patients (18-85 years) were interviewed after different radiological examinations using these devices. 95 % (139/147) of the patients wished for dose and risk information. Symbols (78/182 votes) and verbal scale (56/182) were preferred to reveal the dose, while verbal (83/164) and numerical scale (55/164) on the risk of fatal cancer were preferred to indicate the risks. Wishes concerning the course, options and purpose of the examination were also expressed. Prescriber (3.9 on a scale 1-5), information letter (3.8) and radiographer (3.3) were the preferred sources. Patients aged 66-85 years were reluctant to choose electronic channels. Apart from general information, patients wish for dose and risk information in connection with radiological examinations. The majority preferred symbols to indicate dose and verbal scales to indicate risks, and the preferred source of information was the prescriber or information letter. (orig.)

  17. Evaluation of testicular dose and associated risk from common pelvis radiation therapy in Iran.

    Science.gov (United States)

    Shanei, Ahmad; Baradaran-Ghahfarokhi, Milad

    2014-12-01

    This study aimed to investigate testicular dose (TD) and the associated risk of heritable disease from common pelvis radiotherapy of male patients in Iran. In this work, the relation between TD and changes in beam energy, pelvis size, source to skin distance (SSD) and beam directions (anterior or posterior) was also evaluated. The values of TDs were measured on 67 randomly selected male patients during common pelvis radiotherapy using 1.17 and 1.33 MeV, Theratron Cobalt-60 unit at SSD of 80 cm and 9 MV, Neptun 10 PC and 18 MV, GE Saturne 20 at SSD of 100 cm at Seyed-Al Shohada Hospital, Isfahan, Iran. Results showed that, the maximum TD was up to 12% of the tumor dose. Considering the risk factor for radiation-induced heritable disorders of 0.1% per Sv, an excess risk of hereditary disorders of 72 per 10,000 births was conservatively calculated. There was a significant difference in the measured TD using different treatment machines and energies (P pelvis size (r = 0.275, P < 0.001). Using the student's t-tests, it was found that, there was not a significant difference between TD and beam direction (P = 0.231). Iranian male patients undergoing pelvic radiotherapy have the potential of receiving a TD of more than 1 Gy which might result in temporary azoospermia. The risk for induction of hereditary disorders in future generations should be considered as low but not negligible in comparison with the correspondent nominal risk.

  18. Parity and risk of colorectal cancer: a dose-response meta-analysis of prospective studies.

    Directory of Open Access Journals (Sweden)

    Hong-Bo Guan

    Full Text Available BACKGROUND: Association between parity and colorectal cancer (CRC risk has been investigated by several epidemiological studies but results are controversial, yet a comprehensive and quantitative assessment of this association has not been reported so far. METHODS: Relevant published studies of parity and CRC were identified using MEDLINE, EMBASE and Web of Science databases through end of April 2013. Two authors independently assessed eligibility and extracted data. Eleven prospective studies reported relative risk (RR estimates and 95% confidence intervals (CIs of CRC risk associated with parity. We pooled the RR from individual studies using fixed- or random-effects models and carried out heterogeneity and publication bias analyses. RESULTS: The summary RR for the ever parity vs. nulliparous was 0.95 (95% CI: 0.88-1.02, with no heterogeneity (Q = 9.04, P = 0.443, I (2 = 0.5%. Likewise, no significant association was yielded for the highest vs. lowest parity number (RR = 1.02, 95% CI: 0.89-1.17, with moderate heterogeneity (Q = 17.48, P = 0.094, I (2 = 37.1%. Dose-response analysis still indicated no effect of parity on CRC risk and the summary RR of per one livebirth was 0.99 (95% CI: 0.96-1.02, with moderate of heterogeneity (Q = 16.50, P<0.021, I (2 = 57.6%. Similar results were observed among all the subgroup analyses. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. CONCLUSION: Results of this dose-response meta-analysis of prospective studies found that there was little evidence of an association between parity and CRC risk.

  19. Coffee consumption and risk of fractures: a systematic review and dose-response meta-analysis.

    Science.gov (United States)

    Lee, Dong Ryul; Lee, Jungun; Rota, Matteo; Lee, Juneyoung; Ahn, Hyeong Sik; Park, Sang Min; Shin, Doosup

    2014-06-01

    The data on the association between coffee consumption and the risk of fractures are inconclusive. We performed a comprehensive literature review and meta-analysis to better quantify this association. We identified all potentially relevant articles by searching MEDLINE, EMBASE, Cochrane Library, Web of Science, SCOPUS, and CINAHL (until February 2013). The keywords "coffee," "caffeine," "drink," and "beverage" were used as the exposure factors, and the keyword "fracture" was used as the outcome factor. We determined the overall relative risk (RR) and confidence interval (CI) for the highest and lowest levels of coffee consumption. A dose-response analysis was performed to assess the risk of fractures based on the level of coffee consumption. We included 253,514 participants with 12,939 fracture cases from 9 cohort and 6 case-control studies. The estimated RR of fractures at the highest level of coffee consumption was 1.14 (95% CI: 1.05-1.24; I(2)=0.0%) in women and 0.76 (95% CI: 0.62-0.94; I(2)=7.3%) in men. In the dose-response analysis, the pooled RRs of fractures in women who consumed 2 and 8 cups of coffee per day were 1.02 (95% CI: 1.01-1.04) and 1.54 (95% CI: 1.19-1.99), respectively. Our meta-analysis suggests that daily consumption of coffee is associated with an increased risk of fractures in women and a contrasting decreased risk in men. However, future well-designed studies should be performed to confirm these findings. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Risks of circulatory diseases among Mayak PA workers with radiation doses estimated using the improved Mayak Worker Dosimetry System 2008

    Energy Technology Data Exchange (ETDEWEB)

    Moseeva, Maria B.; Azizova, Tamara V.; Grigoryeva, Evgenia S. [Southern Urals Biophysics Institute (SUBI), Ozyorsk, Chelyabinsk Region (Russian Federation); Haylock, Richard [Public Health of England, London (United Kingdom)

    2014-05-15

    The new Mayak Worker Dosimetry System 2008 (MWDS-2008) was published in 2013 and supersedes the Doses-2005 dosimetry system for Mayak Production Association (PA) workers. It provides revised external and internal dose estimates based on the updated occupational history data. Using MWDS-2008, a cohort of 18,856 workers first employed at one of the main Mayak PA plants during 1948-1972 and followed up to 2005 was identified. Incidence and mortality risks from ischemic heart disease (IHD) (International Classification of Diseases (ICD)-9 codes 410-414) and from cerebrovascular diseases (CVD) (ICD-9 codes 430-438) were examined in this cohort and compared with previously published risk estimates in the same cohort based on the Doses-2005 dosimetry system. Significant associations were observed between doses from external gamma-rays and IHD and CVD incidence and also between internal doses from alpha-radiation and IHD mortality and CVD incidence. The estimates of excess relative risk (ERR)/Gy were consistent with those estimates from the previous studies based on Doses-2005 system apart from the relationship between CVD incidence and internal liver dose where the ERR/Gy based on MWDS-2008 was just over three times higher than the corresponding estimate based on Doses-2005 system. Adjustment for smoking status did not show any effect on the estimates of risk from internal alpha-particle exposure. (orig.)

  1. Bayesian Analysis for Food-Safety Risk Assessment: Evaluation of Dose-Response Functions within WinBUGS

    OpenAIRE

    Williams, Michael S.; Ebel, Eric D.; Jennifer A Hoeting

    2011-01-01

    Bayesian methods are becoming increasingly popular in the field of food-safety risk assessment. Risk assessment models often require the integration of a dose-response function over the distribution of all possible doses of a pathogen ingested with a specific food. This requires the evaluation of an integral for every sample for a Markov chain Monte Carlo analysis of a model. While many statistical software packages have functions that allow for the evaluation of the integral, this functional...

  2. Dose-response modeling for the environmental risk assessment in cases of technogenic soil contamination

    Directory of Open Access Journals (Sweden)

    Shitikov Vladimir Kirilloviсh

    2015-09-01

    Full Text Available The review of regression models for the approximation of dependences "dose- response" was performed based on ecotoxicological results. The advantages and deficiencies of different models as well as the problems arising both in modeling and subsequent interpreting results are discussed for the purpose of ecological rationing and estimation of negative influence risk. Search procedures of best dependences based on statistical criteria and the methods of uncertainty estimation of calculated parameters are shown. Construction of models is illustrated in detail using the analysis of toxicity results of soil samples received from uranium mines tailings in Kadzhi-Say province (Kyrgyzstan. Threshold values of activity for U-238 and Ra-226 radionuclides providing the minimum probability of ecological risk were determined.

  3. Study of dose and relative risk of occupationally exposed individuals in interventional procedures; Estudo de dose e risco relativo de individuos ocupacionalmente expostos em procedimentos intervencionistas

    Energy Technology Data Exchange (ETDEWEB)

    Silveira Filho, Jose A.M.; Reis, Charlene O.; Taniguti, Lana T.; Pacifico, Leonardo C.; SaintYves, Thalis L.A.; Mecca, Fernando A., E-mail: ze_augustomsf@hotmail.com [Instituto Nacional do Cancer (INCA), Rio de Janeiro, RJ (Brazil). Setor de Fisica Medica

    2012-12-15

    This paper estimates the occupational effective dose and the relative risk of leukemia and cancers of the digestive tract mortality through dose study of the most radiosensitive anatomical regions (lens, thyroid, chest and gonads) of the professionals involved in interventional gonad procedures. It was considered a cumulative exposure time of 10,000 hours, which is the occupational exposure time of an IOE in throughout his professional life. It was also considered that they always use Personal Protective Equipment (PPE). Mathematical models derived from epidemiological data contained in the BEIR V and in the IAEA’s TECDOC 870 are used to estimate the relative risk. The results show a significant increase in mortality risk for these types of cancer for individuals occupationally exposed to three different distances from the x-ray beam, and reinforces that radiation protection measures are essential. (author)

  4. Coffee and tea consumption and risk of lung cancer: a dose-response analysis of observational studies.

    Science.gov (United States)

    Wang, Yaopeng; Yu, Xuyi; Wu, Yili; Zhang, Dongfeng

    2012-11-01

    Results from the recent meta-analysis suggested a favorable effect of green tea consumption and risk of lung cancer, while no significant association was found between black tea consumption and risk of lung cancer. Besides, a significantly positive association was found between coffee consumption and risk of lung cancer. However, the relationship of green tea and coffee consumption is unclear. Thus the dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Results suggested that a linear dose-response relationship exists between coffee consumption and risk of lung cancer, while the dose-response relationship is nonlinear between green tea consumption and risk of lung cancer.

  5. Doses and risks from uranium are not increased significantly by interactions with natural background photon radiation.

    Science.gov (United States)

    Tanner, R J; Eakins, J S; Jansen, J T M; Harrison, J D

    2012-08-01

    The impact of depleted uranium (DU) on human health has been the subject of much conjecture. Both the chemical and radiological aspects of its behaviour in the human body have previously been investigated in detail, with the radiological impact being assumed to be linked to the alpha decay of uranium. More recently, it has been proposed that the accumulation in tissue of high-Z materials, such as DU, may give rise to enhanced local energy deposition in the presence of natural background photon radiation due to the high photoelectric interaction cross sections of high-Z atoms. It is speculated that, in addition to producing short-range photoelectrons, these events will be followed by intense Auger and Coster-Kronig electron emission, thereby causing levels of cell damage that are unaccounted for in conventional models of radiological risk. In this study, the physical and biological bases of these claims are investigated. The potential magnitudes of any effect are evaluated and discussed, and compared with the risks from other radiological or chemical hazards. Monte Carlo calculations are performed to estimate likely energy depositions due to the presence of uranium in human tissues in photon fields: whole body doses, organ doses in anthropomorphic phantoms and nano-/micro-dosimetric scenarios are each considered. The proposal is shown generally to be based on sound physics, but overall the impact on human health is expected to be negligible.

  6. Optimal use of β-blockers in high-risk hypertension: A guide to dosing equivalence

    Directory of Open Access Journals (Sweden)

    Janet B McGill

    2010-05-01

    Full Text Available Janet B McGillDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri, USAAbstract: Hypertension is the number one diagnosis made by primary care physicians, placing them in a unique position to prescribe the antihypertensive agent best suited to the individual patient. In individuals with diabetes mellitus, blood pressure (BP levels > 130/80 mmHg confer an even higher risk for cardiovascular and renal disease, and these patients will benefit from aggressive antihypertensive treatment using a combination of agents. β‑blockers are playing an increasingly important role in the management of hypertension in high-risk patients. β‑blockers are a heterogeneous class of agents, and this review presents the differences between β‑blockers and provides evidence-based protocols to assist in understanding dose equivalence in the selection of an optimal regimen in patients with complex needs. The clinical benefits provided by β‑blockers are only effective if patients adhere to medication treatment long term. β‑blockers with proven efficacy, once-daily dosing, and lower side effect profiles may become instrumental in the treatment of hypertensive diabetic and nondiabetic patients.Keywords: antihypertensive, blood pressure, atenolol, carvedilol, labetalol, metoprolol, nebivolol

  7. Risk and preventive factors of low-dose aspirin-induced gastroduodenal injuries: a comprehensive review.

    Science.gov (United States)

    Shiotani, Akiko; Manabe, Noriaki; Kamada, Tomoari; Fujimura, Yoshinori; Sakakibara, Takashi; Haruma, Ken

    2012-04-01

    The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1β (IL-1β)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1β and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA.

  8. Statins intake and risk of liver cancer: A dose-response meta analysis of prospective cohort studies.

    Science.gov (United States)

    Yi, Changhong; Song, Zhenggui; Wan, Maolin; Chen, Ya; Cheng, Xiang

    2017-07-01

    Previous studies have indicated that statins intake was associated with liver cancer risk, but presented controversial results.Studies in PubMed and EMBASE were searched update to February 2017 to identify and quantify the potential dose-response association between statins intake and liver cancer.Six eligible studies involving a total of 11,8961 participants with 9530 incident cases were included in this meta-analysis. Statistically significant association was observed between increasing statins intake and liver cancer risk reduction (OR = 0.46, 95%CI: 0.24-0.68, P risk of liver cancer for an increase of 50 cumulative defined daily dose per year was 0.86 (95%CI: 0.81-0.90, P risk was found (P for nonlinearity risk of liver cancer risk reduction in Asia (OR = 0.44, 95%CI: 0.11-0.77, P risk reduction.

  9. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium at the EMS 2009 Annual Meeting - September 2006

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.; von Borstel, Robert C.; Brenner,; Redpath, J. Leslie; Erickson, Barbra E.; Brooks,

    2009-11-12

    The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigenetic mechanisms and early nutrition and bystander effects.

  10. TU-C-18A-01: Models of Risk From Low-Dose Radiation Exposures: What Does the Evidence Say?

    Energy Technology Data Exchange (ETDEWEB)

    Bushberg, J [UC Davis Medical Center, Sacramento, CA (United States); Boreham, D [McMaster University, Ontario, CA (Canada); Ulsh, B

    2014-06-15

    At dose levels of (approximately) 500 mSv or more, increased cancer incidence and mortality have been clearly demonstrated. However, at the low doses of radiation used in medical imaging, the relationship between dose and cancer risk is not well established. As such, assumptions about the shape of the dose-response curve are made. These assumptions, or risk models, are used to estimate potential long term effects. Common models include 1) the linear non-threshold (LNT) model, 2) threshold models with either a linear or curvilinear dose response above the threshold, and 3) a hormetic model, where the risk is initially decreased below background levels before increasing. The choice of model used when making radiation risk or protection calculations and decisions can have significant implications on public policy and health care decisions. However, the ongoing debate about which risk model best describes the dose-response relationship at low doses of radiation makes informed decision making difficult. This symposium will review the two fundamental approaches to determining the risk associated with low doses of ionizing radiation, namely radiation epidemiology and radiation biology. The strengths and limitations of each approach will be reviewed, the results of recent studies presented, and the appropriateness of different risk models for various real world scenarios discussed. Examples of well-designed and poorly-designed studies will be provided to assist medical physicists in 1) critically evaluating publications in the field and 2) communicating accurate information to medical professionals, patients, and members of the general public. Equipped with the best information that radiation epidemiology and radiation biology can currently provide, and an understanding of the limitations of such information, individuals and organizations will be able to make more informed decisions regarding questions such as 1) how much shielding to install at medical facilities, 2) at

  11. Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in non–small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pedicini, Piernicola, E-mail: ppiern@libero.it [Service of Medical Physics, I.R.C.C.S. Regional Cancer Hospital C.R.O.B, Rionero in Vulture (Italy); Strigari, Lidia [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Benassi, Marcello [Service of Medical Physics, Scientific Institute of Tumours of Romagna I.R.S.T., Meldola (Italy); Caivano, Rocchina [Service of Medical Physics, I.R.C.C.S. Regional Cancer Hospital C.R.O.B, Rionero in Vulture (Italy); Fiorentino, Alba [U.O. of Radiotherapy, I.R.C.C.S. Regional Cancer Hospital C.R.O.B., Rionero in Vulture (Italy); Nappi, Antonio [U.O. of Nuclear Medicine, I.R.C.C.S. Regional Cancer Hospital C.R.O.B., Rionero in Vulture (Italy); Salvatore, Marco [U.O. of Nuclear Medicine, I.R.C.C.S. SDN Foundation, Naples (Italy); Storto, Giovanni [U.O. of Nuclear Medicine, I.R.C.C.S. Regional Cancer Hospital C.R.O.B., Rionero in Vulture (Italy)

    2014-04-01

    To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.

  12. SU-E-I-54: Effective Dose and Radiation Cancer Risks for Scoliosis Patients Undergoing Full Spine Radiography

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Y [Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, 259, Wen-Hwa 1st Road., Kwei-Shan, Taoyuan 333, Taiwan (China); Hwang, Y [Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan (China); Tsai, H [Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, 259, Wen-Hwa 1st Road., Kwei-Shan, Taoyuan 333, Taiwan (China); Medical Physics Research Center, Institute for Radiological Research, Chang Gung University / Chang Gung Memorial Hospital, Linkou, Taoyuan 33302, Taiwan (China); Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan (China)

    2015-06-15

    Purpose: Scoliotic patients underwent a lot of radiologic examinations during the control and treatment periods. This study used the PCXMC program to calculate the effective dose of the patients and assess the radiation cancer risks. Methods: Seventy five scoliotic patients were examined using CR or DR systems during the control and treatment periods in Chang Gung Memorial Hospital. The technical factors were recorded for each patient during his/her control and treatment period. The entrance surface dose was measured using thermoluminence dosimeters and derived from technical factors and irradiated geometry. The effective dose of patients and relative radiation cancer risks were calculated by the PCXMC program. All required information regarding patient age and sex, the x-ray spectra, and the tube voltage and current were registered. The radiation risk were estimated using the model developed by the BEIR VII committee (2006). Results: The effective doses of full spine radiography with anteroposterior and lateral projections were 0.626 mSv for patients using DR systems, and 0.483mSv for patients using CR systems, respectively. The dose using DR system was 29.6% higher than those using CR system. The maximum organ dose was observed in the breast for both projections in all the systems. The risk of exposure—induced cancer death (REID) of patients for DR and CR systems were 0.009% and 0.007%, respectively. Conclusion: The risk estimates were regarded with healthy skepticism, placed more emphasis on the magnitude of the risk. The effective doses estimated in this study could be served as a reference for radiologists and technologists and demonstrate the necessity to optimize patient protection for full spine radiography though the effective doses are not at the level to induce deterministic effects and not significant in the stochastic effect. This study was supported by the grants from the Chang Gung Memorial Hospital (CMRPD1D0421)

  13. Parity and pancreatic cancer risk: a dose-response meta-analysis of epidemiologic studies.

    Directory of Open Access Journals (Sweden)

    Hong-Bo Guan

    Full Text Available BACKGROUND: Previous epidemiologic studies have reported inconsistent results between parity and pancreatic cancer (PC risk. To our knowledge, a comprehensive and quantitative assessment of this association has not been conducted. METHODS: Relevant published studies of parity and PC were identified using MEDLINE (PubMed and Web of Science databases until November 2013. Two authors (H-BG and LW independently assessed eligibility and extracted data. Eleven prospective and 11 case-control studies reported relative risk (RR estimates and 95% confidence intervals (CIs of PC associated with parity. Fixed- and random-effects models were used to estimate the summary RR depending on the heterogeneity of effects. RESULTS: The summary RR for PC comparing the highest versus lowest parity was 0.86 (95% CI: 0.73-1.02; Q = 50.49, P<0.001, I2 = 58.4%. Significant inverse associations were also observed in the studies that adjusted for cigarette smoking (RR = 0.81; 95% CI: 0.68-0.98, Type 2 diabetes mellitus (RR = 0.83; 95% CI: 0.75-0.93, and those that included all confounders or important risk factors (RR = 0.85; 95% CI: 0.76-0.96. Additionally, in the dose-response analysis, the summary RR for per one live birth was 0.97 (95% CI: 0.94-1.01; Q = 62.83, P<0.001, I2 = 69.8%, which also indicated a borderline statistically significant inverse effect of parity on PC risk. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. CONCLUSION: In summary, these findings suggest that higher parity is associated with a decreased risk of PC. Future large consortia or pooled studies are warranted to fully adjust for potential confounders to confirm this association.

  14. Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model.

    Science.gov (United States)

    Lange, Sandra; Steder, Anne; Glass, Änne; Killian, Doreen; Wittmann, Susanne; Machka, Christoph; Werner, Juliane; Schäfer, Stephanie; Roolf, Catrin; Junghanss, Christian

    2016-04-01

    The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P low TNC cell count (P = .044) were identified as significant independent risk factors for graft rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of

  15. Dose - response relationship between noise exposure and the risk of occupational injury

    Directory of Open Access Journals (Sweden)

    Jin-Ha Yoon

    2015-01-01

    Full Text Available Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers′ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively. Workplace dust exposure was classified as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals derived from a logistic regression model were 1.68 (1.27-2.24 and 3.42 (2.26-5.17 at 80-89 dB and ≥90 dB versus <80 dB. These associations remained significant when in a separate analysis according to high or low dust exposure level. Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.

  16. Dose - response relationship between noise exposure and the risk of occupational injury.

    Science.gov (United States)

    Yoon, Jin-Ha; Hong, Jeong-Suk; Roh, Jaehoon; Kim, Chi-Nyon; Won, Jong-Uk

    2015-01-01

    Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers' Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively). Workplace dust exposure was classified as noise exposure as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals) derived from a logistic regression model were 1.68 (1.27-2.24) and 3.42 (2.26-5.17) at 80-89 dB and ≥ 90 dB versus Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.

  17. Estimation of population dose and risk to holding assistants from veterinary X-ray examination in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Hashizume, Tadashi; Suganuma, Tunenori; Shida, Takuo (Azabu Univ., Kanagawa (Japan). School of Veterinary Medicine)

    1989-09-01

    For the estimation of the population doses and risks of stochastic effects to assistants who hold animals during veterinary X-ray examination, a random survey of hospitals and clinics was carried out concerning age distribution of such assistants by groups of facilities. The average organ and tissue dose per examination was evaluated from the experimental data using mean technical factors such as X-ray tube voltage, tube current and field size based on the results of a nationwide survey. The population doses to the assistants were calculated to be about 14 nSv per person per year for the genetically significant dose, 3.5 nSv per person per year for per caput mean marrow dose, 3.3 nSv for the leukemia significant dose and 4.5 nSv for the malignant significant dose, respectively. The total risk of stochastic effects to the Japanese population from holding assistants was estimated using population data and it was estimated to be less than one person per year, but the cancer risks to a number of the assistants were estimated to be more than 4 x 10{sup -5}. (author).

  18. Household physical activity and cancer risk: a systematic review and dose-response meta-analysis of epidemiological studies

    OpenAIRE

    Yun Shi; Tingting Li; Ying Wang; Lingling Zhou; Qin Qin; Jieyun Yin; Sheng Wei; Li Liu; Shaofa Nie

    2015-01-01

    Controversial results of the association between household physical activity and cancer risk were reported among previous epidemiological studies. We conducted a meta-analysis to investigate the relationship of household physical activity and cancer risk quantitatively, especially in dose-response manner. PubMed, Embase, Web of science and the Cochrane Library were searched for cohort or case-control studies that examined the association between household physical activity and cancer risks. R...

  19. Systematic review on physician's knowledge about radiation doses and radiation risks of computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Krille, Lucian, E-mail: lucian.krille@unimedizin-mainz.d [Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg - University Mainz, Obere Zahlbacher Str. 69, 55131 Mainz (Germany); Hammer, Gael P.; Merzenich, Hiltrud [Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg - University Mainz, Obere Zahlbacher Str. 69, 55131 Mainz (Germany); Zeeb, Hajo [Bremen Institute for Prevention Research and Social Medicine (BIPS), Department of Prevention and Evaluation, Linzer Strasse 10, D-28359 Bremen (Germany)

    2010-10-15

    Background: The frequent use of computed tomography is a major cause of the increasing medical radiation exposure of the general population. Consequently, dose reduction and radiation protection is a topic of scientific and public concern. Aim: We evaluated the available literature on physicians' knowledge regarding radiation dosages and risks due to computed tomography. Methods: A systematic review in accordance with the Cochrane and PRISMA statements was performed using eight databases. 3091 references were found. Only primary studies assessing physicians' knowledge about computed tomography were included. Results: 14 relevant articles were identified, all focussing on dose estimations for CT. Overall, the surveys showed moderate to low knowledge among physicians concerning radiation doses and the involved health risks. However, the surveys varied considerably in conduct and quality. For some countries, more than one survey was available. There was no general trend in knowledge in any country except a slight improvement of knowledge on health risks and radiation doses in two consecutive local German surveys. Conclusions: Knowledge gaps concerning radiation doses and associated health risks among physicians are evident from published research. However, knowledge on radiation doses cannot be interpreted as reliable indicator for good medical practice.

  20. Whole-body CT for lymphoma staging: Feasibility of halving radiation dose and risk by iterative image reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, M., E-mail: mathias.meyer@medma.uni-heidelberg.de [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Klein, S.A., E-mail: stefan.klein@umm.de [Department of Hematology and Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Brix, G., E-mail: gbrix@bfs.de [Department of Medical and Occupational Radiation Protection, Federal Office for Radiation Protection, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany); Fink, C., E-mail: Christian.Fink@medma.uni-heidelberg.de [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Pilz, L., E-mail: lothar.pilz@medma.uni-heidelberg.de [Department of Biostatistics, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Jafarov, H., E-mail: Hashim.Jafarov@umm.de [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Hofmann, W.K., E-mail: w.k.hofmann@umm.de [Department of Hematology and Oncology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Schoenberg, S.O., E-mail: Stefan.Schoenberg@umm.de [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); and others

    2014-02-15

    Objectives: Patients with lymphoma are at higher-risk of secondary malignancies mainly due to effects of cancer therapy as well as frequent radiological surveillance. We thus aimed to investigate the objective and subjective image quality as well as radiation exposure and risk of full-dose standard (FDS), full-dose iterative (FDI), and half-dose iterative (HDI) image reconstruction in patients with lymphoma. Material and methods: In 100 lymphoma patients, contrast-enhanced whole-body staging was performed on a dual-source CT. To acquire full-dose and half-dose CT data simultaneously, the total current-time product was equally distributed on both tubes operating at 120 kV. HDI reconstructions were calculated by using only data from one tube. Quantitative image quality was assessed by measuring image noise in different tissues of the neck, thorax, and abdomen. Overall diagnostic image quality was assessed using a 5-point Likert scale. Radiation doses and risks were estimated for a male and female reference person. Results: For all anatomical regions apart from the lungs image noise was significantly lower and the overall subjective image quality significantly better when using FDI and HDI instead of FDS reconstruction (p < 0.05). For the half-dose protocol, the risk to develop a radiation-induced cancer was estimated to be less than 0.11/0.19% for an adult male/female. Conclusions: Image quality of FDI and more importantly of HDI is superior to FDS reconstruction, thus enabling to halve radiation dose and risk to lymphoma patients.

  1. Stray radiation dose and second cancer risk for a pediatric patient receiving craniospinal irradiation with proton beams

    Science.gov (United States)

    Taddei, Phillip J.; Mirkovic, Dragan; Fontenot, Jonas D.; Giebeler, Annelise; Zheng, Yuanshui; Kornguth, David; Mohan, Radhe; Newhauser, Wayne D.

    2009-04-01

    Proton beam radiotherapy unavoidably exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic cancer. The aims of this study were to calculate doses to major organs and tissues and to estimate second cancer risk from stray radiation following craniospinal irradiation (CSI) with proton therapy. This was accomplished using detailed Monte Carlo simulations of a passive-scattering proton treatment unit and a voxelized phantom to represent the patient. Equivalent doses, effective dose and corresponding risk for developing a fatal second cancer were calculated for a 10-year-old boy who received proton therapy. The proton treatment comprised CSI at 30.6 Gy plus a boost of 23.4 Gy to the clinical target volume. The predicted effective dose from stray radiation was 418 mSv, of which 344 mSv was from neutrons originating outside the patient; the remaining 74 mSv was caused by neutrons originating within the patient. This effective dose corresponds to an attributable lifetime risk of a fatal second cancer of 3.4%. The equivalent doses that predominated the effective dose from stray radiation were in the lungs, stomach and colon. These results establish a baseline estimate of the stray radiation dose and corresponding risk for a pediatric patient undergoing proton CSI and support the suitability of passively-scattered proton beams for the treatment of central nervous system tumors in pediatric patients.

  2. Stray radiation dose and second cancer risk for a pediatric patient receiving craniospinal irradiation with proton beams

    Energy Technology Data Exchange (ETDEWEB)

    Taddei, Phillip J; Mirkovic, Dragan; Fontenot, Jonas D; Giebeler, Annelise; Zheng, Yuanshui; Kornguth, David; Mohan, Radhe; Newhauser, Wayne D [University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Unit 94, Houston, TX 77030 (United States)], E-mail: wnewhaus@mdanderson.org

    2009-04-21

    Proton beam radiotherapy unavoidably exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic cancer. The aims of this study were to calculate doses to major organs and tissues and to estimate second cancer risk from stray radiation following craniospinal irradiation (CSI) with proton therapy. This was accomplished using detailed Monte Carlo simulations of a passive-scattering proton treatment unit and a voxelized phantom to represent the patient. Equivalent doses, effective dose and corresponding risk for developing a fatal second cancer were calculated for a 10-year-old boy who received proton therapy. The proton treatment comprised CSI at 30.6 Gy plus a boost of 23.4 Gy to the clinical target volume. The predicted effective dose from stray radiation was 418 mSv, of which 344 mSv was from neutrons originating outside the patient; the remaining 74 mSv was caused by neutrons originating within the patient. This effective dose corresponds to an attributable lifetime risk of a fatal second cancer of 3.4%. The equivalent doses that predominated the effective dose from stray radiation were in the lungs, stomach and colon. These results establish a baseline estimate of the stray radiation dose and corresponding risk for a pediatric patient undergoing proton CSI and support the suitability of passively-scattered proton beams for the treatment of central nervous system tumors in pediatric patients.

  3. Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers.

    Science.gov (United States)

    Negovan, Anca; Iancu, Mihaela; Moldovan, Valeriu; Voidazan, Septimiu; Bataga, Simona; Pantea, Monica; Sarkany, Kinga; Tatar, Cristina; Mocan, Simona; Banescu, Claudia

    2016-01-01

    Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75-325 mg/day). Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (control group). In univariate analysis, factors significantly associated with ulcers were male gender (p = 0.001), anticoagulants (p = 0.029), nonsteroidal anti-inflammatory drugs (p = 0.013), heart failure (p = 0.007), liver (p = 0.011) or cerebrovascular disease (p = 0.004), diabetes mellitus (p = 0.043), ulcer history (p = 0.044), and alcohol consumption (p = 0.018), but not Helicobacter pylori infection (p = 0.2). According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06-8.86), cotreatment with NSAIDs (OR 8, 95% CI 2.09-30.58) or anticoagulants (OR 4.85, 95% CI 1.33-17.68), male gender (OR 5.2, 95% CI 1.77-15.34), and stroke (OR 7.27, 95% CI 1.40-37.74) remained predictors for ulcer on endoscopy. Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease), and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence of H. pylori infection.

  4. Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers

    Directory of Open Access Journals (Sweden)

    Anca Negovan

    2016-01-01

    Full Text Available Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75–325 mg/day. Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group and 108 patients with no mucosal lesions (control group. In univariate analysis, factors significantly associated with ulcers were male gender (p=0.001, anticoagulants (p=0.029, nonsteroidal anti-inflammatory drugs (p=0.013, heart failure (p=0.007, liver (p=0.011 or cerebrovascular disease (p=0.004, diabetes mellitus (p=0.043, ulcer history (p=0.044, and alcohol consumption (p=0.018, but not Helicobacter pylori infection (p=0.2. According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06–8.86, cotreatment with NSAIDs (OR 8, 95% CI 2.09–30.58 or anticoagulants (OR 4.85, 95% CI 1.33–17.68, male gender (OR 5.2, 95% CI 1.77–15.34, and stroke (OR 7.27, 95% CI 1.40–37.74 remained predictors for ulcer on endoscopy. Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease, and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence of H. pylori infection.

  5. Dose evaluation and risk estimation for secondary cancer in contralateral breast and a study of correlation between thorax shape and dose to organs at risk following tangentially breast irradiation during deep inspiration breath-hold and free breathing.

    Science.gov (United States)

    Johansen, Safora; Vikström, Johan; Hjelstuen, Mari Helene Blihovde; Mjaaland, Ingvil; Dybvik, Kjell Ivar; Olsen, Dag Rune

    2011-05-01

    To assess the impact of using breathing adapted radiotherapy on contralateral breast (CB) dose, to relate the thorax shape with the dose to the organs at risk (OARs) and to predict the risk for induced malignancies in CB using linear and non-linear models, following tangential irradiation of breast. Sixteen patients with stage I-II breast cancer treatment planned with tangential fields using deep inspiration breath hold (DIBH) and free breathing (FB) techniques were included in this analysis. The dose results mainly based on DVH analysis were compared. Four parameters were defined to describe thoracic shape. Excess relative risk (ERR) for cancer induction in CB, employing linear and non-linear models was calculated. Average CB volumes exposed to a dose of 1 Gy is 1.3 times higher in DIBH plans than in FB plans. No significant difference in average V3Gy and V5Gy for DIBH and FB plans is observed. The average mean CB dose for DIBH and FB plans is 0.33 and 0.28 Gy, respectively. No correlation between thorax shape parameters and mean OARs dose is observed. The estimated average mean ERR with linear model is lower in FB plans (0.12) than for the DIBH plans (0.14). The estimated ERR with non-linear model is 0.14 for DIBH plans and 0.15 for FB plans. No significant difference in CB dose between DIBH and FB plans is observed. The four thorax shape parameters defined in this study can not be related to the dose at OARs using DIBH and FB radiation techniques. The ERR estimates for secondary CB cancer are nearly the same for FB and DIBH planning when using a linear and non-linear risk prediction models.

  6. Radon Sources and Associated Risk in terms of Exposure and Dose

    Directory of Open Access Journals (Sweden)

    Efstratios Gregory Vogiannis

    2015-01-01

    Full Text Available Radon concern the international scientific community from early 20th century. Initially as radium emanation, almost the second half of the century as severe harmful to human health. Initial brilliant period of use as medicine, followed by a period of intense concern for its health effects. Primary target groups surveyed were miners early in Europe later in U.S. There is now compelling evidence that radon and its progeny can cause lung cancer. Human activities may create or modify pathways increasing indoor radon concentration compared to outdoor background. These pathways can be controlled by preventive and corrective actions. Indoor Radon and its short-lived progeny attached on aerosol particles or free compose an air mixture that carry a significant energy amount (PAEC. Exposure on PAEC and dose delivered reviewed in detail. Special attention was paid to the case of water workers because lack of adequate data. Radon risk assessment and current legislation regulates dose from radon and its progeny, also were reviewed.

  7. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort.

    Directory of Open Access Journals (Sweden)

    Alan T Clarke

    Full Text Available Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment.The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions.Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4-2.6]. High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2-12.7] for HDA, 1.4 [0.9-2.0] for LDA and 1.5 [1.0-2.2] for HDS.The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small.

  8. Out-of-field organ doses and associated radiogenic risks from para-aortic radiotherapy for testicular seminoma

    Energy Technology Data Exchange (ETDEWEB)

    Mazonakis, Michalis, E-mail: mazonak@med.uoc.gr; Berris, Theocharis; Damilakis, John [Department of Medical Physics, Faculty of Medicine, University of Crete, P. O. Box 2208, 71003 Iraklion, Crete (Greece); Varveris, Charalambos; Lyraraki, Efrossyni [Department of Radiotherapy and Oncology, University Hospital of Iraklion, 71110 Iraklion, Crete (Greece)

    2014-05-15

    Purpose: The aims of this study were to (a) calculate the radiation dose to out-of-field organs from radiotherapy for stage I testicular seminoma and (b) estimate the associated radiogenic risks. Methods: Monte Carlo methodology was employed to model radiation therapy with typical anteroposterior and posteroanterior para-aortic fields on an anthropomorphic phantom simulating an average adult. The radiation dose received by all main and remaining organs that defined by the ICRP publication 103 and excluded from the treatment volume was calculated. The effect of field dimensions on each organ dose was determined. Additional therapy simulations were generated by introducing shielding blocks to protect the kidneys from primary radiation. The gonadal dose was employed to assess the risk of heritable effects for irradiated male patients of reproductive potential. The lifetime attributable risks (LAR) of radiotherapy-induced cancer were estimated using gender- and organ-specific risk coefficients for patient ages of 20, 30, 40, and 50 years old. The risk values were compared with the respective nominal risks. Results: Para-aortic irradiation to 20 Gy resulted in out-of-field organ doses of 5.0–538.6 mGy. Blocked field treatment led to a dose change up to 28%. The mean organ dose variation by increasing or decreasing the applied field dimensions was 18.7% ± 3.9% and 20.8% ± 4.5%, respectively. The out-of-field photon doses increased the lifetime intrinsic risk of developing thyroid, lung, bladder, prostate, and esophageal cancer by (0.1–1.4)%, (0.4–1.1)%, (2.5–5.4)%, (0.2–0.4)%, and (6.4–9.2)%, respectively, depending upon the patient age at exposure and the field size employed. A low risk for heritable effects of less than 0.029% was found compared with the natural incidence of these defects. Conclusions: Testicular cancer survivors are subjected to an increased risk for the induction of bladder and esophageal cancer following para-aortic radiotherapy. The

  9. Dose-Response Relation Between Work Hours and Cardiovascular Disease Risk: Findings From the Panel Study of Income Dynamics.

    Science.gov (United States)

    Conway, Sadie H; Pompeii, Lisa A; Roberts, Robert E; Follis, Jack L; Gimeno, David

    2016-03-01

    The aim of this study was to examine the presence of a dose-response relationship between work hours and incident cardiovascular disease (CVD) in a representative sample of U.S. workers. A retrospective cohort study of 1926 individuals from the Panel Study of Income Dynamics (1986 to 2011) employed for at least 10 years. Restricted cubic spline regression was used to estimate the dose-response relationship of work hours with CVD. A dose-response relationship was observed in which an average workweek of 46 hours or more for at least 10 years was associated with an increased risk of CVD. Compared with working 45 hours per week, working an additional 10 hours per week or more for at least 10 years increased CVD risk by at least 16%. Working more than 45 work hours per week for at least 10 years may be an independent risk factor for CVD.

  10. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes

    Science.gov (United States)

    Garcia-Manero, G; Gore, S D; Kambhampati, S; Scott, B; Tefferi, A; Cogle, C R; Edenfield, W J; Hetzer, J; Kumar, K; Laille, E; Shi, T; MacBeth, K J; Skikne, B

    2016-01-01

    CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31–87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2–24) for the 14-day dosing schedule and 6 (1–24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS. PMID:26442612

  11. Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

    Energy Technology Data Exchange (ETDEWEB)

    Hattangadi, Jona A. [Harvard Radiation Oncology Program, Boston, MA (United States); Rombi, Barbara [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Provincial Agency for Proton Therapy, Trento (Italy); Yock, Torunn I.; Broussard, George [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Friedmann, Alison M.; Huang, Mary [Department of Pediatric Hematology-Oncology, Massachusetts General Hospital, Boston, MA (United States); Chen, Yen-Lin E.; Lu, Hsiao-Ming; Kooy, Hanne [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); MacDonald, Shannon M., E-mail: smacdonald@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

    2012-07-01

    Purpose: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. Methods and Materials: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. Results: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. Conclusions: Preliminary outcomes reveal excellent local control with proton therapy

  12. Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

    Directory of Open Access Journals (Sweden)

    Charles H King

    2011-09-01

    Full Text Available Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni-$211 (S. haematobium per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are

  13. Hippocampal dose from stereotactic radiosurgery for 4 to 10 brain metastases: Risk factors, feasibility of dose reduction via re-optimization, and patient outcomes.

    Science.gov (United States)

    Birer, Samuel R; Olson, Adam C; Adamson, Justus; Hood, Rodney; Susen, Matthew; Kim, Grace; Salama, Joseph K; Kirkpatrick, John P

    2017-07-28

    This study aimed to report hippocampal dose from single-fraction stereotactic radiosurgery (SRS) for 4 to 10 brain metastases and determine feasibility of hippocampal-sparing SRS. Patients with 4 to 10 brain metastases receiving single-isocenter, multi-target single-fraction SRS were identified. Hippocampi were contoured using the Radiation Therapy Oncology Group (RTOG) 0933 atlas. RTOG 0933 dose constraints were converted to a biologically effective dose using an alpha/beta of 2 (D100 421 cGy, Dmax 665 cGy). Number of metastases, total target volume, prescribed dose, and distance of nearest metastasis (dmin) were analyzed as risk factors for exceeding hippocampal constraints. If hippocampi exceeded constraints, the SRS plan was re-optimized. Key dosimetric parameters were compared between original and re-optimized plans. To determine if a single target can exceed constraints, all targets but the closest metastasis were removed from the plan, and dosimetry was compared. Forty plans were identified. Fifteen hippocampi (19%) exceeded constraints in 12 SRS plans. Hippocampal sparing was achieved in 10 of 12 replanned cases (83%). Risk factors associated with exceeding hippocampal constraints were decreasing dmin (24.0 vs 8.0 mm, p = 0.002; odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04 to 1.26) and total target volume (5.46 cm(3)vs 1.98 cm(3), p = 0.03; OR 1.14, 95% CI 1.00 to 1.32). There was no difference in exceeding constraints for 4 to 5 vs 6 to 10 metastases (27% vs 21%, p = 0.409) or prescribed dose (18 Gy, p = 0.58). For re-optimized plans, there were no significant differences in planning target volume (PTV) coverage (99.6% vs 99.0%, p = 0.17) or conformality index (1.47 vs 1.4, p = 0.78). Six (50%) plans exceeded constraints with a single target. A substantial minority of hippocampi receive high radiation dose from SRS for 4 to 10 brain metastases. Decreasing distance of the closest metastasis and total target volume

  14. Body mass index and risk of renal cell cancer: a dose-response meta-analysis of published cohort studies.

    Science.gov (United States)

    Wang, Furan; Xu, Yinghua

    2014-10-01

    Obesity is accepted as one of the major risk factors for renal cell cancer (RCC). However, conflicting results persist for the pooled risks based on the results from case-control and cohort studies combined, and the exact shape of the dose-response relationship has not been clearly defined yet. To help elucidate the role of obesity, PubMed and Embase databases were searched for published cohort studies on associations between body mass index (BMI) and risk of RCC. Random-effects models and dose-response meta-analyses were used to pool study results. Subgroup analyses were conducted by the available characteristics of studies and participants. Cohort studies (21) with 15,144 cases and 9,080,052 participants were identified. Compared to normal weight, the pooled relative risks and the corresponding 95% confidence intervals of RCC were 1.28(1.24-1.33) for preobesity and 1.77(1.68-1.87) for obesity, respectively. A nonlinear dose-response relationship was also found for RCC risk with BMI (p = 0.000), and the risk increased by 4% for each 1 kg/m(2) increment in BMI. There was no significant between-study heterogeneity among studies (I(2) = 35.6% for preobesity and I(2) = 44.2% for obesity, respectively). Subgroup analysis showed a basically consistent result with the overall analysis. These results suggest that increased BMI are associated with increased risk of RCC both for men and women. © 2014 UICC.

  15. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium Annual Meeting of the Environmental Mutagen Society: Agenda and Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Veigl, Martina L. [Environmental Mutagen Society (EMS), Reston, VA (United States); Case Western Reserve Univ., Cleveland, OH (United States). Case Comprehensive Cancer Center; Morgan, William F. [Univ. of Maryland, College Park, MD (United States); Schwartz, Jeffrey L. [Univ. of Washington, Seattle, WA (United States)

    2009-11-11

    The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigenetic mechanisms and early nutrition and bystander effects. This report shows the agenda and abstracts for this symposium.

  16. Radiation dose and subsequent risk for stomach cancer in long-term survivors of cervical cancer

    DEFF Research Database (Denmark)

    Kleinerman, Ruth A; Smith, Susan A; Holowaty, Eric

    2013-01-01

    To assess the dose-response relationship for stomach cancer after radiation therapy for cervical cancer.......To assess the dose-response relationship for stomach cancer after radiation therapy for cervical cancer....

  17. Reference computations of public dose and cancer risk from airborne releases of plutonium. Nuclear safety technical report

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, V.L.

    1993-12-23

    This report presents results of computations of doses and the associated health risks of postulated accidental atmospheric releases from the Rocky Flats Plant (RFP) of one gram of weapons-grade plutonium in a form that is respirable. These computations are intended to be reference computations that can be used to evaluate a variety of accident scenarios by scaling the dose and health risk results presented here according to the amount of plutonium postulated to be released, instead of repeating the computations for each scenario. The MACCS2 code has been used as the basis of these computations. The basis and capabilities of MACCS2 are summarized, the parameters used in the evaluations are discussed, and results are presented for the doses and health risks to the public, both the Maximum Offsite Individual (a maximally exposed individual at or beyond the plant boundaries) and the population within 50 miles of RFP. A number of different weather scenarios are evaluated, including constant weather conditions and observed weather for 1990, 1991, and 1992. The isotopic mix of weapons-grade plutonium will change as it ages, the {sup 241}Pu decaying into {sup 241}Am. The {sup 241}Am reaches a peak concentration after about 72 years. The doses to the bone surface, liver, and whole body will increase slightly but the dose to the lungs will decrease slightly. The overall cancer risk will show almost no change over this period. This change in cancer risk is much smaller than the year-to-year variations in cancer risk due to weather. Finally, x/Q values are also presented for other applications, such as for hazardous chemical releases. These include the x/Q values for the MOI, for a collocated worker at 100 meters downwind of an accident site, and the x/Q value integrated over the population out to 50 miles.

  18. Is Androgen Deprivation Therapy Necessary in All Intermediate-Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

    Energy Technology Data Exchange (ETDEWEB)

    Castle, Katherine O., E-mail: kocastle@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hoffman, Karen E.; Levy, Lawrence B.; Lee, Andrew K.; Choi, Seungtaek; Nguyen, Quynh N.; Frank, Steven J.; Pugh, Thomas J.; McGuire, Sean E.; Kuban, Deborah A. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-01

    Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease

  19. The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation.

    Science.gov (United States)

    Brooks, Antone L; Hoel, David G; Preston, R Julian

    2016-08-01

    This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2-30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP ( 2007 ) and BEIR VII (NRC/NAS 2006 ).

  20. SU-D-9A-07: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, L [West China Hospital, Sichuan University, Chengdu, Sichuan (China); Bai, S [West China Hospital, Sichuan University, Chengdu, Sichuan Province (China); Zhang, Y [Beijing Cancer Hospital, Beijing, Beijing (China); Ming, X [TianJin University, Tianjin (China); Zhang, Y [Tianjin University, Tianjin, Tianjin (China); Deng, J [Yale New Haven Hospital, New Haven, CT (United States)

    2014-06-01

    Purpose: To systematically evaluate the imaging doses and cancer risks associated with various imaging procedures involving ionizing radiation during image-guided radiotherapy of an increasingly large number of cancer patients. Methods: 141 patients (52 brain cases, 47 thoracic cases, 42 abdominal cases, aged 3 to 91 years old) treated between October 2009 and March 2010 were included in this IRB-approved retrospective study. During the whole radiotherapy course, each patient underwent at least one type of imaging procedures, i.e., kV portal, MV portal and kVCBCT, besides CT simulations. Based on Monte Carlo modeling and particle transport in human anatomy of various dimensions, the correlations between the radiation doses to the various organs-at-risk (OARs) at the head, the thoracic and the abdominal regions and one's weight, circumference, scan mAs and kVp have been obtained and used to estimate the radiation dose from a specific imaging procedure. The radiation-induced excess relative risk (ERR) was then estimated with BEIR VII formulism based on one's gender, age and radiation dose. 1+ ERR was reported in this study as relative cancer risk. Results: For the whole cohort of 141 patients, the mean imaging doses from various imaging procedures were 8.3 cGy to the brain, 10.5 cGy to the lungs and 19.2 cGy to the red bone marrow, respectively. Accordingly, the cancer risks were 1.140, 1.369 and 2.671, respectively. In comparison, MV portal deposited largest doses to the lungs while kVCBCT delivered the highest doses to the red bone marrow. Conclusion: The compiled imaging doses to a patient during his/her treatment course were patient-specific and site-dependent, varying from 1.2 to 263.5 cGy on average, which were clinically significant and should be included in the treatment planning and overall decision-making. Our results indicated the necessity of personalized imaging to maximize its clinical benefits while reducing the associated cancer risks

  1. Evaluation of Enoxaparin Dosing as a Risk Factor for Bleeding in Lung Transplant Recipients.

    Science.gov (United States)

    Sofjan, Amelia K; Iuppa, Jennifer A; Bain, K Bennett; Deal, Eli N; Witt, Chad A; Hachem, Ramsey R; Yusen, Roger D

    2016-10-01

    Lung transplant recipients commonly develop complications that lead to anticoagulation. Standard FDA-approved enoxaparin dosing in this population results in a high incidence of above-goal anti-Xa levels, but its association with bleeding remains unclear. To evaluate the association between enoxaparin dosing and bleeding in lung transplant recipients and assess the relationship between dosing and anti-Xa levels. We conducted a single-center retrospective cohort study of adult lung transplant recipients who received therapeutic enoxaparin between 2000 and 2012 at a tertiary academic center. We dichotomized enoxaparin dosing regimens into standard dose (FDA-approved doses with a 10% rounding margin) and reduced dose. Clinicians ordered anti-Xa levels as deemed clinically appropriate. The primary outcome was major bleeding or clinically relevant nonmajor bleeding. Of 222 patients treated with enoxaparin, 33 (14.9%) had bleeding events, of which half (17/33) were major. Bleeding occurred in 25/146 (17.1%) patients who received standard-dose enoxaparin versus 8/76 (10.5%) patients who received reduced-dose enoxaparin (P = 0.190). Multiple logistic regression demonstrated an independent association between standard-dose enoxaparin and bleeding, after adjusting for confounders (adjusted odds ratio = 3.04; 95% CI = 1.14-8.10). The median enoxaparin dose in patients with above-goal versus at-goal anti-Xa levels was 0.89 versus 0.76 mg/kg every 12 hours; P = 0.006. However, doses yielding at-goal anti-Xa levels had an interquartile range of 0.67 to 0.90 mg/kg, which overlapped with doses yielding above- and below-goal anti-Xa levels. Enoxaparin dose reduction and anti-Xa level monitoring can improve drug safety and facilitate individualized dose optimization in lung transplant recipients. © The Author(s) 2016.

  2. Dose-response relations between occupational exposures to physical and psychosocial factors and the risk of low back pain.

    NARCIS (Netherlands)

    H. Morgenstern; A. Burdorf (Alex); J.P. Jansen (Jeroen)

    2004-01-01

    textabstractAIMS: To assess dose-response relations between occupational exposures to physical and psychosocial factors and the risk of low back pain. METHODS: A cohort of 523 subjects, working in nursing homes and homes for the elderly, was followed prospectively for one year. Phy

  3. Avoiding Pitfalls in the Use of the Benchmark Dose Approach to Chemical Risk Assessments; Some Illustrative Case Studies (Presentation)

    Science.gov (United States)

    The USEPA's benchmark dose software (BMDS) version 1.2 has been available over the Internet since April, 2000 (epa.gov/ncea/bmds.htm), and has already been used in risk assessments of some significant environmental pollutants (e.g., diesel exhaust, dichloropropene, hexachlorocycl...

  4. Benchmark Dose Analysis from Multiple Datasets: The Cumulative Risk Assessment for the N-Methyl Carbamate Pesticides

    Science.gov (United States)

    The US EPA’s N-Methyl Carbamate (NMC) Cumulative Risk assessment was based on the effect on acetylcholine esterase (AChE) activity of exposure to 10 NMC pesticides through dietary, drinking water, and residential exposures, assuming the effects of joint exposure to NMCs is dose-...

  5. Individualized 3D Reconstruction of Normal Tissue Dose for Patients With Long-term Follow-up: A Step Toward Understanding Dose Risk for Late Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Angela [Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario (Canada); Brock, Kristy K.; Sharpe, Michael B. [Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Moseley, Joanne L. [Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario (Canada); Craig, Tim [Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Hodgson, David C., E-mail: David.Hodgson@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

    2012-11-15

    to organs at risk can be estimated accurately many years after exposure by using limited 2D data. Compared to contemporary involved-field treatments, normal tissue doses were significantly higher in historical mantle-field treatments. These methods build capacity to quantify the relationship between 3D normal tissue dose and observed late effects.

  6. SU-E-J-10: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, L [Yale University, New Haven, CT (United States); Bai, S [Sichuan University, Chengdu, Sichuan (China); Zhang, Y [Key laboratory of Carcinogenesis and Translational Research, Ministry of Ed, Beijing, Beijing (China); Deng, J [Yale University, New Haven, CT (United States)

    2015-06-15

    Purpose: To systematically evaluate imaging doses and cancer risks to organs-at-risk as a Result of cumulative doses from various radiological imaging procedures in image-guided radiotherapy (IGRT) in a large cohort of cancer patients. Methods: With IRB approval, imaging procedures (computed tomography, kilo-voltage portal imaging, megavoltage portal imaging and kilo-voltage cone-beam computed tomography) of 4832 cancer patients treated during 4.5 years were collected with their gender, age and circumference. Correlations between patient’s circumference and Monte Carlo simulated-organ dose were applied to estimate organ doses while the cancer risks were reported as 1+ERR using BEIR VII models. Results: 80 cGy or more doses were deposited to brain, lungs and RBM in 273 patients (maximum 136, 278 and 267 cGy, respectively), due largely to repetitive imaging procedures and non-personalized imaging settings. Regardless of gender, relative cancer risk estimates for brain, lungs, and RBM were 3.4 (n = 55), 2.6 (n = 49), 1.8 (n = 25) for age group of 0–19; 1.2 (n = 87), 1.4 (n = 98), 1.3 (n = 51) for age group of 20–39; 1.0 (n = 457), 1.1 (n = 880), 1.8 (n=360) for age group of 40–59; 1.0 (n = 646), 1.1 (n = 1400), 2.3 (n = 716) for age group of 60–79 and 1.0 (n = 108),1.1 (n = 305),1.6 (n = 147) for age group of 80–99. Conclusion: The cumulative imaging doses and associated cancer risks from multi-imaging procedures were patient-specific and site-dependent, with up to 2.7 Gy imaging dose deposited to critical structures in some pediatric patients. The associated cancer risks in brain and lungs for children of age 0 to 19 were 2–3 times larger than those for adults. This study indicated a pressing need for personalized imaging protocol to maximize its clinical benefits while reducing associated cancer risks. Sichuan University Scholarship.

  7. Estimated cardiovascular relative risk reduction from fixed-dose combination pill (polypill) treatment in a wide range of patients with a moderate risk of cardiovascular disease

    NARCIS (Netherlands)

    Lafeber, Melvin; Webster, Ruth; Visseren, Frank L J; Bots, Michiel L.; Grobbee, Diederick E.; Spiering, W.; Rodgers, Anthony

    2016-01-01

    Aims Recent data indicate that fixed-dose combination (FDC) pills, polypills, can produce sizeable risk factor reductions. There are very few published data on the consistency of the effects of a polypill in different patient populations. It is unclear for example whether the effects of the polypill

  8. What physicians think about the need for informed consent for communicating the risk of cancer from low-dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Karsli, Tijen [Children' s Healthcare of Atlanta, Atlanta, GA (United States); University of Tennessee, Pediatric Intensive Care, Memphis, TN (United States); Kalra, Mannudeep K. [Children' s Healthcare of Atlanta, Department of Radiology, Atlanta, GA (United States); Massachusetts General Hospital, Department of Radiology, Boston, MA (United States); Self, Julie L.; Rosenfeld, Jason Anders; Butler, Susan [Emory University, Department of Behavioral Sciences and Health Education, Atlanta, GA (United States); Simoneaux, Stephen [Children' s Healthcare of Atlanta, Department of Radiology, Atlanta, GA (United States)

    2009-09-15

    The National Institute of Environmental Health Sciences, a subsidiary of the Food and Drug Administration, has declared that X-ray radiation at low doses is a human carcinogen. The purpose of our study was to determine if informed consent should be obtained for communicating the risk of radiation-induced cancer from radiation-based imaging. Institutional review board approval was obtained for the prospective survey of 456 physicians affiliated with three tertiary hospitals by means of a written questionnaire. Physicians were asked to state their subspecialty, number of years in practice, frequency of referral for CT scanning, level of awareness about the risk of radiation-induced cancer associated with CT, knowledge of whether such information is provided to patients undergoing CT, and opinions about the need for obtaining informed consent as well as who should provide information about the radiation-induced cancer risk to patients. Physicians were also asked to specify their preference among different formats of informed consent for communicating the potential risk of radiation-induced cancer. Statistical analyses were performed using the chi-squared test. Most physicians stated that informed consent should be obtained from patients undergoing radiation-based imaging (71.3%, 325/456) and the radiology department should provide information about the risk of radiation-induced cancer to these patients (54.6%, 249/456). The informed consent format that most physicians agreed with included modifications to the National Institute of Environmental Health Services report on cancer risk from low-dose radiation (20.2%, 92/456) or included information on the risk of cancer from background radiation compared to that from low-dose radiation (39.5%, 180/456). Most physicians do not know if patients are informed about cancer risk from radiation-based imaging in their institutions. However, they believe that informed consent for communicating the risk of radiation-induced cancer

  9. The risk of low doses of ionising radiation and the linear no threshold relationship debate; La controverse sur les effets des faibles doses de rayonnements ionisants et la relation lineaire sans seuil

    Energy Technology Data Exchange (ETDEWEB)

    Tubiana, M. [Centre Antoine Beclere, Faculte de Medecine, 75 - Paris (France); Masse, R. [11 rue du Haras, Residence Le Boqueteau, Acacias 2, 91 - Saint-Michel-sur-Orge (France); Vathaire, F. de [Institut Gustave Roussy, INSERM U 605., 94 - Villejuif (France); Averbeck, D. [Institut Curie, Section de Recherche, Lab. Raymond Latarjet, UMR2027 du CNRS, Centre Universitaire d' Orsay, 91 - Orsay (France); Aurengo, A. [Hopital Pitie-Salpetriere, Service Medecine Nucleaire, 75 - Paris (France)

    2007-04-15

    The ICRP and the B.E.I.R. VII reports recommend a linear no threshold (L.N.T.) relationship for the estimation of cancer excess risk induced by ionising radiations (IR), but the 2005 report of Medicine and Science French Academies concludes that it leads to overestimate of risk for low and very low doses. The bases of L.N.T. are challenged by recent biological and animal experimental studies which show that the defence against IR involves the cell microenvironment and the immunologic system. The defence mechanisms against low doses are different and comparatively more effective than for high doses. Cell death is predominant against low doses. DNA repairing is activated against high doses, in order to preserve tissue functions. These mechanisms provide for multicellular organisms an effective and low cost defence system. The differences between low and high doses defence mechanisms are obvious for alpha emitters which show several greys threshold effects. These differences result in an impairment of epidemiological studies which, for statistical power purpose, amalgamate high and low doses exposure data, since it would imply that cancer IR induction and defence mechanisms are similar in both cases. Low IR dose risk estimates should rely on specific epidemiological studies restricted to low dose exposures and taking precisely into account potential confounding factors. The preliminary synthesis of cohort studies for which low dose data (< 100 mSv) were available show no significant risk excess, neither for solid cancer nor for leukemias. (authors)

  10. Radiation-induced noncancer risks in interventional cardiology: optimisation of procedures and staff and patient dose reduction.

    Science.gov (United States)

    Sun, Zhonghua; AbAziz, Aini; Yusof, Ahmad Khairuddin Md

    2013-01-01

    Concerns about ionizing radiation during interventional cardiology have been increased in recent years as a result of rapid growth in interventional procedure volumes and the high radiation doses associated with some procedures. Noncancer radiation risks to cardiologists and medical staff in terms of radiation-induced cataracts and skin injuries for patients appear clear potential consequences of interventional cardiology procedures, while radiation-induced potential risk of developing cardiovascular effects remains less clear. This paper provides an overview of the evidence-based reviews of concerns about noncancer risks of radiation exposure in interventional cardiology. Strategies commonly undertaken to reduce radiation doses to both medical staff and patients during interventional cardiology procedures are discussed; optimisation of interventional cardiology procedures is highlighted.

  11. Radiation-Induced Noncancer Risks in Interventional Cardiology: Optimisation of Procedures and Staff and Patient Dose Reduction

    Science.gov (United States)

    Khairuddin Md Yusof, Ahmad

    2013-01-01

    Concerns about ionizing radiation during interventional cardiology have been increased in recent years as a result of rapid growth in interventional procedure volumes and the high radiation doses associated with some procedures. Noncancer radiation risks to cardiologists and medical staff in terms of radiation-induced cataracts and skin injuries for patients appear clear potential consequences of interventional cardiology procedures, while radiation-induced potential risk of developing cardiovascular effects remains less clear. This paper provides an overview of the evidence-based reviews of concerns about noncancer risks of radiation exposure in interventional cardiology. Strategies commonly undertaken to reduce radiation doses to both medical staff and patients during interventional cardiology procedures are discussed; optimisation of interventional cardiology procedures is highlighted. PMID:24027768

  12. Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease.

    Science.gov (United States)

    Qi, Hui; Li, Shixue

    2014-04-01

    A dose-response meta-analysis was carried out between Parkinson's disease (PD) risk, and coffee, tea and caffeine consumption. A comprehensive search was carried out to identify eligible studies. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline. A total of 13 articles involving 901 764 participants for coffee, eight articles involving 344 895 participants for tea and seven articles involving 492 724 participants for caffeine were included. A non-linear relationship was found between coffee consumption and PD risk overall, and the strength of protection reached the maximum at approximately 3 cups/day (smoking-adjusted relative risk: 0.72, 95% confidence interval 0.65-0.81). A linear relationship was found between tea and caffeine consumption, and PD risk overall, and the smoking-adjusted risk of PD decreased by 26% and 17% for every two cups/day and 200 mg/day increments, respectively. The association of coffee and tea consumption with PD risk was stronger for men than that for women, and the association of caffeine consumption with PD risk was stronger for ever users of hormones than that for never users of hormones among postmenopausal women. The aforementioned associations were weaker for USA relative to Europe or Asia. A linear dose-relationship for decreased PD risk with tea and caffeine consumption was found, whereas the strength of protection reached a maximum at approximately 3 cups/day for coffee consumption overall. Further studies are required to confirm the findings. © 2013 Japan Geriatrics Society.

  13. TU-EF-204-09: A Preliminary Method of Risk-Informed Optimization of Tube Current Modulation for Dose Reduction in CT

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Y; Liu, B; Kalra, M; Caracappa, P [Rensselaer Polytechnic Institute, Troy, NY (United States); Liu, T; Li, X [Massachusetts General Hospital, Boston, MA (United States); Xu, X [Rensselaer Polytechnic Inst., Troy, NY (United States)

    2015-06-15

    Purpose: X-rays from CT scans can increase cancer risk to patients. Lifetime Attributable Risk of Cancer Incidence for adult patients has been investigated and shown to decrease as patient age. However, a new risk model shows an increasing risk trend for several radiosensitive organs for middle age patients. This study investigates the feasibility of a general method for optimizing tube current modulation (TCM) functions to minimize risk by reducing radiation dose to radiosensitive organs of patients. Methods: Organ-based TCM has been investigated in literature for eye lens dose and breast dose. Adopting the concept in organ-based TCM, this study seeks to find an optimized tube current for minimal total risk to breasts and lungs by reducing dose to these organs. The contributions of each CT view to organ dose are determined through simulations of CT scan view-by-view using a GPU-based fast Monte Carlo code, ARCHER. A Linear Programming problem is established for tube current optimization, with Monte Carlo results as weighting factors at each view. A pre-determined dose is used as upper dose boundary, and tube current of each view is optimized to minimize the total risk. Results: An optimized tube current is found to minimize the total risk of lungs and breasts: compared to fixed current, the risk is reduced by 13%, with breast dose reduced by 38% and lung dose reduced by 7%. The average tube current is maintained during optimization to maintain image quality. In addition, dose to other organs in chest region is slightly affected, with relative change in dose smaller than 10%. Conclusion: Optimized tube current plans can be generated to minimize cancer risk to lungs and breasts while maintaining image quality. In the future, various risk models and greater number of projections per rotation will be simulated on phantoms of different gender and age. National Institutes of Health R01EB015478.

  14. A Real World Report on Intravenous High-Dose and Non-High-Dose Proton-Pump Inhibitors Therapy in Patients with Endoscopically Treated High-Risk Peptic Ulcer Bleeding

    Directory of Open Access Journals (Sweden)

    Lung-Sheng Lu

    2012-01-01

    Full Text Available Background and Study Aims. The optimal dose of intravenous proton-pump inhibitor (PPI therapy for the prevention of peptic ulcer (PU rebleeding remains controversial. This study aimed to understand the real world experiences in prescribing high-dose PPI and non-high-dose PPI for preventing rebleeding after endoscopic treatment of high-risk PU. Patients and Methods. A total of 220 subjects who received high-dose and non-high-dose pantoprazole for confirmed acute PU bleeding that were successfully treated endoscopically were enrolled. They were divided into rebleeding (n=177 and non-rebleeding groups (n=43. Randomized matching of the treatment-control group was performed. Patients were randomly selected for non-high-dose and high-dose PPI groups (n=44 in each group. Results. Univariate analysis showed, significant variables related to rebleeding were female, higher creatinine levels, and higher Rockall scores (≧6. Before case-control matching, the high-dose PPI group had higher creatinine level, higher percentage of shock at presentation, and higher Rockall scores. After randomized treatment-control matching, no statistical differences were observed for rebleeding rates between the high-dose and non-high-dose groups after case-control matching. Conclusion. This study suggests that intravenous high-dose pantoprazole may not be superior to non-high-dose regimen in reducing rebleeding in high-risk peptic ulcer bleeding after successful endoscopic therapy.

  15. Radiology Residents' Awareness about Ionizing Radiation Doses in Imaging Studies and Their Cancer Risk during Radiological Examinations

    Energy Technology Data Exchange (ETDEWEB)

    Goekce, Senem Divrik [I. Ikad Community Health Center, Health Directorate, Samsun (Turkmenistan); Gekce, Erkan [Samsun Maternity and Women' s Disease and Pediatrics Hospital, Samsun (Turkmenistan); Coskun, Melek [Faculty of Medicine, Ondokuz May' s University, Samsun (Turkmenistan)

    2012-03-15

    Imaging methods that use ionizing radiation have been more frequent in various medical fields with advances in imaging technology. The aim of our study was to make residents be aware of the radiation dose they are subjected to when they conduct radiological imaging methods, and of cancer risk. A total of 364 residents participated in this descriptive study which was conducted during the period between October, 2008 and January, 2009. The questionnaires were completed under strict control on a one-to-one basis from each department. A X{sup 2}-test was used for the evaluation of data obtained. Only 7% of residents correctly answered to the question about the ionizing radiation dose of a posteroanterior (PA) chest X-ray. The question asking about the equivalent number of PA chest X-rays to the ionizing dose of a brain CT was answered correctly by 24% of residents; the same question regarding abdominal CT was answered correctly by 16% of residents, thorax CT by 16%, thyroid scintigraphy by 15%, intravenous pyelography by 9%, and lumbar spine radiography by 2%. The risk of developing a cancer throughout lifetime by a brain and abdominal CT were 33% and 28%, respectively. Radiologic residents should have updated knowledge about radiation dose content and attendant cancer risks of various radiological imaging methods during both basic medical training period and following practice period.

  16. A snapshot of patients' awareness of radiation dose and risks associated with medical imaging examinations at an Australian radiology clinic.

    Science.gov (United States)

    Singh, N; Mohacsy, A; Connell, D A; Schneider, M E

    2017-05-01

    Cumulative radiation exposure is linked to increasing the lifetime attributable risk of cancer. To avoid unnecessary radiation exposure and facilitate shared decision making, patients should be aware of these issues. This paper examines patients' awareness of radiation dose and risks associated with medical imaging examinations. Consecutive patients attending a private radiology clinic over a nine week period in 2014 in Metropolitan Melbourne were surveyed while waiting to undergo an imaging examination. Patients who were under 18 years of age, did not speak English and/or were referred for interventional imaging procedures were excluded from participation. Survey questions addressed patients' awareness of radiation dose associated with various imaging modalities' and patients' experience and preferences regarding communication of information about radiation. Data was analysed using SPSS (Ver 20.1). A total of 242 surveys were completed. Most participants were male (143/239, 59.8%) and aged between 33 and 52 years (109/242, 45%). Over half of participants were not concerned about radiation from medical imaging (130/238, 54.6%). Only a third of participants (80/234, 34.2%) correctly reported that CT has a higher radiation dose than X-ray. Very few participants correctly identified mammography, DEXA, PET and PET/CT as radiation emitting examinations. The majority of participants (202/236, 85.6%) indicated that they were not informed about radiation dose and risks by their referring doctor in advance. This paper provides information relevant to a single private radiology clinic in Australia. Nevertheless, our results have shown that patients presenting for medical imaging have little awareness of radiation dose and risks associated with these examinations and received little information by their referring physicians or staff at the radiology clinic. Copyright © 2016 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

  17. Stereotactic body radiation therapy for low- and low-intermediate risk prostate cancer: Is there a dose effect?

    Directory of Open Access Journals (Sweden)

    Alan Jay Katz

    2011-12-01

    Full Text Available This study examines the efficacy and toxicity of two stereotactic body radiation therapy (SBRT dose regimens for treatment of early prostate cancer. Forty-one patients treated with 35 Gy were matched with 41 patients treated with 36.25 Gy. Both patient groups received SBRT in 5 fractions over 5 consecutive days using the CyberKnife. Each group had 37 low-risk patients and 4 intermediate-risk patients. No statistically significant differences were present for age, prostate volume, PSA, Gleason score, stage, or risk between the groups. The dose was prescribed to the 83-87% isodose line to cover the prostate and a 5-mm margin all around, except 3 mm posteriorly. The overall median follow-up is 51 months (range, 45-58 months with a median 54 months and 48 months follow-up for the 35-Gy and 36.25-Gy dose groups, respectively. One biochemical failure occurred in each group yielding a 97.5% freedom from biochemical failure. The PSA response has been favorable for all patients with a mean PSA of 0.1 ng/ml at 4-years. Overall toxicity has been mild with 5% late grade 2 rectal toxicity in both dose groups. Late grade 1 urinary toxicity was equivalent between groups; grade 2 urinary toxicity was 5% (2/41 patients and 10% (4/41 patients in the 35-Gy and 36.25-Gy dose groups (p = 0.6969, respectively. Overall, the highly favorable PSA response, limited biochemical failures, limited toxicity, and limited impact on quality of life in these low- to low-intermediate-risk patients are supportive of excellent long-term results for CyberKnife delivered SBRT.

  18. Radiation dose and cancer risk in patients undergoing multiple radiographs in intravenous urography X-ray examinations

    Science.gov (United States)

    Suliman, I. I.; Al-Jabri, Amna J.; Badawi, A. A.; Halato, M. A.; Alzimami, K.; Sulieman, A.

    2014-11-01

    The purpose of the this study was to measure the entrance surface air kerma (ESAK) and body organs, and the effective doses in intravenous urography (IVU) X-ray examinations in Sudanese hospitals. Seventy-two patients who underwent IVU multiple radiographs from five hospitals (six rooms) were examined. ESAK was calculated from incident air kerma (Ki) using patient exposure parameters and tube output Y(d). Dose calculations were performed using CALDOSE X 5.1 Monte Carlo-based software. Risk of cancer induction (4-8) and mortality per million (2-4) varied. The gallbladder, colon, stomach, gonads and uterus received organ doses of 5.3, 3.6, 3.2, 0.61, and 0.8 mGy, respectively. ESAK values ranged from 6.6 to 15.3 mGy (effective doses: 0.70-1.6 mSv). Mean ESAK fall slightly above the diagnostic reference level. Several optimization strategies to improve dose performance were discussed. Reducing the number of radiographs and the use of technique charts according to patient sizes and anatomic areas are among the most important dose optimization tools in IVU.

  19. Balancing the benefits and risks of low-dose glucocorticoid in rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Tânia Santiago

    2015-01-01

    Full Text Available Glucocorticoids have potent anti-inflammatory and immunomodulatory effects and are widely use in the management of rheumatoid arthritis in combination with other synthetic and with biological disease-modifying anti-rheumatic drugs. Concerns about the risk of adverse effects of glucocorticoids, especially if they are given at higher dosages and for a longer time, hamper their use despite the clear symptomatic and disease modifying benefits. However, the evidence base for these concerns for low dose glucocorticoid therapy is quite limited due to the scarcity of quality literature on its safety in rheumatoid arthritis. This review discusses the current understanding about their disease-modifying effects, toxicity data from recent trials and observational studies, recommendations for their management and the current efforts to improve the therapeutic ratio of glucocorticoid through the development of new formulations, such as modified-release prednisone. Introduction With over 60 years of experience, the number of patients treated with glucocorticoids (GCs, and the range of clinical applications are more extensive than with any other treatment. GCs represent a true anchor treatment for rheumatoid arthritis (RA. This is supported by data indicating that up to 60% of all patients with RA in Germany are treated with GCs at some time during the course of their disease (1. Similarly, 34 to 93% of all patients entering recent clinical trials of biologics, and thus with active disease, were receiving GCs at baseline (2. Such data are in contrast with the literature predominantly addressing the risks of these agents and the caution advised by every treatment recommendations. Clinicians, and presumably patients, seem thus to value the anti-inflammatory, immunosuppressive and disease-modifying therapeutic effects of GCs. In contrast, both the literature and the medical community seem to be split between those in favour and those against the use of low-dose

  20. Direct oral anticoagulants in real practice: which doses for which patients. Limitations and bleeding risk compared to vitamin K antagonists

    Directory of Open Access Journals (Sweden)

    Giancarlo Landini

    2013-12-01

    Full Text Available The new oral direct anticoagulants (DOACs could represent a new frontier for management of thromboembolic diseases. However, the new drugs have limitations that need to be considered. Despite the fact that their efficacy and safety profile are at least not inferior to comparators, bleeding risk represents the most feared complication, as for all the antithrombotic drugs. Bleeding risk increases with conditions that interfere with pharmacokinetics, in addition to the risk strictly linked to patients or their co-morbidities. Since all DOACs are excreted from kidneys (even though at different percentages according to the different molecules, renal impairment represents one of the leading causes of DOACs accumulation and bleeding risk. Moderate renal failure is the main condition in which dose adjustment of DOACs could be required, while severe renal impairment represents an absolute contraindication for their use. Renal function must, therefore, be carefully monitored before prescription and during assumption. The older population is at higher bleeding risk, and dose adjustment of DOACs could be required. Although to a lesser degree than oral anticoagulant vitamin K antagonists, DOACs can have drug interactions, especially with P-glycoprotein and cytochrome P3A4 inducers or inhibitors, and these interactions must be taken into account in real practice to avoid accumulation or under dosage. The concomitant use of other drugs, especially antithrombotics, may expose the patients to bleeding risk by reducing the hemostatic properties.

  1. Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis.

    Science.gov (United States)

    Bo, Yacong; Lu, Yan; Zhao, Yan; Zhao, Erjiang; Yuan, Ling; Lu, Weiquan; Cui, Lingling; Lu, Quanjun

    2016-04-15

    While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49-0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer.

  2. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind; Nielsen, Lars Hougaard; Skovlund, Charlotte Wessel;

    2011-01-01

    To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.......To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose....

  3. Realistic approach to estimate lens doses and cataract radiation risk in cardiology when personal dosimeters have not been regularly used.

    Science.gov (United States)

    Vañó, Eliseo; Fernández, José M; Sánchez, Roberto M; Dauer, Lawrence T

    2013-10-01

    Interventional fluoroscopic guided cardiac procedures lead to radiation exposure to the lenses of the eyes of cardiologists, which over time may be associated with an increased risk of cataracts. This study derives radiation doses to the lens of the eye in cardiac catheterization laboratories from measurements of individual procedures to allow for estimates of such doses for those cases when personal dosimeters have not been used regularly. Using active electronic dosimeters at the C-arm (at 95 cm from the isocenter), scatter radiation doses have been measured for cardiac procedures and estimated radiation doses to the lenses of the cardiologists for different groups of procedures (diagnostic, PTCAs, and valvular). Correlation factors with kerma area product included in the patient dose reports have been derived. The mean, median, and third quartile scatter dose values per procedure at the C-arm for 1,969 procedures were 0.99, 0.78 and 1.25 mSv, respectively; for coronary angiography, 0.51, 0.45, and 0.61 mSv, respectively; for PTCAs, 1.29, 1.07, and 1.56 mSv; and for valvular procedures, 1.64, 1.45, and 2.66 mSv, respectively. For all the procedures, the ratio between the scatter dose at the C-arm and the kerma area product resulted in between 10.3-11.3 μSv Gy cm. The experimental results of this study allow for realistic estimations of the dose to the lenses of the eyes from the workload of the cardiologists and from the level of use of radiation protection tools when personal dosimeters have not been regularly used.

  4. Low-dose CT screening in an Asian population with diverse risk for lung cancer: A retrospective cohort study

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Chin A. [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Sungkyunkwan University School of Medicine, Department of Radiology, Samsung Medical Center, Seoul (Korea, Republic of); Shin, Myung-Hee; Cho, Yun Yung [Sungkyunkwan University School of Medicine, Department of Social and Preventive Medicine, Seoul (Korea, Republic of); Choi, Yoon-Ho [Sungkyunkwan University School of Medicine, Center for Health Promotion, Seoul (Korea, Republic of); Kwon, O. Jung [Sungkyunkwan University School of Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Shin, Kyung Eun [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Kyung Hee University Hospital, Department of Diagnostic Radiology, Seoul (Korea, Republic of)

    2015-08-15

    To evaluate the performance of low-dose CT (LDCT) screening for lung cancer (LCA) detection in an Asian population with diverse risks for LCA. LCA screening was performed in 12,427 symptomless Asian subjects using either LDCT (5,771) or chest radiography (CXR) (6,656) in a non-trial setting. Subjects were divided into high-risk and non-high-risk groups. Data were collected on the number of patients with screening-detected LCAs and their survival in order to compare outcomes between LDCT and CXR screening with the stratification of risks considering age, sex and smoking status. In the non-high-risk group, a significant difference was observed for the detection of lung cancer (adjusted OR, 5.07; 95 % CI, 2.72-9.45) and survival (adjusted HR of LCA survival between LDCT vs. CXR group, 0.08; 95 % CI, 0.01-0.62). No difference in detection or survival of LCA was noticed in the high-risk group. LCAs in the non-high-risk group were predominantly adenocarcinomas (96 %), and more likely to be part-solid or non-solid compared with those in the high-risk group (p = 0.023). In the non-high-risk group, LDCT helps detect more LCAs and offers better survival than CXR screening, due to better detection of part solid or non-solid lung adenocarcinomas. (orig.)

  5. [Low-dose aspirin in patients with diabete melitus: risks and benefits regarding macro and microvascular complications].

    Science.gov (United States)

    Camargo, Eduardo G; Gross, Jorge Luiz; Weinert, Letícia S; Lavinsky, Joel; Silveiro, Sandra P

    2007-04-01

    Aspirin is recommended as cardiovascular disease prevention in patients with diabetes mellitus. Due to the increased risk of bleeding and because of the hypothesis that there could be a worsening of microvascular complications related to aspirin, there has been observed an important underutilization of the drug. However, it is now known that aspirin is not associated with a deleterious effect on diabetic retinopathy and there is evidence indicating that it also does not affect renal function with usual doses (150 mg/d). On the other hand, higher doses may prove necessary, since recent data suggest that diabetic patients present the so called "aspirin resistance". The mechanisms of this resistance are not yet fully understood, being probably related to an abnormal intrinsic platelet activity. The employment of alternative antiplatelet strategies or the administration of higher aspirin doses (150-300 mg/d) should be better evaluated regarding effective cardiovascular disease prevention in diabetes as well as the possible effects on microvascular complications.

  6. Radioablation of liver malignancies with interstitial high-dose-rate brachytherapy. Complications and risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Mohnike, Konrad; Wolf, Steffen; Damm, Robert; Seidensticker, Max; Seidensticker, Ricarda; Fischbach, Frank; Pech, Maciej; Ricke, Jens [Otto-von-Guericke-Universitaet, Klinik fuer Radiologie und Nuklearmedizin, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany); Peters, Nils; Hass, Peter; Gademann, Guenther [Otto-von-Guericke-Universitaet, Klinik fuer Strahlentherapie, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany)

    2016-05-15

    To evaluate complications and identify risk factors for adverse events in patients undergoing high-dose-rate interstitial brachytherapy (iBT). Data from 192 patients treated in 343 CT- or MRI-guided interventions from 2006-2009 at our institution were analyzed. In 41 %, the largest tumor treated was ≥ 5 cm, 6 % of the patients had tumors ≥ 10 cm. Prior to iBT, 60 % of the patients had chemotherapy, 22 % liver resection, 19 % thermoablation or transarterial chemoembolization (TACE). Safety was the primary endpoint; survival data were obtained as the secondary endpoints. During follow-up, MRI or CT imaging was performed and clinical and laboratory parameters were obtained. The rate of major complications was below 5 %. Five major bleedings (1.5 %) occurred. The frequency of severe bleeding was significantly higher in patients with advanced liver cirrhosis. One patient developed signs of a nonclassic radiation-induced liver disease. In 3 patients, symptomatic gastrointestinal (GI) ulcers were detected. A dose exposure to the GI wall above 14 Gy/ml was a reliable threshold to predict ulcer formation. A combination of C-reactive protein ≥ 165 mg/l and/or leukocyte count ≥ 12.7 Gpt/l on the second day after the intervention predicted infection (sensitivity 90.0 %; specificity 92.8 %.) Two patients (0.6 %) died within 30 days. Median overall survival after the first liver treatment was 20.1 months for all patients and the local recurrence-free surviving proportion was 89 % after 12 months. Image-guided iBT yields a low rate of major complications and is effective. (orig.) [German] Evaluierung der Komplikationsrate und Identifizierung von Risikofaktoren fuer Komplikationen und Nebenwirkungen bei Patienten mit Lebermalignomen, die mit der hochdosierten interstitiellen Brachytherapie (iBT) behandelt wurden. Von 2006 bis 2009 wurden 192 Patienten in 343 CT- oder MRT-gefuehrten Interventionen behandelt und deren Daten ausgewertet. Der groesste behandelte Tumor war in

  7. Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis.

    Science.gov (United States)

    Zhao, R; Wang, H; Wang, X; Feng, F

    2017-03-01

    This meta-analysis synthesized current evidence from 10 trials to evaluate the association between steroid therapy and osteonecrosis incidence in patients with severe acute respiratory syndrome (SARS). Our results suggest that higher cumulative doses and longer treatment durations of steroids are more likely to lead to the development of osteonecrosis in SARS patients. The link between steroid treatment and the risk of osteonecrosis in SARS patients remains unknown. The present meta-analysis aimed to examine the dose-response association between steroid therapy and osteonecrosis incidence in SARS patients. The sex differences in the development of steroid-induced osteonecrosis were also examined. We searched PubMed, Web of Science, CNKI, and WANFANG for studies that involved steroid therapy and reported osteonecrosis data in SARS patients. Two authors independently extracted the data from the individual studies, and the rate ratio (RR) of osteonecrosis was calculated using random-effect models. Ten studies with 1137 recovered SARS patients met the inclusion criteria. Close relationships between osteonecrosis incidence and both the cumulative dose and treatment duration of steroids were observed. The summary RR of osteonecrosis was 1.57 (95% confidence interval (CI) 1.30-1.89, p SARS patients who received higher cumulative doses and longer treatment durations of steroids were more likely to develop osteonecrosis, and there were no sex differences in this dose-dependent side effect. Our findings suggest that it is important to reduce osteonecrosis risk by modifying the cumulative dose and the treatment duration of steroids in SARS patients.

  8. Occupational exposure to radon for underground tourist routes in Poland: Doses to lung and the risk of developing lung cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna Walczak

    2017-10-01

    Full Text Available Objectives: Radon concentrations for 31 Polish underground tourist routes were analyzed. The equivalent dose to the lung, the effective dose and the relative risk were calculated for employees of the analyzed routes on the grounds of information on radon concentrations, work time, etc. Material and Methods: The relative risk for lung cancers was calculated using the Biological Effects of Ionizing Radiation (BEIR VI Committee model. Equivalent doses to the lungs of workers were determined using the coefficients calculated by the Kendall and Smith. The conversion coefficient proposed by the International Atomic Energy Agency (IAEA in the report No. 33 was used for estimating the effective doses. Results: In 13 routes, the effective dose was found to be above 1 mSv/year, and in 3 routes, it exceeded 6 mSv/year. For 5 routes, the equivalent dose to lungs was higher than 100 mSv/year, and in 1 case it was as high as 490 mSv/year. In 22.6% of underground workplaces the risk of developing lung cancer among employees was about 2 times higher than that for the general population, and for 1 tourist route it was about 5 times higher. The geometric mean of the relative risk of lung cancer for all workers of underground tourist routes was 1.73 (95% confidence interval (CI: 1.6–1.87. Routes were divided into: caves, mines, post-military underground constructions and urban underground constructions. Conclusions: The difference between levels of the relative risk of developing lung cancer for all types of underground tourist routes was not found to be significant. If we include the professional group of the employees of underground tourist routes into the group of occupational exposure, the number of persons who are included in the Category A due to occupational exposure may increase by about 3/4. The professional group of the employees of underground tourist routes should be monitored for their exposure to radon. Int J Occup Med Environ Health 2017;30(5:687

  9. Occupational exposure to radon for underground tourist routes in Poland: Doses to lung and the risk of developing lung cancer.

    Science.gov (United States)

    Walczak, Katarzyna; Olszewski, Jerzy; Politański, Piotr; Zmyślony, Marek

    2017-07-14

    Radon concentrations for 31 Polish underground tourist routes were analyzed. The equivalent dose to the lung, the effective dose and the relative risk were calculated for employees of the analyzed routes on the grounds of information on radon concentrations, work time, etc. The relative risk for lung cancers was calculated using the Biological Effects of Ionizing Radiation (BEIR) VI Committee model. Equivalent doses to the lungs of workers were determined using the coefficients calculated by the Kendall and Smith. The conversion coefficient proposed by the International Atomic Energy Agency (IAEA) in the report No. 33 was used for estimating the effective doses. In 13 routes, the effective dose was found to be above 1 mSv/year, and in 3 routes, it exceeded 6 mSv/year. For 5 routes, the equivalent dose to lungs was higher than 100 mSv/year, and in 1 case it was as high as 490 mSv/year. In 22.6% of underground workplaces the risk of developing lung cancer among employees was about 2 times higher than that for the general population, and for 1 tourist route it was about 5 times higher. The geometric mean of the relative risk of lung cancer for all workers of underground tourist routes was 1.73 (95% confidence interval (CI): 1.6-1.87). Routes were divided into: caves, mines, post-military underground constructions and urban underground constructions. The difference between levels of the relative risk of developing lung cancer for all types of underground tourist routes was not found to be significant. If we include the professional group of the employees of underground tourist routes into the group of occupational exposure, the number of persons who are included in the Category A due to occupational exposure may increase by about 3/4. The professional group of the employees of underground tourist routes should be monitored for their exposure to radon. Int J Occup Med Environ Health 2017;30(5):687-694.

  10. Assessing the risk of birth defects associated with exposure to fixed-dose combined antituberculous agents during pregnancy in rats.

    Science.gov (United States)

    Awodele, O; Patrick, E B; Oluwatoyin Agbaje, Esther; Oremosu, A A; Gbotolorun, S C

    2012-01-01

    Due to the risks of disease progression and transmission to the newborn, treatment of tuberculosis is often pursued during pregnancy and fixed-dose combined antituberculous agents have been found to be beneficial. Unfortunately, there is paucity of data on the safety of the fixed-dose combined antituberculous drugs during pregnancy. This study intends to assess the teratogenic effect of fixed-dose combined antituberculous drugs on the organogenesis stage of fetal development and also investigate the possible roles of vitamin C in modulating the teratogenic effects of these agents on the fetus using animal model. Pregnant rats were divided into 3 groups with 12 animals per group: group 1 received distilled water (10 mL/kg) orally; group 2 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents orally; group 3 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents plus vitamin C (10 mg/kg/day) orally. Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation, and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and hematological examination. The liver, kidney, heart, and brain of all the sacrificed animals were used for histopathological examination. There were significant (P ≤ 0.05) low birth weights of the foetuses of the animals that were treated with fixed-dose combined antituberculous agents. The haematological parameters also revealed a reduction in the platelets counts and neutrophiles at the first filial generation. Significant (P ≤ 0.05) elevations in the levels of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the foetuses of the animals treated with fixed-dose combined antituberculous agents were also observed. However, the combination of vitamin C with fixed-dose combined antituberculous agents significantly

  11. Assessing the Risk of Birth Defects Associated with Exposure to Fixed-Dose Combined Antituberculous Agents during Pregnancy in Rats

    Directory of Open Access Journals (Sweden)

    O. Awodele

    2012-01-01

    Full Text Available Due to the risks of disease progression and transmission to the newborn, treatment of tuberculosis is often pursued during pregnancy and fixed-dose combined antituberculous agents have been found to be beneficial. Unfortunately, there is paucity of data on the safety of the fixed-dose combined antituberculous drugs during pregnancy. This study intends to assess the teratogenic effect of fixed-dose combined antituberculous drugs on the organogenesis stage of fetal development and also investigate the possible roles of vitamin C in modulating the teratogenic effects of these agents on the fetus using animal model. Pregnant rats were divided into 3 groups with 12 animals per group: group 1 received distilled water (10 mL/kg orally; group 2 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents orally; group 3 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents plus vitamin C (10 mg/kg/day orally. Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation, and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and hematological examination. The liver, kidney, heart, and brain of all the sacrificed animals were used for histopathological examination. There were significant (≤0.05 low birth weights of the foetuses of the animals that were treated with fixed-dose combined antituberculous agents. The haematological parameters also revealed a reduction in the platelets counts and neutrophiles at the first filial generation. Significant (≤0.05 elevations in the levels of aspartate aminotransferase (AST and alkaline phosphatase (ALP in the foetuses of the animals treated with fixed-dose combined antituberculous agents were also observed. However, the combination of vitamin C with fixed-dose combined antituberculous agents

  12. A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk.

    Science.gov (United States)

    Butler, Katherine; Ritter, Jana M; Ellis, Shanon; Morris, Monica R; Hanson, Debra L; McNicholl, Janet M; Kersh, Ellen N

    2016-08-01

    Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. It took a median 5.5 viral challenges to infect DMPA-treated macaques and 9 challenges for controls (P = 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA-treated and control macaques, respectively, P = 0.03, t test using the Satterthwaite degrees-of-freedom approximation). SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition.

  13. Mortality risk is dose-dependent on the number of packed red blood cell transfused after coronary artery bypass graft

    OpenAIRE

    dos Santos, Antônio Alceu; de Sousa, Alexandre Gonçalves; Piotto, Raquel Ferrari; Pedroso, Juan Carlos Montano [UNIFESP

    2013-01-01

    Introduction Transfusions of one or more packed red blood cells is a widely strategy used in cardiac surgery, even after several evidences of increased morbidity and mortality. The world's blood shortage is also already evident. Objective To assess whether the risk of mortality is dose-de>pendent on the number of packed red blood cells transfused after coronary artery bypass graft. Methods Between June 2009 and July 2010, were analyzed 3010 patients: transfused and non-transfused. Transfused ...

  14. Coffee, tea, caffeine and risk of depression: A systematic review and dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Grosso, Giuseppe; Micek, Agnieszka; Castellano, Sabrina; Pajak, Andzrej; Galvano, Fabio

    2016-01-01

    The aim of the study was to systematically review and analyze results from observational studies on coffee, caffeine, and tea consumption and association or risk of depression. Embase and PubMed databases were searched from inception to June 2015 for observational studies reporting the odds ratios or relative risks (RRs) and 95% confidence intervals (CI) of depression by coffee/tea/caffeine consumption. Random effects models, subgroup analyses, and dose-response analyses were performed. Twelve studies with 23 datasets were included in the meta-analysis, accounting for a total of 346 913 individuals and 8146 cases of depression. Compared to individuals with lower coffee consumption, those with higher intakes had pooled RR of depression of 0.76 (95% CI: 0.64, 0.91). Dose-response effect suggests a nonlinear J-shaped relation between coffee consumption and risk of depression with a peak of protective effect for 400 mL/day. A borderline nonsignificant association between tea consumption and risk of depression was found (RR 0.70, 95% CI: 0.48, 1.01), while significant results were found only for analysis of prospective studies regarding caffeine consumption (RR = 0.84, 95% CI: 0.75, 0.93). This study suggests a protective effect of coffee and, partially, of tea and caffeine on risk of depression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The Increase in Animal Mortality Risk following Exposure to Sparsely Ionizing Radiation Is Not Linear Quadratic with Dose.

    Directory of Open Access Journals (Sweden)

    Benjamin M Haley

    Full Text Available The US government regulates allowable radiation exposures relying, in large part, on the seventh report from the committee to estimate the Biological Effect of Ionizing Radiation (BEIR VII, which estimated that most contemporary exposures- protracted or low-dose, carry 1.5 fold less risk of carcinogenesis and mortality per Gy than acute exposures of atomic bomb survivors. This correction is known as the dose and dose rate effectiveness factor for the life span study of atomic bomb survivors (DDREFLSS. It was calculated by applying a linear-quadratic dose response model to data from Japanese atomic bomb survivors and a limited number of animal studies.We argue that the linear-quadratic model does not provide appropriate support to estimate the risk of contemporary exposures. In this work, we re-estimated DDREFLSS using 15 animal studies that were not included in BEIR VII's original analysis. Acute exposure data led to a DDREFLSS estimate from 0.9 to 3.0. By contrast, data that included both acute and protracted exposures led to a DDREFLSS estimate from 4.8 to infinity. These two estimates are significantly different, violating the assumptions of the linear-quadratic model, which predicts that DDREFLSS values calculated in either way should be the same.Therefore, we propose that future estimates of the risk of protracted exposures should be based on direct comparisons of data from acute and protracted exposures, rather than from extrapolations from a linear-quadratic model. The risk of low dose exposures may be extrapolated from these protracted estimates, though we encourage ongoing debate as to whether this is the most valid approach. We also encourage efforts to enlarge the datasets used to estimate the risk of protracted exposures by including both human and animal data, carcinogenesis outcomes, a wider range of exposures, and by making more radiobiology data publicly accessible. We believe that these steps will contribute to better estimates

  16. Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers

    OpenAIRE

    2016-01-01

    Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75–325 mg/day). Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (con...

  17. Use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs and risk of glioma

    DEFF Research Database (Denmark)

    Gaist, D; García-Rodríguez, L A; Sørensen, H T;

    2013-01-01

    Background:Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting.Methods:We used...... exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous use for 5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential...... confounders.Results:A total of 2688 glioma cases and 18 848 population controls were included in the study. Ever use of low-dose aspirin (OR=0.90; 95% CI: 0.77-1.04) or NA-NSAIDs (OR=1.05; 95% CI: 0.96-1.14) was not associated with glioma risk. Compared with never use, long-term use of low-dose aspirin...

  18. Assessment of patient dose and radiogenic risks during endoscopic retrograde cholangiopancreatography

    Energy Technology Data Exchange (ETDEWEB)

    Sulieman, A.; Elzaki, M. [Sudan University of Science and Technology, College of Medical Radiologic Science, P. O. Box 1908, Khartoum 11111 (Sudan); Alkhorayef, M.; Babikir, E. [King Saud University, College of Applied Sciences, Radiological Sciences Department, P. O. Box 10219, Riyadh 11433 (Saudi Arabia); Abuzaid, M. [University of Sharjah, College of Health Sciences, Medical Diagnostic Imaging Department, Sharjah (United Arab Emirates); Dalton, A.; Bradley, D., E-mail: Abdelmoneim_a@yahoo.com [University of Surrey, Centre for Nuclear and Radiation Physics, Department of Physics, GU2-7XH, Guildford, Surrey (United Kingdom)

    2015-10-15

    Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive technique that has been used for over 30 years in the diagnosis and management of pancreaticobiliary disorders. The objectives of this study were to evaluate the patient entrance surface air kerma doses (ESAK) and estimate the organ and effective doses during ERCP in three hospitals in Khartoum. A total of 55 patients were examined in three hospitals in Khartoum state, Sudan. Calibrated thermoluminescence dosimeters (TLD)-Gr-200-A)) were used to measure patients ESAK. The overall mean of ESAK for all ERCP procedures was 42.4 mGy. The mean patient ESAK in Fedail, Soba and Ibn sena centers were 26.7 mGy, 26.0 mGy, 72.4 mGy, respectively. The effective doses in three centers were 1.6, 1.56 and 2.67 mSv in that order and the overall mean effective dose was 2.01 mSv. Patient radiation doses vary widely among the different hospitals. Patient ESAK is low compared to previous studies in the light of the current practice. Patient dose was decreased significantly in the last two decades. (Author)

  19. Coffee Consumption and Risk of Stroke: A Dose-Response Meta-Analysis of Prospective Studies

    National Research Council Canada - National Science Library

    Larsson, Susanna C; Orsini, Nicola

    2011-01-01

    Coffee consumption has been inconsistently associated with risk of stroke. The authors conducted a meta-analysis of prospective studies to quantitatively assess the association between coffee consumption and stroke risk...

  20. Human Health Risk Assessment: A case study application of principles in dose response assessment

    Science.gov (United States)

    This case study application workshop will build on fundamental concepts and techniques in risk assessment presented and archived at previous TRAC meeting workshops. Practical examples from publicly available, peer reviewed risk assessments will be used as teaching aids. Course ...

  1. Radiation doses and risks to neonates undergoing radiographic examinations in intensive care units in Tunisia

    Directory of Open Access Journals (Sweden)

    Abir Bouaoun

    2015-12-01

    Full Text Available Purpose: To assess the radiation doses to neonates from diagnostic radiography in order to derive the local diagnostic reference levels (LDRLs for optimisation purposes.Methods: This study was carried out in the neonatal intensive care units (NICU of  two hospitals in Tunis. 134 babies, with weights ranging from 635 g to 6680 g, performed chest-abdomen X-ray examinations. Neonates were categorized into groups of birth weight. For each X-ray examination, patient data and exposure parameters were recorded. Dose area product (DAP was measured and entrance surface dose (ESD was estimated. Effective dose was calculated from the Monte Carlo simulation software PCXMC.Results: DAP values increased with neonatal weight and demonstrated a wide variation (5.0 - 43.0 mGy.cm2, mean 23.4 mGy.cm2 for patient weight from 600 g to 4000 g. A wide variation was also observed for ESD (14 - 93 μGy, mean 55.2 μGy. The LDRLs expressed in term of DAP were estimated to be 17.6 mGy.cm2 and 29.1 mGy.cm2 for the first and the second NICU, respectively. In terms of effective dose, the average value was about 31.6 μSv per single radiological examination. The results show the necessity to use a standardized protocol with high voltage technique combined to lower current time product (mAs values and an adapted collimation which could lead to further reductions in the neonatal doses. Conclusion: This study presents the LDRLs and the effective doses for neonates in two NICUs and demonstrates the necessity to optimize patient protection for this category of patient.

  2. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jansen-van der Weide, Marijke C. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands); Greuter, Marcel J.W.; Pijnappel, Ruud M. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); Jansen, Liesbeth [University Medical Center Groningen, University of Groningen, Department of Surgery, Groningen (Netherlands); Oosterwijk, Jan C. [University Medical Center Groningen, University of Groningen, Department of Clinical Genetics, Groningen (Netherlands); Bock, Geertruida H. de [University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands)

    2010-11-15

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of {>=}5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. (orig.)

  3. Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy.

    Science.gov (United States)

    Mieras, Liesbeth; Anthony, Richard; van Brakel, Wim; Bratschi, Martin W; van den Broek, Jacques; Cambau, Emmanuelle; Cavaliero, Arielle; Kasang, Christa; Perera, Geethal; Reichman, Lee; Richardus, Jan Hendrik; Saunderson, Paul; Steinmann, Peter; Yew, Wing Wai

    2016-06-08

    Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.

  4. Health risk of low-dose pesticides mixtures: a review of the 1985-1998 literature on combination toxicology and health risk assessment.

    Science.gov (United States)

    Carpy, S A; Kobel, W; Doe, J

    2000-01-01

    A literature review covering the last 14 yr has been performed in the field of combination toxicology and human risk assessment from exposure to chemical mixtures, with special emphasis on mixtures of pesticides at low doses, that is, at levels likely to occur in human diet and environment. Despite a large body of knowledge in the field of risk assessment methodologies for exposure to chemical and pesticide mixtures, there is no single methodological approach in "combination toxicology" and health risk assessment of chemical mixtures, and therefore professional judgment is still required. Generally, the dose or response additivity approach that may be applied to evaluate potential risk for chemical mixtures in human toxicology overestimates the risk of a combination of chemicals. The recent endocrine disrupter issue demonstrated the difficulty of reproducibility of data when testing environmental toxicants at very low levels, and the need for more basic work in this field. The use of integrated methodological approaches may provide more reliable predictive data in the risk assessment of chemical mixtures in future. Yet data have demonstrated that exposure to a combination of compounds does not cause effects stronger than the ones of their most active component, provided components are present at low concentration levels, like acceptable daily intake (ADI) or reference dose (RfD) levels, well below their respective no-observed-adverse-effect levels (NOAELs). Although it has been demonstrated that a combination of compounds with the same target organ and the same or very similar mechanisms of action may cause additive or synergistic effects, the chance of such effects will most likely diminish with decreasing exposure levels to such combinations. Synergism and antagonism may both occur at the same time at different organs or targets in the same organism. However, and despite some exceptions, it has been demonstrated that interaction between components is not a common

  5. Assessment of uncertainties in radiation-induced cancer risk predictions at clinically relevant doses

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, J. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114 and Department of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg 69117 (Germany); Moteabbed, M.; Paganetti, H., E-mail: hpaganetti@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114 and Harvard Medical School, Boston, Massachusetts 02114 (United States)

    2015-01-15

    Purpose: Theoretical dose–response models offer the possibility to assess second cancer induction risks after external beam therapy. The parameters used in these models are determined with limited data from epidemiological studies. Risk estimations are thus associated with considerable uncertainties. This study aims at illustrating uncertainties when predicting the risk for organ-specific second cancers in the primary radiation field illustrated by choosing selected treatment plans for brain cancer patients. Methods: A widely used risk model was considered in this study. The uncertainties of the model parameters were estimated with reported data of second cancer incidences for various organs. Standard error propagation was then subsequently applied to assess the uncertainty in the risk model. Next, second cancer risks of five pediatric patients treated for cancer in the head and neck regions were calculated. For each case, treatment plans for proton and photon therapy were designed to estimate the uncertainties (a) in the lifetime attributable risk (LAR) for a given treatment modality and (b) when comparing risks of two different treatment modalities. Results: Uncertainties in excess of 100% of the risk were found for almost all organs considered. When applied to treatment plans, the calculated LAR values have uncertainties of the same magnitude. A comparison between cancer risks of different treatment modalities, however, does allow statistically significant conclusions. In the studied cases, the patient averaged LAR ratio of proton and photon treatments was 0.35, 0.56, and 0.59 for brain carcinoma, brain sarcoma, and bone sarcoma, respectively. Their corresponding uncertainties were estimated to be potentially below 5%, depending on uncertainties in dosimetry. Conclusions: The uncertainty in the dose–response curve in cancer risk models makes it currently impractical to predict the risk for an individual external beam treatment. On the other hand, the ratio

  6. Red Meat and Processed Meat Consumption and Nasopharyngeal Carcinoma Risk: A Dose-response Meta-analysis of Observational Studies.

    Science.gov (United States)

    Li, Fuqin; Duan, Fujiao; Zhao, Xia; Song, Chunhua; Cui, Shuli; Dai, Liping

    2016-01-01

    The purpose of this study is to clarify and quantify the potential dose-response association between the intake of total red and total processed meat and risk of nasopharyngeal carcinoma (NPC). Relevant studies were identified by searching PubMed, EMBASE, and Chinese databases (CNKI and Wanfang). The summary relative risk (RR) with 95% confidence interval (95%CI) was calculated. A total of 15 independent studies with 12,735 subjects were identified. Compared with the low-rank intake, the summary RR of NPC was 1.35 (95%CI, 1.21-1.51) for total red meat and 1.46 (95%CI, 1.34-1.64) for total processed meat. For the moderate-rank intake, the summary RR of NPC was 1.54 (95%CI, 1.36-1.79) for total red meat and 1.59 (95%CI, 1.3-1.90) for total processed meat. The summary RR for high-rank intake was 1.71 (95%CI, 1.14-2.55) for total red meat and 2.11 (95%CI, 1.31-3.42) for total processed meat. The combined estimates showed obvious evidence of statistically significant association between total red and total processed meat consumption dose and risk of NPC (Ptrendprocessed meat is associated with a significantly increased risk of NPC.

  7. Reference computations of public dose and cancer risk from airborne releases of uranium and Class W plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, V.L.

    1995-06-06

    This report presents ``reference`` computations that can be used by safety analysts in the evaluations of the consequences of postulated atmospheric releases of radionuclides from the Rocky Flats Environmental Technology Site. These computations deal specifically with doses and health risks to the public. The radionuclides considered are Class W Plutonium, all classes of Enriched Uranium, and all classes of Depleted Uranium. (The other class of plutonium, Y, was treated in an earlier report.) In each case, one gram of the respirable material is assumed to be released at ground leveL both with and without fire. The resulting doses and health risks can be scaled to whatever amount of release is appropriate for a postulated accident being investigated. The report begins with a summary of the organ-specific stochastic risk factors appropriate for alpha radiation, which poses the main health risk of plutonium and uranium. This is followed by a summary of the atmospheric dispersion factors for unfavorable and typical weather conditions for the calculation of consequences to both the Maximum Offsite Individual and the general population within 80 km (50 miles) of the site.

  8. Long-term high-dose oral morphine in phantom limb pain with no addiction risk

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-01-01

    Full Text Available Chronic phantom limb pain (PLP is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation. Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction.

  9. Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies.

    Science.gov (United States)

    Fedirko, V; Tramacere, I; Bagnardi, V; Rota, M; Scotti, L; Islami, F; Negri, E; Straif, K; Romieu, I; La Vecchia, C; Boffetta, P; Jenab, M

    2011-09-01

    The International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (≤1 drink/day) and moderate (2-3 drinks/day) alcohol drinking, investigation of the dose-response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region. Twenty-seven cohort and 34 case-control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. The summary relative risks (RRs) were estimated by the random effects model. Second-order fractional polynomials and random effects meta-regression models were used for modeling the dose-risk relation. The RRs were 1.21 [95% confidence interval (CI) 1.13-1.28] for moderate and 1.52 (95% CI 1.27-1.81) for heavy (≥4 drinks/day) alcohol drinking. The RR for moderate drinkers, compared with non-/occasional drinkers, was stronger for men (RR = 1.24, 95% CI 1.13-1.37) than for women (RR = 1.08, 95% CI 1.03-1.13; P(heterogeneity) = 0.02). For heavy drinkers, the association was stronger in Asian studies (RR = 1.81, 95% CI 1.33-2.46; P(heterogeneity) = 0.04). The dose-risk analysis estimated RRs of 1.07 (95% CI 1.04-1.10), 1.38 (95% CI 1.28-1.50), and 1.82 (95% CI 1.41-2.35) for 10, 50, and 100 g/day of alcohol, respectively. This meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk.

  10. Cardiovascular risk factors in children after repeat doses of antenatal glucocorticoids: an RCT

    National Research Council Canada - National Science Library

    McKinlay, Christopher J D; Cutfield, Wayne S; Battin, Malcolm R; Dalziel, Stuart R; Crowther, Caroline A; Harding, Jane E

    2015-01-01

    .... We assessed whether exposure to repeat antenatal betamethasone increased risk factors for later cardiometabolic disease in children whose mothers participated in the Australasian Collaborative Trial...

  11. Measurement of mean cardiac dose for various breast irradiation techniques and corresponding risk of major cardiovascular event.

    Directory of Open Access Journals (Sweden)

    Tomas Rodrigo Merino Lara

    2014-10-01

    Full Text Available After breast conserving surgery, early stage breast cancer patients are currently treated with a wide range of radiation techniques including whole breast irradiation (WBI, accelerated partial breast irradiation (APBI using high dose rate (HDR brachytherapy, or 3D conformal radiotherapy (3D-CRT. This study compares the mean heart’s doses for a left breast irradiated with different breast techniques.An anthropomorphic Rando phantom was modified with gelatin-based breast of different sizes and tumors located medially or laterally. The breasts were treated with WBI, 3D-CRT or HDR APBI. The heart’s mean doses were measured with Gafchromic films and controlled with optically stimulated luminescent dosimeters (OSLDs. Following the model reported by Darby (16, major cardiac were estimated assuming a linear risk increase with the mean dose to the heart of 7.4% per gray.Whole breast irradiation lead to the highest mean heart dose (2.99 Gy compared to 3D-CRT APBI, (0.51 Gy, multicatheter (1.58 Gy and balloon HDR (2.17 Gy for a medially located tumor. This translated into long-term coronary event increases of 22%, 3.8%, 11.7%, and 16% respectively. The sensitivity analysis showed that the tumor location had almost no effect on the mean heart dose for 3D-CRT APBI and a minimal impact for HDR APBI. For WBI large breast size and set-up errors lead to sharp increases of the mean heart dose. Its value reached 10.79 Gy for women with large breast and a set-up error of 1.5 cm. Such a high value could increase the risk of having long-term coronary events by 80%.Comparison among different irradiation techniques demonstrates that 3D-CRT APBI appears the safest one with less probability of having cardiovascular events in the future. A sensitivity analysis showed that WBI is the most challenging technique for patients with large breasts or when significant set-up errors are anticipated. In those cases additional heart shielding techniques are required.

  12. Dairy products consumption and risk of type 2 diabetes: systematic review and dose-response meta-analysis.

    Directory of Open Access Journals (Sweden)

    Dengfeng Gao

    Full Text Available BACKGROUND: The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM, but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has not yet been fully explored. METHODS AND RESULTS: We conducted a systematic review and meta-analysis to clarify the dose-response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies, low-fat dairy products (8 studies, cheese (7 studies and yogurt (7 studies and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97 and 0.88 (0.84-0.93 for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69-0.93 and 0.91 (0.82-1.00 for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake. CONCLUSION: A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.

  13. The bottom-up approach to bounding potential low-dose cancer risks from formaldehyde: An update.

    Science.gov (United States)

    Starr, Thomas B; Swenberg, James A

    2016-06-01

    In 2013, we proposed a novel bottom-up approach to bounding low-dose cancer risks that may result from small exogenous exposures to chemicals that are always present in the body as a result of normal biological processes. The approach utilizes the background cancer risk and the background (endogenous) concentration of a cancer-related exposure biomarker in specific target tissues. After allowing for statistical uncertainty in these two parameters, the ratio of the background risk to background exposure provides a conservative slope factor estimate that can be utilized to bound the added risk that may be associated with incremental exogenous exposures. Our original bottom-up estimates were markedly smaller than those obtained previously by the US Environmental Protection Agency (USEPA) with a conventional top-down approach to modeling nasopharyngeal cancer and leukemia mortality data from a US worker cohort. Herein we provide updated bottom-up estimates of risk for these two cancers that are smaller still, and rely upon more robust estimates of endogenous and exogenous formaldehyde-DNA adducts in monkeys and a more robust estimate of the DNA adduct elimination half-life in rats, both obtained very recently. We also re-examine the worker mortality data used by USEPA in developing its estimate of human leukemia incidence from lifetime exposure to 1 ppm airborne formaldehyde. Finally, we compare a new bottom-up slope estimate of the risk of rat nasal cancer with conventional top-down estimates obtained with empirical dose-response modeling of rat nasal cancer bioassay data. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Intensive combined modality therapy including low-dose TBI in high-risk Ewing's sarcoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Kinsella, T.J.; Glaubiger, D.; Diesseroth, A.; Makuch, R.; Waller, B.; Pizzo, P.; Glatstein, E.

    1983-12-01

    Twenty-four high-risk Ewing's sarcoma patients were treated on an intensive combined modality protocol including low-dose fractionated total body irradiaiton (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months. Local failure as a manifestation of initial relapse occurred in only three patients (15%), each having synchronous distant failure. Eight patients failed initially with only distant metastases, usually within 1-2 years following a complete clinical response. Two patterns of granulocyte recovery following consolidative therapy (including TBI and ABMI) were recognized. The time to platelet recovery was different for the groups with early and late granulocyte recovery. Patients with late recovery did not tolerate maintenance chemotherapy. However, there was no difference in disease-free and overall survival, when comparing the groups with early and late granulocyte recovery. It is concluded that these high-risk Ewing's sarcoma patients remain a poor-prognosis group in spite of intensive combined modality therapy including low-dose TBI. The control of microscopic systemic disease remains the major challenge to improving the cure rate. A new combined modality protocol with high-dose 'therapeutic' TBI (800 rad/2 fractions) is being used and the protocol design is outlined.

  15. EMS in Viracept--initial ('traditional') assessment of risk to patients based on linear dose response relations.

    Science.gov (United States)

    Gocke, Elmar; Müller, Lutz; Pfister, Thomas

    2009-11-12

    Prior to having performed in depth toxicological, genotoxicological and DMPK studies on ethyl methanesulfonate (EMS) providing solid evidence for a thresholded dose response relationship, we had prepared and shared with regulatory authorities a preliminary risk estimate based on standard linear dose-effect projections. We estimated that maximal lifetime cancer risk was in the order of 10(-3) (for lifetime ingestion of the maximally contaminated tablets) or 10(-4) for the exposure lasting for 3 months. This estimate was based on a lifetime cancer study with methyl methanesulfonate (MMS; as insufficient data were available for EMS) in rodents and default linear back extrapolation. Analogous estimates were made specifically for breast cancer based on short term tumorigenicity studies with EMS in rats, for the induction of heritable mutations based on specific locus and dominant lethal tests in mice and for the induction of birth defects based on teratogenicity studies in mice. We concluded that even under worst case assumptions of linear dose relations the chance of experiencing these adverse effects would be very small, comprising at most a minute additional burden among the background incidence of the patients.

  16. Influence of dose distribution on risk of lung cancer occurrence after actinide oxide inhalation; Influence de la distribution de dose sur le risque d'apparition de cancers pulmonaires apres inhalation d'oxydes d'actinides

    Energy Technology Data Exchange (ETDEWEB)

    Fritsch, P.; Dudoignon, N.; Guillet, K.; Rateau, G.; Delforge, J. [Lab. de Radiotoxicologie, CEA/DSV/DRR/SRCA, Bruyeres le Chatel (France)

    2002-07-01

    The aim of this work was to estimate risk of lung tumour occurrence after inhalation of actinide oxides from published studies and rat studies in progress. For the same delivered dose, the risk increases when homogeneity of irradiation increases, i.e., the number of particles deposited after inhalation increases (small particles and (or) low specific alpha activity). The dose-effect relationships reported appear linear up to a few gray, depending on the aerosol considered, and then the slope decreases. This slope, which corresponds with the risk, can vary over one order of magnitude de ending on the aerosol used. An effective threshold at about 1 Gy was not observed for the most homogeneous dose distributions. A dosimetric and biological approach is proposed to provide a more realistic risk estimate. (author)

  17. Methods for Estimation of Radiation Risk in Epidemiological Studies Accounting for Classical and Berkson Errors in Doses

    KAUST Repository

    Kukush, Alexander

    2011-01-16

    With a binary response Y, the dose-response model under consideration is logistic in flavor with pr(Y=1 | D) = R (1+R)(-1), R = λ(0) + EAR D, where λ(0) is the baseline incidence rate and EAR is the excess absolute risk per gray. The calculated thyroid dose of a person i is expressed as Dimes=fiQi(mes)/Mi(mes). Here, Qi(mes) is the measured content of radioiodine in the thyroid gland of person i at time t(mes), Mi(mes) is the estimate of the thyroid mass, and f(i) is the normalizing multiplier. The Q(i) and M(i) are measured with multiplicative errors Vi(Q) and ViM, so that Qi(mes)=Qi(tr)Vi(Q) (this is classical measurement error model) and Mi(tr)=Mi(mes)Vi(M) (this is Berkson measurement error model). Here, Qi(tr) is the true content of radioactivity in the thyroid gland, and Mi(tr) is the true value of the thyroid mass. The error in f(i) is much smaller than the errors in ( Qi(mes), Mi(mes)) and ignored in the analysis. By means of Parametric Full Maximum Likelihood and Regression Calibration (under the assumption that the data set of true doses has lognormal distribution), Nonparametric Full Maximum Likelihood, Nonparametric Regression Calibration, and by properly tuned SIMEX method we study the influence of measurement errors in thyroid dose on the estimates of λ(0) and EAR. The simulation study is presented based on a real sample from the epidemiological studies. The doses were reconstructed in the framework of the Ukrainian-American project on the investigation of Post-Chernobyl thyroid cancers in Ukraine, and the underlying subpolulation was artificially enlarged in order to increase the statistical power. The true risk parameters were given by the values to earlier epidemiological studies, and then the binary response was simulated according to the dose-response model.

  18. Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Adkison, Jarrod B.; McHaffie, Derek R.; Bentzen, Soren M.; Patel, Rakesh R.; Khuntia, Deepak [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Petereit, Daniel G. [Department of Radiation Oncology, John T. Vucurevich Regional Cancer Care Institute, Rapid City Regional Hospital, Rapid City, SD (United States); Hong, Theodore S.; Tome, Wolfgang [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Ritter, Mark A., E-mail: ritter@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States)

    2012-01-01

    Purpose: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5 Vulgar-Fraction-One-Half weeks. Methods and Materials: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving {>=}30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 {+-} 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. Conclusions: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose

  19. Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya.

    Directory of Open Access Journals (Sweden)

    Deron C Burton

    Full Text Available There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10. We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance. Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator. A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose. The risk ratio for abscess following injection with the second (41 per 100,000 vs first (33 per 100,000 vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37-4.06. The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12-8.56 and 0.27 (95% CI 0.14-0.54 when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study.

  20. Low vs. higher-dose dark chocolate and blood pressure in cardiovascular high-risk patients.

    Science.gov (United States)

    Desch, Steffen; Kobler, Daniela; Schmidt, Johanna; Sonnabend, Melanie; Adams, Volker; Sareban, Mahdi; Eitel, Ingo; Blüher, Matthias; Schuler, Gerhard; Thiele, Holger

    2010-06-01

    Dark chocolate may have blood pressure-lowering properties. We conducted a prospective randomized open-label blinded end-point design trial to study a potential dose dependency of the presumed antihypertensive effect of dark chocolate by directly comparing low vs. higher doses of dark chocolate over the course of 3 months. We enrolled a total of 102 patients with prehypertension/stage 1 hypertension and established cardiovascular end-organ damage or diabetes mellitus. Patients were randomly assigned to receive either 6 or 25 g/day of flavanol-rich dark chocolate for 3 months. The difference in 24-h mean blood pressure between groups was defined as the primary outcome measure. Significant reductions in mean ambulatory 24-h blood pressure were observed between baseline and follow-up in both groups (6 g/day: -2.3 mm Hg, 95% confidence interval -4.1 to -0.4; 25 g/day: -1.9 mm Hg, 95% confidence interval -3.6 to -0.2). There were no significant differences in blood pressure changes between groups. In the higher-dose group, a slight increase in body weight was noted (0.8 kg, 95% confidence interval 0.06 to 1.6). The findings are consistent with the hypothesis that dark chocolate may be associated with a reduction in blood pressure (BP). However, due to the lack of a control group, confounding may be possible and the results should be interpreted with caution.

  1. Summary of literature review of risk communication: Hanford Environmental Dose Reconstruction Project

    Energy Technology Data Exchange (ETDEWEB)

    Byram, S.J.

    1991-05-01

    The Hanford Environmental Dose Reconstruction (HEDR) Project will estimate radiation exposures people may have received from radioactive materials released during past operations at the Department of Energy's Hanford Site near Richland, Washington. The project is being conducted by Pacific Northwest Laboratory (PNL) under the direction of an independent Technical Steering Panel (TSP). The Centers for Disease Control (CDC) will use HEDR dose estimates in studies to investigate a potential link between thyroid disease and historical Hanford emissions. The HEDR Project was initiated to address public concerns about the possible health impacts from past releases of radioactive materials from Hanford. The TSP recognized early in the project that special mechanisms would be required to communicate effectively to the many different concerned audiences. To identify and develop these mechanisms, the TSP issued Directive 89-7 to PNL in May 1989. The TSP directed PNL to examine methods to communicate the causes and effects of uncertainties in the dose estimates. A literature review was conducted as the first activity in response to the TSP's directive. This report presents the results of the literature review. The objective of the literature review was to identify key principles'' that could be applied to develop communications strategies for the project. 26 refs., 6 figs.

  2. Dietary fiber intake and risk of type 2 diabetes: a dose-response analysis of prospective studies.

    Science.gov (United States)

    Yao, Baodong; Fang, Hong; Xu, Wanghong; Yan, Yujie; Xu, Huilin; Liu, Yinan; Mo, Miao; Zhang, Hua; Zhao, Yanping

    2014-02-01

    Observational studies suggest an association between dietary fiber intake and risk of type 2 diabetes, but the results are inconclusive. We conducted a meta-analysis of prospective studies evaluating the associations of dietary fiber intake and risk of type 2 diabetes. Relevant studies were identified by searching EMBASE (from 1974 to April 2013) and PubMed (from 1966 to April 2013). The fixed or random-effect model was selected based on the homogeneity test among studies. In addition, a 2-stage random-effects dose-response meta-analysis was performed. We identified 17 prospective cohort studies of dietary fiber intake and risk of type 2 diabetes involving 19,033 cases and 488,293 participants. The combined RR (95 % CI) of type 2 diabetes for intake of total dietary fiber, cereal fiber, fruit fiber and insoluble fiber was 0.81 (0.73-0.90), 0.77 (0.69-0.85), 0.94 (0.88-0.99) and 0.75 (0.63-0.89), respectively. A nonlinear relationship was found of total dietary fiber intake with risk of type 2 diabetes (P for nonlinearity fiber intake. Findings from this meta-analysis indicate that the intakes of dietary fiber may be inversely associated with risk of type 2 diabetes.

  3. Tea consumption and risk of stroke: a dose-response meta-analysis of prospective studies

    Institute of Scientific and Technical Information of China (English)

    Li SHEN; Liu-guang SONG; Hong MA; Chun-na JIN; Jian-an WANG; Mei-xiang XIANG

    2012-01-01

    Objective:To determine the association between tea consumption and the risk of stroke.Methods:We searched the PubMed database from January 1966 to March 2012 and reviewed reference lists of retrieved articles to identify relevant studies.Studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of stroke with respect to three or more categories of tea consumption.A random-effects model was used to combine the study-specific risk estimates.Results:Fourteen studies,consisting of 513 804 participants with a median follow-up of 11.5 years,were included in this meta-analysis.We observed a modest but statistically significant inverse association between tea consumption and risk of stroke.An increase of three cups/d in tea consumption was associated with a 13% decreased risk of stroke (RR 0.87; 95% CI,0.81-0.94).The decreased risk of stroke with tea consumption was consistent among most subgroups.Based on the three studies that provided results for stroke subtypes,tea consumption was also inversely associated with the risk of ischemic stroke (RR 0.76; 95% CI,0.69-0.84),but not cerebral hemorrhage (RR 0.96; 95% CI,0.82-1.11 ) or subarachnoid hemorrhage (RR 0.81 ; 95% CI,0.57-1.16).Conclusions:Tea consumption is associated with a decreased risk of stroke,particularly ischemic stroke.More well-designed,rigorously conducted studies are needed in order to make confident conclusions about the association between tea consumption and stroke subtypes.

  4. A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

    Directory of Open Access Journals (Sweden)

    Xu Tony

    2007-03-01

    Full Text Available Abstract Background Hodgkin's lymphoma (HL survivors who undergo radiotherapy experience increased risks of second cancers (SC and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT for HL has largely been replaced by involved field radiotherapy (IFRT. While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. Methods Organ-specific dose-volume histograms (DVH were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. Results Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2% reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. Conclusion The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment.

  5. Dose-response of serum 25-hydroxyvitamin D in association with risk of colorectal cancer: A meta-analysis.

    Science.gov (United States)

    Garland, Cedric F; Gorham, Edward D

    2017-04-01

    Fifteen nested case-control or cohort studies in 14 countries have examined the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of colorectal cancer. A meta-analysis of these studies would provide a useful dose-response gradient curve based on pooling of the results of known studies to date. An up-to-date dose-response curve that combines the findings of these studies has not been reported, to our knowledge. This curve would help in designing interventions for future studies. A new meta-analysis would be more precise than any previous analysis due to its larger sample size. Therefore a search of PubMed and other resources was performed in May 2016 for all cohort or nested case-control observational studies that reported risk of colon or colorectal cancer by quantiles of 25(OH)D. All but two of the 15 studies found a trend toward lower risk of colorectal cancer associated with higher serum 25(OH)D. There was a linear reduction in the odds ratio (OR) with each 10ng/ml-increment in 25(OH)D concentration. The lowest quantile of the serum 25(OH)D concentration was generallyD concentrations was statistically significant in 3 studies. The pooled OR from all studies comparing highest with lowest quantile of 25(OH)D was 0.67 (95% confidence interval [CI], 0.59-0.76), meaning there was a 33% lower risk associated with the highest compared with the lowest quantile of serum 25(OH)D. A dose-response analysis revealed that a serum 25(OH)D of 50ng/ml was associated with an OR of 0.4 (95% CI, 0.2-1.0) compared with a concentration of 5ng/ml. The formula for the linear relationship was OR=0.008x. For example, individuals with a 25(OH)D concentration of 50ng/ml had an approximately 60% lower risk of colorectal cancer than those with a concentration of 5ng/ml. Those with a 25(OH)D concentration of 30ng/ml had a 33% lower risk than those with a concentration of 5ng/ml. The inverse association between serum 25(OH)D and risk of colorectal cancer overall was strong and

  6. New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case-control study in UK general practice.

    Science.gov (United States)

    García Rodríguez, Luis A; Soriano-Gabarró, Montse; Bromley, Susan; Lanas, Angel; Cea Soriano, Lucía

    2017-09-07

    Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease. We investigated the risk of CRC among new-users of low-dose aspirin (75-300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case-control analysis. Two cohorts (N = 170,336 each) aged 40-89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified 'as-treated' independent from baseline exposure status to account for changes in exposure during follow-up. Current users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60-0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63-0·79) and 0.60 (0.53-0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66-1.33) for Dukes Stage A CRC, 0.54 (0.42-0.68) for Dukes B, 0.71 (0.56-0.91) for Dukes C, and 0.60 (0.48-0.74) for Dukes D. After 5 years' therapy, the RR for Dukes Stage A CRC was 0.53 (0.24-1.19). Patients starting low-dose aspirin therapy have a reduced

  7. Measures of Abdominal Adiposity and Risk of Stroke:A Dose-Response Meta-analysis of Prospective Studies

    Institute of Scientific and Technical Information of China (English)

    ZHONG Chong Ke; ZHONG Xiao Yan; XU Tan; ZHANG Yong Hong

    2016-01-01

    ObjectiveWaist circumference, waist-to-hip ratio and waist-to-height ratio, which are the indicators or measures of abdominal adiposity, have long been hypothesized to increase therisk of stroke; yet evidence accumulated till date is not conclusive. Here, we conducted a dose-response meta-analysis to summarize evidences of the association between these measures of abdominal adiposity and the risk of stroke. MethodsPubMed and Web of Science databases were searched from inception to May 2015. Two investigators independently conducted the study selection and data extraction. Dose-response relationships were assessed by the generalized least squares trend estimation, while the summaryeffect estimates were evaluated by the use of fixed- or random-effect models. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Publication biasof the literaturewas evaluated usingBegg’s and Egger’s test. ResultsAltogether 15 prospective cohort studies were identified in this study. The summary of relative risks (95% confidence intervals) of stroke for the highest versus the lowest categories was 1.28 (1.18-1.40) for waist circumference, 1.32 (1.21-1.44) for waist-to-hip ratio, and 1.49 (1.24-1.78) for waist-to-height ratio. For a 10-cm increase in waist circumference, the relative risk of stroke increased by 10%; for a 0.1-unit increase in waist-to-hip ratio, the relative risk increased by 16%; and for a 0.05-unit increase in waist-to-height ratio, the relative risk increased by 13%. There was evidence of a nonlinear association between waist-to-hip ratio and stroke risk,Pnonlinearity=0.028. ConclusionFindings from our meta-analysis indicated that waist circumference, waist-to-hip ratio, and waist-to-height ratio were positively associated with the risk of stroke, particularly ischemic stroke.

  8. Coffee consumption and risk of stroke: a dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Larsson, Susanna C; Orsini, Nicola

    2011-11-01

    Coffee consumption has been inconsistently associated with risk of stroke. The authors conducted a meta-analysis of prospective studies to quantitatively assess the association between coffee consumption and stroke risk. Pertinent studies were identified by searching PubMed and Embase from January 1966 through May 2011 and by reviewing the reference lists of retrieved articles. Prospective studies in which investigators reported relative risks of stroke for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Eleven prospective studies, with 10,003 cases of stroke and 479,689 participants, met the inclusion criteria. There was some evidence of a nonlinear association between coffee consumption and risk of stroke (P for nonlinearity = 0.005). Compared with no coffee consumption, the relative risks of stroke were 0.86 (95% confidence interval (95% CI): 0.78, 0.94) for 2 cups of coffee per day, 0.83 (95% CI: 0.74, 0.92) for 3-4 cups/day, 0.87 (95% CI: 0.77, 0.97) for 6 cups/day, and 0.93 (95% CI: 0.79, 1.08) for 8 cups/day. There was marginal between-study heterogeneity among study-specific trends (I₂ = 12% and I₂ = 20% for the first and second spline transformations, respectively). Findings from this meta-analysis indicate that moderate coffee consumption may be weakly inversely associated with risk of stroke.

  9. Dose reconstruction for birds species exposed to ionizing radiations highlights risk for species reproducing in the Fukushima Prefecture

    Energy Technology Data Exchange (ETDEWEB)

    Adam-Guillermin, C.; Beaugelin-Seiller, K.; Sternalski, A.; Bonzom, J.M.; Garnier-Laplace, J. [Institut de Radioprotection et de Surete Nucleaire - IRSN (France); Brown, J.E. [Norwegian Radiation Protection Authority - NRPA (Norway); Giraudeau, M. [Arizona state university (United States)

    2014-07-01

    The damaged Fukushima Daiichi nuclear power station (FDNPS) in Japan following the earthquake in March 2011 led to a massive release of radioactive isotopes into the environment. The atmospheric releases have created a footprint of radioactive contamination in the terrestrial ecosystems around the site, with a hot spot area that extends up to 80-km northwest. Despite some data are available on medium and biota contamination, there is still a lack of knowledge on possible ecological consequences due to the complexity of the exposure situation. Few papers were published using data observed in situ, reporting a reduction of bird and invertebrate abundance (Moeller et al., 2012, 2013) and morphological effects in butterflies (Hiyama et al., 2012). But as for any contaminant, the biological effects are dependent on the dose received, and an accurate dose estimation is needed to be able to correctly predict ecological risk. An early study has published preliminary radiological dose reconstruction from Fukushima wildlife signaling potential ecological consequences, but without using any quantitative data relating to biological samples (Garnier-Laplace et al., 2011). In this general framework, the work presented here aims at refining the first assessment conducted to evaluate possible consequences of the FDNPS radioactive releases, focusing on some bird species, studied in Fukushima but also in Chernobyl. Public data available on bird and soil contamination were used to check the bird contamination model used, showing that radioactive contamination predictions were within the range of variation of measured data. This model was then applied to estimate doses in bird species living in the Fukushima prefecture and known to reproduce during the period just after the nuclear power plant accident, based on ecological maps established for Japan. The influence of life stages and species ecological characteristics was taken into account on the dose estimates. The heterogeneity of

  10. Measurement of naturally occurring radionuclides in geothermal samples and assessment of radiological risks and radiation doses.

    Science.gov (United States)

    Parmaksiz, A

    2013-12-01

    The analysis of (226)Ra, (232)Th and (40)K radionuclides has been carried out in geothermal water and residue samples collected from six wells of geothermal power plant and disposal site, using gamma-spectrometry system equipped with a high-purity germanium detector. The activity concentrations of nine geothermal water samples were found to be lower than minimum detectable activity (MDA) values. The activity concentration of the residue samples ranged from 40 ± 4 to 2694 ± 85 Bq kg(-1) for (226)Ra, 33 ± 4 to 2388 ± 85 Bq kg(-1) for (232)Th, and MDA value to 967 ± 30 Bq kg(-1) for (40)K. In the study, some radiological indexes were examined and found to be higher than the reference values for majority of the residue samples. The annual effective doses arising from some residue samples were calculated to be higher than the permitted dose rate for the public, i.e. 1 mSv y(-1).

  11. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Hong-xia Xue

    2015-01-01

    Full Text Available Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  12. Impact of delineation uncertainties on dose to organs at risk in CT-guided intracavitary brachytherapy.

    LENUS (Irish Health Repository)

    Duane, Frances K

    2014-08-07

    This study quantifies the inter- and intraobserver variations in contouring the organs at risk (OARs) in CT-guided brachytherapy (BT) for the treatment of cervical carcinoma. The dosimetric consequences are reported in accordance with the current Gynecological Groupe Européen de Curiethérapie\\/European Society for Therapeutic Radiology and Oncology guidelines.

  13. Alcohol drinking and the risk of colorectal adenoma: a dose-response meta-analysis.

    Science.gov (United States)

    Ben, Qiwen; Wang, Lifu; Liu, Jun; Qian, Aihua; Wang, Qi; Yuan, Yaozong

    2015-07-01

    The International Agency for Research on Cancer concluded that alcohol consumption was positively related to colorectal cancer. However, the association between alcohol consumption and colorectal adenoma (CRA), the established precancerous lesion of colorectal cancer, remains unclear. We identified studies from a literature search of MEDLINE, EMBASE, and ISI Web of Science through 31 October 2013, and by searching reference lists of pertinent articles. Summary relative risks with 95% confidence intervals were calculated using a random-effects model. A total of 30 studies with 26,145 incident CRA cases were included. Overall, an increase of 25 g (two drinks) per day of alcohol consumption was related to an increased risk of CRA (summary relative risk=1.27, 95% confidence interval: 1.17-1.37). There was considerable heterogeneity between studies not explained by study design, sex, geographic location, publication year, site or size of the lesions, type of adenoma, number of cases, endoscopic assessment, or adjustment for main confounders. The positive association was evident for both men and women and for colonic adenoma, but not for rectal adenoma. Increased alcohol consumption is associated with an increased risk of CRA for both men and women and for adenoma in the colon, but not in the rectum.

  14. A Small Dose of HIV? HIV Vaccine Mental Models and Risk Communication

    Science.gov (United States)

    Newman, Peter A.; Seiden, Danielle S.; Roberts, Kathleen J.; Kakinami, Lisa; Duan, Naihua

    2009-01-01

    Existing knowledge and beliefs related to HIV vaccines provide an important basis for the development of risk communication messages to support future HIV vaccine dissemination. This study explored HIV vaccine mental models among adults from segments of the population disproportionately affected by HIV/AIDS. Nine focus groups were conducted with…

  15. Potential of a Pharmacogenetic-Guided Algorithm to Predict Optimal Warfarin Dosing in a High-Risk Hispanic Patient

    Directory of Open Access Journals (Sweden)

    Dagmar F. Hernandez-Suarez MD

    2016-12-01

    Full Text Available Deep abdominal vein thrombosis is extremely rare among thrombotic events secondary to the use of contraceptives. A case to illustrate the clinical utility of ethno-specific pharmacogenetic testing in warfarin management of a Hispanic patient is reported. A 37-year-old Hispanic Puerto Rican, non-gravid female with past medical history of abnormal uterine bleeding on hormonal contraceptive therapy was evaluated for abdominal pain. Physical exam was remarkable for unspecific diffuse abdominal tenderness, and general initial laboratory results—including coagulation parameters—were unremarkable. A contrast-enhanced computed tomography showed a massive thrombosis of the main portal, splenic, and superior mesenteric veins. On admission the patient was started on oral anticoagulation therapy with warfarin at 5 mg/day and low-molecular-weight heparin. The prediction of an effective warfarin dose of 7.5 mg/day, estimated by using a recently developed pharmacogenetic-guided algorithm for Caribbean Hispanics, coincided with the actual patient’s warfarin dose to reach the international normalized ratio target. We speculate that the slow rise in patient’s international normalized ratio observed on the initiation of warfarin therapy, the resulting high risk for thromboembolic events, and the required warfarin dose of 7.5 mg/day are attributable in some part to the presence of the NQO1*2 (g.559C>T, p.P187S polymorphism, which seems to be significantly associated with resistance to warfarin in Hispanics. By adding genotyping results of this novel variant, the predictive model can inform clinicians better about the optimal warfarin dose in Caribbean Hispanics. The results highlight the potential for pharmacogenetic testing of warfarin to improve patient care.

  16. The inverse dose-rate effect and the extrapolation of radon risk estimates from exposures of miners to low-level exposures in homes

    Energy Technology Data Exchange (ETDEWEB)

    Pushkin, J.S. (Environmental Protection Agency, Washington, DC (United States))

    1994-04-01

    This letter is written in response to a paper in which the author discusses the inverse dose-rate dependence of oncogenic transformation by high-LET radiation. The author asserts that, as a consequence, the extrapolation of results from miners exposed to high levels of radon daughters could overestimate the risk due to environmental exposures. By using a model increased cell sensitivity in one part of the cell cycle, the author assumes an inverse dose-rate effect should occur only at high doses, but the author of this letter points out that this does not imply a lower risk per unit dose at low doses. According to this letter, the existence of an inverse dose-rate effect for high-LET radiation provides no grounds for projecting lower lung cancer risks per unit exposure at environmental radon levels than at the higher radon level in mines. Failure to adjust for any inverse dose-rate effect in the studies of miners can only lead to an underestimation of the environmental risk.

  17. Causes of Mortality After Dose-Escalated Radiation Therapy and Androgen Deprivation for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tendulkar, Rahul D., E-mail: tendulr@ccf.org [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Hunter, Grant K. [Department of Radiation Oncology, Intermountain Healthcare, Salt Lake City, Utah (United States); Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Abdel-Wahab, May [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stephenson, Andrew J.; Klein, Eric A. [Department of Urology, Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio (United States); Mahadevan, Arul [Seacoast Cancer Center New Hampshire, Dover, New Hampshire (United States); Kupelian, Patrick A. [Department of Radiation Oncology, University of California Los Angeles Health System, Los Angeles, California (United States)

    2013-09-01

    Purpose: Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population. Methods and Materials: A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (≥74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival. Results: The median radiation dose was 78 Gy, median duration of AD was 6 months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ≥1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ≥1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60). Conclusions: Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not.

  18. Exercise, Abdominal Obesity, Skeletal Muscle, and Metabolic Risk: Evidence for a Dose Response

    Science.gov (United States)

    Slentz, Cris A.; Houmard, Joseph A.; Kraus, William E.

    2013-01-01

    The obese are at increased risk for cardiovascular disease and type 2 diabetes. However, some who are obese have no metabolic abnormalities. So, it is not adipose tissue per se, but perhaps where it is located that is important for determining metabolic consequences. Regular exercise is known to reduce risk for metabolic disease through numerous mechanisms. The purpose of this report is to highlight some of the efficacy-based data on the effects of exercise (and also a sedentary lifestyle) on abdominal obesity, visceral fat, and metabolic risk. We also discuss how impaired fatty acid oxidation (FAO) in skeletal muscle may be related to both insulin resistance and a contributor to weight gain. In summary, it is evident that exercise in sufficient amounts can lead to substantial decreases in body weight, total body fat, and visceral fat. Additionally, evidence now supports the conclusion that there is a dose–response relationship between exercise amount and these changes, i.e., more exercise leads to additional benefits. Additionally, there are a number of important cardiometabolic risk factors that were most favorably effected by moderate-intensity compared to vigorous-intensity exercise. Unfortunately, it is also apparent that in sedentary middle-aged men and women, short periods of physical inactivity lead to significant weight gain, substantial increases in visceral fat, and further metabolic deterioration. Finally, favorable modulation of mitochondrial oxidative capacity in skeletal muscle by exercise training may reduce a block for complete oxidation of fatty acids in muscle and thereby relieve a block to effective insulin signaling. PMID:19927142

  19. Probabilistic Risk Model for Organ Doses and Acute Health Effects of Astronauts on Lunar Missions

    Science.gov (United States)

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

    2009-01-01

    Exposure to large solar particle events (SPEs) is a major concern during EVAs on the lunar surface and in Earth-to-Lunar transit. 15% of crew times may be on EVA with minimal radiation shielding. Therefore, an accurate assessment of SPE occurrence probability is required for the mission planning by NASA. We apply probabilistic risk assessment (PRA) for radiation protection of crews and optimization of lunar mission planning.

  20. Effects of low-dose versus placebo or conventional-dose postmenopausal hormone therapy on variables related to cardiovascular risk: a systematic review and meta-analyses of randomized clinical trials.

    Science.gov (United States)

    Casanova, Gislaine; Bossardi Ramos, Ramon; Ziegelmann, Patrícia; Spritzer, Poli Mara

    2015-03-01

    Hormone therapy (HT), the most efficient treatment for menopausal symptoms, might have deleterious cardiovascular (CV) effects. This study aimed to evaluate the effects of low-dose estrogen HT on CV risk factors vs conventional-dose HT and placebo in postmenopausal women with no established CV disease. MEDLINE, Cochrane Central, and EMBASE were searched for trials published in 1990-2013; a hand search of reference lists of selected articles was performed; and ClinicalTrials.gov was searched for unpublished trials. Within randomized controlled trials of healthy postmenopausal women comparing low-dose HT to placebo or conventional-dose HT, 11 418 studies were initially identified. Data were independently extracted by two investigators. Disagreements were resolved by a third author. Twenty-eight trials (3360 patients) were included. Low-dose HT vs placebo or conventional-dose HT did not effect weight, body mass index (BMI), blood pressure, C-reactive protein, or high-density lipoprotein cholesterol (HDL-C). Low-dose HT was associated with lower levels of total cholesterol (-12.16 mg/dL, 95% confidence interval [CI], -17.41 - -6.92) and low-density lipoprotein cholesterol (LDL-C) (-12.16 mg/dL; 95% CI, -16.55 - -7.77) vs placebo. Compared with conventional-dose HT, low-dose HT was associated with higher total cholesterol (5.05 mg/dL; 95% CI, 0.88-9.21) and LDL-C (4.49 mg/dL; 95% CI, 0.59-8.39). Low-dose HT was not associated with differences in triglycerides vs placebo. Oral, low-dose HT was associated with lower triglycerides vs conventional-dose HT (-14.09 mg/dL; 95% CI, -24.2 - -3.93). In this population of apparently healthy postmenopausal women, the effect of low-dose HT did not differ from that of placebo or conventional-dose HT regarding weight, BMI, blood pressure, CRP, or HDL-C. In contrast, low-dose HT was associated with better lipid profile vs placebo, and induced higher total and LDL-C and lower triglycerides vs conventional-dose HT.

  1. Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J; Specht, L; Larsen, S O;

    1987-01-01

    391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t-ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk o...

  2. A tiered approach for integrating exposure and dosimetry with in vitro dose-response data in the modern risk assessment paradigm

    Science.gov (United States)

    High-throughput (HT) risk screening approaches apply in vitro dose-response data to estimate potential health risks that arise from exposure to chemicals. However, much uncertainty is inherent in relating bioactivities observed in an in vitro system to the perturbations of biolog...

  3. Intake of fruit and vegetables and risk of bladder cancer: a dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Yao, Baodong; Yan, Yujie; Ye, Xianwu; Fang, Hong; Xu, Huilin; Liu, Yinan; Li, Sheran; Zhao, Yanping

    2014-12-01

    Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial. We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose-response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013. Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69-0.99) for total fruit and vegetables, 0.81 (0.70-0.93) for total vegetables, 0.77 (0.69-0.87) for total fruit, 0.84 (0.77-0.91) for cruciferous vegetables, 0.79 (0.68-0.91) for citrus fruits, and 0.74 (0.66-0.84) for yellow-orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78-0.96), 0.80 (0.67-0.94), 0.79 (0.66-0.94), 0.79 (0.65-0.96), and 0.79 (0.64-0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow-orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow-orange vegetables. This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.

  4. Health Risk Assessment for Uranium in Groundwater - An Integrated Case Study Based on Hydrogeological Characterization and Dose Calculation

    Science.gov (United States)

    Franklin, M. R.; Veiga, L. H.; Py, D. A., Jr.; Fernandes, H. M.

    2010-12-01

    The uranium mining and milling facilities of Caetité (URA) is the only active uranium production center in Brazil. Operations take place at a very sensitive semi-arid region in the country where water resources are very scarce. Therefore, any contamination of the existing water bodies may trigger critical consequences to local communities because their sustainability is closely related to the availability of the groundwater resources. Due to the existence of several uranium anomalies in the region, groundwater can present radionuclide concentrations above the world average. The radiological risk associated to the ingestion of these waters have been questioned by members of the local communities, NGO’s and even regulatory bodies that suspected that the observed levels of radionuclide concentrations (specially Unat) could be related to the uranium mining and milling operations. Regardless the origin of these concentrations the fear that undesired health effects were taking place (e.g. increase in cancer incidence) remain despite the fact that no evidence - based on epidemiological studies - is available. This paper intends to present the connections between the local hydrogeology and the radiological characterization of groundwater in the neighboring areas of the uranium production center to understand the implications to the human health risk due to the ingestion of groundwater. The risk assessment was performed, taking into account the radiological and the toxicological risks. Samples from 12 wells have been collected and determinations of Unat, Thnat, 226Ra, 228Ra and 210Pb were performed. The radiation-related risks were estimated for adults and children by the calculation of the annual effective doses. The potential non-carcinogenic effects due to the ingestion of uranium were evaluated by the estimation of the hazard index (HI). Monte Carlo simulations were used to calculate the uncertainty associated with these estimates, i.e. the 95% confidence interval

  5. Task 3 Report - PCBs in the Environment Near the Oak Ridge Reservation - A Reconstruction of Historical Doses and Health Risks

    Energy Technology Data Exchange (ETDEWEB)

    Price, Paul S; Widner, Thomas; Bonnevie, Nancy; Schmidt, Charlie; McCrodden-Hamblen, Jane; Vantaggio, Joanne; Gwinn, Patrick

    1999-07-01

    from non -cancer effects of PCBs. However, for Watts Bar, these risks were mainly due to sources of PCBs other than the ORR; the releases from the ORR appear to have placed an additional one to two percent of the total number of fish consumers potentially at risk. This percentage corresponds to approximately 1,000-2,000 fish consumers over the last 50 years. This report is one in a set of eight technical reports on the Oak Ridge Offsite Dose Reconstruction.

  6. Probabilistic modelling of exposure doses and implications for health risk characterization: glycoalkaloids from potatoes.

    Science.gov (United States)

    Ruprich, J; Rehurkova, I; Boon, P E; Svensson, K; Moussavian, S; Van der Voet, H; Bosgra, S; Van Klaveren, J D; Busk, L

    2009-12-01

    Potatoes are a source of glycoalkaloids (GAs) represented primarily by alpha-solanine and alpha-chaconine (about 95%). Content of GAs in tubers is usually 10-100 mg/kg and maximum levels do not exceed 200 mg/kg. GAs can be hazardous for human health. Poisoning involve gastrointestinal ailments and neurological symptoms. A single intake of >1-3 mg/kg b.w. is considered a critical effect dose (CED). Probabilistic modelling of acute and chronic (usual) exposure to GAs was performed in the Czech Republic, Sweden and The Netherlands. National databases on individual consumption of foods, data on concentration of GAs in tubers (439 Czech and Swedish results) and processing factors were used for modelling. Results concluded that potatoes currently available at the European market may lead to acute intakes >1 mg GAs/kg b.w./day for upper tail of the intake distribution (0.01% of population) in all three countries. 50 mg GAs/kg raw unpeeled tubers ensures that at least 99.99% of the population does not exceed the CED. Estimated chronic (usual) intake in participating countries was 0.25, 0.29 and 0.56 mg/kg b.w./day (97.5% upper confidence limit). It remains unclear if the incidence of GAs poisoning is underreported or if assumptions are the worst case for extremely sensitive persons.

  7. Low-dose acetylsalicylic acid and bleeding risks with ventriculoperitoneal shunt placement.

    Science.gov (United States)

    Kamenova, Maria; Croci, Davide; Guzman, Raphael; Mariani, Luigi; Soleman, Jehuda

    2016-09-01

    OBJECTIVE Ventriculoperitoneal (VP) shunt placement is a common procedure for the treatment of hydrocephalus following diverse neurosurgical conditions. Most of the patients present with other comorbidities and receive antiplatelet therapy, usually acetylsalicylic acid (ASA). Despite its clinical relevance, the perioperative management of these patients has not been sufficiently investigated. The aim of this study was to compare the peri- and postoperative bleeding complication rates associated with ASA intake in patients undergoing VP shunt placement. METHODS Of 172 consecutive patients undergoing VP shunt placement between June 2009 and December 2015, 40 (23.3%) patients were receiving low-dose ASA treatment. The primary outcome measure was bleeding events in ASA users versus nonusers, whereas secondary outcome measures were postoperative cardiovascular events, hematological findings, morbidity, and mortality. A subgroup analysis was conducted in patients who discontinued ASA treatment for < 7 days (n = 4, ASA Group 1) and for ≥ 7 days (n = 36, ASA Group 2). RESULTS No statistically significant difference for bleeding events was observed between ASA users and nonusers (p = 0.30). Cardiovascular complications, surgical morbidity, and mortality did not differ significantly between the groups either. Moreover, there was no association between ASA discontinuation regimens (< 7 days and ≥ 7 days) and hemorrhagic events. CONCLUSIONS Given the lack of guidelines regarding perioperative management of neurosurgical patients with antiplatelet therapy, these findings elucidate one issue, showing comparable bleeding rates in ASA users and nonusers undergoing VP shunt placement.

  8. 40 CFR Appendix V to Part 266 - Risk Specific Doses (10−5)

    Science.gov (United States)

    2010-07-01

    ...−04 4.5E−02 1,4-Dioxane 123-91-1 1.4E−06 7.1E+00 Epichlorohydrin 106-89-8 1.2E−06 8.3E+00 Ethylene.... Unit risk (m3/μg) RsD (μg/m3) Acrylamide 79-06-1 1.3E−03 7.7E−03 Acrylonitrile 107-13-1 6.8E−05 1.5E−01 Aldrin 309-00-2 4.9E−03 2.0E−03 Aniline 62-53-3 7.4E−06 1.4E+00 Arsenic 7440-38-2 4.3E−03 2.3E−03...

  9. Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity

    Directory of Open Access Journals (Sweden)

    David Thomson

    2012-01-01

    Results. Median followup was 84 months. Five-year overall survival (OS was 83% and biochemical progression-free survival (bPFS was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

  10. Limitations in dose-response and surrogate species methodologies for risk assessment of Cry toxins on arthropod natural enemies.

    Science.gov (United States)

    Paula, Débora P; Andow, David A; Bellinati, André; Timbó, Renata Velozo; Souza, Lucas M; Pires, Carmen S S; Sujii, Edison R

    2016-04-01

    Dose-response assays and surrogate species are standard methods for risk analysis for environmental chemicals. These assume that individuals within a species have unimodal responses and that a surrogate species can predict responses of other related taxa. We exposed immature individuals of closely related aphidophagous coccinellid predators, Cycloneda sanguinea and Harmonia axyridis, to Cry1Ac and Cry1F toxins through uniform and constant artificial tritrophic exposure through Myzus persicae aphids. Both toxins were detected in coccinellid pupae, with individual and interspecific variation. Uptake was significantly higher in H. axyridis than in C. sanguinea, both in the proportion of individuals and the concentrations per individual. We also observed bimodal uptake of the Cry toxins by H. axyridis, which indicated that some individuals had low bioaccumulation and some had high bioaccumulation. This suggests that standard dose-response assays need to be interpreted with caution and future assays should examine the modality of the responses. In addition, the similarity in the biological effects of the Cry toxins in the two predators was due to different biological exposure mechanisms. The majority of H. axyridis were exposed both internally and in the gut, while C. sanguinea was exposed primarily in the gut. Thus, despite their close phylogenetic relatedness, these species would not be good surrogates for each other and the surrogate species methodology should be tested more rigorously.

  11. Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia

    Science.gov (United States)

    Castro, JE; Sandoval-Sus, JD; Bole, J; Rassenti, L; Kipps, TJ

    2017-01-01

    We examined the clinical response of fludarabine-refractory CLL patients treated with high-dose methylprednisolone (HDMP) and rituximab. Fourteen patients were treated with three cycles of rituximab (375mg/m2 weekly for 4 weeks) in combination with HDMP (1gm/m2 daily for 5 days). All patients were refractory to fludarabine and 86% had high-risk disease by the modified Rai classification. In all, 79% of the patients had CLL cells that expressed ZAP-70 and three patients had poor prognostic cytogenetics. The overall response rate was 93% and the complete remission rate was 36%. The median time-to-progression was 15 months and the median time-to-next treatment was 22 months. Median survival has not been reached after a median follow up of 40 months. Four patients have died of progressive disease. Patients tolerated the treatment well and serious adverse events were rare. This allowed patients to receive all planned treatments on schedule with no dose modifications. All but one patient responded to treatment and the overall survival and time-to-progression were superior to those of other published salvage regimens. PMID:18754025

  12. High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

    Energy Technology Data Exchange (ETDEWEB)

    Barkati, Maroie [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Williams, Scott G., E-mail: scott.williams@petermac.org [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Dyk, Sylvia van [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); See, Andrew [Ballarat Austin Radiation Oncology Centre, Ballarat (Australia); Duchesne, Gillian M. [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia)

    2012-04-01

    Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable-risk

  13. Lung nodule detection in a high-risk population: Comparison of magnetic resonance imaging and low-dose computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, Gregor, E-mail: gregor.sommer@usb.ch [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Clinic of Radiology and Nuclear Medicine, University of Basel Hospital, Basel (Switzerland); Tremper, Jan, E-mail: j.tremper@dkfz.de [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Koenigkam-Santos, Marcel, E-mail: marcelk46@yahoo.com.br [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik Heidelberg gGmbH, Amalienstr. 5, 69126 Heidelberg (Germany); Department of Radiology, University Hospital of the School of Medicine of Ribeirao Preto – University of Sao Paulo, Av. Bandeirantes 3900, Campus Universitario Monte Alegre, 14048 900 Ribeirao Preto, SP (Brazil); Delorme, Stefan, E-mail: s.delorme@dkfz.de [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Becker, Nikolaus, E-mail: n.becker@dkfz.de [Division of Cancer Epidemiology (C020), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg (Germany); Biederer, Jürgen, E-mail: juergen.biederer@uni-heidelberg.de [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); and others

    2014-03-15

    Objective: To investigate the potential of MRI for lung nodule detection in a high-risk population in comparison to low-dose CT. Methods: 49 participants (31 men, 18 women, 51–71 years) of the German Lung Cancer Screening and Intervention Trial (LUSI) with a cancer-suspicious lung lesion in CT were examined with non-contrast-enhanced MRI of the lung at 1.5 T. Data were pseudonymized and presented at random order together with 30 datasets (23 in men, 7 in women, 18–64 years) from healthy volunteers. Two radiologists read the data for the presence of nodules. Sensitivity and specificity were calculated. Gold standard was either histology or long-term follow-up. Contrast-to-Noise-Ratio (CNR) was measured for all detected lesions in all MRI sequences. Results: Average maximum diameter of the lesions was 15 mm. Overall sensitivity and specificity of MRI were 48% (26/54) and 88% (29/33) compared to low-dose CT. Sensitivity of MRI was significantly higher for malignant nodules (78% (12.5/16)) than for benign ones (36% (13.5/38); P = 0.007). There was no statistically significant difference in sensitivity between nodules (benign and malignant) larger or smaller than 10 mm (P = 0.7). Inter observer agreement was 84% (κ = 0.65). Lesion-to-background CNR of T2-weighted single-shot turbo-spin-echo was significantly higher for malignant nodules (89 ± 27) than for benign ones (56 ± 23; P = 0.002). Conclusion: The sensitivity of MRI for detection of malignant pulmonary nodules in a high-risk population is 78%. Due to its inherent soft tissue contrast, MRI is more sensitive to malignant nodules than to benign ones. MRI may therefore represent a useful test for early detection of lung cancer.

  14. Circulating hormones and breast cancer risk in premenopausal women: a randomized trial of low-dose tamoxifen and fenretinide.

    Science.gov (United States)

    Johansson, Harriet; Bonanni, Bernardo; Gandini, Sara; Guerrieri-Gonzaga, Aliana; Cazzaniga, Massimiliano; Serrano, Davide; Macis, Debora; Puccio, Antonella; Sandri, Maria Teresa; Gulisano, Marcella; Formelli, Franca; Decensi, Andrea

    2013-12-01

    Tamoxifen and fenretinide have been extensively studied and exhibit breast cancer-preventing activity. We aimed to assess their effect on sex hormones, sex hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events. In a double-blind, placebo-controlled trial, premenopausal women at risk for breast cancer were randomized to tamoxifen 5 mg/day, fenretinide, both agents, or placebo for 2 years. We measured MD and circulating concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, testosterone, androstenedione, dehydro-epiandrosteronesulfate, prolactin, SHBG, and retinol at baseline and on yearly intervals. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models. Low-dose tamoxifen markedly and enduringly increased SHBG, whereas the increases in testosterone, estradiol, and prolactin and reduction in LH weakened after 1 year. Fenretinide increased testosterone and androstenedione and decreased retinol. MD correlated directly with SHBG and inversely with retinol. After a median follow-up of 12 years, the 10-year cumulative incidence of breast cancer events was 37 % in women with SHBG ≤ 59.3 nmol/L, 22 % in women with SHBG between 59.3 and 101 nmol/L, and 19 % in women with SHBG > 101 nmol/L (P = 0.018). The difference among SHBG tertiles remained statistically significant at multivariable analysis: HR = 2.26 (95 % CI 1.04, 4.89) for the lowest versus the highest tertile. We conclude that low-dose tamoxifen or fenretinide exhibits favorable hormonal profiles as single agents, further supporting their administration for prevention of breast cancer in premenopause. Notably, SHBG levels were inversely associated with breast neoplastic events.

  15. Body Mass Index and Risk of Parkinson's Disease: A Dose-Response Meta-Analysis of Prospective Studies.

    Directory of Open Access Journals (Sweden)

    Yun-Liang Wang

    Full Text Available A number of epidemiologic studies examining the relationship between body mass index (BMI and the future occurrence of Parkinson's disease (PD reported largely inconsistent findings. We conducted a dose-response meta-analysis of prospective studies to clarify this association.Eligible prospective studies were identified by a search of PubMed and by checking the references of related publications. The generalized least squares trend estimation was employed to compute study-specific relative risks (RR and 95% confidence intervals (CI for an increase in BMI of 5 kg/m2, and the random-effects model was used to compute summary RR and 95% CI.A total of 10 prospective studies were included in the final analysis. An increase in BMI of 5 kg/m2 was not associated with PD risk, with a summary RR of 1.00 (95% CI = 0.89-1.12. Results of subgroup analysis found similar results except for a week positive association in studies that adjusted for alcohol consumption (RR = 1.13, 95% CI = 0.99-1.29, and a week inverse association in studies that did not (RR = 0.90, 95% CI = 0.78-1.04. In a separate meta-analysis, no significant association between overweight (25 kg/m2 ≤ BMI ≤29.9 kg/m2, obesity (BMI≥30 kg/m2 or excess weight (BMI≥25 kg/m2 and PD risk was observed.This meta-analysis does not support the notion that higher BMI materially increases PD risk. However, a week positive BMI-PD association that may be masked by confounders still cannot be excluded, and future prospective studies with a good control for potential confounding factors are needed.

  16. Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

    Directory of Open Access Journals (Sweden)

    Shakespeare TP

    2016-03-01

    Full Text Available Thomas P Shakespeare,1,2 Shea W Wilcox,1 Noel J Aherne1,2 1Department of Radiation Oncology, North Coast Cancer Institute, 2Faculty of Medicine, Rural Clinical School, The University of New South Wales, Coffs Harbour, New South Wales, Australia Background: Both dose-escalated external beam radiotherapy (DE-EBRT and androgen deprivation therapy (ADT improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings: In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion: There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. Keywords: radiotherapy, IMRT, dose, dose escalation, dose de-escalation, androgen deprivation therapy

  17. POTENTIAL APPLICATIONS OF IMAGE-GUIDED RADIOTHERAPY FOR RADIATION DOSE ESCALATION IN PATIENTS WITH EARLY STAGE HIGH-RISK PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    Nam Phong Nguyen

    2015-02-01

    Full Text Available Patients with early stage high-risk prostate cancer (PSA >20, Gleason score >7 are at high risk of recurrence following prostate cancer irradiation. Radiation dose escalation to the prostate may improve biochemical free survival for these patients. However, high rectal and bladder dose with conventional three-dimensional conformal radiotherapy (3D-CRT may lead to excessive gastrointestinal and genitourinary toxicity. Image-guided radiotherapy (IGRT, by virtue of combining the steep dose gradient of intensity-modulated radiotherapy (IMRT and daily pretreatment imaging, may allow for radiation dose escalation and decreased treatment morbidity. Reduced treatment time is feasible with hypofractionated IGRT and it may improve patient quality of life.

  18. Lack of benefit for the addition of androgen deprivation therapy to dose-escalated radiotherapy in the treatment of intermediate- and high-risk prostate cancer.

    LENUS (Irish Health Repository)

    Krauss, Daniel

    2012-02-01

    PURPOSE: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). METHODS AND MATERIALS: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng\\/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA >\\/=20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. RESULTS: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason >\\/=8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. CONCLUSION: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.

  19. Coffee consumption and risk of endometrial cancer: a dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Zhou, Quan; Luo, Mei-Ling; Li, Hui; Li, Min; Zhou, Jian-Guo

    2015-08-25

    This is a dose-response (DR) meta-analysis to evaluate the association of coffee consumption on endometrial cancer (EC) risk. A total 1,534,039 participants from 13 published articles were added in this meta-analysis. The RR of total coffee consumption and EC were 0.80 (95% CI: 0.74-0.86). A stronger association between coffee intake and EC incidence was found in patients who were never treated with hormones, 0.60 (95% CI: 0.50-0.72), and subjects with a BMI ≥25 kg/m(2), 0.57 (95% CI: 0.46-0.71). The overall RRs for caffeinated and decaffeinated coffee were 0.66 (95% CI: 0.52-0.84) and 0.77 (95% CI: 0.63-0.94), respectively. A linear DR relationship was seen in coffee, caffeinated coffee, decaffeinated coffee and caffeine intake. The EC risk decreased by 5% for every 1 cup per day of coffee intake, 7% for every 1 cup per day of caffeinated coffee intake, 4% for every 1 cup per day of decaffeinated intake of coffee, and 4% for every 100 mg of caffeine intake per day. In conclusion, coffee and intake of caffeine might significantly reduce the incidence of EC, and these effects may be modified by BMI and history of hormone therapy.

  20. The Correlation of Age Factor, Administration, and Metformin Dose Against Risk of Side Effect on Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Magdarita Riwu

    2015-09-01

    Full Text Available Metformin is an antidiabetic oral medicine commonly recommended as first line treatment on type 2 diabetes mellitus. Metformin can caused drug related problems (DRPs such as gastrointestinal disorders, e.g. diarrhea, nausea, and flatulence. This study aimed to analyze correlation profiles on age, administration, and metformin dosage factors against risk of gastrointestinal disorders among newly diagnosed diabetic outpatients of National Health Insurance in RSAU Dr. M. Salamun Bandung. This study was an analytic observational study with a cross sectional method. The study was carried out in the internal medicine outpatient clinic and data were extracted from patients medical records from April to June 2014. Metformin-treated patients were interviewed using a form check. The number of patients were 65 with the median rate was 48 years old. Side effect reported were flatulence (58.46% and nausea (41.54%. Administration and metformin dosage factors were correlated to the risk of side effects such as nausea and flatulence on type 2 diabetes mellitus (p0.05. The administration of metformin is recommended after meals and with a lower initial dose titrated slowly to reduce and avoid the side effects of nausea and flatulence in patients with type 2 diabetes mellitus.

  1. Potential Offsite Radiological Doses Estimated for the Proposed Divine Strake Experiment, Nevada Test Site

    Energy Technology Data Exchange (ETDEWEB)

    Ron Warren

    2006-12-01

    An assessment of the potential radiation dose that residents offsite of the Nevada Test Site (NTS) might receive from the proposed Divine Strake experiment was made to determine compliance with Subpart H of Part 61 of Title 40 of the Code of Federal Regulations, National Emission Standards for Emissions of Radionuclides Other than Radon from Department of Energy Facilities. The Divine Strake experiment, proposed by the Defense Threat Reduction Agency, consists of a detonation of 700 tons of heavy ammonium nitrate fuel oil-emulsion above the U16b Tunnel complex in Area 16 of the NTS. Both natural radionuclides suspended, and historic fallout radionuclides resuspended from the detonation, have potential to be transported outside the NTS boundary by wind. They may, therefore, contribute radiological dose to the public. Subpart H states ''Emissions of radionuclides to the ambient air from Department of Energy facilities shall not exceed those amounts that would cause any member of the public to receive in any year an effective dose equivalent of 10 mrem/yr'' (Title 40 of the Code of Federal Regulations [CFR] 61.92) where mrem/yr is millirem per year. Furthermore, application for U.S. Environmental Protection Agency (EPA) approval of construction of a new source or modification of an existing source is required if the effective dose equivalent, caused by all emissions from the new construction or modification, is greater than or equal to 0.1 mrem/yr (40 CFR 61.96). In accordance with Section 61.93, a dose assessment was conducted with the computer model CAP88-PC, Version 3.0. In addition to this model, a dose assessment was also conducted by the National Atmospheric Release Advisory Center (NARAC) at the Lawrence Livermore National Laboratory. This modeling was conducted to obtain dose estimates from a model designed for acute releases and which addresses terrain effects and uses meteorology from multiple locations. Potential radiation dose to a

  2. Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies

    Directory of Open Access Journals (Sweden)

    Xin Fang

    2016-11-01

    Full Text Available The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs, odds ratios (ORs or hazard ratios (HRs, for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%–13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.

  3. Risk Factors of anemia in head and neck cancer patients undergoing chemotherapy with high-dose cisplatin

    Directory of Open Access Journals (Sweden)

    Johan Kurnianda

    2008-12-01

    Full Text Available Cisplatin is well-known for its effectiveness against cancer, as well as its toxicity to human tissues. Of several documented side effects, anemia was reported to have significant association with decreased quality of life. This study was conducted to investigate development of cisplatin-induced anemia, and to identify independent factors contributing to anemia. Clinical data from head and neck cancer patients treated with high-dose cisplatin between December 2002 and December 2005 were obtained in this study. Incidence and risk factors of anemia were assessed in a model including age, sex, baseline hemoglobin level, baseline creatinine clearance, and occurrence of distant metastases. Multivariate logistic regression was used to define independent predictors of anemia. Among 86 eligible patients, 26 (30.2% developed anemia, defined as Hb level lower than 11 g/dL. Age > 55 years old (RR = 2.2, 95% CI, 1.2-4.0, female sex (RR = 2.0, 95% CI, 1.2-3.8, baseline Hb ≤ 13 g/dL (RR = 4.2, 95% CI, 1.9-9.4 and baseline CrCl < 50 mL/min (RR = 2.9, 95% CI, 1.7-5.1 were significantly correlated with incidence of anemia (P < 0.05. In multivariate analysis, baseline Hb and baseline CrCl were identified as independent risk factors for anemia. However, considerable confounding was observed in baseline CrCl after stratified by age (aRR = 2.2, 95% CI, 1.1-4.7. Thus, baseline Hb level was the strongest predictor of anemia. The findings suggested that baseline Hb and CrCl were useful to recognize cisplatin-treated patients at risk for anemia who might benefits from preventive measures. (Med J Indones 2008; 17: 248-54Keywords: anemia, cisplatin, chemotherapy, hemoglobin, creatinine clearance

  4. Dose-response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women

    Science.gov (United States)

    Yang, Yang; Gao, Jing; Li, Hong-Lan; Zheng, Wei; Yang, Gong; Zhang, Wei; Ma, Xiao; Tan, Yu-Ting; Rothman, Nat; Gao, Yu-Tang; Chow, Wong-Ho; Shu, Xiao-Ou; Xiang, Yong-Bing

    2016-01-01

    We aimed at evaluating the risk of liver cancer in different levels of HBsAg among Chinese men and women. We carried out a nested case-control study including 363 cases and 3,511 controls in two population-based cohorts in Shanghai. Plasma samples collected at enrollment were quantified for HBsAg levels using the Architect QT assay. Conditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95%CIs) for liver cancer, with adjustment for potential confounders. HBsAg was detected in 6.29% of control subjects overall (7.02% in men and 4.98% in women). HBsAg levels were positively associated with liver cancer risk in a dose-response manner (Ptrend<0.001). Such association showed a significant gender disparity. With increasing levels of HBsAg, liver cancer risks rose more steeply in men than in women. In men, the adjusted ORs increased from 7.27 (95%CI: 3.49–15.15) at the lowest detectable level of HBsAg (5–9 IU/ml) to 7.16 (95%CI: 3.21–15.96), 34.30 (95%CI: 16.94–69.44), and 47.33 (95%CI: 23.50–95.34) at the highest level of HBsAg (≥1,000 IU/ml) compared to those negative for HBsAg. The corresponding ORs were much lower for women, from 1.37 (95%CI: 0.25–7.47) to 3.81 (95%CI: 1.09–13.28), 7.36 (95%CI: 2.41–22.46), and 16.86 (95%CI: 7.24–39.27), respectively. HBsAg quantification has potential to distinguish individuals at different risks of liver cancer. Men with the lowest detectable level of HBsAg should still pay attention to their liver cancer risks, but those with a higher level may be given a higher priority in future liver cancer surveillance program. PMID:26990915

  5. High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma.

    Science.gov (United States)

    Yalçin, Bilgehan; Kremer, Leontien C M; van Dalen, Elvira C

    2015-10-05

    Despite the development of new treatment options, the prognosis of high-risk neuroblastoma patients is still poor; more than half of patients experience disease recurrence. High-dose chemotherapy and haematopoietic stem cell rescue (i.e. myeloablative therapy) might improve survival. This review is the second update of a previously published Cochrane review. Primary objectiveTo compare the efficacy, that is event-free and overall survival, of high-dose chemotherapy and autologous bone marrow or stem cell rescue with conventional therapy in children with high-risk neuroblastoma. Secondary objectivesTo determine adverse effects (e.g. veno-occlusive disease of the liver) and late effects (e.g. endocrine disorders or secondary malignancies) related to the procedure and possible effects of these procedures on quality of life. We searched the electronic databases The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, issue 11), MEDLINE/PubMed (1966 to December 2014) and EMBASE/Ovid (1980 to December 2014). In addition, we searched reference lists of relevant articles and the conference proceedings of the International Society for Paediatric Oncology (SIOP) (from 2002 to 2014), American Society for Pediatric Hematology and Oncology (ASPHO) (from 2002 to 2014), Advances in Neuroblastoma Research (ANR) (from 2002 to 2014) and American Society for Clinical Oncology (ASCO) (from 2008 to 2014). We searched for ongoing trials by scanning the ISRCTN register (www.isrct.com) and the National Institute of Health Register (www.clinicaltrials.gov). Both registers were screened in April 2015. Randomised controlled trials (RCTs) comparing the efficacy of myeloablative therapy with conventional therapy in high-risk neuroblastoma patients. Two authors independently performed study selection, data extraction and risk of bias assessment. If appropriate, we pooled studies. The risk ratio (RR) and 95% confidence interval (CI) was calculated for dichotomous

  6. The toxicity of radiotherapy following high-dose chemotherapy with peripheral blood serum cell support in high-risk breast cancer: a preliminary analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wall, E. van der; Schaake-Koning, C.C.E.; Zandwijk, N. van [Nederlands Kanker Inst. `Antoni van Leeuwenhoekhuis`, Amsterdam (Netherlands)] [and others

    1996-08-01

    High-dose chemotherapy with autologous bone marrow and/or peripheral blood stem cell (PBSC) support is increasingly employed in the adjuvant treatment of high-risk breast cancer. Subsequent radiotherapy has been reported to be associated with morbidity and mortality resulting from pulmonary toxicity. In addition, the course of radiation therapy may be hampered by excess myelosuppression. The aim of this study was to investigate the contribution to radiation-induced toxicity of a high-dose chemotherapy regimen (CTC) that incorporates cyclophosphamide, thiotepa and carboplatin, in patients with high-risk breast cancer. (author).

  7. Permanent interstitial low-dose-rate brachytherapy for patients with low risk prostate cancer. An interim analysis of 312 cases

    Energy Technology Data Exchange (ETDEWEB)

    Badakhshi, Harun; Graf, Reinhold; Budach, Volker; Wust, Peter [University Hospital Berlin, Department for Radiation Oncology of Charite School of Medicine, Berlin (Germany)

    2015-04-01

    The biochemical relapse-free survival (bRFS) rate after treatment with permanent iodine-125 seed implantation (PSI) or combined seeds and external beam radiotherapy (COMB) for clinical stage T1-T2 localized prostate cancer is a clinically relevant endpoint. The goal of this work was to evaluate the influence of relevant patient- and treatment-related factors. The study population comprised 312 consecutive patients treated with permanent seed implantation. All patients were evaluable for analysis of overall survival (OS) and disease-specific survival (DSS), 230 for bRFS, of which 192 were in the PSI group and 38 in the COMB group. The prescribed minimum peripheral dose was 145 Gy for PSI, for COMB 110 Gy implant and external beam radiotherapy of 45 Gy. The median follow-up time was 33 months (range 8-66 months). bRFS was defined as a serum prostate-specific antigen (PSA) level ≤ 0.2 ng/ml at last follow-up. Overall, the actuarial bRFS at 50 months was 88.4 %. The 50-month bRFS rate for PSI and COMB was 90.9 %, and 77.2 %, respectively. In the univariate analysis, age in the categories ≤ 63 and > 63 years (p < 0.00), PSA nadir (≤ 0.5 ng/ml and > 0.5 ng/ml) and PSA bounce (yes/no) were the significant predicting factors for bRFS. None of the other patient and treatment variables (treatment modality, stage, PSA, Gleason score, risk group, number of risk factors, D90 and various other dose parameters) were found to be a statistically significant predictor of 50-month bRFS. The biochemical failure rates were low in this study. As a proof of principle, our large monocenteric analysis shows that low-dose-rate brachytherapy is an effective and safe procedure for patients with early stage prostate cancer. (orig.) [German] Das biochemisch rezidivfreie Ueberleben (bRFS) nach der Brachytherapie mit permanenter Iod-125-Seed-Implantation (PSI) oder in Kombination mit externer Radiotherapie (COMB) ist beim Patienten mit fruehem Prostatakarzinom (T1/T2) ein relevanter

  8. Health risks from arsenic-contaminated soil in Flin Flon-Creighton, Canada: Integrating geostatistical simulation and dose-response model

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Hua [Environmental Systems Engineering Program, Faculty of Engineering, University of Regina, Regina, Saskatchewan, S4S 0A2 (Canada); Huang Guohe, E-mail: huang@iseis.or [Environmental Systems Engineering Program, Faculty of Engineering, University of Regina, Regina, Saskatchewan, S4S 0A2 (Canada); Zeng Guangming [College of Environmental Science and Engineering, Hunan University, Changsha, Hunan 410082 (China)

    2009-08-15

    Elevated concentrations of arsenic were detected in surface soils adjacent to a smelting complex in northern Canada. We evaluated the cancer risks caused by exposure to arsenic in two communities through combining geostatistical simulation with demographic data and dose-response models in a framework. Distribution of arsenic was first estimated using geostatistical circulant-embedding simulation method. We then evaluated the exposures from inadvertent ingestion, inhalation and dermal contact. Risks of skin caner and three internal cancers were estimated at both grid scale and census-unit scale using parametric dose-response models. Results indicated that local residents could face non-negligible cancer risks (skin cancer and liver cancer mainly). Uncertainties of risk estimates were discussed from the aspects of arsenic concentrations, exposed population and dose-response model. Reducing uncertainties would require additional soil sampling, epidemic records as well as complementary studies on land use, demographic variation, outdoor activities and bioavailability of arsenic. - Cancer risks induced by arsenic in soil were evaluated using geostatistical simulation and dose-response model.

  9. The Impact of Clinical Stage on Radiation Doses to Organs at Risk Following Intensity-modulated Radiotherapy in Nasopharyngeal Carcinoma: A Prospective Analysis.

    Science.gov (United States)

    Xu, Lin; Yao, Ji-Jin; Zhou, Guan-Qun; Zhang, Wang-Jian; Liu, Guo-Long; Liu, Li-Zhi; Ma, Jun; Sun, Ying

    2016-01-01

    Background: The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to investigate the impact of clinical stage on radiation doses to organs at risk (OARs) in NPC. Material and Methods: One hundred and forty-eight patients with newly diagnosed and untreated NPC were prospectively enrolled. Based on the anatomic definition and pathogenesis of radiation induced injury, a total of 28 OARs surrounding the nasopharynx were contoured on axial computed tomography (CT) planning images in each patient. Dose-volume histograms, as well as the mean and maximal doses for each structure, were calculated. Results: Radiation doses to 15 OARs (including the brain stem, temporal lobe and eye) were positively correlated with T stage, the radiation doses to 13 OARs (including the brachial plexus, parotid and thyroid) increased significantly with N stage, and the radiation doses to the spinal cord and mandible had no association with T or N stage. Based on the characteristic of excess rates, 9 OARs (e.g. spinal cord, eye, trachea, and et al.) met tolerance doses easily in all stages, 9 OARs (e.g. brain stem, temporal lobe, brachial plexus, and et al.) easily in early stages but with difficulty in advanced stages, and 10 OARs (e.g. cochlea, parotid, thyroid, and et al.) with difficulty in all stages. Conclusions: The radiation doses to most of OARs are associated with T or N stage, and there are three kinds of patterns for them: 1) meet tolerance doses easily in all stages; 2) meet tolerance doses easily in early stages but with difficulty in advanced stages; and 3) meet tolerance doses with difficulty in all stages.

  10. Radiation passport: an iPhone and iPod touch application to track radiation dose and estimate associated cancer risks.

    Science.gov (United States)

    Baerlocher, Mark Otto; Talanow, Roland; Baerlocher, Adrian F

    2010-04-01

    The rapid increase in the use of radiology and related exams and procedures has led to a concomitant increase in associated radiation risk. An application for the iPhone and iPod Touch called 'Radiation Passport' is described, which provides radiation dose estimates and associated cancer risks (non fatal and fatal) and serves as a method by which to track an individual's cumulative exposure.

  11. Quantification of Contralateral Breast Dose and Risk Estimate of Radiation-Induced Contralateral Breast Cancer Among Young Women Using Tangential Fields and Different Modes of Breathing

    Energy Technology Data Exchange (ETDEWEB)

    Zurl, Brigitte, E-mail: brigitte.zurl@klinikum-graz.at [Department of Therapeutic Radiology and Oncology, Medical University of Graz (Austria); Stranzl, Heidi; Winkler, Peter; Kapp, Karin Sigrid [Department of Therapeutic Radiology and Oncology, Medical University of Graz (Austria)

    2013-02-01

    Purpose: Whole breast irradiation with deep-inspiration breath-hold (DIBH) technique among left-sided breast cancer patients significantly reduces cardiac irradiation; however, a potential disadvantage is increased incidental irradiation of the contralateral breast. Methods and Materials: Contralateral breast dose (CBD) was calculated by comparing 400 treatment plans of 200 left-sided breast cancer patients whose tangential fields had been planned on gated and nongated CT data sets. Various anatomic and field parameters were analyzed for their impact on CBD. For a subgroup of patients (aged {<=}45 years) second cancer risk in the contralateral breast (CB) was modeled by applying the linear quadratic model, compound models, and compound models considering dose-volume information (DVH). Results: The mean CBD was significantly higher in DIBH with 0.69 Gy compared with 0.65 Gy in normal breathing (P=.01). The greatest impact on CBD was due to a shift of the inner field margin toward the CB in DIBH (mean 0.4 cm; range, 0-2), followed by field size in magnitude. Calculation with different risk models for CBC revealed values of excess relative risk/Gy ranging from 0.48-0.65 vs 0.46-0.61 for DIBH vs normal breathing, respectively. Conclusion: Contralateral breast dose, although within a low dose range, was mildly but significantly increased in 200 treatment plans generated under gated conditions, predominately due to a shift in the medial field margin. Risk modeling for CBC among women aged {<=}45 years also pointed to a higher risk when comparing DIBH with normal breathing. This risk, however, was substantially lower in the model considering DVH information. We think that clinical decisions should not be affected by this small increase in CBD with DIBH because DIBH is effective in reducing the dose to the heart in all patients.

  12. Benefit of standard versus low-dose tirofiban for percutaneous coronary intervention in very elderly patients with high-risk acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    Yun-ling LIN; Liang-long CHEN; Yu-kun LUO; Xing-chun ZHENG; Wei-wei LI

    2009-01-01

    Aim: This study aimed to compare the efficacy and safety between standard and low-dose tirofiban in the treatment of elderly high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients who underwent percutaneous coronary intervention (PCI).Methods: Ninety-four very elderly (≥80 years) high-risk patients with NSTE-ACS were randomly assigned to the standard myocardial infarction (TIMI) grade flow were assessed. The major adverse cardiac events (MACEs), including death, myocardial infarction, recurrent angina and urgent target-vessel revascularization (TVR), were documented at 7 d, 30 d, and 6 months, and bleeding events were recorded at 7 d.Results: Although a significantly higher inhibition of platelet aggregation was observed in the standard-dose group (P0.05). The rate of MACEs was not significantly different at 7 days (2.1% vs 4.4%, P=0.61), 30 days(6.3% vs 8.7%, P=0.71) and 6 months (14.6% vs 17.4%, P=0.71). Major bleeding events were significantly higher in the standard-dose group (10.4% vs 0.0%, P=0.03).Conclusion: In very elderly high-risk patients with NSTE-ACS undergoing PCI, low-dose tirofiban offered about the same level of protection from major ischemic events that standard doses did, with less associated bleeding.

  13. A dose-response of consuming high fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults

    Science.gov (United States)

    National Health and Nutrition Examination Survey data show increased risk of cardiovascular disease (CVD) mortality with increased intake of added sugar across quintiles. Objective: To determine the dose response effects of consuming beverages sweetened with high fructose corn syrup (HFCS) at zero, ...

  14. Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients

    NARCIS (Netherlands)

    Nieboer, P; de Vries, Elisabeth G. E.; Mulder, Nanno; Rodenhuis, S; Bontenbal, M; van der Wall, E; van Hoesel, Q G; Smit, W M; Hupperets, P; Voest, E E; Nooij, M A; Boezen, H M; van der Graaf, W T A

    2008-01-01

    Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and

  15. Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients.

    NARCIS (Netherlands)

    Nieboer, P.; Vries, E.G. de; Mulder, N.H.; Rodenhuis, S.; Bontenbal, M.; Wall, E. van der; Hoesel, Q.G.C.M. van; Smit, W.M.; Hupperets, P.; Voest, E.E.; Nooij, M.A.; Boezen, H.M.; Graaf, W.T.A. van der

    2008-01-01

    Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and

  16. Occupational Exposure to Knee Loading and the Risk of Osteoarthritis of the Knee: A Systematic Review and a Dose-Response Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Jos Verbeek

    2017-06-01

    Conclusion: There is moderate quality evidence that longer cumulative exposure to kneeling or squatting at work leads to a higher risk of osteoarthritis of the knee. For other exposure, there was no exposure dose-response or there were insufficient data to establish this. More reliable exposure measurements would increase the quality of the evidence.

  17. The effect of induction chemotherapy on tumor volume and organ-at-risk doses in patients with locally advanced oropharyngeal cancer

    NARCIS (Netherlands)

    Doornaert, Patricia; Dahele, Max; Verbakel, Wilko F. A. R.; Bohoudi, Omar; Slotman, Ben J.; Langendijk, Johannes A.

    2013-01-01

    Background and purpose: To retrospectively report changes in gross tumor volume (GTV) and organ-at-risk (OAR) doses after induction chemotherapy (IC) in oropharyngeal cancer using different contouring strategies. Materials and methods: GTV and OARs were delineated on pre- and post-IC planning CT. Tw

  18. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

    DEFF Research Database (Denmark)

    Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach

    2011-01-01

    Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hy...

  19. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study

    NARCIS (Netherlands)

    Hylckama Vlieg, van A.; Helmerhorst, F.M.; Vandenbroucke, J.P.; Doggen, C.J.M.; Rosendaal, F.R.

    2009-01-01

    Objective To assess the thrombotic risk associated with oral contraceptive use with a focus on dose of oestrogen and type of progestogen of oral contraceptives available in the Netherlands. Design Population based case-control study. Setting Six participating anticoagulation clinics in the Nethe

  20. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

    DEFF Research Database (Denmark)

    Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach;

    2011-01-01

    Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization...

  1. EDITORIAL Complexity of advanced radiation therapy necessitates multidisciplinary inquiry into dose reconstruction and risk assessment Complexity of advanced radiation therapy necessitates multidisciplinary inquiry into dose reconstruction and risk assessment

    Science.gov (United States)

    Newhauser, Wayne

    2010-07-01

    from the symposium are interrelated and focus on dose and risk assessments related to radiation exposures from advanced radiation therapies. These research topics have become increasingly complex and require the combined expertise of researchers with highly specialized and diverse investigational skills. Innovative multidisciplinary teams will be needed to achieve breakthroughs and, ultimately, to translate the research into clinical practice (Disis and Slattery 2010). The symposium's scientific goals included fostering and promoting such multidisciplinary teams, which will work to solve these complex problems and thereby improve cancer outcomes. To help clarify how the 13 articles each contribute to the goal of improving cancer outcomes, a brief digression is necessary. The proportion of patients surviving their cancers for five years or more is large and increasing (Jemal et al 2009). Unfortunately, in survivors who received radiation therapy, the prevalence of radiogenic late effects is likewise large and increasing (cf Altekruse et al 2010, Meadows et al 2009, Hudson et al 2009, Friedman et al 2010), with the potential to become a public health issue of considerable scale (Travis 2006). A multitude of late effects are associated with radiation exposure, including the development of second cancers, cardiac toxicity, cognitive deficits, and musculoskeletal growth abnormalities in children. In modern radiation therapy, much effort is devoted to developing personalized treatments that control the tumor while minimizing acute toxicities to surrounding healthy tissues; comparatively less attention has been paid to minimizing late effects (Durante and Loeffler 2010). In recent years, however, there has been an encouraging increase in research activities seeking to quantify radiation exposures (Stovall et al 2006) and the associated risks of late effects from modern external-beam therapies (Xu et al 2008). In this issue, Zhang et al (2010) report on Monte Carlo and

  2. The European strategy on low dose risk research and the role of radiation quality according to the recommendations of the "ad hoc" High Level and Expert Group (HLEG).

    Science.gov (United States)

    Belli, Mauro; Ottolenghi, Andrea; Weiss, Wolfgang

    2010-08-01

    Health effects of exposures at low doses and/or low dose rates are recognized as requiring intensive research activity to answer several questions. To address these issues at a strategic level in Europe, with the perspective of integrating national and EC efforts (in particular those within the Euratom research programmes), a "European High Level and Expert Group (HLEG) on low dose risk research" was formed and carried out its work during 2008. The Group produced a report published by the European Commission in 2009 and available on the website http://www.hleg.de . The more important research issues identified by the HLEG were as follows: (a) the shape of dose-response for cancer; (b) the tissue sensitivities for cancer induction; (c) the individual variability in cancer risk; (d) the effects of radiation quality (type); (e) the risks from internal radiation exposure; and (f) the risks of, and dose response relationships for, non-cancer diseases. In this paper, the radiation quality issues are especially considered, since they are closely linked to health problems and related radioprotection in space and in emerging radiotherapeutic techniques (i.e., hadrontherapy). The peculiar features of low-fluence, high-LET radiation exposures can question in particular the validity of the radiation-weighting factor (w ( R )) approach. Specific strategies are therefore needed to assess such risks. A multi-scale/systems biology approach, based on mechanistic studies coordinated with molecular-epidemiological studies, is considered essential to elucidate differences and similarities between specific effects of low- and high-LET radiation.

  3. Red and processed meat consumption and the risk of lung cancer: a dose-response meta-analysis of 33 published studies.

    Science.gov (United States)

    Xue, Xiu-Juan; Gao, Qing; Qiao, Jian-Hong; Zhang, Jie; Xu, Cui-Ping; Liu, Ju

    2014-01-01

    This meta-analysis was to summarize the published studies about the association between red/processed meat consumption and the risk of lung cancer. 5 databases were systematically reviewed, and random-effect model was used to pool the study results and to assess dose-response relationships. Results shown that six cohort studies and twenty eight case-control studies were included in this meat-analysis. The pooled Risk Radios (RR) for total red meat and processed meat were 1.44 (95% CI, 1.29-1.61) and 1.23 (95% CI, 1.10-1.37), respectively. Dose-response analysis revealed that for every increment of 120 grams red meat per day the risk of lung cancer increases 35% and for every increment of 50 grams red meat per day the risk of lung cancer increases 20%. The present dose-response meta-analysis suggested that both red and processed meat consumption showed a positive effect on lung cancer risk.

  4. Investigation of sinonasal anatomy via low-dose multidetector CT examination in chronic rhinosinusitis patients with higher risk for perioperative complications.

    Science.gov (United States)

    Fraczek, Marcin; Guzinski, Maciej; Morawska-Kochman, Monika; Krecicki, Tomasz

    2017-02-01

    The aim of the study was to compare visualisation of the surgically relevant anatomical structures via low- and standard-dose multidetector CT protocol in patients with chronic rhinosinusitis (CRS) and higher risk for perioperative complications (i.e. presence of bronchial asthma, history of sinus surgery and advanced nasal polyposis). 135 adult CRS patients were divided randomly into standard-dose (120 kVp, 100 mAs) or low-dose CT groups (120 kVp, 45 mAs). The detectability of the vital anatomical structures (anterior ethmoid artery, optic nerve, cribriform plate and lamina papyracea) was scored using a five-point scale (from excellent to unacceptable) by a radiologist and sinus surgeon. Polyp sizes were quantified endoscopically according to the Lildholdt's scale (LS). Olfactory function was tested with the "Sniffin' Sticks" test. On the low-dose CT images, detectability ranged from 2.42 (better than poor) for cribriform plate among anosmic cases to 4.11 (better than good) for lamina papyracea in cases without nasal polyps. Identification of lamina papyracea on low-dose scans was significantly worse in each group and the same was the case with cribriform plates in patients with advanced polyposis and anosmia. Cribriform plates were the most poorly identified (between poor and average) among all the structures on low-dose images. Identification of anterior ethmoid artery (AEA) with reduced dose was insignificantly worse than with standard-dose examination. The AEA was scored as an average-defined structure and was the second weakest visualised. In conclusion, preoperatively, low-dose protocols may not sufficiently visualise the surgically relevant anatomical structures in patients with CRS and bronchial asthma, advanced nasal polyps (LS > 2) and history of sinus surgery. Low mAs value enables comparable detectability of sinonasal landmarks with standard-dose protocols in patients without analysed risk factors. In the context of planned surgery, the current

  5. Low-dose head computed tomography in children: a single institutional experience in pediatric radiation risk reduction: clinical article.

    Science.gov (United States)

    Morton, Ryan P; Reynolds, Renee M; Ramakrishna, Rohan; Levitt, Michael R; Hopper, Richard A; Lee, Amy; Browd, Samuel R

    2013-10-01

    In this study, the authors describe their experience with a low-dose head CT protocol for a preselected neurosurgical population at a dedicated pediatric hospital (Seattle Children's Hospital), the largest number of patients with this protocol reported to date. All low-dose head CT scans between October 2011 and November 2012 were reviewed. Two different low-dose radiation dosages were used, at one-half or one-quarter the dose of a standard head CT scan, based on patient characteristics agreed upon by the neurosurgery and radiology departments. Patient information was also recorded, including diagnosis and indication for CT scan. Six hundred twenty-four low-dose head CT procedures were performed within the 12-month study period. Although indications for the CT scans varied, the most common reason was to evaluate the ventricles and catheter placement in hydrocephalic patients with shunts (70%), followed by postoperative craniosynostosis imaging (12%). These scans provided adequate diagnostic imaging, and no patient required a follow-up full-dose CT scan as a result of poor image quality on a low-dose CT scan. Overall physician comfort and satisfaction with interpretation of the images was high. An additional 2150 full-dose head CT scans were performed during the same 12-month time period, making the total number of CT scans 2774. This value compares to 3730 full-dose head CT scans obtained during the year prior to the study when low-dose CT and rapid-sequence MRI was not a reliable option at Seattle Children's Hospital. Thus, over a 1-year period, 22% of the total CT scans were able to be converted to low-dose scans, and full-dose CT scans were able to be reduced by 42%. The implementation of a low-dose head CT protocol substantially reduced the amount of ionizing radiation exposure in a preselected population of pediatric neurosurgical patients. Image quality and diagnostic utility were not significantly compromised.

  6. Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose–volume histograms

    Energy Technology Data Exchange (ETDEWEB)

    Sugano, Yasutaka [Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Mizuta, Masahiro [Laboratory of Advanced Data Science, Information Initiative Center, Hokkaido University, Kita-11, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0811 (Japan); Takao, Seishin; Shirato, Hiroki; Sutherland, Kenneth L. [Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Date, Hiroyuki, E-mail: date@hs.hokudai.ac.jp [Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan)

    2015-11-15

    Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.

  7. Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study

    Science.gov (United States)

    Dalichampt, Marie; Raguideau, Fanny; Ricordeau, Philippe; Blotière, Pierre-Olivier; Rudant, Jérémie; Alla, François; Zureik, Mahmoud

    2016-01-01

    Objective To assess the risk of pulmonary embolism, ischaemic stroke, and myocardial infarction associated with combined oral contraceptives according to dose of oestrogen (ethinylestradiol) and progestogen. Design Observational cohort study. Setting Data from the French national health insurance database linked with data from the French national hospital discharge database. Participants 4 945 088 women aged 15-49 years, living in France, with at least one reimbursement for oral contraceptives and no previous hospital admission for cancer, pulmonary embolism, ischaemic stroke, or myocardial infarction, between July 2010 and September 2012. Main outcome measures Relative and absolute risks of first pulmonary embolism, ischaemic stroke, and myocardial infarction. Results The cohort generated 5 443 916 women years of oral contraceptive use, and 3253 events were observed: 1800 pulmonary embolisms (33 per 100 000 women years), 1046 ischaemic strokes (19 per 100 000 women years), and 407 myocardial infarctions (7 per 100 000 women years). After adjustment for progestogen and risk factors, the relative risks for women using low dose oestrogen (20 µg v 30-40 µg) were 0.75 (95% confidence interval 0.67 to 0.85) for pulmonary embolism, 0.82 (0.70 to 0.96) for ischaemic stroke, and 0.56 (0.39 to 0.79) for myocardial infarction. After adjustment for oestrogen dose and risk factors, desogestrel and gestodene were associated with statistically significantly higher relative risks for pulmonary embolism (2.16, 1.93 to 2.41 and 1.63, 1.34 to 1.97, respectively) compared with levonorgestrel. Levonorgestrel combined with 20 µg oestrogen was associated with a statistically significantly lower risk than levonorgestrel with 30-40 µg oestrogen for each of the three serious adverse events. Conclusions For the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial

  8. Risk of upper gastrointestinal bleeding in a cohort of new users of low-dose ASA for secondary prevention of cardiovascular outcomes

    Directory of Open Access Journals (Sweden)

    Lucía Cea Soriano

    2010-10-01

    Full Text Available The Health Improvement Network UK primary care database was used to identify a cohort of 38 077 individuals aged 50–84 years with a first prescription of low-dose acetylsalicylic acid (ASA; 75–300 mg/day for secondary prevention of cardiovascular or cerebrovascular events during 2000–2007. From this cohort, 169 incident cases of upper gastrointestinal bleeding (UGIB were identified. Controls with no UGIB (n = 2000 were frequency-matched to the cases by age, sex and follow-up time. A nested case–control analysis was performed to determine risk factors associated with UGIB. The incidence of UGIB was 1.1 per 1000 person-years (95% CI, 1.0–1.3. Low-dose ASA users with a history of peptic ulcer disease had an increased risk of UGIB compared with those without (rate ratio [RR], 4.59; 95% CI, 2.87–7.33. Concomitant use of ASA and clopidogrel (RR, 1.61; 95% CI, 0.85–3.05 or non-steroidal anti-inflammatory drugs (NSAIDs; RR, 2.92; 95% CI, 1.77–4.82 conferred an increased risk of UGIB compared with ASA monotherapy. Discontinuation of ASA therapy (RR: 0.71, 95% CI, 0.42–1.20 and PPI co-treatment given since the start of ASA therapy (RR, 0.56; 95% CI, 0.33–0.96 were associated with a reduced risk of UGIB. In conclusion, in a cohort of individuals receiving low-dose ASA for secondary prevention of cardiovascular or cerebrovascular events, patients with a history of peptic ulcer disease, or who were receiving clopidogrel or NSAIDs had an increased risk of UGIB. The prescription of PPI therapy at the initiation of low-dose ASA reduced the risk of UGIB by almost half.

  9. Dose-response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial.

    Science.gov (United States)

    Schmitz, Kathryn H; Williams, Nancy I; Kontos, Despina; Domchek, Susan; Morales, Knashawn H; Hwang, Wei-Ting; Grant, Lorita L; DiGiovanni, Laura; Salvatore, Domenick; Fenderson, Desire'; Schnall, Mitchell; Galantino, Mary Lou; Stopfer, Jill; Kurzer, Mindy S; Wu, Shandong; Adelman, Jessica; Brown, Justin C; Good, Jerene

    2015-11-01

    Medical and surgical interventions for elevated breast cancer risk (e.g., BRCA1/2 mutation, family history) focus on reducing estrogen exposure. Women at elevated risk may be interested in less aggressive approaches to risk reduction. For example, exercise might reduce estrogen, yet has fewer serious side effects and less negative impact than surgery or hormonal medications. Randomized controlled trial. Increased risk defined by risk prediction models or BRCA mutation status. Eligibility: Age 18-50, eumenorrheic, non-smokers, and body mass index (BMI) between 21 and 50 kg/m(2). 139 were randomized. Treadmill exercise: 150 or 300 min/week, five menstrual cycles. Control group maintained exercise estrogen. Secondary measures: urinary progesterone, quantitative digitized breast dynamic contrast-enhanced magnetic resonance imaging background parenchymal enhancement. Mean age 34 years, mean BMI 26.8 kg/m(2). A linear dose-response relationship was observed such that every 100 min of exercise is associated with 3.6 % lower follicular phase estrogen AUC (linear trend test, p = 0.03). No changes in luteal phase estrogen or progesterone levels. There was also a dose-response effect noted: for every 100 min of exercise, there was a 9.7 % decrease in background parenchymal enhancement as measured by imaging (linear trend test, p = 0.009). Linear dose-response effect observed to reduce follicular phase estrogen exposure measured via urine and hormone sensitive breast tissue as measured by imaging. Future research should explore maintenance of effects and extent to which findings are repeatable in lower risk women. Given the high benefit to risk ratio, clinicians can inform young women at increased risk that exercise may blunt estrogen exposure while considering whether to try other preventive therapies.

  10. Evaluation of risk for graft-versus-host disease in children who receive less than the full doses of mini-dose methotrexate for graft-versus-host disease prophylaxis in allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Sook Kyung Yum

    2013-11-01

    Full Text Available Purpose: The use of cyclosporine and mini-dose methotrexate (MTX is a common strategy for graftversus- host disease (GVHD prophylaxis in allogeneic transplants. We investigated whether patients who receive fewer than the planned MTX doses are at increased risk for GVHD. Methods: The study cohort included 103 patients who received allogeneic transplants at the Department of Pediatrics of The Catholic University of Korea College of Medicine, from January 2010 to December 2011. MTX was administered on days 1, 3, 6, and 11 after transplant at a dose of 5 mg/ m2 each. Within the cohort, 76 patients (74% received all 4 doses of MTX [MTX(4 group], while 27 patients (26% received 0&#8211;3 doses [MTX(0–3 group]. Results: Although there was no difference in neutrophil engraftment between the 2 groups, platelet engraftment was significantly faster in the MTX(4 group (median, 15 days, compared to the MTX(0&#8211; 3 group (median, 25 days; P =0.034. The incidence of grades II&#8211;IV acute GVHD was not different between the MTX(4 and MTX(0&#8211;3 groups (P =0.417. In the multivariate study, human leukocyte antigen mismatch was the most significant factor causing grades II&#8211;IV acute GVHD (P =0.002, followed by female donor to male recipient transplant (P =0.034. No difference was found between the MTX(4 and MTX (0&#8211;3 groups regarding grades III&#8211;IV acute GVHD, chronic GVHD, and disease-free survival. Conclusion: Our results indicate that deviations from the full dose schedule of MTX for GVHD prophylaxis do not lead to increased incidence of either acute or chronic GVHD.

  11. Time-driven activity-based costing of low-dose-rate and high-dose-rate brachytherapy for low-risk prostate cancer.

    Science.gov (United States)

    Ilg, Annette M; Laviana, Aaron A; Kamrava, Mitchell; Veruttipong, Darlene; Steinberg, Michael; Park, Sang-June; Burke, Michael A; Niedzwiecki, Douglas; Kupelian, Patrick A; Saigal, Christopher

    Cost estimates through traditional hospital accounting systems are often arbitrary and ambiguous. We used time-driven activity-based costing (TDABC) to determine the true cost of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy for prostate cancer and demonstrate opportunities for cost containment at an academic referral center. We implemented TDABC for patients treated with I-125, preplanned LDR and computed tomography based HDR brachytherapy with two implants from initial consultation through 12-month followup. We constructed detailed process maps for provision of both HDR and LDR. Personnel, space, equipment, and material costs of each step were identified and used to derive capacity cost rates, defined as price per minute. Each capacity cost rate was then multiplied by the relevant process time and products were summed to determine total cost of care. The calculated cost to deliver HDR was greater than LDR by $2,668.86 ($9,538 vs. $6,869). The first and second HDR treatment day cost $3,999.67 and $3,955.67, whereas LDR was delivered on one treatment day and cost $3,887.55. The greatest overall cost driver for both LDR and HDR was personnel at 65.6% ($4,506.82) and 67.0% ($6,387.27) of the total cost. After personnel costs, disposable materials contributed the second most for LDR ($1,920.66, 28.0%) and for HDR ($2,295.94, 24.0%). With TDABC, the true costs to deliver LDR and HDR from the health system perspective were derived. Analysis by physicians and hospital administrators regarding the cost of care afforded redesign opportunities including delivering HDR as one implant. Our work underscores the need to assess clinical outcomes to understand the true difference in value between these modalities. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  12. Prenatal alcohol exposure and language delay in 2-year-old children: the importance of dose and timing on risk.

    Science.gov (United States)

    O'Leary, Colleen; Zubrick, Stephen R; Taylor, Catherine L; Dixon, Glenys; Bower, Carol

    2009-02-01

    The aim of this study was to investigate the association of dose and timing of prenatal alcohol exposure with early language acquisition. We examined language delay in a randomly selected, population-based sample of Western Australian children born in 1995-1996 whose mothers had agreed to participate in a longitudinal study on health-related behaviors and who had completed the 2-year questionnaire (N = 1739). Information on alcohol consumption was collected at 3 months after birth for four periods; the three months pre-pregnancy and for each trimester separately. Prenatal alcohol exposure was grouped into none, low, moderate-heavy and binge (>5) based on the total quantity consumed per week, quantity consumed per occasion, and frequency of consumption. The communication scale from the Ages & Stages Questionnaire was used to evaluate language delay. Logistic regression analysis was used to generate odds ratios and 95% confidence intervals, adjusted for confounding factors. There was no association between low levels of alcohol consumption and language delay at any time period, although there was a nonsignificant 30% increase in risk when moderate-to-heavy levels of alcohol were consumed in the third trimester. Children exposed to a binge pattern of maternal alcohol consumption in the second trimester had nonsignificant, three-fold increased odds of language delay, with a similar estimate following third trimester alcohol exposure after controlling for covariates. This study did not detect an association between low levels of prenatal alcohol exposure and language delay when compared with women who abstained from alcohol during pregnancy. A nonsignificant threefold increase in the likelihood of language delay was seen in children whose mothers binged during late pregnancy. However, the small numbers of women with a binge-drinking pattern in late pregnancy limited the power of this study; studies analyzing larger numbers of children exposed to binge drinking in late

  13. Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial

    DEFF Research Database (Denmark)

    Hansson, Johan; Aamdal, Steinar; Bastholt, Lars;

    2011-01-01

    Adjuvant high-dose interferon alfa-2b improves relapse-free survival (RFS) in patients with high-risk melanoma, although benefits in overall survival are uncertain. Because of the toxic effects of high-dose regimens, intermediate doses are being explored. We investigated whether adjuvant therapy ...

  14. Does beer, wine or liquor consumption correlate with the risk of renal cell carcinoma? A dose-response meta-analysis of prospective cohort studies

    Science.gov (United States)

    Xu, Xin; Zhu, Yi; Zheng, Xiangyi; Xie, Liping

    2015-01-01

    Despite plenty of evidence supports an inverse association between alcohol drinking and risk of renal cell carcinoma (RCC), sex-specific and beverage-specific dose-response relationships have not been well established. We examined this association by performing a systematic review and meta-analysis of prospective studies. Studies were identified by comprehensively searching PubMed and EMBASE databases through February 21, 2015. Categorical and dose-response meta-analyses were conducted to identify the effects of alcohol on RCC. A total of eight publications (including seven cohort studies and one pooled analysis of 12 cohort studies) were eligible for this meta-analysis. Dose-response analysis showed that each 5 g/day increment of alcohol intake corresponded to a 5% decrease in risk of RCC for males and 9% for females. Alcohol intakes from wine, beer, and liquor were each associated with a reduced risk of RCC. When these associations were examined separately by gender, statistically significant inverse associations were restricted to alcohol from wine among females (RR = 0.82, 95% CI 0.73–0.91) and to alcohol from beer and from liquor among males (RR = 0.87, 95% CI 0.83–0.91 and RR = 0.95, 95% CI 0.92–0.99, respectively). In conclusion, there exist gender-specific and beverage-specific differences in the association between alcohol intake and RCC risk. PMID:25965820

  15. Effect of Carotene and Lycopene on the Risk of Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

    Directory of Open Access Journals (Sweden)

    Yulan Wang

    Full Text Available Many epidemiologic studies have investigated the association between carotenoids intake and risk of Prostate cancer (PCa. However, results have been inconclusive.We conducted a systematic review and dose-response meta-analysis of dietary intake or blood concentrations of carotenoids in relation to PCa risk. We summarized the data from 34 eligible studies (10 cohort, 11 nested case-control and 13 case-control studies and estimated summary Risk Ratios (RRs and 95% confidence intervals (CIs using random-effects models.Neither dietary β-carotene intake nor its blood levels was associated with reduced PCa risk. Dietary α-carotene intake and lycopene consumption (both dietary intake and its blood levels were all associated with reduced risk of PCa (RR for dietary α-carotene intake: 0.87, 95%CI: 0.76-0.99; RR for dietary lycopene intake: 0.86, 95%CI: 0.75-0.98; RR for blood lycopene levels: 0.81, 95%CI: 0.69-0.96. However, neither blood α-carotene levels nor blood lycopene levels could reduce the risk of advanced PCa. Dose-response analysis indicated that risk of PCa was reduced by 2% per 0.2mg/day (95%CI: 0.96-0.99 increment of dietary α-carotene intake or 3% per 1mg/day (95%CI: 0.94-0.99 increment of dietary lycopene intake.α-carotene and lycopene, but not β-carotene, were inversely associated with the risk of PCa. However, both α-carotene and lycopene could not lower the risk of advanced PCa.

  16. Development of Dose-Response Models of Creutzfeldt-Jakob Disease Infection in Nonhuman Primates for Assessing the Risk of Transfusion-Transmitted Variant Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Gregori, Luisa; Anderson, Steven A.; Asher, David M.

    2014-01-01

    ABSTRACT Estimates for the risk of transmitting variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion have relied largely on data from rodent experiments, but the relationship between dose (amount of infected blood) and response (vCJD infection) has never been well quantified. The goal of this study was to develop a dose-response model based on nonhuman primate data to better estimate the likelihood of transfusion-transmitted vCJD (TTvCJD) in humans. Our model used dose-response data from nonhuman primates inoculated intracerebrally (i.c.) with brain tissues of patients with sporadic and familial CJD. We analyzed the data statistically by using a beta-Poisson dose-response model. We further adjusted model parameters to account for the differences in infectivity between blood and brain tissue and in transmission efficiency between intravenous (i.v.) and i.c. routes to estimate dose-dependent TTvCJD infection. The model estimates a mean infection rate of 76% among recipients who receive one unit of whole blood collected from an infected donor near the end of the incubation period. The nonhuman primate model provides estimates that are more consistent with those derived from a risk analysis of transfused nonleukoreduced red blood cells in the United Kingdom than prior estimates based on rodent models. IMPORTANCE TTvCJD was recently identified as one of three emerging infectious diseases posing the greatest immediate threat to the safety of the blood supply. Cases of TTvCJD were reported in recipients of nonleukoreduced red blood cells and coagulation factor VIII manufactured from blood of United Kingdom donors. As the quantity of abnormal prions (the causative agent of TTvCJD) varies significantly in different blood components and products, it is necessary to quantify the dose-response relationship for a wide range of doses for the vCJD agent in transfused blood and plasma derivatives. In this paper, we suggest the first mechanistic dose-response model for

  17. Coronary calcium score in 12-year breast cancer survivors after adjuvant radiotherapy with low to moderate heart exposure - Relationship to cardiac radiation dose and cardiovascular risk factors.

    Science.gov (United States)

    Tjessem, Kristin Holm; Bosse, Gerhard; Fosså, Kristian; Reinertsen, Kristin V; Fosså, Sophie D; Johansen, Safora; Fosså, Alexander

    2015-03-01

    We explored the relation between coronary artery calcium (CAC) and cardiac radiation doses in breast cancer survivors (BCS) treated with radiotherapy (RT). Additionally, we examined the impact of other risk factors and biomarkers of coronary artery disease (CAD). 236 BCS (median age 51years [range 30-70], median observation time 12years [9.2-15.7]), treated with 4-field RT of 50GY, were included and examined in 2004 (T1), 2007 (T2) and 2011 (T3) with clinical examination, blood tests and questionnaires. At T3, cardiac computed tomography was performed with quantification of CAC using Agatston score (AS). For 106 patients cardiac dose volume histograms were available. The cohort-based median of the mean cardiac dose was 2.5 (range 0.5-7.0) Gy. There was no correlation between measures of cardiac dose and AS. AS was correlated with high cholesterol at T1/T2 (p=0.022), high proBNP at T1/T2 (p<0.022) and T3 (p<0.022) and high HbA1c at T3 (p=0.022). In addition, a high AS was significantly associated with hypertension (p=0.022). Age (p<0.001) and cholesterol at T1/T2 (p=0.001) retained significant associations in multivariate analysis. Traditional, modifiable risk factors of CAD correlate with CAC and may be important for the long term risk of CAD after RT. With low to moderate cardiac radiation exposure, a contribution of radiation dose to CAC could not be demonstrated. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Optimizing the radiation therapy dose prescription for pediatric medulloblastoma: Minimizing the life years lost attributable to failure to control the disease and late complication risk

    DEFF Research Database (Denmark)

    Brodin, N. Patrik; Vogelius, Ivan R.; Bjork-Eriksson, Thomas

    2014-01-01

    Background. A mathematical framework is presented for simultaneously quantifying and evaluating the trade-off between tumor control and late complications for risk-based radiation therapy (RT) decision-support. To demonstrate this, we estimate life years lost (LYL) attributable to tumor recurrence......, late cardiac toxicity and secondary cancers for standard-risk pediatric medulloblastoma (MB) patients and compare the effect of dose re-distribution on a common scale. Methods. Total LYL were derived, based on the LYL attributable to radiation-induced late complications and the LYL from not controlling...... in this context, the gain is small compared to estimated uncertainty, this study demonstrates a framework for all-cause mortality risk estimation, rather than evaluates direct clinical applicability of risk-adapted strategies....

  19. RADIATION DOSES AND CANCER RISKS IN THE MARSHALL ISLANDS ASSOCIATED WITH EXPOSURE TO RADIOACTIVE FALLOUT FROM BIKINI AND ENEWETAK NUCLEAR WEAPONS TESTS: SUMMARY

    OpenAIRE

    Simon, Steven L.; Bouville, André; Land, Charles E.; Beck, Harold L.

    2010-01-01

    Nuclear weapons testing conducted at Bikini and Enewetak Atolls during 1946–1958 resulted in exposures of the resident population of the present-day Republic of the Marshall Islands to radioactive fallout. This paper summarizes the results of a thorough and systematic reconstruction of radiation doses to that population, by year, age at exposure, and atoll of residence, and the related cancer risks. Detailed methods and results are presented in a series of companion papers in this volume. Fro...

  20. Risk of gastrointestinal complications associated to NSAIDs, low-dose aspirin and their combinations: Results of a pharmacovigilance reporting system.

    Science.gov (United States)

    Rafaniello, Concetta; Ferrajolo, Carmen; Sullo, Maria Giuseppa; Sessa, Maurizio; Sportiello, Liberata; Balzano, Antonio; Manguso, Francesco; Aiezza, Maria Luisa; Rossi, Francesco; Scarpignato, Carmelo; Capuano, Annalisa

    2016-02-01

    Gastrointestinal (GI) complications are one of the most limiting cause of use of NSAIDs. Beyond others well defined factors, history of peptic ulcer, older age, Helicobacter pylori infection and use of gastrotoxic drugs may affect their GI safety profile. In particular, the risk of GI complications associated to the use of antiplatelet drugs, especially low-dose acetylsalicylic acid (LDA) should deserve much attention. However, only few studies have focused on the effect of combination LDA/NSAIDs on the GI tract compared with the monotherapy and much less studies assessed this effect with multiple NSAIDs use. We aimed to characterize the GI safety profile of NSAIDs and LDA as monotherapy or their combinations in real-life conditions by analysing spontaneous adverse drug reactions (ADRs) reporting system in a Southern Italy. We used the case/non-case method in the Italian Pharmacovigilance Network (RNF). Cases were reports of GI events in the RNF between January 2007 and December 2011. Non-cases were all other reports during the same period. The association between NSAID and suspected GI ADRs was calculated using the reporting odds ratio (ROR) with 95% confidence intervals as a measure of disproportionality while adjusting for age, and concomitant use of antineoplastic agents or drugs for cardiovascular diseases. Sub-analysis were performed within the NSAID class. Among the 2816 adverse drug reactions recorded, we identified 374 (13.3%) cases of GI complications. Upper GI complications were the most frequently reported type of events. The highest associations were found for the combined use of NSAIDs and/or LDA, whilst the lowest associations were for their respective monotherapy. Looking at individual NSAIDs the highest association with GI events was observed for ketorolac exposure followed by nimesulide, diclofenac, aspirin, ketoprofen, and ibuprofen. This study highlights the primary role of the national spontaneous reporting system to bring out potential signals

  1. Maternal Caffeine Consumption during Pregnancy and Risk of Low Birth Weight: A Dose-Response Meta-Analysis of Observational Studies.

    Science.gov (United States)

    Rhee, Jongeun; Kim, Rockli; Kim, Yongjoo; Tam, Melanie; Lai, Yizhen; Keum, NaNa; Oldenburg, Catherine Elizabeth

    2015-01-01

    Epidemiologic studies have shown inconsistent conclusions about the effect of caffeine intake during pregnancy on the risk of low birth weight (LBW). We performed a meta-analysis and linear-dose response analysis examining the association between caffeine consumption during pregnancy and risk of LBW. PubMed and EMBASE were searched for relevant articles published up to March 2014. Eight cohort and four case-control studies met all inclusion criteria. Using a random-effects model of the twelve studies, the pooled odds ratio (OR) for the risk of LBW comparing the highest versus lowest level of caffeine intake during pregnancy was 1.38 (95% CI: 1.10, 1.73). Linear dose-response analysis showed that every additional 100 mg of caffeine intake (1 cup of coffee or 2 cups of tea) per day during pregnancy was associated with a 3.0% increase in OR for LBW. There was a moderate level of overall heterogeneity with an I-squared value of 55% (95% CI: 13, 76%), and no evidence of publication bias based on Egger's test (P = 0.20) and the funnel plot. Thus, high caffeine intake during pregnancy is associated with a significant increase in the risk of LBW, and this risk appears to increase linearly as caffeine intake increases.

  2. Maternal Caffeine Consumption during Pregnancy and Risk of Low Birth Weight: A Dose-Response Meta-Analysis of Observational Studies.

    Directory of Open Access Journals (Sweden)

    Jongeun Rhee

    Full Text Available Epidemiologic studies have shown inconsistent conclusions about the effect of caffeine intake during pregnancy on the risk of low birth weight (LBW. We performed a meta-analysis and linear-dose response analysis examining the association between caffeine consumption during pregnancy and risk of LBW. PubMed and EMBASE were searched for relevant articles published up to March 2014. Eight cohort and four case-control studies met all inclusion criteria. Using a random-effects model of the twelve studies, the pooled odds ratio (OR for the risk of LBW comparing the highest versus lowest level of caffeine intake during pregnancy was 1.38 (95% CI: 1.10, 1.73. Linear dose-response analysis showed that every additional 100 mg of caffeine intake (1 cup of coffee or 2 cups of tea per day during pregnancy was associated with a 3.0% increase in OR for LBW. There was a moderate level of overall heterogeneity with an I-squared value of 55% (95% CI: 13, 76%, and no evidence of publication bias based on Egger's test (P = 0.20 and the funnel plot. Thus, high caffeine intake during pregnancy is associated with a significant increase in the risk of LBW, and this risk appears to increase linearly as caffeine intake increases.

  3. RADIATION DOSES AND CANCER RISKS IN THE MARSHALL ISLANDS ASSOCIATED WITH EXPOSURE TO RADIOACTIVE FALLOUT FROM BIKINI AND ENEWETAK NUCLEAR WEAPONS TESTS: SUMMARY

    Science.gov (United States)

    Simon, Steven L.; Bouville, André; Land, Charles E.; Beck, Harold L.

    2014-01-01

    Nuclear weapons testing conducted at Bikini and Enewetak Atolls during 1946–1958 resulted in exposures of the resident population of the present-day Republic of the Marshall Islands to radioactive fallout. This paper summarizes the results of a thorough and systematic reconstruction of radiation doses to that population, by year, age at exposure, and atoll of residence, and the related cancer risks. Detailed methods and results are presented in a series of companion papers in this volume. From our analysis, we concluded that 20 of the 66 nuclear tests conducted in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall Islands. In this work, we estimated deposition densities (kBq m−2) of all important dose-contributing radionuclides at each of the 32 atolls and separate reef islands of the Marshall Islands. Quantitative deposition estimates were made for 63 radionuclides from each test at each atoll. Those estimates along with reported measurements of exposure rates at various times after fallout were used to estimate radiation absorbed doses to the red bone marrow, thyroid gland, stomach wall, and colon wall of atoll residents from both external and internal exposure. Annual doses were estimated for six age groups ranging from newborns to adults. We found that the total deposition of 137Cs, external dose, internal organ doses, and cancer risks followed the same geographic pattern with the large population of the southern atolls receiving the lowest doses. Permanent residents of the southern atolls who were of adult age at the beginning of the testing period received external doses ranging from 5 to 12 mGy on average; the external doses to adults at the mid-latitude atolls ranged from 22 to 59 mGy on average, while the residents of the northern atolls received external doses in the hundreds to over 1,000 mGy. Internal doses varied significantly by age at exposure, location, and organ. Except

  4. Radiation doses and cancer risks in the Marshall Islands associated with exposure to radioactive fallout from Bikini and Enewetak nuclear weapons tests: summary.

    Science.gov (United States)

    Simon, Steven L; Bouville, André; Land, Charles E; Beck, Harold L

    2010-08-01

    Nuclear weapons testing conducted at Bikini and Enewetak Atolls during 1946-1958 resulted in exposures of the resident population of the present-day Republic of the Marshall Islands to radioactive fallout. This paper summarizes the results of a thorough and systematic reconstruction of radiation doses to that population, by year, age at exposure, and atoll of residence, and the related cancer risks. Detailed methods and results are presented in a series of companion papers in this volume. From our analysis, we concluded that 20 of the 66 nuclear tests conducted in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall Islands. In this work, we estimated deposition densities (kBq m(-2)) of all important dose-contributing radionuclides at each of the 32 atolls and separate reef islands of the Marshall Islands. Quantitative deposition estimates were made for 63 radionuclides from each test at each atoll. Those estimates along with reported measurements of exposure rates at various times after fallout were used to estimate radiation absorbed doses to the red bone marrow, thyroid gland, stomach wall, and colon wall of atoll residents from both external and internal exposure. Annual doses were estimated for six age groups ranging from newborns to adults. We found that the total deposition of 137Cs, external dose, internal organ doses, and cancer risks followed the same geographic pattern with the large population of the southern atolls receiving the lowest doses. Permanent residents of the southern atolls who were of adult age at the beginning of the testing period received external doses ranging from 5 to 12 mGy on average; the external doses to adults at the mid-latitude atolls ranged from 22 to 59 mGy on average, while the residents of the northern atolls received external doses in the hundreds to over 1,000 mGy. Internal doses varied significantly by age at exposure, location, and organ. Except

  5. Comparison of dose distributions and organs at risk (OAR) doses in conventional tangential technique (CTT) and IMRT plans with different numbers of beam in left-sided breast cancer.

    Science.gov (United States)

    Ayata, Hande Bas; Güden, Metin; Ceylan, Cemile; Kücük, Nadir; Engin, Kayihan

    2011-01-01

    Our aim was to improve dose distribution to the left breast and to determine the dose received by the ipsilateral lung, heart, contralateral lung and contralateral breast during primary left-sided breast irradiation by using intensity modulated radiotherapy (IMRT) techniques compared to conventional tangential techniques (CTT). At the same time, different beams of IMRT plans were compared to each other in respect to CI, HI and organs at risk (OAR) dose. Conventional early breast cancer treatment consists of lumpectomy followed by whole breast radiation therapy. CTT is a traditional method used for whole breast radiotherapy and includes standard wedged tangents (two opposed wedged tangential photon beams). The IMRT technique has been widely used for many treatment sites, allowing both improved sparing of normal tissues and more conformal dose distributions. IMRT is a new technique for whole breast radiotherapy. IMRT is used to improve conformity and homogeneity and used to reduce OAR doses. Thirty patients with left-sided breast carcinoma were treated between 2005 and 2008 using 6, 18 or mixed 6/18 MV photons for primary breast irradiation following breast conserving surgery (BCS). The clinical target volume [CTV] was contoured as a target volume and the contralateral breast, ipsilateral lung, contralateral lung and heart tissues as organs at risk (OAR). IMRT with seven beams (IMRT7), nine beams (IMRT9) and 11 beams (IMRT11) plans were developed and compared with CTT and among each other. The conformity index (CI), homogeneity index (HI), and doses to OAR were compared to each other. ALL OF IMRT PLANS SIGNIFICANTLY IMPROVED CI (CTT: 0.76; IMRT7: 0.84; IMRT9: 0.84; IMRT11: 0.85), HI (CTT: 1.16; IMRT7: 1.12; IMRT9: 1.11; IMRT11: 1.11), volume of the ipsilateral lung receiving more than 20 Gy (>V20 Gy) (CTT: 14.6; IMRT7: 9.08; IMRT9: 8.10; IMRT11: 8.60), and volume of the heart receiving more than 30 Gy (>V30 Gy) (CTT: 6.7; IMRT7: 4.04; IMRT9: 2.80; IMRT11: 2

  6. The effect of positional realignment on dose delivery to the prostate and organs-at-risk for 3DCRT.

    Science.gov (United States)

    Wang, Zhou; Rajagopalan, Balu; Malhotra, Harish K; Kuettel, Michael R; Podgorsak, Matthew B

    2007-01-01

    In this study, we evaluate the impact of daily image-guided patient repositioning on dose delivery to prostate and sensitive organs in the treatment of prostate carcinoma with 3-dimensional conformal radiation therapy (3DCRT). Five patients with substantial ultrasound-documented interfractional prostate motion during their 3DCRT treatment course were selected. Starting with the original treatment plan, 2 additional plans were retrospectively generated for each patient. In one set, organ contours were moved for each fraction, thus simulating positioning with misalignment caused by organ motion if ultrasound guidance were not used. In a second set of plans, the isocenter was shifted, as were the organ contours, simulating realignment based on the ultrasound image. In all cases, the number of planned monitor units was set to those of the original plan. For a given patient, isodose distributions, dose-volume histograms (DVHs), equivalent uniform dose (EUD) for prostate, and generalized equivalent uniform dose (gEUDs) for bladder and rectum were calculated for each fraction and then combined for each shift condition. In all reconstructed plans, the results show no substantial changes in dose coverage of the prostate <0.21% change in EUD) compared to the original plan. However, in some cases with no realignment, a larger volume of the bladder or rectum gets higher dose, with the consequent gEUD for each organ significantly greater compared to the original plan.

  7. Risks Associated with High-Dose Lactobacillus rhamnosus in an Escherichia coli Model of Piglet Diarrhoea: Intestinal Microbiota and Immune Imbalances

    Science.gov (United States)

    Yue, Yuan; Cai, Zheng-Xing; Lu, Qing-Ping; Zhang, Lu; Weng, Xiao-Gang; Zhang, Fan-Jian; Zhou, Dong; Yang, Jin-Cai; Wang, Jiu-Feng

    2012-01-01

    Probiotic could be a promising alternative to antibiotics for the prevention of enteric infections; however, further information on the dose effects is required. In this study, weanling piglets were orally administered low- or high-dose Lactobacillus rhamnosus ACTT 7469 (1010 CFU/d or 1012 CFU/d) for 1 week before F4 (K88)-positive Escherichia coli challenge. The compositions of faecal and gastrointestinal microbiota were recorded; gene expression in the intestines was assessed by real-time PCR; serum tumour necrosis factor-α (TNF-α) concentrations and intestinal Toll-like receptor 4 (TLR4) were detected by ELISA and immunohistochemistry, respectively. Unexpectedly, high-dose administration increased the incidence of diarrhoea before F4+ETEC challenge, despite the fact that both doses ameliorated F4+ETEC-induced diarrhoea with increased Lactobacillus and Bifidobacterium counts accompanied by reduced coliform shedding in faeces. Interestingly, L. rhamnosus administration reduced Lactobacillus and Bifidobacterium counts in the colonic contents, and the high-dose piglets also had lower Lactobacillius and Bacteroides counts in the ileal contents. An increase in the concentration of serum TNF-α induced by F4+ETEC was observed, but the increase was delayed by L. rhamnosus. In piglets exposed to F4+ETEC, jejunal TLR4 expression increased at the mRNA and protein levels, while jejunal interleukin (IL)-8 and ileal porcine β-defensins 2 (pBD2) mRNA expression increased; however, these increases were attenuated by administration of L. rhamnosus. Notably, expression of jejunal TLR2, ileal TLR9, Nod-like receptor NOD1 and TNF-α mRNA was upregulated in the low-dose piglets after F4+ETEC challenge, but not in the high-dose piglets. These findings indicate that pretreatment with a low dose of L. rhamnosus might be more effective than a high dose at ameliorating diarrhoea. There is a risk that high-dose L. rhamnosus pretreatment may negate the preventative effects, thus

  8. Risks associated with high-dose Lactobacillus rhamnosus in an Escherichia coli model of piglet diarrhoea: intestinal microbiota and immune imbalances.

    Directory of Open Access Journals (Sweden)

    Xiao-Qiong Li

    Full Text Available Probiotic could be a promising alternative to antibiotics for the prevention of enteric infections; however, further information on the dose effects is required. In this study, weanling piglets were orally administered low- or high-dose Lactobacillus rhamnosus ACTT 7469 (10(10 CFU/d or 10(12 CFU/d for 1 week before F4 (K88-positive Escherichia coli challenge. The compositions of faecal and gastrointestinal microbiota were recorded; gene expression in the intestines was assessed by real-time PCR; serum tumour necrosis factor-α (TNF-α concentrations and intestinal Toll-like receptor 4 (TLR4 were detected by ELISA and immunohistochemistry, respectively. Unexpectedly, high-dose administration increased the incidence of diarrhoea before F4(+ETEC challenge, despite the fact that both doses ameliorated F4(+ETEC-induced diarrhoea with increased Lactobacillus and Bifidobacterium counts accompanied by reduced coliform shedding in faeces. Interestingly, L. rhamnosus administration reduced Lactobacillus and Bifidobacterium counts in the colonic contents, and the high-dose piglets also had lower Lactobacillius and Bacteroides counts in the ileal contents. An increase in the concentration of serum TNF-α induced by F4(+ETEC was observed, but the increase was delayed by L. rhamnosus. In piglets exposed to F4(+ETEC, jejunal TLR4 expression increased at the mRNA and protein levels, while jejunal interleukin (IL-8 and ileal porcine β-defensins 2 (pBD2 mRNA expression increased; however, these increases were attenuated by administration of L. rhamnosus. Notably, expression of jejunal TLR2, ileal TLR9, Nod-like receptor NOD1 and TNF-α mRNA was upregulated in the low-dose piglets after F4(+ETEC challenge, but not in the high-dose piglets. These findings indicate that pretreatment with a low dose of L. rhamnosus might be more effective than a high dose at ameliorating diarrhoea. There is a risk that high-dose L. rhamnosus pretreatment may negate the preventative

  9. Geosciences help to protect human health: estimation of the adsorbed radiation doses while flight journeys, as important step to radiation risk assessment

    Science.gov (United States)

    Chernov, Anatolii; Shabatura, Olexandr

    2016-04-01

    Estimation of the adsorbed radiation dose while flight journeys is a complex problem, which should be solved to get correct evaluation of equivalent effective doses and radiation risk assessment. Direct measurements of the adsorbed dose in the aircrafts during regional flights (3-10 hours) has shown that the radiation in the plane may increase 10-15 times (to 2-4 mSv/h) compared to the values on the surface of the Earth (0.2-0.5 mSv/h). Results of instrumental research confirmed by the other investigations. It is a fact that adsorbed doses per year while flight journeys are less than doses from medical tests. However, while flight journeys passengers get the same doses as nuclear power plant staff, people in zones of natural radiation anomalies and so should be evaluated. According to the authors' research, flight journeys are safe enough, when solar activity is normal and if we fly under altitude of 18 km (as usual, while intercontinental flights). Most of people travel by plane not so often, but if flight is lasting in dangerous periods of solar activity (powerful solar winds and magnetic field storms), passengers and flight crew can adsorb great amount of radiation doses. People, who spend more than 500 hours in flight journeys (pilots, business oriented persons', government representatives, etc.) get amount of radiation, which can negatively influence on health and provoke diseases, such as cancer. Authors consider that problem actual and researches are still going on. It is revealed, that radiation can be calculated, using special equations. Great part of radiation depends on very variable outer-space component and less variable solar. Accurate calculations of doses will be possible, when we will take into account all features of radiation distribution (time, season of year and exact time of the day, duration of flight), technical features of aircraft and logistics of flight (altitude, latitude). Results of first attempts of radiation doses modelling confirmed

  10. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kuk, Deborah; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-03-15

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.

  11. Estimation of radiation dose and risk to children undergoing cardiac catheterization for the treatment of a congenital heart disease using Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Yakoumakis, Emmanuel; Kostopoulou, Helen; Dimitriadis, Anastastios; Georgiou, Evaggelos [University of Athens, Medical Physics Department, Medical School, Athens (Greece); Makri, Triantafilia [' Agia Sofia' Hospital, Medical Physics Unit, Athens (Greece); Tsalafoutas, Ioannis [Anticancer-Oncology Hospital of Athens ' Agios Savvas' , Medical Physics Department, Athens (Greece)

    2013-03-15

    Children diagnosed with congenital heart disease often undergo cardiac catheterization for their treatment, which involves the use of ionizing radiation and therefore a risk of radiation-induced cancer. The purpose of this study was to calculate the effective and equivalent organ doses (H{sub T}) in those children and estimate the risk of exposure-induced death. Fifty-three children were divided into three groups: atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). In all procedures, the exposure conditions and the dose-area product meters readings were recorded for each individual acquisition. Monte Carlo simulations were run using the PCXMC 2.0 code and mathematical phantoms simulating a child's anatomy. The H{sub T} values to all irradiated organs and the resulting E and risk of exposure-induced death values were calculated. The average dose-area product values were, respectively, 40 {+-} 12 Gy.cm{sup 2} for the ASD, 17.5 {+-} 0.7 Gy.cm{sup 2} for the VSD and 9.5 {+-} 1 Gy.cm{sup 2} for the PDA group. The average E values were 40 {+-} 12, 22 {+-} 2.5 and 17 {+-} 3.6 mSv for ASD, VSD and PDA groups, respectively. The respective estimated risk of exposure-induced death values per procedure were 0.109, 0.106 and 0.067%. Cardiac catheterizations in children involve a considerable risk for radiation-induced cancer that has to be further reduced. (orig.)

  12. SU-F-P-26: Study of Radiation Dose Evaluation for Organs at Risk Using MRI in Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gong, G; Guo, Y; Yin, Y [Shandong Cancer Hospital and Institute, Jinan, Shandong (China)

    2016-06-15

    Purpose: To study the contour and dosimetric feature of organs at risk (OARs) applying magnetic resonance imaging (MRI) images in intensity modulated radiation therapy (IMRT) of nasopharyngeal carcinoma (NPC) compared to computed tomography (CT) images. Methods: 35 NPC patients was selected into this trail. CT simulation with non-contrast and contrast enhanced scan, MRI simulation with non-contrast and contrast enhanced T1, T2 and diffusion weighted imaging were achieved sequentially. And the OARs were contoured on the CT and MRI images after rigid registration respectively. 9 beams IMRT plan with equal division angle were designed for every patients, and the prescription dose for tumor target was set as 72Gy (2.4Gy/ fration). The boundary display, volume and dose-volume indices of each organ were compared between on MRI and CT images. Results: Compared to CT, MRI showed clearer boundary of brainstem, spinal cord, the deep lobe of Parotid gland and the optical nerve in canal. MRI images increase the volume of lens, optical nerve, while reducing the volume of eye slightly, and the maximum dose of lens, the mean dose of eyes and optical raised in different percentage, while there was no statistical differences were found. The left and right parotid volume on MRI increased by 7.07%, 8.13%, and the mean dose raised by 14.95% (4.01Gy), 18.76% (4.95Gy) with statistical significant difference (p<0.05). The brainstem volume reduced by 9.33% (p<0.05), and the dose of 0.1cm3 volume (D0.1cm3) reduced by mean 8.46% (4.32Gy), and D0.1cm3 of spinal cord increased by 1.5Gy on MRI. Conclusion: It is credible to evaluate the radiation dose of lens, eye and the spinal cord, while it should be necessary to evaluate the dose of brainstem, parotid and the optical nerve applying MRI images sometime, it will be more meaningful for these organs with high risk of radiation injury.

  13. Nonsteroidal anti-inflammatory drugs: add an anti-ulcer drug for patients at high risk only. Always limit the dose and duration of treatment with NSAIDs.

    Science.gov (United States)

    2011-09-01

    In addition to their cardiac, renal, hepatic, cutaneous and neuropsychological adverse effects, nonsteroidal anti-inflammatory drugs (NSAIDs) can have severe effects on the entire gastrointestinal tract, including bleeding, perforation and occlusion. Which anti-ulcer drugs reduce the risk of the severe gastrointestinal adverse effects of NSAIDs, and which patients should receive them? To answer these questions, we conducted a review of the literature, using the standard Prescrire methodology. The main risk factors for severe gastrointestinal adverse effects during NSAID therapy are: a high dose regimen; age over 65 years; a history of gastric or duodenal ulcer or gastrointestinal bleeding; heavy use of both alcohol and tobacco; and concomitant treatment with a corticosteroid, antiplatelet drug, anticoagulant, or selective serotonin reuptake inhibitor (SSRI) antidepressant. Gastrointestinal symptoms and ulceration (on endoscopy) are poor predictors of severe gastrointestinal reactions. A meta-analysis examined randomised placebo-controlled trials of misoprostol in more than 11 000 patients. The results were mainly based on a large trial including about 9000 rheumatoid arthritis patients with an average age of 68 years. Misoprostol (400 microg to 800 microg/day, in 4 doses) prevented about 4 severe gastroduodenal events when 1000 patients over 60 years of age were treated for 6 months. Diarrhoea and other mild gastrointestinal disorders were frequent. There are no randomised trials comparing proton pump inhibitors (PPIs) and histamine H2 receptor antagonists versus misoprostol or versus placebo therapy for the prevention of severe adverse effects associated with NSAIDs. PPIs and H2 antagonists both reduce the incidence of gastric or duodenal ulceration detected by routine endoscopy. A randomised trial compared an H2 antagonist (famotidine) versus a PPI (pantoprazole) in 128 patients with an average age of 69 years who had a very high risk of serious gastrointestinal

  14. Candesartan cilexetil/hydrochlorothiazide combination treatment versus high-dose candesartan cilexetil monotherapy in patients with mild to moderate cardiovascular risk (CHILI Triple T

    Directory of Open Access Journals (Sweden)

    Bramlage P

    2011-02-01

    Full Text Available Gerd Bönner1, Bernhard Landers2, Peter Bramlage31Park-Klinikum Bad Krozingen, Germany; 2Internal Medicine Practice, Diabetes Center, Mayen, Germany; 3Institute for Cardiovascular Pharmacology and Epidemiology, Mahlow, GermanyBackground: Candesartan cilexetil has been shown to effectively reduce blood pressure and cardiovascular risk. Whether it is advantageous to combine candesartan cilexetil with low-dose hydrochlorothiazide (HCTZ or uptitrate it in cases of insufficient blood pressure control has not been fully investigated under routine clinical conditions.Methods: CHILI Triple T is a prospective, noninterventional, observational study. Patients with uncontrolled hypertension and added cardiovascular risk received a fixed-dose combination of candesartan cilexetil 16 mg and HCTZ 12.5 mg (combination therapy group or high-dose monotherapy with candesartan cilexetil 32 mg (high-dose monotherapy group.Results: A total of 4600 patients with a mean age of 63.1 ± 11.0 years, of which 44.7% were female, was included. The combination therapy group had 3337 patients, and the high-dose monotherapy group 1263 patients. Patients in both treatment groups were comparable with respect to age and gender, but patients receiving high-dose monotherapy had a slightly higher mean systolic blood pressure, more prior revascularizations, renal insufficiency, diabetic nephropathy, peripheral artery disease, and a lower ankle brachial index. The use of combination therapy resulted in a blood pressure reduction of -28.5 ± 13.8/-14.2 ± 9.4 mm Hg (P < 0.001 vs 160.2 ± 13.3/94.5 ± 8.2 mm Hg at baseline. The use of high-dose monotherapy reduced blood pressure by -29.73 ± 15.3/-14.1 ± 9.6 mm Hg (P < 0.001 vs 162.4 ± 14.7/94.7 ± 8.7 mm Hg at baseline. Differences in subgroups of patients defined by age, gender, body mass index, dyslipidemia, waist circumference, smoking, prior cardiovascular event, glomerular filtration rate, and microalbuminuria were minor

  15. SBRT for the Primary Treatment of Localized Prostate Cancer: The Effect of Gleason Score, Dose and Heterogeneity of Intermediate risk on Outcome Utilizing 2.2014 NCCN Risk Stratification Guidelines

    Directory of Open Access Journals (Sweden)

    Matthew eBernetich

    2014-11-01

    Full Text Available Purpose: To report an update of our previous experience using stereotactic body radiation therapy (SBRT for the primary treatment of prostate cancer, risk stratified by the updated NCCN version 2.2014, reporting efficacy and toxicity in a community hospital setting.Methods: From 2007 to 2012, 142 localized prostate cancer patients were treated with SBRT using CyberKnife. NCCN guidelines Version 2.2014 risk groups analyzed included very low (20%, low (23%, intermediate (35%, and high (22% risk. To further explore group heterogeneity and to comply with new guidelines, we separated our prior intermediate risk group into favorable intermediate and unfavorable intermediate groups depending on how many intermediate risk factors were present (one vs. >one. The unfavorable intermediate group was further analyzed in combination with the high risk group as per NCCN guidelines Version 2.2014.Various dose levels were used over the years of treatment, and have been categorized into low dose (35 Gy, n=5 or 36.25 Gy, n=107 and high dose (37.5 Gy, n=30. All treatments were delivered in five fractions. Toxicity was assessed using Radiation Therapy Oncology Group criteria.Results: 5-year actuarial freedom from biochemical failure (FFBF was 100%, 91.7%, 95.2%, 90.0% and 86.7% for very low, low, intermediate and high risk patients, respectively (NS. A significant difference in 5 year FFBF was noted for patients with Gleason score >8 vs. 7 vs. 5/6 (p=0.03 and low vs. high dose (p=0.05. T-stage, pretreatment PSA, age, risk stratification group and use of ADT did not affect 5-year FFBF. Multivariate analysis revealed Gleason score and dose to be the most predictive factors for 5-year FFBF.Conclusion: Our experience with SBRT for the primary treatment of localized prostate cancer demonstrates favorable efficacy and toxicity comparable to the results reported for IMRT in literature. Gleason score remains the single most important pretreatment predictor of outcome.

  16. Bimonthly half-dose ranibizumab in large pigment epithelial detachment and retinal angiomatous proliferation with high risk of retinal pigment epithelium tear: a case report

    Directory of Open Access Journals (Sweden)

    Monés J

    2013-06-01

    Full Text Available Jordi Monés,1,2 Marc Biarnés,1 Josep Badal11Institut de la Màcula i de la Retina, Barcelona, Spain; 2Barcelona Macula Foundation, Barcelona, SpainIntroduction: The management of large pigment epithelial detachments (PEDs associated with retinal angiomatous proliferation (RAP remains a challenge due to the high risk of retinal pigment epithelial (RPE tear. We describe the successful progressive anatomical result and the maintenance of visual acuity to bimonthly, half-dose ranibizumab in a patient with this condition.Purpose: To describe the management of a large PED secondary to RAP with bimonthly, half-dose ranibizumab.Method: Case report.Patient: A 71-year-old woman presented with visual symptoms due to an enlarged PED, compared with previous visits, secondary to a RAP lesion, with a visual acuity of 20/32. To reduce the risk of an RPE tear and a significant decrease in vision, we discussed with the patient the possibility of treating the lesion in a progressive manner, with more frequent but smaller doses of ranibizumab. The patient was treated biweekly with 0.25 mg of ranibizumab until flattening of the PED.Results: The large PED flattened progressively, and visual acuity was preserved with no adverse events.Discussion: The use of half-dose antiangiogenic therapy may be useful in managing large vascularized PED associated with RAP, in an attempt to reduce the risk of RPE tear.Keywords: age-related macular degeneration, pigment epithelial detachment, ranibizumab, retinal angiomatous proliferation, RPE tear

  17. Risk evaluation of the Arctic environmental POP exposure based on critical body residue and critical daily dose using captive Greenland sledge dogs (Canis familiaris) as surrogate species.

    Science.gov (United States)

    Sonne, Christian; Gustavson, Kim; Eulaers, Igor; Desforges, Jean-Pierre; Letcher, Robert J; Rigét, Frank F; Styrishave, Bjarne; Dietz, Rune

    2016-03-01

    The risk from POP (persistent organic pollutant) exposure and subsequent reproductive, immunotoxic and liver histopathological effects was evaluated in a classical parallel trial on Greenland sledge dogs (Canis familiaris) fed contaminated minke whale (Balaenoptera acutorostrata) blubber. First the critical body residues (CBRs) were estimated using the physiologically-based pharmacokinetic (PBPK) model for seven POP compounds based on rat critical daily doses (CDDs). These were then compared with the actual daily oral POP doses (DD) and body residues (BR) in the sledge dogs by calculating risk quotients (RQDD: DD/CDD; RQBR: BR/CBR; ≥1 indicates risk). The results showed that risk quotients for reproductive, immunotoxic and liver histopathological effects were significantly lowest in the control group (pPOP exposure negatively impacts steroid hormones, various immune parameters, as well as liver histopathology in sledge dogs. It is also clear that RQBR is the best reflector of health effects from POP exposure and that it is especially accurate in predicting immune and reproductive effects. We recommend that PBPK modelled (CBR) and RQBR should be used in the assessment of POP exposure and health effects in Arctic top predators. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Long-term coffee consumption and risk of cardiovascular disease: a systematic review and a dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Ding, Ming; Bhupathiraju, Shilpa N; Satija, Ambika; van Dam, Rob M; Hu, Frank B

    2014-02-11

    Considerable controversy exists on the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. PubMed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1 279 804 participants and 36 352 CVD cases. A nonlinear relationship of coffee consumption with CVD risk was identified (P for heterogeneity=0.09, P for trend coffee consumption (median, 0 cups per day), the relative risk of CVD was 0.95 (95% confidence interval, 0.87-1.03) for the highest category (median, 5 cups per day) category, 0.85 (95% confidence interval, 0.80-0.90) for the second highest category (median, 3.5 cups per day), and 0.89 (95% confidence interval, 0.84-0.94) for the third highest category (median, 1.5 cups per day). Looking at separate outcomes, coffee consumption was nonlinearly associated with both coronary heart disease (P for heterogeneity=0.001, P for trend 0.05) risks. A nonlinear association between coffee consumption and CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.

  19. Adaptive dosing approaches to the individualization of 13-cis-retinoic acid (isotretinoin) treatment for children with high-risk neuroblastoma

    Science.gov (United States)

    Veal, Gareth J.; Errington, Julie; Rowbotham, Sophie E.; Illingworth, Nicola A.; Malik, Ghada; Cole, Michael; Daly, Ann K.; Pearson, Andrew D.J.; Boddy, Alan V.

    2012-01-01

    Purpose To investigate the feasibility of adaptive dosing and the impact of pharmacogenetic variation on 13-cisRA disposition in high-risk neuroblastoma patients. Experimental Design 13cisRA (160mg/m2 or 5.33mg/kg/day) was administered to 103 patients ≤21 years and plasma concentrations of 13-cisRA and 4-oxo-13-cisRA quantitated on day 14 of treatment. 71 patients were recruited to a dose adjustment group, targeting a 13-cisRA Cmax of 2μM, with dose increases of 25-50% implemented for patients with Cmax values 2μM. Dose increases carried out in 20 patients in the dose adjustment study group led to concentrations >2μM in 18 patients (90%). 8/11 (73%) patients <12kg, receiving a dose of 5.33mg/kg, failed to achieve a Cmax ≥2μM. Significantly lower Cmax values were observed for patients treated with 5.33mg/kg versus 160mg/m2 (1.9±1.2 versus 3.1±2.0μM; mean±SD; P=0.023). Cmax was higher in patients who swallowed 13-cisRA capsules as compared to receiving the drug extracted from capsules (4.0±2.2 versus 2.6±1.8μM; P=0.0012). The target Cmax was achieved by 93% (25/27) versus 55% (42/76) of patients in these two groups respectively. No clear relationships were found between genetic variants and 13-cisRA pharmacokinetic parameters. Conclusions Dosing regimen and method of administration have a marked influence on 13-cisRA plasma concentrations. Body weight-based dosing should not be implemented for children <12kg and pharmacological data support higher doses for children unable to swallow 13-cisRA capsules. PMID:23087409

  20. Differentiation therapy in poor risk myeloid malignancies: Results of a dose finding study of the combination bryostatin-1 and GM-CSF.

    Science.gov (United States)

    Smith, B Douglas; Jones, Richard J; Cho, Eunpi; Kowalski, Jeanne; Karp, Judith E; Gore, Steven D; Vala, Milada; Meade, Brooke; Baker, Sharyn D; Zhao, Ming; Piantadosi, Steven; Zhang, Zhe; Blumenthal, Gideon; Warlick, Erica D; Brodsky, Robert A; Murgo, Anthony; Rudek, Michelle A; Matsui, William H

    2011-01-01

    Pharmacologic differentiating agents have had relatively limited clinical success outside of the use of ATRA in acute promyelocytic leukemia and DNA methyltransferase inhibitors in myelodysplastic syndromes. The differentiating effects of such agents can be enhanced in combination with lineage-specific growth factors. We developed a dose finding trial to assess toxicity, differentiating activity, and clinical impact of the combination of bryostatin-1 and GM-CSF. Patients with poor risk myeloid malignancies were eligible to enroll in a dose finding study of continuous infusion bryostatin-1 combined with a fixed dose of daily GM-CSF. Toxicities were graded per NCI CTC version 2.0 and pharmacokinetic and correlative study samples were obtained to assess the combination's clinical and biologic differentiating effects. Thirty-two patients were treated with the combination therapy and the dose determined to be most suitable for study in a larger trial was continuous infusion broystatin-1 at 16μg/m(2) for 14 days and subcutaneous GM-CSF at 125μg/m(2) daily for 14 days every 28 days. Arthralgias and myalgias limited further dose escalation. Clinically, the combination impacted differentiation with improvement of absolute neutrophil counts (p=0.0001) in the majority of patients. Interestingly, there were two objective clinical responses, including a CR after a single cycle. Both the bryostatin-1 plasma concentrations and the correlative studies supported biologic activity of the combination at the doses where clinical responses were observed. Combining growth factors with pharmacologic differentiating agents may increase their clinical effectiveness and further studies should focus on such combinations. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Emerging risk factors and the dose-response relationship between physical activity and lone atrial fibrillation: a prospective case-control study.

    Science.gov (United States)

    Calvo, Naiara; Ramos, Pablo; Montserrat, Silvia; Guasch, Eduard; Coll-Vinent, Blanca; Domenech, Mònica; Bisbal, Felipe; Hevia, Sara; Vidorreta, Silvia; Borras, Roger; Falces, Carles; Embid, Cristina; Montserrat, Josep Maria; Berruezo, Antonio; Coca, Antonio; Sitges, Marta; Brugada, Josep; Mont, Lluís

    2016-01-01

    The role of high-intensity exercise and other emerging risk factors in lone atrial fibrillation (Ln-AF) epidemiology is still under debate. The aim of this study was to analyse the contribution of each of the emerging risk factors and the impact of physical activity dose in patients with Ln-AF. Patients with Ln-AF and age- and sex-matched healthy controls were included in a 2:1 prospective case-control study. We obtained clinical and anthropometric data transthoracic echocardiography, lifetime physical activity questionnaire, 24-h ambulatory blood pressure monitoring, Berlin questionnaire score, and, in patients at high risk for obstructive sleep apnoea (OSA) syndrome, a polysomnography. A total of 115 cases and 57 controls were enrolled. Conditional logistic regression analysis associated height [odds ratio (OR) 1.06 [1.01-1.11

  2. Very low dose fetal exposure to Chernobyl contamination resulted in increases in infant leukemia in Europe and raises questions about current radiation risk models.

    Science.gov (United States)

    Busby, Christopher C

    2009-12-01

    Following contamination from the Chernobyl accident in April 1986 excess infant leukemia (0-1 y) was reported from five different countries, Scotland, Greece, Germany, Belarus and Wales and Scotland combined. The cumulative absorbed doses to the fetus, as conventionally assessed, varied from 0.02 mSv in the UK through 0.06 mSv in Germany, 0.2 mSv in Greece and 2 mSv in Belarus, where it was highest. Nevertheless, the effect was real and given the specificity of the cohort raised questions about the safety of applying the current radiation risk model of the International Commission on Radiological Protection (ICRP) to these internal exposures, a matter which was discussed in 2000 by Busby and Cato and also in the reports of the UK Committee examining Radiation Risk from Internal Emitters. Data on infant leukemia in the United Kingdom, chosen on the basis of the cohorts defined by the study of Greece were supplied by the UK Childhood Cancer Research Group. This has enabled a study of leukemia in the combined infant population of 15,466,845 born in the UK, Greece, and Germany between 1980 and 1990. Results show a statistically significant excess risk RR = 1.43 (95% CI 1.13 < RR < 1.80 (2-tailed); p = 0.0025) in those born during the defined peak exposure period of 01/07/86 to 31/12/87 compared with those born between 01/01/80 and 31/12/85 and 01/01/88 and 31/12/90. The excess risks in individual countries do not increase monotonically with the conventionally calculated doses, the relation being biphasic, increasing sharply at low doses and falling at high doses. This result is discussed in relation to fetal/cell death at higher doses and also to induction of DNA repair. Since the cohort is chosen specifically on the basis of exposure to internal radionuclides, the result can be expressed as evidence for a significant error in the conventional modeling for such internal fetal exposures.

  3. Very Low Dose Fetal Exposure to Chernobyl Contamination Resulted in Increases in Infant Leukemia in Europe and Raises Questions about Current Radiation Risk Models

    Directory of Open Access Journals (Sweden)

    Christopher C. Busby

    2009-12-01

    Full Text Available Following contamination from the Chernobyl accident in April 1986 excess infant leukemia (0–1 y was reported from five different countries, Scotland, Greece, Germany, Belarus and Wales and Scotland combined. The cumulative absorbed doses to the fetus, as conventionally assessed, varied from 0.02 mSv in the UK through 0.06 mSv in Germany, 0.2 mSv in Greece and 2 mSv in Belarus, where it was highest. Nevertheless, the effect was real and given the specificity of the cohort raised questions about the safety of applying the current radiation risk model of the International Commission on Radiological Protection (ICRP to these internal exposures, a matter which was discussed in 2000 by Busby and Cato [7,8] and also in the reports of the UK Committee examining Radiation Risk from Internal Emitters. Data on infant leukemia in the United Kingdom, chosen on the basis of the cohorts defined by the study of Greece were supplied by the UK Childhood Cancer Research Group. This has enabled a study of leukemia in the combined infant population of 15,466,845 born in the UK, Greece, and Germany between 1980 and 1990. Results show a statistically significant excess risk RR = 1.43 (95% CI 1.13 < RR < 1.80 (2-tailed; p = 0.0025 in those born during the defined peak exposure period of 01/07/86 to 31/12/87 compared with those born between 01/01/80 and 31/12/85 and 01/01/88 and 31/12/90. The excess risks in individual countries do not increase monotonically with the conventionally calculated doses, the relation being biphasic, increasing sharply at low doses and falling at high doses. This result is discussed in relation to fetal/cell death at higher doses and also to induction of DNA repair. Since the cohort is chosen specifically on the basis of exposure to internal radionuclides, the result can be expressed as evidence for a significant error in the conventional modeling for such internal fetal exposures.

  4. Measurement of mean cardiac dose for various breast irradiation techniques and corresponding risk of major cardiovascular event

    NARCIS (Netherlands)

    T.R. Merino Lara (Tomas Rodrigo); E. Fleury (Emmanuelle); S. Mashouf (Shahram); J. Helou (Joelle); C. McCann (Claire); M. Ruschin (Mark); A. Kim (Anthony); N. Makhani (Nadiya); A. Ravi (Ananth); J.-P. Pignol (Jean-Philippe)

    2014-01-01

    textabstractAfter breast conserving surgery, early stage breast cancer patients are currently treated with a wide range of radiation techniques including whole breast irradiation (WBI), accelerated partial breast irradiation (APBI) using high-dose rate (HDR) brachytherapy, or 3D-conformal radiothera

  5. Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Air Way Cells

    Science.gov (United States)

    In vitro exposures to air pollutants could, in theory, facilitate a rapid and detailed assessment of molecular mechanisms of toxicity. However, it is difficult to ensure that the dose of a gaseous pollutant to cells in tissue culture is similar to that of the same cells during in...

  6. Benefit of low-dose tamoxifen in a large observational cohort of high risk ER positive breast DCIS.

    Science.gov (United States)

    Guerrieri-Gonzaga, Aliana; Sestak, Ivana; Lazzeroni, Matteo; Serrano, Davide; Rotmensz, Nicole; Cazzaniga, Massimiliano; Varricchio, Clara; Pruneri, Giancarlo; Leonardi, Maria Cristina; Orecchia, Roberto; Galimberti, Viviana; Bonanni, Bernardo; DeCensi, Andrea

    2016-11-01

    Low-dose tamoxifen has comparable antiproliferative effect to the standard dose of 20 mg/day in biomarker trials, but its clinical efficacy remains unclear. We assessed the effect of low-dose tamoxifen on ipsilateral recurrence in ductal carcinoma in situ (DCIS) patients treated in a referral Institution between 1996 and 2008. Following conserving surgery, women received radiotherapy and/or low-dose tamoxifen upon clinical judgment and patient preferences. Cox regression analyses were used with and without confounding factors. Among 1,091 women with DCIS and median age 53 years (IQR: 46-62), 544 (49.9%) received radiotherapy. Of the 833 women with oestrogen receptor (ER) positive DCIS, 467 (56.1%) received low-dose tamoxifen. After a median of 7.7 years, 235 ipsilateral recurrences and 62 contralateral breast tumors were observed. Low-dose tamoxifen significantly decreased any breast event (HR = 0.70, 95% CI: 0.54-0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95% CI: 0.49-0.88), but not ipsilateral invasive recurrence or contralateral tumors. Radiotherapy showed a large significant reduction for any breast event (HR = 0.55, 95% CI: 0.42-0.72). Tamoxifen was more effective on all breast events in women aged >50 years than in women aged ≤50 (HR = 0.51, 95% CI: 0.33-0.77 versus HR = 0.84, 95% CI: 0.60-1.18, p-interaction = 0.03). Age ≤50 years, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase of endometrial cancers and fewer deaths (p = 0.015) were observed on tamoxifen. Low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence in ER positive DCIS in women aged >50 years. A randomized trial is underway to confirm these findings.

  7. Doses to internal organs for various breast radiation techniques - implications on the risk of secondary cancers and cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Keller Brian M

    2011-01-01

    Full Text Available Abstract Background Breast cancers are more frequently diagnosed at an early stage and currently have improved long term outcomes. Late normal tissue complications induced by adjuvant radiotherapy like secondary cancers or cardiomyopathy must now be avoided at all cost. Several new breast radiotherapy techniques have been developed and this work aims at comparing the scatter doses of internal organs for those techniques. Methods A CT-scan of a typical early stage left breast cancer patient was used to describe a realistic anthropomorphic phantom in the MCNP Monte Carlo code. Dose tally detectors were placed in breasts, the heart, the ipsilateral lung, and the spleen. Five irradiation techniques were simulated: whole breast radiotherapy 50 Gy in 25 fractions using physical wedge or breast IMRT, 3D-CRT partial breast radiotherapy 38.5 Gy in 10 fractions, HDR brachytherapy delivering 34 Gy in 10 treatments, or Permanent Breast 103Pd Seed Implant delivering 90 Gy. Results For external beam radiotherapy the wedge compensation technique yielded the largest doses to internal organs like the spleen or the heart, respectively 2,300 mSv and 2.7 Gy. Smaller scatter dose are induced using breast IMRT, respectively 810 mSv and 1.1 Gy, or 3D-CRT partial breast irradiation, respectively 130 mSv and 0.7 Gy. Dose to the lung is also smaller for IMRT and 3D-CRT compared to the wedge technique. For multicatheter HDR brachytherapy a large dose is delivered to the heart, 3.6 Gy, the spleen receives 1,171 mSv and the lung receives 2,471 mSv. These values are 44% higher in case of a balloon catheter. In contrast, breast seeds implant is associated with low dose to most internal organs. Conclusions The present data support the use of breast IMRT or virtual wedge technique instead of physical wedges for whole breast radiotherapy. Regarding partial breast irradiation techniques, low energy source brachytherapy and external beam 3D-CRT appear safer than 192Ir HDR

  8. Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies

    Science.gov (United States)

    Ding, Ming; Bhupathiraju, Shilpa N; Satija, Ambika; van Dam, Rob M; Hu, Frank B

    2013-01-01

    Background Considerable controversy exists regarding the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. Methods and Results Pubmed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1,279,804 participants and 36,352 CVD cases. A non-linear relationship of coffee consumption with CVD risk was identified (P for heterogeneity = 0.09, P for trend coffee consumption (median: 0 cups/d), the relative risk of CVD was 0.95 (95% CI, 0.87 to 1.03) for the highest (median: 5 cups/d) category, 0.85 (0.80 to 0.90) for the second highest (median: 3.5 cups/d), and 0.89 (0.84 to 0.94) for the third highest category (median: 1.5 cups/d). Looking at separate outcomes, coffee consumption was non-linearly associated with both CHD (P for heterogeneity = 0.001, P for trend 0.05). Conclusions A non-linear association between coffee consumption with CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups/d, and heavy coffee consumption was not associated with elevated CVD risk. PMID:24201300

  9. Toward optimal organ at risk sparing in complex volumetric modulated arc therapy: An exponential trade-off with target volume dose homogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Tol, Jim P., E-mail: j.tol@vumc.nl; Dahele, Max; Doornaert, Patricia; Slotman, Ben J.; Verbakel, Wilko F. A. R. [Department of Radiation Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam (Netherlands)

    2014-02-15

    Purpose: Conventional radiotherapy typically aims for homogenous dose in the planning target volume (PTV) while sparing organs at risk (OAR). The authors quantified and characterized the trade-off between PTV dose inhomogeneity (IH) and OAR sparing in complex head and neck volumetric modulated arc therapy plans. Methods: Thirteen simultaneous integrated boost plans were created per patient, for ten patients. PTV boost{sub (B)}/elective{sub (E)} optimization priorities were systematically increased. IH{sub B} and IH{sub E}, defined as (100% − V95%) + V107%, were evaluated against the average of the mean dose to the combined composite swallowing and combined salivary organs (D-OAR{sub comp}). To investigate the influence of OAR size and position with respect to PTV{sub B/E}, OAR dose was evaluated against a modified Euclidean distance (DM{sub B}/DM{sub E}) between OAR and PTV. Results: Although the achievable D-OAR{sub comp} for a given level of PTV IH differed between patients, excellent logarithmic fits described the D-OAR{sub comp}/IH{sub B} and IH{sub E} relationship in all patients (mean R{sup 2} of 0.98 and 0.97, respectively). Allowing an increase in average IH{sub B} and IH{sub E} over a clinically acceptable range, e.g., from 0.4% ± 0.5% to 2.0% ± 2.0% and 6.9% ± 2.8% to 14.8% ± 2.7%, respectively, corresponded to a decrease in average dose to the composite salivary and swallowing structures from 30.3 ± 6.5 to 23.6 ± 4.7 Gy and 32.5 ± 8.3 to 26.8 ± 9.3 Gy. The increase in PTV{sub E} IH was mainly accounted for by an increase in V107, by on average 5.9%, rather than a reduction in V95, which was on average only 2%. A linear correlation was found between the OAR dose to composite swallowing structures and contralateral parotid and submandibular gland, with DM{sub E} (R{sup 2} = 0.83, 0.88, 0.95). Only mean ipsilateral parotid dose correlated with DM{sub B} (R{sup 2} = 0.87). Conclusions: OAR sparing is highly dependent on the permitted PTV{sub B

  10. Comparative risk assessment of radiation and other mutagenic agents. Low dose relative risk of different ionizing radiations and comparison with UV-radiation

    NARCIS (Netherlands)

    Leenhouts HP; Chadwick KH; Pruppers MJM; Wijngaard E; Sijsma MJ; Bouwens BT

    1990-01-01

    This report is the final report of a research contract of RIVM in the framework of the Radiation Protection Programme of the Commission of the European Communities. The aim of the project was to investigate the nature of the dose-effect relationship for radiobiological effects after different types

  11. Factors that elevate the internal radionuclide and chemical retention, dose and health risks to infants and children in a radiological-nuclear emergency.

    Science.gov (United States)

    Richardson, Richard B

    2009-06-01

    The factors that influence the dose and risk to vulnerable population groups from exposure and internal uptake of chemicals are examined and, in particular, the radionuclides released in chemical, biological, radiological, nuclear and explosive events. The paper seeks to identify the areas that would benefit from further research. The intake and body burdens of carbon and calcium were assessed as surrogates for contaminants that either act like or bind to hydrocarbons (e.g. tritium and (14)C) or bone-seeking radionuclides (e.g. (90)Sr and (239)Pu). The shortest turnover times for such materials in the whole body were evaluated for the newborn: 11 d and 0.5 y for carbon and calcium, respectively. However, their biokinetic behaviour is complicated by a particularly high percentage of the gut-absorbed dietary intake of carbon (approximately 16%) and calcium (approximately 100%) that is incorporated into the soft tissue and skeleton of the growing neonate. The International Commission on Radiological Protection dose coefficients (Sv Bq(-1)) were examined for 14 radionuclides, including 9 of concern because of their potential use in radiological dispersal devices. The dose coefficients for a 3-month-old are greater than those for adults (2-56 times more for ingestion and 2-12 times for inhalation). The age-dependent dose and exposure assessment of contaminant intakes would improve by accounting for gender and growth where it is currently neglected. Health risk is evaluated as the product of the exposure and hazard factors, the latter being about 10-fold greater in infants than in adults. The exposure factor is also approximately 10-fold higher for ingestion by infants than by adults, and unity for inhalation varying with the contaminant. Qualitative and quantitative physiological and epidemiological evidence supports infants being more vulnerable to cancer and neurological deficit than older children.

  12. Evaluating genotoxicity data to identify a mode of action and its application in estimating cancer risk at low doses: A case study involving carbon tetrachloride.

    Science.gov (United States)

    Eastmond, David A

    2008-03-01

    In the new USEPA cancer risk assessment guidelines, mode of action (MoA) information, combined with a determination of whether or not a chemical is mutagenic, plays an important role in determining whether a linear or nonlinear approach should be used to estimate cancer risks at low doses. In this article, carbon tetrachloride (CT) is used as an example to illustrate how mixed genotoxicity data can be evaluated and used to identify a likely MoA. CT is essentially negative in inducing gene mutations in Salmonella, but is consistently positive in inducing recombination and aneuploidy in fungi. Negative or equivocal results were seen in most in vitro and in vivo studies in mammals, including mutation studies in transgenic mice. However, DNA adducts, primarily those derived from oxidation- and lipid-peroxidation-derived products as well as DNA double-strand breaks and micronucleated cells, have been seen repeatedly in the liver of CT-treated animals. On the basis of the weight of evidence, CT should not be considered a directly mutagenic agent. Mutagenic as well as other genotoxic effects, as they occur, will most likely be generated through indirect mechanisms resulting from oxidative and lipid peroxidative damage and/or damage occurring during necrosis or apoptosis. As key events in this process are expected to occur in a nonlinear fashion, the expected relationship between CT dose and carcinogenic response in the liver is likely to be nonlinear with a steep dose response. This conclusion is consistent with rodent cancer bioassay results in which steep nonlinear dose responses have been seen.

  13. Hyperuricemia and the risk for coronary heart disease morbidity and mortality a systematic review and dose-response meta-analysis

    Science.gov (United States)

    Li, Min; Hu, Xiaolan; Fan, Yingli; Li, Kun; Zhang, Xiaowei; Hou, Wenshang; Tang, Zhenyu

    2016-01-01

    Considerable controversy exists regarding the association between hyperuricemia and coronary heart disease (CHD). Therefore, we performed a systematic review and dose-response meta-analysis of prospective studies to examine the controversy. Prospective cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) for CHD according to serum uric acid levels in adults were eligible. A random-effects model was used to compute the pooled risk estimate. The search yielded 29 prospective cohort studies (n = 958410 participants). Hyperuricemia was associated with increased risk of CHD morbidity (adjusted RR 1.13; 95% CI 1.05 to 1.21) and mortality (adjusted RR 1.27; 95% CI 1.16 to 1.39). For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR of CHD mortality was 1.13 (95% CI 1.06 to 1.20). Dose-response analysis indicated that the combined RR of CHD mortality for an increase of 1 mg uric acid level per dl was 1.02 (95% CI 0.84 to 1.24) without heterogeneity among males (P = 0.879, I2 = 0%) and 2.44 (95% CI 1.69 to 3.54) without heterogeneity among females (P = 0.526, I2 = 0%). The increased risk of CHD associated with hyperuricemia was consistent across most subgroups. Hyperuricemia may increase the risk of CHD events, particularly CHD mortality in females. PMID:26814153

  14. The risk of fever following one dose of trivalent inactivated influenza vaccine in children aged ≥6 months to <36 months: a comparison of published and unpublished studies.

    Science.gov (United States)

    Kaczmarek, Marlena C; Duong, Uyen T; Ware, Robert S; Lambert, Stephen B; Kelly, Heath A

    2013-11-01

    There are limited summary data published on the risk of fever and febrile seizures in children following influenza vaccination. We performed a review of the risk of fever and febrile seizures following receipt of trivalent inactivated influenza vaccine (TIV) in children aged ≥6 months to fever. We reviewed articles and collated results using a standard data extraction template. We identified a total of 909 published papers and unpublished trials from a search conducted on 23 January 2013, 669 from Google Scholar, 114 from PubMed and 126 from the Clinicaltrials.gov online database. After excluding 890 published papers or unpublished trials, 5 published papers and 14 unpublished trials were included in this review. Extracted data on number of events, children at risk and time of follow-up were converted to the risk of fever, which was averaged per week of follow-up (referred to as 'averaged weekly risk'). Following one dose of TIV, the median averaged weekly risk of any fever (≥37.5°C) was 26.0% (range 10.3-70.0%) in unpublished trials compared to 8.2% (range 5.3-28.3%) in published papers (p=0.04). The median averaged weekly risk of severe fever (≥39.0°C) was 3.2% (range 0-10.0%) and 2.0% (range 0.6-17.0%), respectively (p=0.91). Variation in the reporting of fever by participant age groups, time since vaccination and the definition or measurement of fever resulted in a wide range of risk estimates. Reporting of febrile reactions should be standardised to allow comparison between manufacturers and influenza seasons.

  15. The relationship between dietary protein consumption and risk of fracture: a subgroup and dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Wu, Ai-Min; Sun, Xiao-Lei; Lv, Qing-Bo; Zhou, Yong; Xia, Dong-Dong; Xu, Hua-Zi; Huang, Qi-Shan; Chi, Yong-Long

    2015-03-16

    It is still debate of the relationship between the dietary protein consumption and risk of fracture. We searched Medline and Embase to assess the effects of dietary protein consumption on risk of fracture. Twelve prospective cohort studies with 407,104 participants were included, higher total protein consumption may be decrease 11% risk of hip fractures, with adj. RR of 0.89 (0.82, 0.97), no significant difference was found for total protein and risk of all fractures and limb fracture; for animal protein consumption and risk of all fractures and hip fracture, with adj.RR of 0.79 (032, 1.96) and 1.04 (0.70, 1.54); for vegetable protein consumption and risk of all fractures, hip fracture and limb fractures with adj.RR of 0.77 (0.52, 1.12), 1.00 (0.53, 1.91), and 0.94 (0.40, 2.22), the subgroup of vegetable protein consumption and risk of all fractures of postmenopausal women with adj.RR of 0.78(0.52,1.16). Dose-response meta-analysis the relationship of total/animal/vegetable protein and hip fracture was consistent to the results of forest plot, the line of total protein and hip fracture was below the Y = 1.0 line. This meta-analysis showed that total dietary protein consumption may be decrease the risk of hip fracture, but not for animal or vegetable protein.

  16. High-Dose Corticosteroid Use and Risk of Hip Osteonecrosis: Meta-Analysis and Systematic Literature Review.

    Science.gov (United States)

    Mont, Michael A; Pivec, Robert; Banerjee, Samik; Issa, Kimona; Elmallah, Randa K; Jones, Lynne C

    2015-09-01

    The effect of varying corticosteroid regimens on hip osteonecrosis incidence remains unclear. We performed a meta-analysis and systematic literature review to determine osteonecrosis occurrences in patients taking corticosteroids at varying mean and cumulative doses and treatment durations, and whether medical diagnoses affected osteonecrosis incidence. Fifty-seven studies (23,561 patients) were reviewed. Regression analysis determined significance between corticosteroid usage and osteonecrosis incidence. Osteonecrosis incidence was 6.7% with corticosteroid treatment of >2 g (prednisone-equivalent). Systemic lupus erythematosus patients had positive correlations between dose and osteonecrosis incidence. Each 10 mg/d increase was associated with a 3.6% increase in osteonecrosis rate, and >20 mg/d resulted in a higher osteonecrosis incidence. Clinicians must be wary of osteonecrosis in patients on high corticosteroid regimens, particularly in systematic lupus erythematosus.

  17. Body Mass Index and Risk of Parkinson’s Disease: A Dose-Response Meta-Analysis of Prospective Studies

    OpenAIRE

    Yun-Liang Wang; Yu-Tong Wang; Jin-Feng Li; Yu-Zheng Zhang; Hong-Lei Yin; Bing Han

    2015-01-01

    Background A number of epidemiologic studies examining the relationship between body mass index (BMI) and the future occurrence of Parkinson’s disease (PD) reported largely inconsistent findings. We conducted a dose-response meta-analysis of prospective studies to clarify this association. Methods Eligible prospective studies were identified by a search of PubMed and by checking the references of related publications. The generalized least squares trend estimation was employed to compute stud...

  18. Local Control With Reduced-Dose Radiotherapy for Low-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group D9602 Study

    Energy Technology Data Exchange (ETDEWEB)

    Breneman, John, E-mail: john.breneman@uchealth.com [Department of Radiation Oncology, University of Cincinnati and Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Meza, Jane [Department of Biostatistics, University of Nebraska Medical Center College of Public Health, Omaha, NE (United States); Donaldson, Sarah S. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Raney, R. Beverly [Children' s Cancer Hospital and Division of Pediatrics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Children' s Ambulatory Blood and Cancer Center, Dell Children' s Medical Center of Central Texas, Austin, TX (United States); Wolden, Suzanne [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (United States); Michalski, Jeff [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Laurie, Fran [Quality Assurance Review Center, Lincoln, RI (United States); Rodeberg, David A. [Department of Surgery, East Carolina University, Greenville, NC (United States); Meyer, William [Section of Pediatric Hematology/Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Walterhouse, David [Division of Hematology/Oncology, Children' s Memorial Medical Center, Chicago, IL (United States); Hawkins, Douglas S. [Department of Pediatrics, Seattle Children' s Hospital, University of Washington, Seattle, WA (United States)

    2012-06-01

    Purpose: To analyze the effect of reduced-dose radiotherapy on local control in children with low-risk rhabdomyosarcoma (RMS) treated in the Children's Oncology Group D9602 study. Methods and Materials: Patients with low-risk RMS were nonrandomly assigned to receive radiotherapy doses dependent on the completeness of surgical resection of the primary tumor (clinical group) and the presence of involved regional lymph nodes. After resection, most patients with microscopic residual and uninvolved nodes received 36 Gy, those with involved nodes received 41.4 to 50.4 Gy, and those with orbital primary tumors received 45 Gy. All patients received vincristine and dactinomycin, with cyclophosphamide added for patient subsets with a higher risk of relapse in Intergroup Rhabdomyosarcoma Study Group III and IV studies. Results: Three hundred forty-two patients were eligible for analysis; 172 received radiotherapy as part of their treatment. The cumulative incidence of local/regional failure was 15% in patients with microscopic involved margins when cyclophosphamide was not part of the treatment regimen and 0% when cyclophosphamide was included. The cumulative incidence of local/regional failure was 14% in patients with orbital tumors. Protocol-specified omission of radiotherapy in girls with Group IIA vaginal tumors (n = 5) resulted in three failures for this group. Conclusions: In comparison with Intergroup Rhabdomyosarcoma Study Group III and IV results, reduced-dose radiotherapy does not compromise local control for patients with microscopic tumor after surgical resection or with orbital primary tumors when cyclophosphamide is added to the treatment program. Girls with unresected nonbladder genitourinary tumors require radiotherapy for postsurgical residual tumor for optimal local control to be achieved.

  19. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukaemia. A Nordic Society of Paediatric Haematology and Oncology (NOPHO) pilot study

    DEFF Research Database (Denmark)

    Frandsen, Thomas L; Abrahamsson, Jonas; Lausen, Birgitte;

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m(2), ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m(2...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  20. A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood 'high-risk' acute lymphoblastic leukaemia: a study of the AIEOP group.

    Science.gov (United States)

    Testi, Anna Maria; Del Giudice, Ilaria; Arcese, William; Moleti, Maria Luisa; Giona, Fiorina; Basso, Giuseppe; Biondi, Andrea; Conter, Valentino; Messina, Chiara; Rondelli, Roberto; Micozzi, Alessandra; Micalizzi, Concetta; Barisone, Elena; Locatelli, Franco; Dini, Giorgio; Aricò, Maurizio; Casale, Fiorina; Comis, Margherita; Ladogana, Saverio; Lippi, Alma; Mura, Rossella; Pinta, Marie France; Santoro, Nicola; Valsecchi, Maria Grazia; Masera, Giuseppe; Mandelli, Franco

    2002-09-01

    The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52.5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4-year overall survival and event-free survival were 25% and 21% respectively. Disease-free survival at 4 years was 25.8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation.

  1. DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PESTICIDES

    Science.gov (United States)

    The US EPAs N-Methyl Carbamate Cumulative Risk Assessment (NMCRA) assesses the effect on acetylcholine esterase (AChE) activity of exposure to 10 N-methyl carbamate (NMC) pesticides through dietary, drinking water, and residential exposures.

  2. Radiation dose and cancer risk to out-of-field and partially in-field organs from radiotherapy for symptomatic vertebral hemangiomas

    Energy Technology Data Exchange (ETDEWEB)

    Mazonakis, Michalis, E-mail: mazonak@med.uoc.gr; Damilakis, John [Department of Medical Physics, Faculty of Medicine, University of Crete, P.O. Box 2208, Iraklion, Crete 71003 (Greece); Tzedakis, Antonis [Department of Medical Physics, University Hospital of Iraklion, Iraklion, Crete 71110 (Greece); Lyraraki, Efrossyni [Department of Radiotherapy and Oncology, University Hospital of Iraklion, Iraklion, Crete 71110 (Greece)

    2016-04-15

    Purpose: Vertebral hemangiomas (VHs) are the most common benign tumors of the spine that may cause bone resorption. Megavoltage irradiation is usually the treatment of choice for the management of symptomatic VHs. The current study was conducted to estimate the risk for carcinogenesis from radiotherapy of this benign disease on the basis of the calculated radiation doses to healthy organs. Methods: The Monte Carlo N-particle transport code was employed to simulate the irradiation with 6 MV x-rays of a VH presented in the cervical, upper thoracic, lower thoracic, and lumbar spine. The average radiation dose (D{sub av}) received by each critical organ located outside the primarily irradiated area was calculated. Three-dimensional treatment plans were also generated for the VHs occurring at the four different sites of the spinal cord based on patients’ computed tomography data. The organ equivalent dose (OED) to each radiosensitive structure, which was partly encompassed by the applied treatment fields, was calculated with the aid of differential dose–volume histograms. The D{sub av} and the OED values were combined with a linear-no-threshold model and a nonlinear mechanistic model, respectively, to estimate the organ-, age-, and gender-specific lifetime attributable risks (LARs) for cancer development. The estimated risks were compared with the respective nominal lifetime intrinsic risks (LIRs) for the unexposed population. Results: For a standard target dose of 34 Gy, the OED varied from 0.39–5.15 Gy by the organ of interest and the irradiation site. The D{sub av} range for the out-of-field organs was 4.9 × 10{sup −4} to 0.56 Gy. The LAR for the appearance of malignancies in the partially in-field organs after radiotherapy of male and female patients was (0.08%–1.8%) and (0.09%–1.9%), respectively. These risk values were 1.5–15.5 times lower when compared to the respective LIRs. The lifetime probability for out-of-field cancer induction in irradiated

  3. Comparison of second cancer risk due to out-of-field doses from 6-MV IMRT and proton therapy based on 6 pediatric patient treatment plans

    Science.gov (United States)

    Athar, Basit S.; Paganetti, Harald

    2010-01-01

    Background and Purpose This study compared 6-MV IMRT and proton therapy in terms of organ specific second cancer lifetime attributable risks (LARs) caused by scattered and secondary out-of-field radiation. Material and Methods Based on simulated organ doses, excess relative and excess absolute risk models were applied to assess organ-specific LARs. Two treatment sites (cranium and central spine) were considered involving 6 treatment volumes and 6 patient ages (9-month, 4-year, 8-year, 11-year, 14-year, and adult). Results The LARs for thyroid cancer from a 6 cm diameter field treating a brain lesion in a 4-year old patient were estimated to be 1.1% and 0.3% in passive proton therapy and IMRT, respectively. However, estimated LARs for bladder cancer, more than 25 cm from the field edge for the same patient and treatment field, were estimated to be 0.2% and 0.02% from IMRT and proton therapy, respectively. Risks for proton beam scanning was found to be an order of magnitude smaller compared to passive proton therapy. Conclusion In terms of out-of-field risks, IMRT offers advantage close to the primary field and an increasing advantage for passive proton therapy is noticed with increasing distance to the field. Scanning proton beam therapy shows the lowest risks. PMID:21159398

  4. High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Edelman, Scott [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States); Liauw, Stanley L. [Department of Radiation Oncology, University of Chicago, Chicago, IL (United States); Rossi, Peter J.; Cooper, Sherrie [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States); Jani, Ashesh B., E-mail: abjani@emory.edu [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States)

    2012-08-01

    Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy

  5. GENII-LIN-2.1: an open source software system for calculating radiation dose and risk from radionuclides released to the environment.

    Science.gov (United States)

    Teodori, Francesco; Sumini, Marco

    2008-12-01

    GENII-LIN is an open source radiation protection environmental software system running on the Linux operating system. It has capabilities for calculating radiation dose and risk to individuals or populations from radionuclides released to the environment and from pre-existing environmental contamination. It can handle exposure pathways that include ingestion, inhalation and direct exposure to air, water and soil. The package is available for free and is completely open source, i.e., transparent to the users, who have full access to the source code of the software.

  6. Coupling a continuous watershed-scale microbial fate and transport model with a stochastic dose-response model to estimate risk of illness in an urban watershed.

    Science.gov (United States)

    Liao, Hehuan; Krometis, Leigh-Anne H; Kline, Karen

    2016-05-01

    Within the United States, elevated levels of fecal indicator bacteria (FIB) remain the leading cause of surface water-quality impairments requiring formal remediation plans under the federal Clean Water Act's Total Maximum Daily Load (TMDL) program. The sufficiency of compliance with numerical FIB criteria as the targeted endpoint of TMDL remediation plans may be questionable given poor correlations between FIB and pathogenic microorganisms and varying degrees of risk associated with exposure to different fecal pollution sources (e.g. human vs animal). The present study linked a watershed-scale FIB fate and transport model with a dose-response model to continuously predict human health risks via quantitative microbial risk assessment (QMRA), for comparison to regulatory benchmarks. This process permitted comparison of risks associated with different fecal pollution sources in an impaired urban watershed in order to identify remediation priorities. Results indicate that total human illness risks were consistently higher than the regulatory benchmark of 36 illnesses/1000 people for the study watershed, even when the predicted FIB levels were in compliance with the Escherichia coli geometric mean standard of 126CFU/100mL. Sanitary sewer overflows were associated with the greatest risk of illness. This is of particular concern, given increasing indications that sewer leakage is ubiquitous in urban areas, yet not typically fully accounted for during TMDL development. Uncertainty analysis suggested the accuracy of risk estimates would be improved by more detailed knowledge of site-specific pathogen presence and densities. While previous applications of the QMRA process to impaired waterways have mostly focused on single storm events or hypothetical situations, the continuous modeling framework presented in this study could be integrated into long-term water quality management planning, especially the United States' TMDL program, providing greater clarity to watershed

  7. Whole grain and refined grain consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies.

    Science.gov (United States)

    Aune, Dagfinn; Norat, Teresa; Romundstad, Pål; Vatten, Lars J

    2013-11-01

    Several studies have suggested a protective effect of intake of whole grains, but not refined grains on type 2 diabetes risk, but the dose-response relationship between different types of grains and type 2 diabetes has not been established. We conducted a systematic review and meta-analysis of prospective studies of grain intake and type 2 diabetes. We searched the PubMed database for studies of grain intake and risk of type 2 diabetes, up to June 5th, 2013. Summary relative risks were calculated using a random effects model. Sixteen cohort studies were included in the analyses. The summary relative risk per 3 servings per day was 0.68 (95% CI 0.58-0.81, I(2) = 82%, n = 10) for whole grains and 0.95 (95% CI 0.88-1.04, I(2) = 53%, n = 6) for refined grains. A nonlinear association was observed for whole grains, p nonlinearity grains, p nonlinearity = 0.10. Inverse associations were observed for subtypes of whole grains including whole grain bread, whole grain cereals, wheat bran and brown rice, but these results were based on few studies, while white rice was associated with increased risk. Our meta-analysis suggests that a high whole grain intake, but not refined grains, is associated with reduced type 2 diabetes risk. However, a positive association with intake of white rice and inverse associations between several specific types of whole grains and type 2 diabetes warrant further investigations. Our results support public health recommendations to replace refined grains with whole grains and suggest that at least two servings of whole grains per day should be consumed to reduce type 2 diabetes risk.

  8. Approximating dose and risk for contaminants in groundwater from the underground nuclear test areas of the Nevada National Security Site (NNSS)

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, Jeffrey I. [Desert Research Inst. (DRI), Las Vegas, NV (United States); Chapman, Jenny [Desert Research Inst. (DRI), Las Vegas, NV (United States); Pohlmann, Karl F. [Desert Research Inst. (DRI), Las Vegas, NV (United States)

    2015-03-01

    As part of the Environmental Management Program at the Nevada National Security Site (NNSS), the Underground Test Area (UGTA) Activity investigates the potential impacts of radionuclides that were introduced into groundwater from the underground nuclear tests conducted near or below the NNSS water table between 1951 and 1992. Groundwater models are being used to simulate contaminant transport and forecast contaminant boundaries that encompass areas where the groundwater has a five percent or greater probability of containing contaminants above the Safe Drinking Water Act Maximum Contaminant Levels (SDWA MCLs) at any time during the next 1,000 years. Transport modeling conducted for the Frenchman Flat Corrective Action Unit (CAU) at the NNSS identified the beta/photon-emitting radionuclides tritium (3H), carbon-14 (14C), chlorine-36 (36Cl), technetium-99 (99Tc), and iodine-129 (129I) as having the greatest influence in defining the farthest extent of the modeled CAU contaminant boundary. These same radionuclides are assumed here as the contaminants of concern (COCs) for all underground nuclear tests at the NNSS because models are not yet complete for the other CAUs.Potential public exposure to the COCs will only occur and be of concern if the COCs migrate into the groundwater beneath public or private lands at levels that exceed either individual SDWA MCLs or dose and risk limits. Groundwater flow directions strongly suggest that any contaminant boundary predicted by contaminant fate and transport modeling to overlap public or private lands is more likely to occur to the west and/or southwest of the NNSS and the adjacent Nevada Test and Training Range (NTTR). Well-established, rural communities exist in these directions. Estimates of representative activity concentrations at the applicable SDWA MCL were developed for the five COCs. It is assumed that these COC concentrations may collectively occur at some public or private location in the future, but that situation

  9. Dose-response association of uncontrolled blood pressure and cardiovascular disease risk factors with hyperuricemia and gout.

    Directory of Open Access Journals (Sweden)

    Stephen P Juraschek

    Full Text Available First-line therapy of hypertension includes diuretics, known to exert a multiplicative increase on the risk of gout. Detailed insight into the underlying prevalence of hyperuricemia and gout in persons with uncontrolled blood pressure (BP and common comorbidities is informative to practitioners initiating antihypertensive agents. We quantify the prevalence of hyperuricemia and gout in persons with uncontrolled BP and additional cardiovascular disease (CVD risk factors.We performed a cross-sectional study of non-institutionalized US adults, 18 years and older, using the National Health and Nutrition Examination Surveys in 1988-1994 and 1999-2010. Hyperuricemia was defined as serum uric acid >6.0 mg/dL in women; >7.0 mg/dL in men. Gout was ascertained by self-report of physician-diagnosed gout. Uncontrolled BP was based on measured systolic BP≥140 mmHg and diastolic BP≥90 mmHg. Additional CVD risk factors included obesity, reduced glomerular filtration rate, and dyslipidemia. The prevalence of hyperuricemia was 6-8% among healthy US adults, 10-15% among adults with uncontrolled BP, 22-25% with uncontrolled BP and one additional CVD risk factor, and 34-37% with uncontrolled BP and two additional CVD risk factors. Similarly, the prevalence of gout was successively greater, at 1-2%, 4-5%, 6-8%, and 8-12%, respectively, across these same health status categories. In 2007-2010, those with uncontrolled BP and 2 additional CVD risk factors compared to those without CVD risk factors had prevalence ratios of 4.5 (95% CI 3.5-5.6 and 4.5 (95% CI: 3.1-6.3 for hyperuricemia and gout respectively (P<0.01.Health care providers should be cognizant of the incrementally higher prevalence of hyperuricemia and gout among patients with uncontrolled BP and additional CVD risk factors. With one in three people affected by hyperuricemia among those with several CVD risk factors, physicians should consider their anti-hypertensive regimens carefully and potentially

  10. Consumption of fruit and vegetables and risk of frailty: a dose-response analysis of 3 prospective cohorts of community-dwelling older adults.

    Science.gov (United States)

    García-Esquinas, Esther; Rahi, Berna; Peres, Karine; Colpo, Marco; Dartigues, Jean-François; Bandinelli, Stefania; Feart, Catherine; Rodríguez-Artalejo, Fernando

    2016-07-01

    Consuming fruit and vegetables (FVs) may protect against frailty, but to our knowledge no study has yet assessed their prospective dose-response relation. We sought to examine the dose-response association between FV consumption and the risk of frailty in older adults. Data were taken from 3 independent cohorts of community-dwelling older adults: the Seniors-ENRICA (Study on Nutrition and Cardiovascular Risk Factors in Spain) cohort (n = 1872), Three-City (3C) Bordeaux cohort (n = 581), and integrated multidisciplinary approach cohort (n = 473). Baseline food consumption was assessed with a validated computerized diet history (Seniors-ENRICA) or with a food-frequency questionnaire (3C Bordeaux and AMI). In all cohorts, incident frailty was assessed with the use of the Fried criteria. Results across cohorts were pooled with the use of a random-effects model. During a mean 2.5-y follow-up, 300 incident frailty cases occurred. Fully adjusted models showed that the pooled ORs (95% CIs) of incident frailty comparing participants who consumed 1, 2, or ≥3 portions of fruit/d to those with no consumption were, respectively, 0.59 (0.27, 0.90), 0.58 (0.29, 0.86), and 0.48 (0.20, 0.75), with a P-trend of 0.04. The corresponding values for vegetables were 0.69 (0.42, 0.97), 0.56 (0.35, 0.77), and 0.52 (0.13, 0.92), with a P-trend fruit and risk of exhaustion, low physical activity, and slow walking speed, whereas the consumption of vegetables was associated with a decreased risk of exhaustion and unintentional weight loss. Among community-dwelling older adults, FV consumption was associated with a lower short-term risk of frailty in a dose-response manner, and the strongest association was obtained with 3 portions of fruit/d and 2 portions of vegetables/d. © 2016 American Society for Nutrition.

  11. Review of cobalt toxicokinetics following oral dosing: Implications for health risk assessments and metal-on-metal hip implant patients.

    Science.gov (United States)

    Tvermoes, Brooke E; Paustenbach, Dennis J; Kerger, Brent D; Finley, Brent L; Unice, Kenneth M

    2015-05-01

    Cobalt (Co) can stimulate erythropoietin production in individuals at doses exceeding 25 mg CoCl2/day. Co has also been shown to exert effects on the thyroid gland, heart and nervous system at sufficient doses. The biological activity of Co is dictated by the concentration of free (unbound) ionic Co(2+). Blood concentrations, as well as, urinary excretion rates of Co are reliable biomarkers for systemic Co exposure. A recent series of human volunteer Co-supplement studies simultaneously measured Co blood and urine concentrations, as well as, Co speciation in serum, and a number of biochemical and clinical parameters. It was found in these studies that peak Co whole blood concentration as high as 117 μg/L were not associated with changes in hematological parameters such as increased red blood cell (RBC) count, hemoglobin (Hgb) or hematocrit (Hct) levels, nor with changes in cardiac, neurological or, thyroid function. Using a Co biokinetic model, the estimated Co systemic tissue concentrations (e.g., liver, kidney, and heart) following 90-days of Co-dietary supplementation with ∼1 mg Co/day were found to be similar to estimated tissue concentrations in implant patients after 10 years of exposure at continuous steady state Co blood concentration of ∼10 μg/L. This study is the first to present modeled Co tissue concentrations at various doses following sub-chronic and chronic exposure. The modeled steady state tissue Co concentrations in combination with the data on adverse health effects in humans should help in the characterization of potential hazards associated with increased blood Co concentrations due to exposure to dietary supplements or cobalt-chromium (Co-Cr) containing implants.

  12. Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

    Science.gov (United States)

    Sood, Sumit; Pokhrel, Damodar; McClinton, Christopher; Lominska, Christopher; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

    2017-08-16

    A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of D100%) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50

  13. Dose and induction to cancer risk evaluation associated to use of X ray body scanners by transmission at airports; Avaliacao da dose e do risco de inducao ao cancer associados ao uso de escaneres corporais de raios X por transmissao em aeroportos

    Energy Technology Data Exchange (ETDEWEB)

    Correa, Samanda Cristine Arruda; Aquino, Josilto Oliveira de, E-mail: scorrea@cnen.gov.b, E-mail: josilto@cnen.gov.b [Comissao Nacional de Energia Nuclear (DIAPI/CGMI/CNEN), Rio de Janeiro, RJ (Brazil). Coordenacao Geral de Instalacoes Medicas e Industriais. Div. de Aplicacoes Industriais; Souza, Edmilson Monteiro de, E-mail: emonteiro@nuclear.ufrj.b [Centro Universitario Estadual da Zona Oeste (CAPI/UEZO), Campo Grande, RJ (Brazil). Colegiado da Area de Producao Industrial; Silva, Ademir Xavier da, E-mail: ademir@nuclear.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (PEN/COPPE/UFRJ), RJ (Brazil). Programa de Engenharia Nuclear

    2011-07-01

    This paper uses the Monte Carlo MCNPX and the phantoms in male voxel and female voxel to evaluate the absorbed doses effective doses and the induction risk and the mortality due to cancer associated to exposures of individual submitted to X ray body scanners by transmission at various projections. The values of effective dose were calculated according to the recommended by the new ICRP 103 and the values of induction risks and mortality due to cancer were estimated through the document BEIR VII. (author)

  14. Magnetic resonance imaging left ventricular mass reduction with fixed-dose angiotensin-converting enzyme inhibitor-based regimens in patients with high-risk hypertension.

    Science.gov (United States)

    Reichek, Nathaniel; Devereux, Richard B; Rocha, Ricardo A; Hilkert, Robert; Hall, Donna; Purkayastha, Das; Pitt, Bertram

    2009-10-01

    Left ventricular hypertrophy, a major cardiovascular risk factor for morbidity and mortality, is commonly caused by arterial hypertension. The renin-angiotensin-aldosterone system may contribute to the pathogenesis of left ventricular hypertrophy. The Assessment of Lotrel in Left Ventricular Hypertrophy and Hypertension Study compared a single-pill combination of amlodipine/benazepril at doses 5.0/20.0 mg, 5.0/40.0 mg, and 10.0/40.0 mg with hydrochlorothiazide/benazepril at doses 12.5/20.0 mg, 12.5/40.0 mg, and 25.0/40.0 mg on the reduction of left ventricular mass index measured by cardiac MRI in stage 2 hypertensive patients over 52 weeks of treatment in a randomized clinical trial. A total of 125 male and female patients, > or =55 years of age, with echocardiographic left ventricular hypertrophy and high-risk hypertension defined as blood pressure > or =160/100 mm Hg or current antihypertensive treatment were enrolled. After 52 weeks of treatment, left ventricular mass index was significantly reduced from baseline with amlodipine/benazepril (mean: 10.16 g/m(2)) or hydrochlorothiazide/benazepril (mean: 6.74 g/m(2); both Pamlodipine/benazepril (P=0.02). Both treatments were well tolerated.

  15. Chronic inflammation and low-dose glucocorticoid effects on glucose metabolism in premenopausal females with rheumatoid arthritis free of conventional metabolic risk factors.

    Science.gov (United States)

    Penesová, A; Rádiková, Z; Vlček, M; Kerlik, J; Lukáč, J; Rovenský, J; Imrich, R

    2013-01-01

    Chronic systemic inflammation is associated with increased cardiovascular mortality in patients with rheumatoid arthritis (RA). The aim of our study was to investigate association of glucose metabolism and inflammatory markers in a group of patients with rheumatoid arthritis free of other metabolic risk factors. Twenty-two premenopausal RA females (11 patients on low-dose GC (glucocorticoid therapy) and 15 age- and BMI-matched healthy females underwent the oral glucose tolerance test. The insulin sensitivity indices according Matsuda (ISI(MAT)) and Cederholm (ISI(CED)) as well as HOMA2 %S were calculated. Cytokines, lipid profile, non-esterified fatty acids (NEFA) and plasminogen activator inhibitor-1 (PAI-1) were measured in baseline blood samples. Despite elevated interleukin IL-6 and TNF alpha, glucose, insulin and C-peptide responses to oral glucose load as well as ISI(MAT), ISI(CED), PAI-1 and NEFA were comparable in both RA groups and healthy controls. HOMA2 %S correlated with disease activity. In conclusions, low-dose glucocorticoid treatment does not lead to glucose metabolism impairment in RA patients without other metabolic risk factors. Increased cardiovascular mortality and morbidity is probably due to a direct effect of systemic inflammation on myocardium and/or blood vessels.

  16. Long-Term Efficacy and Toxicity of Low-Dose-Rate {sup 125}I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kittel, Jeffrey A.; Reddy, Chandana A.; Smith, Kristin L.; Stephans, Kevin L.; Tendulkar, Rahul D. [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States); Ulchaker, James; Angermeier, Kenneth; Campbell, Steven; Stephenson, Andrew; Klein, Eric A. [Department of Urology, Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio (United States); Wilkinson, D. Allan [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States); Ciezki, Jay P., E-mail: ciezkij@ccf.org [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States)

    2015-07-15

    Purpose/Objectives: To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. Methods and Materials: From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with {sup 125}I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer–specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. Results: The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. Conclusions: Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy.

  17. Linear reduction in thyroid cancer risk by oral contraceptive use: a dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Wu, Lang; Zhu, Jingjing

    2015-09-01

    Is there an association between oral contraceptive (OC) use and thyroid cancer risk in females? OC use is inversely associated with the risk of thyroid cancer in females. OC use may be relevant to the risk of thyroid cancer as suggested by some epidemiological studies. However, the findings are inconsistent regarding the effect direction and size. This systematic review and meta-analysis included a total of 1906 patients from about 1.3 million individuals who had participated in 9 prospective cohort studies. The follow-up length ranged 7.5-15.9 years. PubMed (MEDLINE) was searched through to January 2015 for eligible studies. References of relevant review articles were also manually screened. Prospective cohort studies that evaluated the association between OC use and thyroid cancer risk were included. Study characteristics including patients' characteristics, length of the follow-up and risk estimates were extracted. The quality of the studies was also assessed. The included studies were of high methodological quality according to the Newcastle-Ottawa Quality Assessment Scale. After pooling risk estimates from all the studies, there was a significant inverse association between the longest versus shortest duration of OC use and the risk of thyroid cancer [relative risk (RR) = 0.84, 95% confidence interval (CI) 0.73-0.97], with no considerable heterogeneity (I(2) = 26.1%). There was no significant publication bias. The significant association persisted in the subgroup of high-quality studies (RR = 0.84, 95% CI 0.72-0.97). By dose-response analysis, there was a linear relationship (P = 0.0001) between the duration of OC use and thyroid cancer risk. The summary RR for an increment of 1 year of OC use was 0.96 (95% CI 0.94-0.98), with no significant heterogeneity. Individual patient data were unavailable for a more accurate estimation. These results indicate that OC use may decrease the risk of thyroid cancer in females. This may have implications for women

  18. The Application of Internal Dose Measures, Biokinetics, and Biomonitoring Data in the Risk Assessment of Dioxin-Like Compounds

    NARCIS (Netherlands)

    Aylward, L.L.

    2009-01-01

    This thesis presents a series of investigations into the biokinetic behavior of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds and the application of biokinetic modeling and biomonitoring data in quantitative risk assessment for these compounds. The biokinetic properties of TCDD an

  19. Dose to the contralateral breast from radiotherapy and risk of second primary breast cancer in the WECARE study

    DEFF Research Database (Denmark)

    Stovall, M.; Smith, S.A.; Langholz, B.M.

    2008-01-01

    PURPOSE: To quantify the risk of second primary breast cancer in the contralateral breast (CB) after radiotherapy (RT) for first breast cancer. METHODS AND MATERIALS: The study population included participants in the Women's Environmental, Cancer, and Radiation Epidemiology study: 708 cases (wome...

  20. Probabilistic risk assessment model for allergens in food: sensitivity analysis of the minimum eliciting dose and food consumption

    NARCIS (Netherlands)

    Kruizinga, A.G.; Briggs, D.; Crevel, R.W.R.; Knulst, A.C.; Bosch, L.M.C.v.d.; Houben, G.F.

    2008-01-01

    Previously, TNO developed a probabilistic model to predict the likelihood of an allergic reaction, resulting in a quantitative assessment of the risk associated with unintended exposure to food allergens. The likelihood is estimated by including in the model the proportion of the population who is a

  1. Urinary cadmium concentration and risk of breast cancer: a systematic review and dose-response meta-analysis.

    Science.gov (United States)

    Larsson, Susanna C; Orsini, Nicola; Wolk, Alicja

    2015-09-01

    Cadmium is a toxic and persistent heavy metal with estrogenic activities. We conducted a systematic review and meta-analysis of cohort, case-control, and cross-sectional studies of the association between urinary cadmium concentration, a biomarker of cadmium exposure, and breast cancer risk. Studies were identified by searching PubMed and Embase (to March 15, 2015) and by reviewing the reference lists of pertinent articles. Study-specific risk estimates were combined by using a random-effects model. We identified 2 cohort studies (with 67 breast cancer deaths) and 5 case-control studies and 1 cross-sectional study (with 1,416 cases and 5,083 controls) on urinary cadmium concentration in relation to breast cancer risk. The studies were published during the past 10 years (2006-2015). There was no consistent association between urinary cadmium and breast cancer mortality in the cohort studies. In case-control and cross-sectional studies, the pooled odds ratios were 2.24 (95% confidence interval: 1.50, 3.34; I(2) = 63.4%) for the highest versus lowest category of cadmium concentration and 1.66 (95% confidence interval: 1.23, 2.25) for each 0.5-µg/g creatinine increase of cadmium concentration. This meta-analysis suggests that a high cadmium exposure may be a risk factor for breast cancer, but large prospective studies are needed to confirm this finding.

  2. Late Cardiac Toxicity After Mediastinal Radiation Therapy for Hodgkin Lymphoma: Contributions of Coronary Artery and Whole Heart Dose-Volume Variables to Risk Prediction.

    Science.gov (United States)

    Hahn, Ezra; Jiang, Haiyan; Ng, Angela; Bashir, Shaheena; Ahmed, Sameera; Tsang, Richard; Sun, Alexander; Gospodarowicz, Mary; Hodgson, David

    2017-08-01

    Mediastinal radiation therapy (RT) for Hodgkin lymphoma (HL) is associated with late cardiotoxicity, but there are limited data to indicate which dosimetric parameters are most valuable for predicting this risk. This study investigated which whole heart dosimetric measurements provide the most information regarding late cardiotoxicity, and whether coronary artery dosimetry was more predictive of this outcome than whole heart dosimetry. A random sample of 125 HL patients treated with mediastinal RT was selected, and 3-dimensional cardiac dose-volume data were generated from historical plans using validated methods. Cardiac events were determined by linking patients to population-based datasets of inpatient and same-day hospitalizations and same-day procedures. Variables collected for the whole heart and 3 coronary arteries included the following: Dmean, Dmax, Dmin, dose homogeneity, V5, V10, V20, and V30. Multivariable competing risk regression models were generated for the whole heart and coronary arteries. There were 44 cardiac events documented, of which 70% were ischemic. The best multivariable model included the following covariates: whole heart Dmean (hazard ratio [HR] 1.09, P=.0083), dose homogeneity (HR 0.94, P=.0034), male sex (HR 2.31, P=.014), and age (HR 1.03, P=.0049). When any adverse cardiac event was the outcome, models using coronary artery variables did not perform better than models using whole heart variables. However, in a subanalysis of ischemic cardiac events only, the model using coronary artery variables was superior to the whole heart model and included the following covariates: age (HR 1.05, Pcoronary artery models. However, when events were limited to ischemic cardiotoxicity, the coronary artery-based model was superior. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Dose of physical activity, physical functioning and disability risk in mobility-limited older adults: Results from the LIFE study randomized trial

    Science.gov (United States)

    Guralnik, Jack M.; King, Abby C.; Pahor, Marco; McDermott, Mary M.; Tudor-Locke, Catrine; Manini, Todd M.; Glynn, Nancy W.; Marsh, Anthony P.; Axtell, Robert S.; Hsu, Fang-Chi; Rejeski, W. Jack

    2017-01-01

    Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70–89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes. Trial registration: ClinicalsTrials.gov NCT00116194 PMID:28820909

  4. Low-dose acetylsalicylic acid use and the risk of upper gastrointestinal bleeding: a meta-analysis of randomized clinical trials and observational studies.

    Science.gov (United States)

    Valkhoff, Vera E; Sturkenboom, Miriam C J M; Hill, Catherine; Veldhuyzen van Zanten, Sander; Kuipers, Ernst J

    2013-03-01

    Low-dose acetylsalicylic acid (LDA, 75 mg/day to 325 mg/day) is recommended for primary and secondary prevention of cardiovascular events, but has been linked to an increased risk of upper gastrointestinal bleeding (UGIB). To analyze the magnitude of effect of LDA use on UGIB risk. The PubMed and Embase databases were searched for randomized controlled trials (RCTs) reporting UGIB rates in individuals receiving LDA, and observational studies of LDA use in patients with UGIB. Studies were pooled for analysis of UGIB rates. Eighteen studies were included. Seven RCTs reported UGIB rates in individuals randomly assigned to receive LDA (n=22,901) or placebo (n=22,923). Ten case-control studies analyzed LDA use in patients with UGIB (n=10,816) and controls without UGIB (n=30,519); one cohort study reported 207 UGIB cases treated with LDA only. All studies found LDA use to be associated with an increased risk of UGIB. The mean number of extra UGIB cases associated with LDA use in the RCTs was 1.2 per 1000 patients per year (95% CI 0.7 to 1.8). The number needed to harm was 816 (95% CI 560 to 1500) for RCTs and 819 (95% CI 617 to 1119) for observational studies. Meta-analysis of RCT data showed that LDA use was associated with a 50% increase in UGIB risk (OR 1.5 [95% CI 1.2 to 1.8]). UGIB risk was most pronounced in observational studies (OR 3.1 [95% CI 2.5 to 3.7]). LDA use was associated with an increased risk of UGIB.

  5. Evaluation of Promotional Materials To Promote Low-Dose Computed Tomography (LDCT) Screening to High-Risk Consumers and Health Care Providers.

    Science.gov (United States)

    Hudson, Janella N; Quinn, Gwendolyn P; Wilson, Lauren E; Simmons, Vani N

    2017-03-11

    Low-dose computed tomography (LDCT) screening is a promising screening modality for increasing the detection rate of early stage lung cancers among high-risk individuals. Despite being recommended by the US Preventative Services Task Force, uptake of LDCT remains low. The objective of the current study was to gather feedback from high-risk consumers and health care providers on LDCT promotional materials. Focus group discussions were conducted with high-risk individuals (8 focus groups; N = 38) and primary care providers (9 focus groups; N = 23). Participants reviewed existing LDCT promotional materials to assess their perceptions of media materials created to publicize LDCT. Data were analyzed using the constant comparative method. Several key themes emerged from focus groups that can be used to inform development of future LDCT promotional materials. High-risk (HR) participants expressed greater receptivity for promotional materials that did not further stigmatize lung cancer and/or smoking and expressed preferences for materials that clearly outlined the risks/benefits of screening. Primary care providers (PCPs) offered suggestions to facilitate the referral process such as diagnostic codes and requested a design that clearly outlined eligibility criteria. A clear and thorough explanation of LDCT eligibility, cost, harms, and benefits was of chief importance for both PCP and HR audiences. Given that PCPs and HR audiences are not well informed on the specifics of LDCT screening eligibility and insurance coverage, creating provider and patient education opportunities will aid in shared decision-making opportunities. Promotional materials that meet the needs of the target audience are needed to facilitate discussions of risks/benefits of screening with HR individuals.

  6. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-04-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  7. Annual effective dose due to residential radon progeny in Sweden: Evaluations based on current risk projections models and on risk estimates from a nation-wide Swedish epidemiological study

    Energy Technology Data Exchange (ETDEWEB)

    Doi, M. [National Inst. of Radiological Sciences, Chiba (Japan); Lagarde, F. [Karolinska Inst., Stockholm (Sweden). Inst. of Environmental Medicine; Falk, R.; Swedjemark, G.A. [Swedish Radiation Protection Inst., Stockholm (Sweden)

    1996-12-01

    Effective dose per unit radon progeny exposure to Swedish population in 1992 is estimated by the risk projection model based on the Swedish epidemiological study of radon and lung cancer. The resulting values range from 1.29 - 3.00 mSv/WLM and 2.58 - 5.99 mSv/WLM, respectively. Assuming a radon concentration of 100 Bq/m{sup 3}, an equilibrium factor of 0.4 and an occupancy factor of 0.6 in Swedish houses, the annual effective dose for the Swedish population is estimated to be 0.43 - 1.98 mSv/year, which should be compared to the value of 1.9 mSv/year, according to the UNSCEAR 1993 report. 27 refs, tabs, figs.

  8. Dose-effect relationship and risk factors for vaginal stenosis after definitive radio(chemo)therapy with image-guided brachytherapy for locally advanced cervical cancer in the EMBRACE study.

    Science.gov (United States)

    Kirchheiner, Kathrin; Nout, Remi A; Lindegaard, Jacob C; Haie-Meder, Christine; Mahantshetty, Umesh; Segedin, Barbara; Jürgenliemk-Schulz, Ina M; Hoskin, Peter J; Rai, Bhavana; Dörr, Wolfgang; Kirisits, Christian; Bentzen, Søren M; Pötter, Richard; Tanderup, Kari

    2016-01-01

    To identify risk factors for vaginal stenosis and to establish a dose-effect relationship for image-guided brachytherapy in locally advanced cervical cancer. Patients from the ongoing EMBRACE study with prospectively assessed morbidity (CTCAEv3.0) at baseline and at least one follow-up were selected. Patient-, disease- and treatment characteristics were tested as risk factors for vaginal stenosis G ⩾ 2 in univariate and multivariable analyses (Cox proportional hazards model) and a dose-effect curve was deduced from the estimates. The ICRU rectum point was used to derive the recto-vaginal reference point dose. In 630 patients included (median follow-up 24months), 2-year actuarial estimate for vaginal stenosis G ⩾ 2 was 21%. Recto-vaginal reference point dose (HR=1.025, p=0.029), external beam radiotherapy (EBRT) dose >45 Gy/25 fractions (HR=1.770, p=0.056) and tumor extension in the vagina (HR=2.259, p ⩽ 0.001) were risk factors for vaginal stenosis, adjusted for center reporting effects. Based on the model curve, the risk was 20% at 65 Gy, 27% at 75 Gy and 34% at 85 Gy (recto-vaginal reference point dose). Keeping the EBRT dose at 45 Gy/25 fractions and decreasing the dose contribution of brachytherapy to the vagina decrease the risk of stenosis. A planning aim of ⩽65 Gy EQD2 (EBRT+brachytherapy dose) to the recto-vaginal reference point is therefore proposed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Estimation of the Dose and Dose Rate Effectiveness Factor

    Science.gov (United States)

    Chappell, L.; Cucinotta, F. A.

    2013-01-01

    Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

  10. Incidence and risk factors of gastrointestinal bleeding in patients on low-dose aspirin therapy after percutaneous coronary intervention in Japan.

    Science.gov (United States)

    Nadatani, Yuji; Watanabe, Toshio; Tanigawa, Tetsuya; Sogawa, Mitsue; Yamagami, Hirokazu; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Yoshiyama, Minoru; Arakawa, Tetsuo

    2013-03-01

    Low-dose aspirin (LDA) is the most commonly prescribed antiplatelet agent for prevention of cardiovascular events following percutaneous coronary intervention (PCI). Long-term treatment with LDA has serious adverse effects, including gastrointestinal (GI) hemorrhage. Most studies have focused only on upper GI bleeding and few studies have evaluated the effect of LDA on total GI bleeding. The aims of this study were to investigate the incidence and risk factors of total GI bleeding within 30 days after PCI in Japanese patients taking LDA. A retrospective chart review was conducted for 364 patients undergoing LDA therapy following PCI at Osaka City University Hospital. A retrospective case-control study evaluated risk factors using the chi-squared test and logistic regression. The incidence of total GI bleeding after PCI within 30 days was 4.3%. The source of the GI bleeding was located throughout the GI tract. Risk factors identified by univariate analysis were age ≥ 75 years, history of peptic ulcer disease, chronic renal failure, proton pump inhibitor use, and histamine H2 receptor antagonist use. By multivariate logistic regression only age ≥ 75 years (odds ratio = 5.26; 95% confidence interval: 1.13-24.51; p = 0.035) was found to be an independent risk factor of GI bleeding. The incidence of GI bleeding in patients undergoing LDA therapy following PCI is high. The bleeding episodes were located in the upper, middle, and lower GI tract. Age of ≥ 75 years was an independent risk factor for GI bleeding after PCI in patients on LDA therapy.

  11. Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis.

    Science.gov (United States)

    Ding, Ming; Bhupathiraju, Shilpa N; Chen, Mu; van Dam, Rob M; Hu, Frank B

    2014-02-01

    Previous meta-analyses identified an inverse association of coffee consumption with the risk of type 2 diabetes. However, an updated meta-analysis is needed because new studies comparing the trends of association for caffeinated and decaffeinated coffee have since been published. PubMed and Embase were searched for cohort or nested case-control studies that assessed the relationship of coffee consumption and risk of type 2 diabetes from 1966 to February 2013. A restricted cubic spline random-effects model was used. Twenty-eight prospective studies were included in the analysis, with 1,109,272 study participants and 45,335 cases of type 2 diabetes. The follow-up duration ranged from 10 months to 20 years. Compared with no or rare coffee consumption, the relative risk (RR; 95% CI) for diabetes was 0.92 (0.90-0.94), 0.85 (0.82-0.88), 0.79 (0.75-0.83), 0.75 (0.71-0.80), 0.71 (0.65-0.76), and 0.67 (0.61-0.74) for 1-6 cups/day, respectively. The RR of diabetes for a 1 cup/day increase was 0.91 (0.89-0.94) for caffeinated coffee consumption and 0.94 (0.91-0.98) for decaffeinated coffee consumption (P for difference = 0.17). Coffee consumption was inversely associated with the risk of type 2 diabetes in a dose-response manner. Both caffeinated and decaffeinated coffee was associated with reduced diabetes risk.

  12. Coupling a continuous watershed-scale microbial fate and transport model with a stochastic dose-response model to estimate risk of illness in an urban watershed

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Hehuan, E-mail: hehuan86@vt.edu [Department of Biological Systems Engineering, Virginia Tech, 155 Ag Quad Lane, Blacksburg, VA 24061 (United States); Krometis, Leigh-Anne H. [Department of Biological Systems Engineering, Virginia Tech, 155 Ag Quad Lane, Blacksburg, VA 24061 (United States); Kline, Karen [Department of Biological Systems Engineering, Virginia Tech, 155 Ag Quad Lane, Blacksburg, VA 24061 (United States); Center for Watershed Studies, Virginia Tech, 155 Ag Quad Lane, Blacksburg, VA 24061 (United States)

    2016-05-01

    Within the United States, elevated levels of fecal indicator bacteria (FIB) remain the leading cause of surface water-quality impairments requiring formal remediation plans under the federal Clean Water Act's Total Maximum Daily Load (TMDL) program. The sufficiency of compliance with numerical FIB criteria as the targeted endpoint of TMDL remediation plans may be questionable given poor correlations between FIB and pathogenic microorganisms and varying degrees of risk associated with exposure to different fecal pollution sources (e.g. human vs animal). The present study linked a watershed-scale FIB fate and transport model with a dose-response model to continuously predict human health risks via quantitative microbial risk assessment (QMRA), for comparison to regulatory benchmarks. This process permitted comparison of risks associated with different fecal pollution sources in an impaired urban watershed in order to identify remediation priorities. Results indicate that total human illness risks were consistently higher than the regulatory benchmark of 36 illnesses/1000 people for the study watershed, even when the predicted FIB levels were in compliance with the Escherichia coli geometric mean standard of 126 CFU/100 mL. Sanitary sewer overflows were associated with the greatest risk of illness. This is of particular concern, given increasing indications that sewer leakage is ubiquitous in urban areas, yet not typically fully accounted for during TMDL development. Uncertainty analysis suggested the accuracy of risk estimates would be improved by more detailed knowledge of site-specific pathogen presence and densities. While previous applications of the QMRA process to impaired waterways have mostly focused on single storm events or hypothetical situations, the continuous modeling framework presented in this study could be integrated into long-term water quality management planning, especially the United States' TMDL program, providing greater clarity to

  13. High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

    Energy Technology Data Exchange (ETDEWEB)

    Ghilezan, Michel, E-mail: mghilezan@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States); Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States)

    2012-07-01

    Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy Multiplication-Sign 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy Multiplication-Sign 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of {<=}12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable-risk

  14. Nutrient intake and nutrient patterns and risk of lung cancer among heavy smokers: results from the COSMOS screening study with annual low-dose CT.

    Science.gov (United States)

    Gnagnarella, Patrizia; Maisonneuve, Patrick; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia

    2013-06-01

    The role of nutrients in lung cancer aetiology remains controversial and has never been evaluated in the context of screening. Our aim was to investigate the role of single nutrients and nutrient patterns in the aetiology of lung cancer in heavy smokers. Asymptomatic heavy smokers (≥20 pack-years) were invited to undergo annual low-dose computed tomography. We assessed diet using a self-administered food frequency questionnaire and collected information on multivitamin supplement use. We performed principal component analysis identifying four nutrient patterns and used Cox proportional Hazards regression to assess the association between nutrients and nutrients patterns and lung cancer risk. During a mean follow-up of 5.7 years, 178 of 4,336 participants were diagnosed with lung cancer by screening. We found a significant risk reduction of lung cancer with increasing vegetable fat consumption (HR for highest vs. lowest quartile = 0.50, 95% CI = 0.31-0.80; P-trend = 0.02). Participants classified in the high "vitamins and fiber" pattern score had a significant risk reduction of lung cancer (HR = 0.57; 95% CI = 0.36-0.90, P-trend = 0.01). Among heavy smokers enrolled in a screening trial, high vegetable fat intake and adherence to the "vitamin and fiber" nutrient pattern were associated with reduced lung cancer incidence.

  15. The efficacy and safety of initial use of irbesartan/hydrochlorothiazide fixed-dose combination in hypertensive patients with and without high cardiovascular risk.

    Science.gov (United States)

    Weir, Matthew R; Neutel, Joel M; Bhaumik, Amitabha; De Obaldia, Maria Elena; Lapuerta, Pablo

    2007-12-01

    A post hoc pooled analysis of 2 multicenter, randomized, double-blind, active-controlled force-titration studies assessed the antihypertensive efficacy and tolerability of 7 to 8 weeks' once-daily fixed-dose irbesartan/hydrochlorothiazide (HCTZ) 300/25 mg in 796 stage 1 or 2 hypertensive patients according to age (65 years or older or younger than 65) (n=121 or 675) and presence or absence of obesity (n=378 or 414), type 2 diabetes (n=99 or 697), and high World Health Organization-defined cardiovascular risk (n=593 or 202). Systolic/diastolic blood pressure reductions (27-31/16-22 mm Hg) were similar regardless of age, obesity, and type 2 diabetes status and were greater in high- vs low-risk patients. Dizziness (2.0%-3.7%), hypotension (0%-0.7%), and syncope (0%) were rare and not centered in any subgroup. There was no hypotension in the elderly or in type 2 diabetics. Irbesartan/HCTZ provided consistent blood pressure lowering and tolerability regardless of age, obesity, and type 2 diabetes and greater efficacy in patients with high cardiovascular risk.

  16. Who should receive a statin drug to lower cardiovascular risk? Does the drug and the dose of the drug matter?

    Directory of Open Access Journals (Sweden)

    JV (Ian Nixon

    2006-12-01

    Full Text Available JV (Ian NixonDivision of Cardiology, Medical College of Virginia at Virginia Commonwealth University, Richmond VA, USAAbstract: As the numbers of completed outcomes based clinical trials evaluating the use of statin drugs for the management of cardiovascular risk continue to increase, it is clear that the numbers of patients that may benefit from these drugs continues to grow. The recently published studies are reviewed in this summary. The distinction is made between patients requiring either primary or secondary cardiovascular preventive management. The review identifies the increasing numbers of patients who may benefit from the use of statins as primary preventive management, and the changing concepts of the utilization of statin drugs for secondary preventive management, including the more aggressive titration of the drugs to provide incremental improvement in patient outcomes. Available data on the use of statins in the elderly patient are reviewed, and observations are made regarding the intrinsic properties and adverse effects of the drugs. Keywords: cardiovascular risk, statins, elderly patient.

  17. Sci—Fri PM: Topics — 04: What if bystander effects influence cell kill within a target volume? Potential consequences of dose heterogeneity on TCP and EUD on intermediate risk prostate patients

    Energy Technology Data Exchange (ETDEWEB)

    Balderson, M.J.; Kirkby, C. [Department of Physics and Astronomy, University of Calgary, Calgary, Alberta (Canada); Department of Medical Physics, Tom Baker Cancer Centre, Calgary, Alberta (Canada); Department of Medical Physics, Jack Ady Cancer Centre, Lethbridge, Alberta (Canada)

    2014-08-15

    In vitro evidence has suggested that radiation induced bystander effects may enhance non-local cell killing which may influence radiotherapy treatment planning paradigms. This work applies a bystander effect model, which has been derived from published in vitro data, to calculate equivalent uniform dose (EUD) and tumour control probability (TCP) and compare them with predictions from standard linear quadratic (LQ) models that assume a response due only to local absorbed dose. Comparisons between the models were made under increasing dose heterogeneity scenarios. Dose throughout the CTV was modeled with normal distributions, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. The bystander model suggests a moderate degree of dose heterogeneity yields as good or better outcome compared to a uniform dose in terms of EUD and TCP. Intermediate risk prostate prescriptions of 78 Gy over 39 fractions had maximum EUD and TCP values at SD of around 5Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. The bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV is varies. The results suggest the potential for allowing some degree of dose heterogeneity within a CTV, although further investigations of the assumptions of the bystander model are warranted.

  18. Low dose and short-term therapy of tibolone reduces the cardiovascular disease risk in postmenopausal women

    Institute of Scientific and Technical Information of China (English)

    Ye Bi-lu; Cheng Jing; Ye Lian

    2004-01-01

    Objective:To investigate the effects of low dose tibolone short-term therapy on clinic, endocrine and markers of cardiovascular disease in healthy postmenopausal women.Methods: A prospective study involved a total of 42 eligible postmenopausal women. 22 cases as group A and 20 cases as group B. Complete baseline work-up including Kupperman score,body mass index (BMI), gonadotropin (FSH, LH), estrogen (E2), testosterone (T), sex hormone binding globulin (SHBG), plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (tPA), high-sensitivity C-response protein (hs-CRP), nitrogen oxide (NO)and fasting lipid, glucose(FPG), insulin(FINS) were performed in all subjects. Postmenopausal women in group A were treated with 1.25 mg tibolone daily. Women in group B were treated with 0. 625 mg tibolone daily. Women both in group A and group B were given calcium 600 mg with vitamin D 125IU per day. At the end of the 12-weeks therapy, subjects were re-evaluated and above parameters were measured.Results:No significant differences between group A and group B were found at baseline.Twenty-eight cases (fourteen cases in each group) completed the study. Kupperman score decreased from (22.1±8.0) and (25.4±7.5) to (7.7±4.5) and (5.2±4.5) and plasminogen activator inhibitor type 1 decreased from (95.8±32.4)μg/L and (102.9±42.6)μg/L to (72.2±39.6)μg/L and (79.9±30. 1) μg/L significantly in group A and group B respectively after treatment. In group A, Blood pressure decreased significantly from (120 ± 10)/(83 ± 6) mmHg to (110±14)/(77± 9) mmHg (P<0.05), testosterone increased significantly from (0. 6 ±0. 4)nmol/L to (1.3 ± 1.1) nmol/L (P<0. 05), free testosterone increased from (0. 001 ±0. 002)nmol/L to (0. 003±0. 003) nmol/L significantly (P<0.01), SHBG decreased from (7.6±4. 9)nmol/L to (4. 3±2.9) nmol/L significantly (P<0.05), total cholesterol decreased from (5.4±0. 8) mmol/L to (5.0±0.8) mmol/L significantly (P<0.01), Apo

  19. Fludarabine-Busulfan Reduced-Intensity Conditioning in Comparison with Fludarabine-Melphalan Is Associated with Increased Relapse Risk In Spite of Pharmacokinetic Dosing.

    Science.gov (United States)

    Damlaj, Moussab; Alkhateeb, Hassan B; Hefazi, Mehrdad; Partain, Daniel K; Hashmi, Shahrukh; Gastineau, Dennis A; Al-Kali, Aref; Wolf, Robert C; Gangat, Naseema; Litzow, Mark R; Hogan, William J; Patnaik, Mrinal M

    2016-08-01

    Fludarabine with busulfan (FB) and fludarabine with melphalan (FM) are commonly used reduced-intensity conditioning (RIC) regimens. Pharmacokinetic dosing of busulfan (Bu) is frequently done for myeloablative conditioning, but evidence for its use is limited in RIC transplants. We compared transplant outcomes of FB versus FM using i.v. Bu targeted to the area under the curve (AUC). A total of 134 RIC transplants (47 FB and 87 FM) for acute myelogenous leukemia and myelodysplastic syndrome were identified, and median follow-up of the cohort was 40 months (range, 0 to 63.3). A significantly higher 2-year cumulative incidence of relapse (CIR) was associated with FB versus FM at 35.6% versus 17.3%, respectively (P = .0058). Furthermore, 2-year progression-free survival rates were higher for FM versus FB at 60.5% versus 48.7%, respectively (P = .04). However, 2-year rates of nonrelapse mortality (NRM) and overall survival (OS) were similar. The need for dose adjustment based on AUC did not alter relapse risk or NRM. Patients with Karnofsky performance status ≥ 90 who received FM had a 2-year OS rate of 74.8% versus 48.3% for FB (P = .03). FB use remained prognostic for relapse in multivariable analysis (hazard ratio, 2.75; 95% confidence interval, 1.28 to 5.89; P = .0097). In summary, in spite of AUC-directed dosing, FB compared with FM was associated with a significantly higher CIR.

  20. Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

    Science.gov (United States)

    Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

    2015-04-01

    Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

  1. Long-Term Coffee Consumption and Risk of Gastric Cancer: A PRISMA-Compliant Dose-Response Meta-Analysis of Prospective Cohort Studies.

    Science.gov (United States)

    Zeng, Shao-Bo; Weng, Hong; Zhou, Meng; Duan, Xiao-Li; Shen, Xian-Feng; Zeng, Xian-Tao

    2015-09-01

    Association between coffee consumption and gastric cancer risk remains controversial. Hence, we performed a meta-analysis to investigate and quantify the potential dose-response association between long-term coffee consumption and risk of gastric cancer.Pertinent studies were identified by searching PubMed and Embase from January 1996 through February 10, 2015 and by reviewing the reference lists of retrieved publications. Prospective cohort studies in which authors reported effect sizes and corresponding 95% confidence intervals (CIs) of gastric cancer for 3 or more categories of coffee consumption were eligible. Results from eligible studies were aggregated using a random effect model. All analyses were carried out using the STATA 12.0 software.Nine studies involving 15 independent prospective cohorts were finally included. A total of 2019 incident cases of gastric cancer were ascertained among 1,289,314 participants with mean follow-up periods ranging from 8 to 18 years. No nonlinear relationship of coffee consumption with gastric cancer risk was indentified (P for nonlinearity = 0.53; P for heterogeneity = 0.004). The linear regression model showed that the combined relative risk (RR) of every 3 cups/day increment of total coffee consumption was 1.07 (95% CI = 0.95-1.21). Compared with the lowest category of coffee consumption, the RR of gastric cancer was 1.18 (95% CI = 0.90-1.55) for the highest (median 6.5 cups/day) category, 1.06 (95% CI = 0.85-1.32) for the second highest category (median 3.5 cups/day), and 0.97 (95% CI = 0.79-1.20) for the third highest category (median 1.5 cups/day). Subgroup analysis showed an elevated risk in the US population (RR = 1.36, 95% CI = 1.06-1.75) and no adjustment for smoking (RR = 1.67, 95% CI = 1.08-2.59) for 6.5 cups/day.Current evidence indicated there was no nonlinear association between coffee consumption and gastric cancer risk. However, high coffee consumption (more

  2. Predictors of and health- and fall-related program outcomes resulting from complete and adequate doses of a fall risk reduction program.

    Science.gov (United States)

    Mielenz, Thelma J; Durbin, Laura L; Hertzberg, Fern; Nobile-Hernandez, Diana; Jia, Haomiao

    2017-06-01

    Falls are dangerous and costly for older adults. The A Matter of Balance/Volunteer Lay Leader (AMOB/VLL) program is an evidence-based fall risk reduction program that could help reduce this burden. This study introduced a door-through-door transportation program to improve program delivery (N = 126). Characteristics predicting completion of all eight AMOB/VLL sessions were identified using logistic regression. Individual growth models were employed to determine the immediate, intermediate, and long-term goal outcomes resulting from receiving an adequate dose of the program (five to eight sessions). Self-restriction of activities due to fear of falling (OR 5.04, 95 % CI 1.86-13.69) and a lower frequency of moderate and vigorous physical activity (OR 1.14, 95 % CI 1.04-1.27) were significantly predictive of receiving a complete dose. Three outcome goals were significant, including (1) immediate-improved self-efficacy of managing medications and treatments, (2) intermediate-reduced activity limitations, and (3) intermediate-reduced physical disability. Self-restriction of activities due to a fear of falling and physical activity levels may be simple and effective screening questions to prevent AMOB/VLL attrition. In our study, those who did receive the program improved on a specific type of self-efficacy and on self-reported physical functioning.

  3. A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Awad A. [Temple University School of Medicine, Philadelphia, Pennsylvania (United States); Egleston, Brian [Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Alcantara, Pino [Department of Radiation Oncology, Hospital Universitario Clínico San Carlos, Madrid (Spain); Li, Linna [Department of Radiation Oncology, Bryn Mawr Hospital, Bryn Mawr, Pennsylvania (United States); Pollack, Alan [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Horwitz, Eric M. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Buyyounouski, Mark K., E-mail: mark.buyyounouski@fccc.edu [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States)

    2013-07-15

    Background: There are no well-established normal tissue sparing dose–volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed. Methods and Materials: From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years). Results: Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P<.05) in multivariable analysis. Overall, bladder wall CPE values were higher than solid bladder values. The AUHC for bladder wall provided the greatest discrimination for late bladder toxicity when compared with alternative DVH points, with CPE values of 0.68 for age ≤68 years and 0.81 for age >68 years. Conclusion: The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored.

  4. Optimal Vitamin D Supplementation Doses that Minimize the Risk for Both Low and High Serum 25-Hydroxyvitamin D Concentrations in the General Population.

    Science.gov (United States)

    Veugelers, Paul J; Pham, Truong-Minh; Ekwaru, John Paul

    2015-12-04

    The Recommended Dietary Allowance (RDA) is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of the population. Recent reports revealed a statistical error in the calculation of the RDA for vitamin D opening the question of what the recommendation should be. We took a dual approach to answer this question: (1) we aggregated 108 published estimates on vitamin D supplementation and vitamin D status; and (2) we analyzed 13,987 observations of program participants. The aggregation of published data revealed that 2909 IU of vitamin D per day is needed to achieve serum 25-hydroxyvitamin D (25(OH)D) concentrations of 50 nmol/L or more in 97.5% of healthy individuals. For normal weight, overweight and obese program participants this was 3094, 4450 and 7248 IU respectively. These supplementation doses would also result in 2.5% of normal weight, overweight and obese participants having 25(OH)D concentrations above 210, 200 and 214 nmol/L respectively. As these concentrations are high, an approach that minimizes the risk for both low and high concentrations seems desirable. With this approach we estimated, for example, that doses of 1885, 2802 and 6235 IU per day are required for normal weight, overweight and obese individuals respectively to achieve natural 25(OH)D concentrations (defined as 58 to 171 nmol/L). In conclusion, the large extent of variability in 25(OH)D concentrations makes a RDA for vitamin D neither desirable nor feasible. We therefore propose recommendations be articulated in the form of an optimal intake that minimizes the risk for both low and high serum 25(OH)D concentrations. This contribution includes body weight specific recommendations for optimal intakes for various combinations of lower and upper 25(OH)D concentration targets.

  5. Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Guo, Jing; Astrup, Arne; Lovegrove, Julie A; Gijsbers, Lieke; Givens, David I; Soedamah-Muthu, Sabita S

    2017-04-03

    With a growing number of prospective cohort studies, an updated dose-response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up to September 2016. Random-effect meta-analyses with summarised dose-response data were performed for total (high-fat/low-fat) dairy, milk, fermented dairy, cheese and yogurt. Non-linear associations were investigated using the spine models and heterogeneity by subgroup analyses. A total of 29 cohort studies were available for meta-analysis, with 938,465 participants and 93,158 mortality, 28,419 CHD and 25,416 CVD cases. No associations were found for total (high-fat/low-fat) dairy, and milk with the health outcomes of mortality, CHD or CVD. Inverse associations were found between total fermented dairy (included sour milk products, cheese or yogurt; per 20 g/day) with mortality (RR 0.98, 95% CI 0.97-0.99; I(2) = 94.4%) and CVD risk (RR 0.98, 95% CI 0.97-0.99; I(2) = 87.5%). Further analyses of individual fermented dairy of cheese and yogurt showed cheese to have a 2% lower risk of CVD (RR 0.98, 95% CI 0.95-1.00; I(2) = 82.6%) per 10 g/day, but not yogurt. All of these marginally inverse associations of totally fermented dairy and cheese were attenuated in sensitivity analyses by removing one large Swedish study. This meta-analysis combining data from 29 prospective cohort studies demonstrated neutral associations between dairy products and cardiovascular and all-cause mortality. For future studies it is important to investigate in more detail how dairy products can be replaced by other foods.

  6. Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

    Science.gov (United States)

    Cortelazzo, Sergio; Tarella, Corrado; Gianni, Alessandro Massimo; Ladetto, Marco; Barbui, Anna Maria; Rossi, Andrea; Gritti, Giuseppe; Corradini, Paolo; Di Nicola, Massimo; Patti, Caterina; Mulé, Antonino; Zanni, Manuela; Zoli, Valerio; Billio, Atto; Piccin, Andrea; Negri, Giovanni; Castellino, Claudia; Di Raimondo, Francesco; Ferreri, Andrés J M; Benedetti, Fabio; La Nasa, Giorgio; Gini, Guido; Trentin, Livio; Frezzato, Maurizio; Flenghi, Leonardo; Falorio, Simona; Chilosi, Marco; Bruna, Riccardo; Tabanelli, Valentina; Pileri, Stefano; Masciulli, Arianna; Delaini, Federica; Boschini, Cristina; Rambaldi, Alessandro

    2016-11-20

    Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

  7. Dose-response relationships of oral habits associated with the risk of oral pre-malignant lesions among men who chew betel quid.

    Science.gov (United States)

    Yen, Amy Ming-Fang; Chen, Shao-Ching; Chen, Tony Hsiu-Hsi

    2007-08-01

    Betel quid, cigarettes and alcohol are well-recognized risk factors for oral cancer. However, the combined effect of the frequency and duration of these oral habits on the risk for developing oral pre-malignancies among betel quid users has not been fully addressed. In this study, an oral screening programme for men chewing betel quid was carried out by well-trained dentists for early detection of oral pre-malignancy lesions. Using generalized logit model and proportional odds model, we found that, compared with the occasional user, the adjusted odds ratios of developing leukoplakia for men chewing one to 10 pieces of betel quid, 11-20 pieces, and more than 20 pieces per day were estimated as 2.14 (95% confidence interval [CI] 1.62-2.81), 2.99 (95% CI 2.06-4.27), and 5.37 (95% CI 3.76-7.47), respectively. The corresponding figures for erythroleukoplakia were 3.69 (95% CI 1.55-8.79), 13.78 (95% CI 5.76-32.98), and 36.64 (95% CI 15.94-84.16), respectively. Similar results were found while the duration was considered. The dose-response relationships were not as noteworthy for cigarette and alcohol drinking.

  8. Risk of bladder cancer among patients with diabetes treated with a 15 mg pioglitazone dose in Korea: a multi-center retrospective cohort study.

    Science.gov (United States)

    Jin, Sang-Man; Song, Sun Ok; Jung, Chang Hee; Chang, Jin-Sun; Suh, Sunghwan; Kang, Seung Min; Jung, Inkyung; Park, Cheol-Young; Kim, Jae Hyeon; Cho, Jae Hyoung; Lee, Byung-Wan

    2014-02-01

    It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had ≥ 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.

  9. Age-specific models for evaluating dose and risk from internal exposures to radionuclides: Report of current work of the Metabolism and Dosimetry Research Group, July 1, 1985-June 30, 1987

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, R.W.; Warren, B.P. (eds.)

    1987-09-01

    A projection of the health risk to a population internally exposed to a radionuclide requires explicit or implicit use of demographic, biokinetic, dosimetric, and dose-response models. Exposure guidelines have been based on models for a reference adult with a fixed life span. In this report, we describe recent efforts to develop a comprehensive methodology for estimation of radiogenic risk to individuals and to heterogeneous populations. Emphasis is on age-dependent biokinetics and dosimetry for internal emitters, but consideration also is given to conversion of age-specific doses to estimates of risk using realistic, site-specific demographic models and best available age-specific dose-response functions. We discuss how the methods described here may also improve estimates for the reference adult usually considered in radiation protection. 159 refs.

  10. Split-dosed MiraLAX/Gatorade is an effective, safe, and tolerable option for bowel preparation in low-risk patients: a randomized controlled study.

    Science.gov (United States)

    Samarasena, Jason B; Muthusamy, V Raman; Jamal, M Mazen

    2012-07-01

    MiraLAX with Gatorade is a low-volume bowel preparation regimen that has been used widely in community practice and is anecdotally better tolerated than Golytely. Despite its widespread use, there are little data on the efficacy and tolerability of this solution and no safety data in the literature. The primary aim of this study was to compare the efficacy, safety, and tolerability of single-dosed and split-dosed regimens of MiraLAX/Gatorade with Golytely for bowel preparation before colonoscopy. Adults presenting for outpatient colonoscopy were screened for enrollment into this single-blinded randomized controlled trial. Patients with severe cardiac or renal disease and patients with electrolyte abnormalities were excluded. Subjects were randomized into four groups: 4 l Golytely single-dosed (Go-Si), 4 l Golytely split-dosed (Go-Sp), 238 g MiraLAX in 64 oz of Gatorade single-dosed (Mlax-Si), and MiraLAX/Gatorade split-dosed (Mlax-Sp) groups. Laboratory data including complete blood count, comprehensive metabolic panel, and osmolality were collected before the day of bowel preparation and just before the start of colonoscopy. Subjects completed a survey assessing taste and tolerability of the solution. Colonoscopies were recorded using video recording software and de-identified. Colonoscopy videos were evaluated for efficacy of cleansing by two blinded endoscopists. Two validated bowel preparation scales were used to assess bowel cleansing: the Boston Bowel Preparation Scale (BBPS; 0-9 best) and Ottawa Scale (0-14 worst). A total of 222 patients were evaluated in this study (86.2% male, mean age 59.4). Of these, 57 subjects were randomized to the Go-Si group, 51 to Go-Sp group, 60 to Mlax-Si group, and 54 to Mlax-Sp group. There was no significant difference in age, gender, or timing of colonoscopy between the groups (P>0.05). Mean BBPS scores were: Go-Si=6.07, Go-Sp=8.33, Mlax-Si=6.62, and Mlax-Sp=8.01. Mean Ottawa score for the groups were: Go-Si group=6.77, Go

  11. Final results of a phase I/II pilot study of capecitabine with or without vinorelbine after sequential dose-dense epirubicin and paclitaxel in high-risk early breast cancer

    Directory of Open Access Journals (Sweden)

    Müller Volkmar

    2010-08-01

    Full Text Available Abstract Background The integration of the non-cross-resistant chemotherapeutic agents capecitabine and vinorelbine into an intensified dose-dense sequential anthracycline- and taxane-containing regimen in high-risk early breast cancer (EBC could improve efficacy, but this combination was not examined in this context so far. Methods Patients with stage II/IIIA EBC (four or more positive lymph nodes received post-operative intensified dose-dense sequential epirubicin (150 mg/m² every 2 weeks and paclitaxel (225 mg/m² every 2 weeks with filgrastim and darbepoetin alfa, followed by capecitabine alone (dose levels 1 and 3 or with vinorelbine (dose levels 2 and 4. Capecitabine was given on days 1-14 every 21 days at 1000 or 1250 mg/m2 twice daily (dose levels 1/2 and 3/4, respectively. Vinorelbine 25 mg/m2 was given on days 1 and 8 of each 21-day course (dose levels 2 and 4. Results Fifty-one patients were treated. There was one dose-limiting toxicity (DLT at dose level 1. At dose level 2 (capecitabine and vinorelbine, five of 10 patients experienced DLTs. Therefore evaluation of vinorelbine was abandoned and dose level 3 (capecitabine monotherapy was expanded. Hand-foot syndrome and diarrhoea were dose limiting with capecitabine 1250 mg/m2 twice daily. At 35.2 months' median follow-up, the estimated 3-year relapse-free and overall survival rates were 82% and 91%, respectively. Conclusions Administration of capecitabine monotherapy after sequential dose-dense epirubicin and paclitaxel is feasible in node-positive EBC, while the combination of capecitabine and vinorelbine as used here caused more DLTs. Trial registration Current Controlled Trials ISRCTN38983527.

  12. Approximating dose and risk for contaminants in groundwater from the underground nuclear test areas of the Nevada National Security Site (NNSS)

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, Jeffrey I. [Desert Research Inst. (DRI), Las Vegas, NV (United States); Chapman, Jenny [Desert Research Inst. (DRI), Las Vegas, NV (United States); Pohlmann, Karl F. [Desert Research Inst. (DRI), Las Vegas, NV (United States)

    2015-03-01

    As part of the Environmental Management Program at the Nevada National Security Site (NNSS), the Underground Test Area (UGTA) Activity investigates the potential impacts of radionuclides that were introduced into groundwater from the underground nuclear tests conducted near or below the NNSS water table between 1951 and 1992. Groundwater models are being used to simulate contaminant transport and forecast contaminant boundaries that encompass areas where the groundwater has a five percent or greater probability of containing contaminants above the Safe Drinking Water Act Maximum Contaminant Levels (SDWA MCLs) at any time during the next 1,000 years. Transport modeling conducted for the Frenchman Flat Corrective Action Unit (CAU) at the NNSS identified the beta/photon-emitting radionuclides tritium (3H), carbon-14 (14C), chlorine-36 (36Cl), technetium-99 (99Tc), and iodine-129 (129I) as having the greatest influence in defining the farthest extent of the modeled CAU contaminant boundary. These same radionuclides are assumed here as the contaminants of concern (COCs) for all underground nuclear tests at the NNSS because models are not yet complete for the other CAUs.Potential public exposure to the COCs will only occur and be of concern if the COCs migrate into the groundwater beneath public or private lands at levels that exceed either individual SDWA MCLs or dose and risk limits. Groundwater flow directions strongly suggest that any contaminant boundary predicted by contaminant fate and transport modeling to overlap public or private lands is more likely to occur to the west and/or southwest of the NNSS and the adjacent Nevada Test and Training Range (NTTR). Well-established, rural communities exist in these directions. Estimates of representative activity concentrations at the applicable SDWA MCL were developed for the five COCs. It is assumed that these COC concentrations may collectively occur at some public or private location in the future, but that situation

  13. High-dose-rate interstitial brachytherapy in combination with androgen deprivation therapy for prostate cancer. Are high-risk patients good candidates

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ken; Narumi, Yoshifumi [Osaka Medical College, Department of Radiology, Takatsuki, Osaka (Japan); Yamazaki, Hideya; Masui, Koji [Kyoto Prefectural University of Medicine, Department of Radiology, Kyoto (Japan); Takenaka, Tadashi [National Hospital Organization Osaka National Hospital, Department of Radiology, Osaka city, Osaka (Japan); Kotsuma, Tadayuki; Yoshida, Mineo; Tanaka, Eiichi [National Hospital Organization Osaka National Hospital, Department of Radiation Oncology, Osaka city, Osaka (Japan); Yoshioka, Yasuo [Osaka University Graduate School of Medicine, Department of Radiation Oncology, Suita, Osaka (Japan); Oka, Toshitsugu [National Hospital Organization Osaka National Hospital, Department of Urology, Osaka city, Osaka (Japan)

    2014-11-15

    To evaluate the effectiveness of high-dose-rate interstitial brachytherapy (HDR-ISBT) as the only form of radiotherapy for high-risk prostate cancer patients. Between July 2003 and June 2008, we retrospectively evaluated the outcomes of 48 high-risk patients who had undergone HDR-ISBT at the National Hospital Organization Osaka National Hospital. Risk group classification was according to the criteria described in the National Comprehensive Cancer Network (NCCN) guidelines. Median follow-up was 73 months (range 12-109 months). Neoadjuvant androgen deprivation therapy (ADT) was administered to all 48 patients; 12 patients also received adjuvant ADT. Maximal androgen blockade was performed in 37 patients. Median total treatment duration was 8 months (range 3-45 months). The planned prescribed dose was 54 Gy in 9 fractions over 5 days for the first 13 patients and 49 Gy in 7 fractions over 4 days for 34 patients. Only one patient who was over 80 years old received 38 Gy in 4 fractions over 3 days. The clinical target volume (CTV) was calculated for the prostate gland and the medial side of the seminal vesicles. A 10-mm cranial margin was added to the CTV to create the planning target volume (PTV). The 5-year overall survival and biochemical control rates were 98 and 87 %, respectively. Grade 3 late genitourinary and gastrointestinal complications occurred in 2 patients (4 %) and 1 patient (2 %), respectively; grade 2 late genitourinary and gastrointestinal complications occurred in 5 patients (10 %) and 1 patient (2 %), respectively. Even for high-risk patients, HDR-ISBT as the only form of radiotherapy combined with ADT achieved promising biochemical control results, with acceptable late genitourinary and gastrointestinal complication rates. (orig.) [German] Beurteilung der Wirksamkeit von interstitieller Brachytherapie mit Hochdosisraten (''high-dose-rate interstitial brachytherapy'', HDR-ISBT) als einzige Form der Radiotherapie fuer Hochrisiko

  14. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial.

    Science.gov (United States)

    Cannon, Christopher P; Cariou, Bertrand; Blom, Dirk; McKenney, James M; Lorenzato, Christelle; Pordy, Robert; Chaudhari, Umesh; Colhoun, Helen M

    2015-05-14

    To compare the efficacy [low-density lipoprotein cholesterol (LDL-C) lowering] and safety of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin 9, compared with ezetimibe, as add-on therapy to maximally tolerated statin therapy in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia. COMBO II is a double-blind, double-dummy, active-controlled, parallel-group, 104-week study of alirocumab vs. ezetimibe. Patients (n = 720) with high cardiovascular risk and elevated LDL-C despite maximal doses of statins were enrolled (August 2012-May 2013). This pre-specified analysis was conducted after the last patient completed 52 weeks. Patients were randomized to subcutaneous alirocumab 75 mg every 2 weeks (plus oral placebo) or oral ezetimibe 10 mg daily (plus subcutaneous placebo) on a background of statin therapy. At Week 24, mean ± SE reductions in LDL-C from baseline were 50.6 ± 1.4% for alirocumab vs. 20.7 ± 1.9% for ezetimibe (difference 29.8 ± 2.3%; P < 0.0001); 77.0% of alirocumab and 45.6% of ezetimibe patients achieved LDL-C <1.8 mmol/L (P < 0.0001). Mean achieved LDL-C at Week 24 was 1.3 ± 0.04 mmol/L with alirocumab and 2.1 ± 0.05 mmol/L with ezetimibe, and were maintained to Week 52. Alirocumab was generally well tolerated, with no evidence of an excess of treatment-emergent adverse events. In patients at high cardiovascular risk with inadequately controlled LDL-C, alirocumab achieved significantly greater reductions in LDL-C compared with ezetimibe, with a similar safety profile. clinicaltrials.gov Identifier: NCT01644188. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  15. Fruits and vegetables intake and risk of bladder cancer: a PRISMA-compliant systematic review and dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Xu, Chang; Zeng, Xian-Tao; Liu, Tong-Zu; Zhang, Chao; Yang, Zhong-Hua; Li, Sheng; Chen, Xiao-Yan

    2015-05-01

    Clinical practice recommends eating ≥2.5 cups of fruits and vegetables (FVs) each day for cancer prevention, in which the evidence from epidemiological studies for the association between FVs intake and bladder cancer (BC) prevention is inconsistent.We searched the PubMed, Embase, and Willy online Library for relevant studies published up to September 27, 2014. Prospective cohort studies investigated FVs intake, and the risk of BC with ≥3 categories of exposure was included. A dose-response meta-analysis was carried out to evaluate the association between FVs intake and risk of BC.Fourteen cohorts with 17 studies including 9447 cases were identified. No evidence of nonlinear association was examined between FVs intake and risk of BC. The summarized relevant risk (RR) of every 0.2 serving increment a day was 1.00 (95%CI: 0.99, 1.00; P = 0.17; I = 41.7%; n = 14) for total fruits; 0.99 (95%CI: 0.96, 1.01; P = 0.28; I = 37.0%; n = 13) for total vegetables; and 0.99 (95%CI: 0.97, 1.01; P = 0.24; I = 57.5%; n = 8) for both FVs. In further analysis, we observed inverse association between every 0.2 serving increment of green leafy vegetables intake a day and risk of BC (RR = 0.98, 95%CI: 0.96, 0.99; I = 0.0%; P cruciferous vegetables (RR = 0.97, 95%CI: 0.93, 1.01; P = 0.19; I = 55.8%; n = 8) nor for citrus (RR = 1.00, 95%CI: 1.00, 1.00; P = 0.83; I = 0.0%; n = 7). Subgroup analysis showed consistent results.Little evidence supports a beneficial effect for total fruits, vegetables, both FVs, and citrus intake against bladder cancer. Green leafy vegetables may help prevent bladder cancer.

  16. SU-E-J-08: Comparison of Unintended Radiation Doses to Organs at Risk Resulting From the Out-Of-Field Therapeutic Beams and From Image-Guidance X-Ray Procedures

    Energy Technology Data Exchange (ETDEWEB)

    Ding, G; Wang, L [Vanderbilt University, Nashville, TN (United States)

    2015-06-15

    Purpose: The unintended radiation dose to organs at risk (OAR) can be contributed from imaging guidance procedures as well as from leakage and scatter of therapeutic beams. This study compares the imaging dose with the unintended out-of-field therapeutic dose to patient sensitive organs. Methods: The Monte Carlo EGSnrc user codes, BEAMnrc and DOSXYZnrc, were used to simulate kV X-ray sources from imaging devices as well as the therapeutic IMRT/VMAT beams and to calculate doses to target and OARs on patient treatment planning CT images. The accuracy of the Monte Carlo simulations was benchmarked against measurements in phantoms. The dose-volume histogram was utilized in analyzing the patient organ doses. Results: The dose resulting from Standard Head kV-CBCT scans to bone and soft tissues ranges from 0.7 to 1.1 cGy and from 0.03 to 0.3 cGy, respectively. The dose resulting from Thorax scans on the chest to bone and soft tissues ranges from 1.1 to 1.8 cGy and from 0.3 to 0.6 cGy, respectively. The dose resulting from Pelvis scans on the abdomen to bone and soft tissues range from 3.2 to 4.2 cGy and from 1.2 to 2.2 cGy, respectively. The out-of-field doses to OAR are sensitive to the distance between the treated target and the OAR. For a typical Head-and-Neck IMRT/VMAT treatment the out-of-field doses to eyes are 1–3% of the target dose, or 2–6 cGy per fraction. Conclusion: The imaging doses to OAR are predictable based on the imaging protocols used when OARs are within the imaged volume and can be estimated and accounted for by using tabulated values. The unintended out-of-field doses are proportional to the target dose, strongly depend on the distance between the treated target and OAR, and are generally higher comparing to the imaging dose. This work was partially supported by Varian research grant VUMC40590.

  17. Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin.

    Science.gov (United States)

    Chan, Francis K L; Kyaw, Moe; Tanigawa, Tetsuya; Higuchi, Kazuhide; Fujimoto, Kazuma; Cheong, Pui Kuan; Lee, Vivian; Kinoshita, Yoshikazu; Naito, Yuji; Watanabe, Toshio; Ching, Jessica Y L; Lam, Kelvin; Lo, Angeline; Chan, Heyson; Lui, Rashid; Tang, Raymond S Y; Sakata, Yasuhisa; Tse, Yee Kit; Takeuchi, Toshihisa; Handa, Osamu; Nebiki, Hiroko; Wu, Justin C Y; Abe, Takashi; Mishiro, Tsuyoshi; Ng, Siew C; Arakawa, Tetsuo

    2017-01-01

    It is not clear whether H2-receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186. Copyright © 2017 AGA

  18. Low-dose oral sirolimus and the risk of menstrual-cycle disturbances and ovarian cysts: analysis of the randomized controlled SUISSE ADPKD trial.

    Directory of Open Access Journals (Sweden)

    Matthias Braun

    Full Text Available UNLABELLED: Sirolimus has been approved for clinical use in non proliferative and proliferative disorders. It inhibits the mammalian target of rapamycin (mTOR signaling pathway which is also known to regulate ovarian morphology and function. Preliminary observational data suggest the potential for ovarian toxicity but this issue has not been studied in randomized controlled trials. We reviewed the self-reported occurrence of menstrual cycle disturbances and the appearance of ovarian cysts post hoc in an open label randomized controlled phase II trial conducted at the University Hospital Zürich between March 2006 and March 2010. Adult females with autosomal dominant polycystic kidney disease, an inherited kidney disease not known to affect ovarian morphology and function, were treated with 1.3 to 1.5 mg sirolimus per day for a median of 19 months (N = 21 or standard care (N = 18. Sirolimus increased the risk of both oligoamenorrhea (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.1 to 29 and ovarian cysts (HR 4.4, CI 1.1 to 26; one patient was cystectomized five months after starting treatment with sirolimus. We also studied mechanisms of sirolimus-associated ovarian toxicity in rats. Sirolimus amplified signaling in rat ovarian follicles through the pro-proliferative phosphatidylinositol 3-kinase pathway. Low dose oral sirolimus increases the risk of menstrual cycle disturbances and ovarian cysts and monitoring of sirolimus-associated ovarian toxicity is warranted and might guide clinical practice with mammalian target of rapamycin inhibitors. TRIAL REGISTRATION: ClinicalTrials.gov NCT00346918.

  19. HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy

    Directory of Open Access Journals (Sweden)

    Fountzilas George

    2012-01-01

    Full Text Available Abstract Background HER2 and TOP2A parameters (gene status, mRNA and protein expression have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy. Methods In a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization, mRNA expression (quantitative reverse transcription PCR, as well as HER2 and TopoIIa protein expression (immunohistochemistry. Results HER2 and TOP2A amplification did not share the same effects on their downstream molecules, with consistent patterns observed in HER2 mRNA and protein expression according to HER2 amplification (all parameters strongly inter-related, p values Conclusions This study confirms the favorable prognostic value of HER2/TOP2A co-amplification and the adverse prognostic value of high TOP2A mRNA expression extending it to the adjuvant treatment setting in early high-risk breast cancer. The strong adverse prognostic impact of high HER2/TOP2A mRNA co-expression needs further validation in studies designed to evaluate markers predictive for anthracyclines. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12611000506998.

  20. Effect of ultra-low dose and standard heparin locks on early tunnelled dialysis catheter outcomes in low-risk dialysis patients.

    Science.gov (United States)

    Renaud, Claude J; Lim, Eng Kuang; Tho, Samuel J; Yeoh, Lee Ying

    2015-02-01

    Initial heparin locks instilled after tunnelled dialysis catheter (TDC) insertion can leak causing systemic anticoagulation and also promote staphyloccocal biofilm formation, predisposing to catheter-related infection (CRI). The 1000 U/mL concentration is thus advocated as the optimal dose for preventing catheter bleeding and malfunction. The effect of lower heparin concentrations on further lowering these complications is not known. We compared early TDC outcomes between a non-standard ultra-low (500 U/mL) and standard initial heparin locks (1000 and 5000 U/mL). This was a retrospective study on prospectively collected data on 238 de novo internal jugular TDCs placed by nephrologists. Cases were categorized into groups 1, 2 and 3, according to initial heparin lock: 500 [n = 30], 1000 [n = 180] and 5000 U/mL [n = 28] respectively. Bleeding and malfunction within 24 h of TDC insertion, 30 days CRI-free catheter survival and the effects of clinical and laboratory factors on bleeding were evaluated. Bleeding events were similar in groups 1, 2 and 3 (7 vs 14 vs 13%, respectively, P = 0.61). Malfunction was only seen in group 2 (3.3%). Thirty-day CRI-free catheter survival was comparable (96 vs 98 vs 97%, respectively, P = 0.22), giving a cumulative CRI rate of 0.76/1000 catheter days. All CRIs were staphylococcal. Univariate analysis did not reveal any significant predictors of catheter bleeding. Immediate TDC bleeding, malfunction and CRI rate are not influenced by heparin lock concentrations ≤5000 U/mL in this low-risk cohort. However this needs to be corroborated in higher risk patients. © 2014 Asian Pacific Society of Nephrology.

  1. Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose-response meta-analysis.

    Science.gov (United States)

    Amadou, A; Ferrari, P; Muwonge, R; Moskal, A; Biessy, C; Romieu, I; Hainaut, P

    2013-08-01

    The association of overweight and obesity with premenopausal breast cancer remained unclear, ethnicity could play a role. A MEDLINE and PUBMED search of all studies on obesity and premenopausal breast cancer published from 2000 to 2010 was conducted. Dose-response meta-analysis was used to determine the risk of premenopausal breast cancer associated with different anthropometric measurements in different ethnic groups. For body mass index (BMI), each 5 kg m(-2) increase was inversely associated with the risk of premenopausal breast cancer (RR = 0.95, 95% confidence interval [CI]: 0.94, 0.97). After stratification by ethnicity, the inverse association remained significant only among Africans (RR = 0.95, 95% CI: 0.91, 0.98) and Caucasians (RR = 0.93, 95% CI: 0.91, 0.95). In contrast, among Asian women, a significant positive association was observed. For waist-to-hip ratio (WHR), each 0.1 unit increase was positively associated with premenopausal breast cancer (RR = 1.08, 95% CI: 1.01, 1.16); the largest effect was detected in Asian women (RR = 1.19, 95% CI: 1.15, 1.24), while small effects of 5% and 6% were observed in African and Caucasian women, respectively. Our results suggest the importance of considering both fat distribution and ethnicity when studying premenopausal breast cancer. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

  2. Posttraumatic Stress Disorder After High-Dose-Rate Brachytherapy for Cervical Cancer With 2 Fractions in 1 Application Under Spinal/Epidural Anesthesia: Incidence and Risk Factors

    Energy Technology Data Exchange (ETDEWEB)

    Kirchheiner, Kathrin, E-mail: kathrin.kirchheiner@meduniwien.ac.at [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria); Czajka-Pepl, Agnieszka [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Ponocny-Seliger, Elisabeth [Department of Psychology, Sigmund Freud Private University Vienna, Vienna (Austria); Scharbert, Gisela; Wetzel, Léonore [Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Nout, Remi A. [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Sturdza, Alina [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Dimopoulos, Johannes C. [Metropolitan Hospital, Athens (Greece); Dörr, Wolfgang; Pötter, Richard [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria)

    2014-06-01

    Purpose: To investigate the psychological consequences of high-dose-rate brachytherapy with 2 fractions in 1 application under spinal/epidural anesthesia in the treatment of locally advanced cervical cancer. Methods and Materials: In 50 patients with locally advanced cervical cancer, validated questionnaires were used for prospective assessment of acute and posttraumatic stress disorder (ASD/PTSD) (Impact of Event Scale–Revision), anxiety/depression (Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30/Cervical Cancer 24), physical functioning (World Health Organization performance status), and pain (visual analogue scale), before and during treatment and 1 week and 3 months after treatment. Qualitative interviews were recorded in open format for content analysis. Results: Symptoms of ASD occurred in 30% of patients 1 week after treatment; and of PTSD in 41% 3 months after treatment in association with this specific brachytherapy procedure. Pretreatment predictive variables explain 82% of the variance of PTSD symptoms. Helpful experiences were the support of the treatment team, psychological support, and a positive attitude. Stressful factors were pain, organizational problems during treatment, and immobility between brachytherapy fractions. Conclusions: The specific brachytherapy procedure, as performed in the investigated mono-institutional setting with 2 fractions in 1 application under spinal/epidural anesthesia, bears a considerable risk of traumatization. The source of stress seems to be not the brachytherapy application itself but the maintenance of the applicator under epidural anesthesia in the time between fractions. Patients at risk may be identified before treatment, to offer targeted psycho-social support. The patients' open reports regarding helpful experiences are an encouraging feedback for the treatment team; the reported stressful

  3. A systematic review comparing the appropriateness of the intravenous urogram and the Computed Tomography Urogram in terms of diagnostic accuracy and risk of radiation dose for patients with urolithiasis

    Energy Technology Data Exchange (ETDEWEB)

    Crompton, G., E-mail: gemmacrompton@hotmail.co.uk [University of Teesside, School of Health and Social Care, Borough Road, Middlesbrough TS1 3BA (United Kingdom); Cosson, P. [University of Teesside, School of Health and Social Care, Borough Road, Middlesbrough TS1 3BA (United Kingdom)

    2011-11-15

    Background: Urolithiasis affects 5-15% of the population, with 70% of suffers between the ages 18 and 50. Guidelines detail Intravenous Urography (IVU) as the 'gold standard' for diagnosis; however advances in Computed Tomography Urography (CTU) have led to adoption of this alternative test. The radiation risks from CTU have not been widely reported. Objectives: To compare IVU and CTU for diagnostic accuracy and radiation risk. Consideration criteria: Prospective, randomised control trials, diagnostic accuracy and adverse effects studies comparing IVU and CTU accuracy and/or radiation dose were included. Participants were adults with confirmed or suspected urolithiasis. Search strategy: A search of the databases; AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE and Science Direct, was conducted between 1995 and week 40, 2009. Secondary searches of reference lists and main subject journals were completed. Methods of review: A systematic review method was employed using 'a priori' standardised forms, by two independent reviewers, to select studies, assess quality and extract data. Results: Ten studies from 283 potential references met the inclusion criteria. Diagnostic accuracy results showed consensus that CTU provides better sensitivity with comparable specificity to IVU. Dose results showed CTU to be associated with greater dose and risk of cancer than IVU. Conclusion: Decisions regarding which test should be used for urolithiasis should be taken with regard to their age and associated risk from ionising radiation. IVU represents a specific and low dose method of assessment.

  4. Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors

    Science.gov (United States)

    Kang, Ji-Man; Lee, Ji Won; Yoo, Keon Hee; Kim, Yae-Jean; Sung, Ki Woong; Koo, Hong Hoe

    2016-01-01

    We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children. PMID:27627440

  5. Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk myeloma: analysis of SWOG trial S0115

    Science.gov (United States)

    Sanchorawala, V; Hoering, A; Seldin, DC; Finn, KT; Fennessey, SA; Sexton, R; Mattar, B; Safah, HF; Holmberg, LA; Dean, RM; Orlowski, RZ; Barlogie, B

    2013-01-01

    We designed a trial using two sequential cycles of modified high-dose melphalan at 100 mg/m2 and autologous SCT (mHDM/SCT) in AL amyloidosis (light-chain amyloidosis, AL), AL with myeloma (ALM) and host-based high-risk myeloma (hM) patients through SWOG-0115. The primary objective was to evaluate OS. From 2004 to 2010, 93 eligible patients were enrolled at 17 centers in the United States (59 with AL, 9 with ALM and 25 with hM). The median OS for patients with AL and ALM was 68 months and 47 months, respectively, and has not been reached for patients with hM. The median PFS for patients with AL and ALM was 38 months and 16 months, respectively, and has not been reached for patients with hM. The treatment-related mortality (TRM) was 12% (11/ 93) and was observed only in patients with AL after SCT. Grade 3 and higher non-hematologic adverse events were experienced by 81%, 67% and 57% of patients with AL, ALM and hM, respectively, during the first and second HDM/SCT. This experience demonstrates that with careful selection of patients and use of mHDM for SCT in patients with AL, ALM and hM, even in the setting of a multicenter study, OS can be improved with acceptable TRM and morbidity. PMID:23852321

  6. Six months of daily high-dose xylitol in high-risk schoolchildren: a randomized clinical trial on plaque pH and salivary mutans streptococci.

    Science.gov (United States)

    Campus, G; Cagetti, M G; Sacco, G; Solinas, G; Mastroberardino, S; Lingström, P

    2009-01-01

    A randomized clinical trial was designed to evaluate the effect of daily high-dose xylitol chewing gum on plaque pH and salivary mutans streptococci (MS) in a sample of schoolchildren at high risk of caries. The study was performed on 204 subjects (acceptance rate 88.3%). Inclusion criteria were: >1 and salivary MS concentration >10(5) CFU/ml. Subjects were randomly assigned to the xylitol or control group. Study design included one examination at baseline (t(0)), one after 3 months of chewing (t(1)), one after 6 months of chewing (t(2)) and the last 3 months after the end of chewing period (t(3)). Plaque pH was assessed using the MicroTouch technique, following a sucrose challenge. The area under the curve (AUC(5.7) and AUC(6.2)) was recorded. Whole saliva was collected in sterile vials and MS CFU/ml were counted. Data were analysed using repeated-measures ANOVA. The main result was that plaque acidogenicity was reduced in both groups. The differences between treatments were statistically significant both for plaque pH and MS concentration; the interaction term for treatment and time was statistically significant (p salivary MS concentration >10(5) and those with pH, and that this effect was statistically greater when using xylitol chewing gums, both on plaque pH and MS salivary concentration.

  7. Efeito dose-resposta de fatores de risco para a doença isquêmica do coração Dose-response effect of risk factors to ischaemic heart disease

    Directory of Open Access Journals (Sweden)

    Suzana Alves de Moraes

    1996-10-01

    Full Text Available Resultados de diversos estudos têm apontado a relevância da hipertensão arterial, do hábito de fumar e da hipercolesterolemia como fatores de risco para a doença isquêmica do coração (DIC. Poucos autores têm investigado a existência de gradiente linear relacionando a quantidade destas exposições com os eventos coronarianos. Com o objetivo de avaliar o efeito de diferentes graus de exposição a estas variáveis sobre a DIC, procedendo-se ao ajustamento para possíveis variáveis de confusão, foi feito estudo planejado sob a forma de desenho tipo caso-controle, tendo a coleta de dados se estendido de março de 1993 a fevereiro de 1994. Foram estudados 833 indivíduos de ambos os sexos, na faixa etária compreendida entre 30 e 69 anos completos, sendo todos residentes no Município de São Paulo, SP (Brasil. Foram comparados 280 casos com 553 controles (285 controles de vizinhança e 268 controles hospitalares. A técnica estatística utilizada para a análise dos dados foi a regressão logística multivariada. Os resultados permitiram identificar gradiente linear para as variáveis duração da hipertensão arterial e para número de cigarros consumidos/dia. As variáveis duração do hábito de fumar e duração da hipercolesterolemia, embora tendo apresentado "odds ratios" significantes para as respectivas categorias de exposição, não apresentaram gradiente linear. Foram discutidos aspectos metodológicos que poderiam exercer influência sobre