Risk of eye lens radiation exposure for members of the public.

PubMed

Chevallier, M-A; Rannou, A; Villagrasa, C; Clairand, I

2016-01-01

In 2011, the International Commission on Radiological Protection (ICRP) reviewed its recommendation concerning the equivalent dose limit for the eye lens, lowering it to 20 mSv in a year, for occupational exposure in planned exposure situations. The ICRP's statement does not contain any explicit recommendations regarding the organ dose limit for the eye lens for public exposure. For the moment, no change is proposed. But, to be coherent in the overall approach, the current equivalent limit for the public might be lowered. A similar yardstick than in the former recommendation may be used, that is to say a reduction of 10 times lower than that for occupational exposure. In this context, additional data on potential scenarios for public exposure of the eye lens are necessary. This paper, mainly based on a literature study, aims to provide, as far as possible, an exhaustive list of the situations in which members of the public can be exposed at the level of the eye lens. Once these situations have been defined, some calculations, made to assess the associated doses to the eye lens, are presented. This literature study did not reveal any current situations where members of the public would receive significant radiation doses to the eye lens. Indeed, the situations in which the dose to the eye lens might reach around 1 mSv per year for the public are extremely rare. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Annual limits on intake (ALI) values in ICRP 61 and 10 CFR Part 20 (1991)

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

Zhu, M.; Kearfott, K.J.

The newest major revision of Nuclear Regulatory Commission`s 10 CFR Part 20 (1991) incorporates the new dose methodology system, revised limits, and improved internal dose computations presented in International Commission on Radiation Protection (ICRP) Publication 30 (1979). A year before the issue of this revised 10 CFR Part 20, the ICRP dispatched Publication 61 (1990). This new ICRP report employed different dose limits, in addition to incorporating more recent biological information and variations in physiological and different tissue weighing factors for various organs. An investigation of the numerical differences in the Annual Limit on Intake (ALI) reported in this moremore » recent international regulations and those of the new regulations was thus undertaken. Overall means, medians, modes, maximum, minimum, and ranges of the percent changes are almost identical for ingestion and inhalation, although the percent difference between 10 CFR and ICRP Publication 61 showed minor differences for individual radionuclides. Approximately 334 of 1,351 radionuclides for inhalation and 173 of 771 radionuclides for ingestion have much less restrictive ALIs in the new ICRP recommendations than in the old, with some of those limits increased by at least a factor of two. Approximately 51% of the radionuclides for ingestion intake and 48% of radionuclides for inhalation intake showed changes of greater than 25%. The radionuclides observed to have much less restrictive ALIs are primarily the radionuclides of thorium, mercury, plutonium, uranium, and americium which have short effective clearance rates. While many countries have already applied the ICRP 61 recommendations to their radiation protection standards, using the ICRP 30 recommendation in the United States does not match the international standards even when the values of the ALIs are adjusted for differences in dose limits.« less

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline.

PubMed

Arrossi, Silvina; Temin, Sarah; Garland, Suzanne; Eckert, Linda O'Neal; Bhatla, Neerja; Castellsagué, Xavier; Alkaff, Sharifa Ezat; Felder, Tamika; Hammouda, Doudja; Konno, Ryo; Lopes, Gilberto; Mugisha, Emmanuel; Murillo, Rául; Scarinci, Isabel C; Stanley, Margaret; Tsu, Vivien; Wheeler, Cosette M; Adewole, Isaac Folorunso; de Sanjosé, Silvia

2017-10-01

To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus-related cancers and diseases. Basic settings: vaccinating boys is not recommended. It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Tanning facility use: are we exceeding Food and Drug Administration limits?

PubMed

Hornung, Robin L; Magee, Kristin H; Lee, Willie J; Hansen, Lori A; Hsieh, Yi-Ching

2003-10-01

The US Food and Drug Administration (FDA) recommends exposure limits for tanning bed use. Tanning patrons may not be following these recommendations and may be overexposed to damaging ultraviolet radiation (UV). This study was conducted to assess tanning patrons' adherence to FDA-recommended exposure limits and to measure the amount of UVA and UVB radiation emitted by tanning beds. A community-based survey was administered during routine state inspections of North Carolina tanning facilities (n = 50). At each facility, patron records were randomly selected (n = 483) for a survey of exposure records, and UVA and UVB outputs were measured for each tanning bed. The recommended limits were exceeded by 95% of patrons, and 33% of patrons began tanning at the maximum doses recommended for maintenance tanning. Average tanning bed output was 192.1 W/m(2) UVA and 0.35 W/m(2) erythemally weighted UVB. Interventions for tanning bed operators and patrons are needed to increase compliance with federally recommended exposure limits.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline

PubMed Central

Arrossi, Silvina; Temin, Sarah; Garland, Suzanne; Eckert, Linda O’Neal; Bhatla, Neerja; Castellsagué, Xavier; Alkaff, Sharifa Ezat; Felder, Tamika; Hammouda, Doudja; Konno, Ryo; Lopes, Gilberto; Mugisha, Emmanuel; Murillo, Rául; Scarinci, Isabel C.; Stanley, Margaret; Tsu, Vivien; Wheeler, Cosette M.; Adewole, Isaac Folorunso; de Sanjosé, Silvia

2017-01-01

Purpose To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. Methods The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. Results Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. Recommendations In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus–related cancers and diseases. Basic settings: vaccinating boys is not recommended. It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines. PMID:29094100

A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

PubMed

Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

2002-03-01

To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being

Space radiation concerns for manned exploration.

PubMed

Stanford, M; Jones, J A

1999-07-01

Spaceflight exposes astronaut crews to natural ionizing radiation. To date, exposures in manned spaceflight have been well below the career limits recommended to NASA by the National Council of Radiation Protection and Measurements (NCRP). This will not be the case for long-duration exploratory class missions. Additionally. International Space Station (ISS) crews will receive higher doses than earlier flight crews. Uncertainties in our understanding of long-term bioeffects, as well as updated analyses of the Hiroshima. Nagasaki and Chernobyl tumorigenesis data, have prompted the NCRP to recommend further reductions by 30-50% for career dose limit guidelines. Intelligent spacecraft design and material selection can provide a shielding strategy capable of maintaining crew exposures within recommended guidelines. Current studies on newer radioprotectant compounds may find combinations of agents which further diminish the risk of radiation-induced bioeffects to the crew.

Persistence and dissipation kinetics of chlorantraniliprole 0.4G in the soil of tropical sugarcane ecosystem.

PubMed

Ramasubramanian, T; Paramasivam, M; Jayanthi, R; Nirmala, R

2016-01-01

Chlorantraniliprole 0.4 % GR has been in use for managing early shoot borer and top borer of sugarcane. Persistence and dissipation kinetics of granular formulation of chlorantraniliprole were studied in the soil of tropical sugarcane ecosystem by employing simple and sensitive analytical method. Limit of quantification of the method was 0.01 mg/kg and the recovery of chlorantraniliprole was in the range of 92.3-99.7 % with RSD of 1.14-3.0 %. The initial deposit of chlorantraniliprole in the soil was 0.513 and 1.031 mg/kg for the recommended (75 g a.i./ha) and double the recommended (150 g a.i./ha) doses, respectively. The residues were quantified up to 30 days after treatment irrespective of the doses applied. Half-life (t 1/2) was 6.60 and 6.73 days, respectively, for recommended and double the recommended doses of chlorantraniliprole.

The incidence of phlebitis with intravenous amiodarone at guideline dose recommendations.

PubMed

Slim, Ahmad M; Roth, Jason E; Duffy, Benjamin; Boyd, Sheri Y N; Rubal, Bernard J

2007-12-01

Postoperative atrial fibrillation following cardiothoracic surgery is common and frequently managed with intravenous (IV) amiodarone. Phlebitis is the most common complication with peripheral infusion of this agent. Current practice guidelines for peripheral IV administration of <2 mg/mL amiodarone were established to reduce the risk of phlebitis. The present study examines the incidence of phlebitis in a postoperative patient population given current dose recommendations. A total of 273 patient charts were reviewed. The incidence of phlebitis in patients given IV amiodarone (n = 36) was 13.9% (95% confidence interval, 2.6-25.2%; p = 0.001). Logistic regression analysis with backward elimination of other therapeutic risk factors suggests that the odds ratio for phlebitis using current dose regimens without IV filters is 19-fold greater than baseline risk in this population. Phlebitis remains a significant complication associated with peripheral infusion of amiodarone within recommended dosing limits.

Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer.

PubMed

Bruera, Gemma; Massacese, Silvia; Galvano, Antonio; Mas, Antonella Dal; Guadagni, Stefano; Calvisi, Giuseppe; Ciacco, Eugenio; Russo, Antonio; Ricevuto, Enrico

2018-04-17

Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity. Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m 2 /d 1-2, 8-9, 15-16, 22-23, with 100 mg/m 2 /d increase for dose level; DTX 50 mg/m 2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m 2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned. Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m 2 /d and 80 mg/m 2 , respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leucopenia 20%, hypoalbuminemia 10%, mucositis 10%, asthenia 20%. Limiting toxicity syndromes were 30%, 25% in young-elderly, all multiple site. Objective response rate intent-to-treat 60%, disease control rate 90%. After 15 months follow-up, progression-free and overall survival, 6 and 17 months, respectively. First line intensive FD/FOx regimen adding DXT/5-FU/OXP can be safely administered at recommended doses in advanced GC, with promising high activity and efficacy.

Are Recommended Doses of Acetaminophen Effective for Children Aged 2 to 3 Years? A Pharmacokinetic Modeling Answer.

PubMed

Abourbih, Daniel Asher; Gosselin, Sophie; Villeneuve, Eric; Kazim, Sara

2016-01-01

Acetaminophen (APAP) elixir is a widely used pediatric antipyretic medication. It has been shown that up to 30% of febrile children presenting to a large urban pediatric emergency department received inadequate APAP dosages at home with errors primarily due to age-based dosing. Parental education material in the form of weight-based dosing guides has been proposed; however, validation of current recommended APAP dosages using pharmacokinetic models is needed. This study used a mathematical model of APAP absorption to predict plasma concentrations and to compare them with the range required to reach and achieve antipyresis (10-20 μg/mL). A common APAP preparation (Children's Tylenol Elixir) was tested (children aged 2-3 years, 10.9-15.9 kg). The manufacturer's suggested dose of 160 mg was compared with the standard 10 to 15 mg/kg dose range. The model predicts a peak plasma concentration between 6.38 and 8.55 μg/mL for 10 mg/kg dose and 9.57 and 12.8 μg/mL for 15 mg/kg dose. The manufacturer's suggested dose of 160 mg was tested across the limits of the weight range (10.9-15.9 kg). A peak plasma concentration between 9.36 and 12.6 μg/mL was found for the lower weight limit (10.9 kg child) and 6.42 to 8.61 μg/mL for the upper weight limit (15.9 kg child). With the use of this model, the 10 mg/kg dose does not reach the plasma concentration value for antipyresis (10-20 μg/mL), whereas 15 mg/kg is adequate only if assuming a greater absorption constant. The 160 mg dose is effective only for children weighing 10.9 kg. Individual differences in drug bioavailability, volume of distribution, and absorption/elimination constants undoubtedly exist, and future studies directly measuring plasma APAP concentration and pharmacokinetics are needed. However, these results indicate that dosages for APAP in children should be weight based and manufacturers should review their dosing recommendations.

Radiation exposure of aviation crewmembers and cancer.

PubMed

Bramlitt, Edward T; Shonka, Joseph J

2015-01-01

Crewmembers are exposed to galactic cosmic radiation on every flight and occasionally to solar protons on polar flights. Data are presented showing that the proton occasions are seven times more frequent than generally believed. Crewmembers are also exposed to neutrons and gamma rays from the sun and to gamma rays from terrestrial thunderstorms. Solar neutrons and gamma rays (1) expose the daylight side of Earth, (2) are most intense at lower latitudes, (3) may be as or more frequent than solar protons, and (4) have relativistic energies. The U.S. agency responsible for crewmember safety only considers the galactic component with respect to its recommended 20 mSv y(-1) limit, but it has an estimate for a thunderstorm dose of 30 mSv. In view of overlooked sources, possible over-limit doses, and lack of dosimetry, dose reconstructions are needed. However, using the agency dose estimates and the compensation procedure for U.S. nuclear weapon workers, the probability of crewmember cancers can be at least as likely as not. Ways to improve the quality of dose estimates are suggested, and a worker's compensation program specific to aviation crewmembers is recommended.

Celecoxib interferes to a limited extent with aspirin‐mediated inhibition of platelets aggregation

PubMed Central

Ruzov, Mark; Rimon, Gilad; Pikovsky, Oleg

2015-01-01

Aims The aim of the study was to analyze the interaction between celecoxib and low dose aspirin for COX‐1 binding and its consequences on the aspirin‐mediated antiplatelet effects. Methods We investigated ex vivo the interaction between celecoxib and aspirin for COX‐1 binding and measured the resulting antiplatelet effects. We applied mechanism‐based pharmacokinetic−pharmacodynamic (PKPD) modelling to analyze these data and to predict in vivo platelet aggregation for different doses and administration schedules of aspirin and celecoxib. Results The predictions of the PK‐PD model were consistent with results from previous studies that investigated interaction between aspirin and celecoxib. The modelling results indicate that celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. The extent of this interaction can be substantial (up to 15% increase in platelet aggregation by 200 mg day−1 celecoxib when combined with low dose aspirin) during the first days of aspirin administration in patients who are already treated with celecoxib, and it cannot be prevented by separate administration of the interacting drugs. Conclusions At the recommended therapeutic doses, celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. Patients receiving a combination of low dose aspirin and the recommended doses of celecoxib were not identified to have increased risk of cardiovascular and cerebrovascular events due to competition between these drugs for COX‐1 binding. Interaction between low dose aspirin and other COX‐2 inhibitors and its clinical consequences requires further investigation. PMID:26456703

High variability in the dosing of commonly used antibiotics revealed by a Europe-wide point prevalence study: implications for research and dissemination.

PubMed

Metsvaht, Tuuli; Nellis, Georgi; Varendi, Heili; Nunn, Anthony J; Graham, Susan; Rieutord, Andre; Storme, Thomas; McElnay, James; Mulla, Hussain; Turner, Mark A; Lutsar, Irja

2015-04-16

Antibiotic dosing in neonates varies between countries and centres, suggesting suboptimal exposures for some neonates. We aimed to describe variations and factors influencing the variability in the dosing of frequently used antibiotics in European NICUs to help define strategies for improvement. A sub-analysis of the European Study of Neonatal Exposure to Excipients point prevalence study was undertaken. Demographic data of neonates receiving any antibiotic on the study day within one of three two-week periods from January to June 2012, the dose, dosing interval and route of administration of each prescription were recorded. The British National Formulary for Children (BNFC) and Neofax were used as reference sources. Risk factors for deviations exceeding ±25% of the relevant BNFC dosage recommendation were identified by multivariate logistic regression analysis. In 89 NICUs from 21 countries, 586 antibiotic prescriptions for 342 infants were reported. The twelve most frequently used antibiotics - gentamicin, penicillin G, ampicillin, vancomycin, amikacin, cefotaxime, ceftazidime, meropenem, amoxicillin, metronidazole, teicoplanin and flucloxacillin - covered 92% of systemic prescriptions. Glycopeptide class, GA <32 weeks, 5(th) minute Apgar score <5 and geographical region were associated with deviation from the BNFC dosage recommendation. While the doses of penicillins exceeded recommendations, antibiotics with safety concerns followed (gentamicin) or were dosed below (vancomycin) recommendations. The current lack of compliance with existing dosing recommendations for neonates needs to be overcome through the conduct of well-designed clinical trials with a limited number of antibiotics to define pharmacokinetics/pharmacodynamics, efficacy and safety in this population and by efficient dissemination of the results.

HLW Flexible jumper materials compatibility evaluation

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

Skidmore, T. E.

H-Tank Farm Engineering tasked SRNL/Materials Science & Technology (MS&T) to evaluate the compatibility of Goodyear Viper® chemical transfer hose with HLW solutions. The hose is proposed as a flexible Safety Class jumper for up to six months service. SRNL/MS&T performed various tests to evaluate the effects of radiation, high pH chemistry and elevated temperature on the hose, particularly the inner liner. Test results suggest an upper dose limit of 50 Mrad for the hose. Room temperature burst pressure values at 50 Mrad are estimated at 600- 800 psi, providing a safety factor of 4.0-5.3X over the anticipated operating pressure ofmore » 150 psi and a safety factor of 3.0-4.0X over the working pressure of the hose (200 psi), independent of temperature effects. Radiation effects are minimal at doses less than 10 Mrad. Doses greater than 50 Mrad may be allowed, depending on operating conditions and required safety factors, but cannot be recommended at this time. At 250 Mrad, burst pressure values are reduced to the hose working pressure. At 300 Mrad, burst pressures are below 150 psi. At a bounding continuous dose rate of 57,870 rad/hr, the 50 Mrad dose limit is reached within 1.2 months. Actual dose rates may be lower, particularly during non-transfer periods. Refined dose calculations are therefore recommended to justify longer service. This report details the tests performed and interpretation of the results. Recommendations for shelf-life/storage, component quality verification, and post-service examination are provided.« less

Dose limits to the lens of the eye: International Basic Safety Standards and related guidance.

PubMed

Boal, T J; Pinak, M

2015-06-01

The International Atomic Energy Agency (IAEA) safety requirements: 'General Safety Requirements Part 3--Radiation protection and safety of radiation sources: International Basic Safety Standards' (BSS) was approved by the IAEA Board of Governors at its meeting in September 2011, and was issued as General Safety Requirements Part 3 in July 2014. The equivalent dose limit for the lens of the eye for occupational exposure in planned exposure situations was reduced from 150 mSv year(-1) to 20 mSv year(-1), averaged over defined periods of 5 years, with no annual dose in a single year exceeding 50 mSv. This reduction in the dose limit for the lens of the eye followed the recommendation of the International Commission on Radiological Protection in its statement on tissue reactions of 21 April 2011. IAEA has developed guidance on the implications of the new dose limit for the lens of the eye. This paper summarises the process that led to the inclusion of the new dose limit for the lens of the eye in the BSS, and the implications of the new dose limit. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Current situations and discussions in Japan in relation to the new occupational equivalent dose limit for the lens of the eye.

PubMed

Yokoyama, Sumi; Hamada, Nobuyuki; Hayashida, Toshiyuki; Tsujimura, Norio; Tatsuzaki, Hideo; Kurosawa, Tadahiro; Nabatame, Kuniaki; Ohguchi, Hiroyuki; Ohno, Kazuko; Yamauchi-Kawaura, Chiyo; Iimoto, Takeshi; Ichiji, Takeshi; Hotta, Yutaka; Iwai, Satoshi; Akahane, Keiichi

2017-09-25

Since the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens of the eye in 2011, there have been extensive discussions in various countries. This paper reviews the current situation in radiation protection of the ocular lens and the discussions on the potential impact of the new lens dose limit in Japan. Topics include historical changes to the lens dose limit, the current situation with occupational lens exposures (e.g., in medical workers, nuclear workers, and Fukushima nuclear power plant workers) and measurements, and the current status of biological studies and epidemiological studies on radiation cataracts. Our focus is on the situation in Japan, but we believe such information sharing will be useful in many other countries.

Analysis of the track- and dose-averaged LET and LET spectra in proton therapy using the geant4 Monte Carlo code

PubMed Central

Guan, Fada; Peeler, Christopher; Bronk, Lawrence; Geng, Changran; Taleei, Reza; Randeniya, Sharmalee; Ge, Shuaiping; Mirkovic, Dragan; Grosshans, David; Mohan, Radhe; Titt, Uwe

2015-01-01

Purpose: The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the geant 4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from geant 4 simulations to correlate with biological effectiveness of therapeutic protons. Methods: The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LETt and dose-averaged LET, LETd) using geant 4 for different tracking step size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LETt and LETd of protons with six different step limits ranging from 1 to 500 μm in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Results: Simulation results showed that the step limit effect was small for LETt but significant for LETd. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in geant 4 can result in incorrect LETd calculation results in the dose plateau region for small step limits. The erroneous LETd results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in geant 4. The incorrect LETd values lead to substantial differences in the calculated RBE. Conclusions: When the geant 4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 μm, the authors recommend the use of LETt in the dose plateau region and LETd around the Bragg peak. For a large step limit, i.e., 500 μm, LETd is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LETd and LETt becomes positive. PMID:26520716

Tracking Cumulative Radiation Exposure in Orthopaedic Surgeons and Residents: What Dose Are We Getting?

PubMed

Gausden, Elizabeth B; Christ, Alexander B; Zeldin, Roseann; Lane, Joseph M; McCarthy, Moira M

2017-08-02

The purpose of this study was to determine the amount of cumulative radiation exposure received by orthopaedic surgeons and residents in various subspecialties. We obtained dosimeter measures over 12 months on 24 residents and 16 attending surgeons. Monthly radiation exposure was measured over a 12-month period for 24 orthopaedic residents and 16 orthopaedic attending surgeons. The participants wore a Landauer Luxel dosimeter on the breast pocket of their lead apron. The dosimeters were exchanged every rotation (5 to 7 weeks) for the resident participants and every month for the attending surgeon participants. Radiation exposure was compared by orthopaedic subspecialty, level of training, and type of fluoroscopy used (regular C-arm compared with mini C-arm). Orthopaedic residents participating in this study received monthly mean radiation exposures of 0.2 to 79 mrem/month, lower than the dose limits of 5,000 mrem/year recommended by the United States Nuclear Regulatory Commission (U.S. NRC). Senior residents rotating on trauma were exposed to the highest monthly radiation (79 mrem/month [range, 15 to 243 mrem/month]) compared with all other specialty rotations (p < 0.001). Similarly, attending orthopaedic surgeons who specialize in trauma or deformity surgery received the highest radiation exposure of their peers, and the mean exposure was 53 mrem/month (range, 0 to 355 mrem/month). Residents and attending surgeons performing trauma or deformity surgical procedures are exposed to significantly higher doses of radiation compared with all other subspecialties within orthopaedic surgery, but the doses are still within the recommended limits. The use of ionizing radiation in the operating room has become an indispensable part of orthopaedic surgery. Although all surgeons in our study received lower than the yearly recommended dose limit, it is important to be aware of how much radiation we are exposed to as surgeons and to take measures to further limit that exposure.

The lens of the eye: exposures in the UK medical sector and mechanistic studies of radiation effects.

PubMed

Bouffler, S D; Peters, S; Gilvin, P; Slack, K; Markiewicz, E; Quinlan, R A; Gillan, J; Coster, M; Barnard, S; Rothkamm, K; Ainsbury, E

2015-06-01

The recommendation from the International Commission on Radiological Protection that the occupational equivalent dose limit for the lens of the eye should be reduced to 20 mSv year(-1), averaged over 5 years with no year exceeding 50 mSv, has stimulated a discussion on the practicalities of implementation of this revised dose limit, and the most appropriate risk and protection framework to adopt. This brief paper provides an overview of some of the drivers behind the move to a lower recommended dose limit. The issue of implementation in the medical sector in the UK has been addressed through a small-scale survey of doses to the lens of the eye amongst interventional cardiologists and radiologists. In addition, a mechanistic study of early and late post-irradiation changes in the lens of the eye in in-vivo-exposed mice is outlined. Surveys and studies such as those described can contribute to a deeper understanding of fundamental and practical issues, and therefore contribute to a robust evidence base for ensuring adequate protection of the eye while avoiding undesirable restrictions to working practices. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Finding Uncertainties that Cause the Age Dependence of Dose Limits to Be Immature

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.

2007-01-01

Space radiation permissible exposure limits (PEL) are intended to set acceptable levels of cancer risks, and avoid any clinical significant non-cancer effects. The 1989 recommendation of the National Council of Radiation Protection and Measurements (NCRP) recommended a strong age dependence of dose limits that departed drastically from the then mature 1970 dose limits recommendations from the National Academy of Science, which were independent of age. In 2000, the NCRP recommended revised limits that showed a similar trend of risk with age to the 1989 report. In this model, the cancer risk per Sv varies by more than 2-fold for ages between 30- and 50-yr. Therefore for galactic cosmic rays exposure, astronaut age has a larger influence on risk then radiation shielding mass or material composition, vehicle propulsion method, or position in the solar cycle. For considering the control of mission costs and resources, the possibility of using astronaut age as a trade variable in mission design could be considered. However, the uncertainties in describing the age dependence on risk have not been fully explored. We discuss biological factors that influence the age dependence of radiation risks, including susceptibility, expression and latency, and radiation quality. These factors depend not only on the individual s age, but also their genetic sensitivity and interaction with other environmental factors. Epidemiological data is limited in describing the age dependence on risk. The 2005, BEIR VII report recommends an age dependence for cancer risk attributable solely to the life-table disagreeing strongly with the NCRP model. However, BEIR VII also noted the limited power of human data for concomitantly describing both age and age after exposure dependences of cancer risks. Many experimental studies have shown that high LET radiation (e.g., high charge and energy (HZE) nuclei and neutrons) display reduced latency compared to low LET radiation, suggesting distinct biological factors are important. We discuss potential molecular mechanisms that would influence the age dependence of radiation risks. A probability distribution function for the uncertainties in age-dependence of risk models is described and predictions for Mars missions discussed. Our report suggests that theoretical considerations based on new experimental studies are needed to ensure the correct age dependence in space radiation risk models and the resulting Astronaut PEL.

Medical and occupational dose reduction in pediatric barium meal procedures

NASA Astrophysics Data System (ADS)

Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Ledesma, J. A.; Legnani, A.; Bunick, A. P.; Sauzen, J.; Yagui, A.; Vosiak, P.

2017-11-01

Doses received in pediatric Barium Meal procedure can be rather high. It is possible to reduce dose values following the recommendations of the European Communities (EC) and the International Commission on Radiological Protection (ICRP). In the present work, the modifications of radiographic techniques made in a Brazilian hospital according to the EC and the ICRP recommendations and their influence on medical and occupational exposure are reported. The procedures of 49 patients before and 44 after the optimization were studied and air kerma-area product (PK,A) values and the effective doses were evaluated. The occupational equivalent doses were measured next to the eyes, under the thyroid shield and on each hand of both professionals who remained inside the examination room. The implemented modifications reduced by 70% and 60% the PK,A and the patient effective dose, respectively. The obtained dose values are lower than approximately 75% of the results from similar studies. The occupational annual equivalent doses for all studied organs became lower than the limits set by the ICRP. The equivalent doses in one examination were on average below than 75% of similar studies.

Dose limits for astronauts

NASA Technical Reports Server (NTRS)

Sinclair, W. K.

2000-01-01

Radiation exposures to individuals in space can greatly exceed natural radiation exposure on Earth and possibly normal occupational radiation exposures as well. Consequently, procedures limiting exposures would be necessary. Limitations were proposed by the Radiobiological Advisory Panel of the National Academy of Sciences/National Research Council in 1970. This panel recommended short-term limits to avoid deterministic effects and a single career limit (of 4 Sv) based on a doubling of the cancer risk in men aged 35 to 55. Later, when risk estimates for cancer had increased and were recognized to be age and sex dependent, the NCRP, in Report No. 98 in 1989, recommended a range of career limits based on age and sex from 1 to 4 Sv. NCRP is again in the process of revising recommendations for astronaut exposure, partly because risk estimates have increased further and partly to recognize trends in limiting radiation exposure occupationally on the ground. The result of these considerations is likely to be similar short-term limits for deterministic effects but modified career limits.

Analysis of the track- and dose-averaged LET and LET spectra in proton therapy using the GEANT4 Monte Carlo code

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

Guan, Fada; Peeler, Christopher; Taleei, Reza

Purpose: The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the GEANT 4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from GEANT 4 simulations to correlate with biological effectiveness of therapeutic protons. Methods: The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LET{sub t} and dose-averaged LET, LET{sub d}) using GEANT 4 for different tracking stepmore » size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LET{sub t} and LET{sub d} of protons with six different step limits ranging from 1 to 500 μm in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Results: Simulation results showed that the step limit effect was small for LET{sub t} but significant for LET{sub d}. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in GEANT 4 can result in incorrect LET{sub d} calculation results in the dose plateau region for small step limits. The erroneous LET{sub d} results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in GEANT 4. The incorrect LET{sub d} values lead to substantial differences in the calculated RBE. Conclusions: When the GEANT 4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 μm, the authors recommend the use of LET{sub t} in the dose plateau region and LET{sub d} around the Bragg peak. For a large step limit, i.e., 500 μm, LET{sub d} is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LET{sub d} and LET{sub t} becomes positive.« less

Occupational Exposure of the Eye Lens in Interventional Procedures: How to Assess and Manage Radiation Dose.

PubMed

Ciraj-Bjelac, Olivera; Carinou, Eleftheria; Ferrari, Paolo; Gingaume, Merce; Merce, Marta Sans; O'Connor, Una

2016-11-01

Occupational exposure from interventional x-ray procedures is one of the areas in which increased eye lens exposure may occur. Accurate dosimetry is an important element to investigate the correlation of observed radiation effects with radiation dose, to verify the compliance with regulatory dose limits, and to optimize radiation protection practice. The objective of this work is to review eye lens dose levels in clinical practice that may occur from the use of ionizing radiation. The use of a dedicated eye lens dosimeter is the recommended methodology; however, in practice it cannot always be easily implemented. Alternatively, the eye lens dose could be assessed from measurements of other dosimetric quantities or other indirect parameters, such as patient dose. The practical implementation of monitoring eye lens doses and the use of adequate protective equipment still remains a challenge. The use of lead glasses with a good fit to the face, appropriate lateral coverage, and/or ceiling-suspended screens is recommended in workplaces with potential high eye lens doses. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study.

PubMed

Dupuis, Jehan; Morschhauser, Franck; Ghesquières, Hervé; Tilly, Hervé; Casasnovas, Olivier; Thieblemont, Catherine; Ribrag, Vincent; Bossard, Céline; Le Bras, Fabien; Bachy, Emmanuel; Hivert, Bénédicte; Nicolas-Virelizier, Emmanuelle; Jardin, Fabrice; Bastie, Jean-Noel; Amorim, Sandy; Lazarovici, Julien; Martin, Antoine; Coiffier, Bertrand

2015-04-01

Romidepsin is a histone deacetylase inhibitor approved in the USA for patients with recurrent or refractory peripheral T-cell lymphoma and has shown activity in this setting with mainly haematological and gastrointestinal toxicity. Although it has limited efficacy, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used for treatment of de-novo peripheral T-cell lymphoma. We aimed to assess the safety, tolerability, and activity of romidepsin combined with CHOP in patients with previously untreated disease. We enrolled patients aged 18-80 years with histologically proven, previously untreated, peripheral T-cell lymphoma (Eastern Cooperative Oncology Group performance status ≤2) into a dose-escalation (phase 1b) and expansion (phase 2) study at nine Lymphoma Study Association centres in France. In the dose-escalation phase, we allocated consecutive blocks of three participants to receive eight 3 week cycles of CHOP (intravenous cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) [maximum 2 mg] on day 1 and oral prednisone 40 mg/m(2) on days 1-5) in association with varying doses of romidepsin. The starting dose was 10 mg/m(2) intravenously on days 1 and 8 of each cycle, and we used a 3 + 3 design. We assessed dose-limiting toxicities only during the first two cycles. The primary endpoint was to determine the recommended dose for the combination. For the phase 2 study, we aimed to increase the cohort of patients receiving the recommended dose to a total of 25 patients. Patients were assessed for safety outcomes at least twice per cycle according to the Common Terminology Criteria for Adverse Events, version 4.0. Safety analyses included all patients who received at least one dose of romidepsin and CHOP. This trial is registered at the European Clinical Trials Database (EudraCT), number 2010-020962-91 and ClinicalTrials.gov, number NCT01280526. Between Jan 13, 2011, and May 21, 2013, we enrolled 37 patients (18 treated in phase 1b and 19 patients in phase 2). Three of six patients initially treated at 10 mg/m(2) had a dose-limiting toxicity. The dose-escalation committee decided to modify the study protocol to redefine dose-limiting toxicities with regard to haematological toxicity. Three patients were treated with 8 mg/m(2) of romidepsin, an additional three at 10 mg/m(2) (one dose-limiting toxicity), and six patients at 12 mg/m(2) (three dose-limiting toxicities). We chose romidepsin 12 mg/m(2) as the recommended dose for phase 2. Of the 37 patients treated, three had early cardiac events (two myocardial infarctions and one acute cardiac failure). No deaths were attributable to toxicity. 25 (68%) of 37 patients had at least one serious adverse event. Overall, the most frequent serious adverse events were febrile neutropenia (five [14%] of 37 patients), physical health deterioration (five [14%]), lung infection (four [11%]), and vomiting (three [8%]). 33 (89%) of patients had grade 3-4 neutropenia, and 29 (78%) had grade 3-4 thrombocytopenia. Romidepsin can be combined with CHOP but this combination should now be tested in comparison to CHOP alone in a randomised trial. Celgene. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer

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

Robertson, John M., E-mail: jrobertson@beaumont.edu; Margolis, Jeffrey; Jury, Robert P.

2012-02-01

Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m{sup 2}) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additionalmore » 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.« less

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer.

PubMed

Takeoka, Hiroaki; Yamada, Kazuhiko; Azuma, Koichi; Zaizen, Yoshiaki; Yamashita, Fumie; Yoshida, Tsukasa; Naito, Yoshiko; Okayama, Yusuke; Miyamoto, Maki; Hoshino, Tomoaki

2014-05-01

The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (≥75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer. Patients received escalated doses of carboplatin at an area under the concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy. A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months). The combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was determined as the recommended dose in chemotherapy-naïve elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.

Space radiation dosimetry in low-Earth orbit and beyond.

PubMed

Benton, E R; Benton, E V

2001-09-01

Space radiation dosimetry presents one of the greatest challenges in the discipline of radiation protection. This is a result of both the highly complex nature of the radiation fields encountered in low-Earth orbit (LEO) and interplanetary space and of the constraints imposed by spaceflight on instrument design. This paper reviews the sources and composition of the space radiation environment in LEO as well as beyond the Earth's magnetosphere. A review of much of the dosimetric data that have been gathered over the last four decades of human space flight is presented. The different factors affecting the radiation exposures of astronauts and cosmonauts aboard the International Space Station (ISS) are emphasized. Measurements made aboard the Mir Orbital Station have highlighted the importance of both secondary particle production within the structure of spacecraft and the effect of shielding on both crew dose and dose equivalent. Roughly half the dose on ISS is expected to come from trapped protons and half from galactic cosmic rays (GCRs). The dearth of neutron measurements aboard LEO spacecraft and the difficulty inherent in making such measurements have led to large uncertainties in estimates of the neutron contribution to total dose equivalent. Except for a limited number of measurements made aboard the Apollo lunar missions, no crew dosimetry has been conducted beyond the Earth's magnetosphere. At the present time we are forced to rely on model-based estimates of crew dose and dose equivalent when planning for interplanetary missions, such as a mission to Mars. While space crews in LEO are unlikely to exceed the exposure limits recommended by such groups as the NCRP, dose equivalents of the same order as the recommended limits are likely over the course of a human mission to Mars. c2001 Elsevier Science B.V. All rights reserved.

Leaded eyeglasses substantially reduce radiation exposure of the surgeon's eyes during acquisition of typical fluoroscopic views of the hip and pelvis.

PubMed

Burns, Sean; Thornton, Raymond; Dauer, Lawrence T; Quinn, Brian; Miodownik, Daniel; Hak, David J

2013-07-17

Despite recommendations to do so, few orthopaedists wear leaded glasses when performing operative fluoroscopy. Radiation exposure to the ocular lens causes cataracts, and regulatory limits for maximum annual occupational exposure to the eye continue to be revised downward. Using anthropomorphic patient and surgeon phantoms, radiation dose at the surgeon phantom's lens was measured with and without leaded glasses during fluoroscopic acquisition of sixteen common pelvic and hip views. The magnitude of lens dose reduction from leaded glasses was calculated by dividing the unprotected dose by the dose measured behind leaded glasses. On average, the use of leaded glasses reduced radiation to the surgeon phantom's eye by tenfold, a 90% reduction in dose. However, there was widespread variation in the amount of radiation that reached the phantom surgeon's eye among the various radiographic projections we studied. Without leaded glasses, the dose measured at the surgeon's lens varied more than 250-fold among these sixteen different views. In addition to protecting the surgeon's eye from the deleterious effects of radiation, the use of leaded glasses could permit an orthopaedist to perform fluoroscopic views on up to ten times more patients before reaching the annual dose limit of 20 mSv of radiation to the eye recommended by the International Commission on Radiological Protection. Personal safety and adherence to limits of occupational radiation exposure should compel orthopaedists to wear leaded glasses for fluoroscopic procedures if other protective barriers are not in use. Leaded glasses are a powerful tool for reducing the orthopaedic surgeon's lens exposure to radiation during acquisition of common intraoperative fluoroscopic views.

Recommended treatment for urinary tract infection in pregnancy.

PubMed

Vercaigne, L M; Zhanel, G G

1994-02-01

To establish and recommend a therapeutic regimen for the treatment of urinary tract infection (UTI) in pregnancy based on the published studies. An English-language literature search employing MEDLINE, Index Medicus, and bibliographic reviews of the references obtained were searched (key terms: urinary tract infection, UTI, pregnancy, bacteriuria). All identified human studies dealing with bacteriuria or UTI in pregnancy were analyzed. Limited data are available regarding the appropriate antibiotic management of UTI in pregnancy. Single-dose cure rates with amoxicillin are approximately 80 percent. Trimethoprim/sulfamethoxazole provides cure rates of greater than 80 percent. Cephalosporins and nitrofurantoin produce variable results. We recommend separating pregnant subjects with UTI into two groups. Those with asymptomatic bacteriuria can be treated with a single dose of an antimicrobial to which the organism is susceptible. For those with symptomatic UTI, we recommend amoxicillin 500 mg tid for three days. Urine cultures should be repeated seven days following therapy to assess cure or failure. Well-designed studies need to be performed, comparing single-dose and three-day therapy for UTI in pregnancy.

American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance.

PubMed

Manchikanti, Laxmaiah; Abdi, Salahadin; Atluri, Sairam; Balog, Carl C; Benyamin, Ramsin M; Boswell, Mark V; Brown, Keith R; Bruel, Brian M; Bryce, David A; Burks, Patricia A; Burton, Allen W; Calodney, Aaron K; Caraway, David L; Cash, Kimberly A; Christo, Paul J; Damron, Kim S; Datta, Sukdeb; Deer, Timothy R; Diwan, Sudhir; Eriator, Ike; Falco, Frank J E; Fellows, Bert; Geffert, Stephanie; Gharibo, Christopher G; Glaser, Scott E; Grider, Jay S; Hameed, Haroon; Hameed, Mariam; Hansen, Hans; Harned, Michael E; Hayek, Salim M; Helm, Standiford; Hirsch, Joshua A; Janata, Jeffrey W; Kaye, Alan D; Kaye, Adam M; Kloth, David S; Koyyalagunta, Dhanalakshmi; Lee, Marion; Malla, Yogesh; Manchikanti, Kavita N; McManus, Carla D; Pampati, Vidyasagar; Parr, Allan T; Pasupuleti, Ramarao; Patel, Vikram B; Sehgal, Nalini; Silverman, Sanford M; Singh, Vijay; Smith, Howard S; Snook, Lee T; Solanki, Daneshvari R; Tracy, Deborah H; Vallejo, Ricardo; Wargo, Bradley W

2012-07-01

Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. ( good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. ( limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. ( good to fair) D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. ( good) 2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. ( good) B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient, to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. ( good) C) Stratify patients into one of the 3 risk categories - low, medium, or high risk. D) A pain management consultation, may assist non-pain physicians, if high-dose opioid therapy is utilized. ( fair) 3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. ( good) 4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. ( good) 5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. ( fair) B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. ( fair to limited) 6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. ( fair) 7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. ( fair for short-term effectiveness, limited for long-term effectiveness) B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. ( fair) C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. ( good) 8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. ( limited) B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. ( fair) 9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. ( fair) 10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. ( good) 11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. ( fair). The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Maintaining radiation exposures as low as reasonably achievable (ALARA) for dental personnel operating portable hand-held x-ray equipment.

PubMed

McGiff, Thomas J; Danforth, Robert A; Herschaft, Edward E

2012-08-01

Clinical experience indicates that newly available portable hand-held x-ray units provide advantages compared to traditional fixed properly installed and operated x-ray units in dental radiography. However, concern that hand-held x-ray units produce higher operator doses than fixed x-ray units has caused regulatory agencies to mandate requirements for use of hand-held units that go beyond those recommended by the manufacturer and can discourage the use of this technology. To assess the need for additional requirements, a hand-held x-ray unit and a pair of manikins were used to measure the dose to a simulated operator under two conditions: exposures made according to the manufacturer's recommendations and exposures made according to manufacturer's recommendation except for the removal of the x-ray unit's protective backscatter shield. Dose to the simulated operator was determined using an array of personal dosimeters and a pair of pressurized ion chambers. The results indicate that the dose to an operator of this equipment will be less than 0.6 mSv y⁻¹ if the device is used according to the manufacturer's recommendations. This suggests that doses to properly trained operators of well-designed, hand-held dental x-ray units will be below 1.0 mSv y⁻¹ (2% of the annual occupational dose limit) even if additional no additional operational requirements are established by regulatory agencies. This level of annual dose is similar to those reported as typical dental personnel using fixed x-ray units and appears to satisfy the ALARA principal for this class of occupational exposures.

Review of the safety and efficacy of vitamin A supplementation in the treatment of children with severe acute malnutrition.

PubMed

Iannotti, Lora L; Trehan, Indi; Manary, Mark J

2013-09-12

World Health Organization (WHO) guidelines recommend for children with severe acute malnutrition (SAM), high-dose vitamin A (VA) supplements be given on day 1 of admission, and on days 2 and 14 in the case of clinical signs of vitamin A deficiency (VAD). Daily low-dose VA follows, delivered in a premix added to F-75 and F-100. This study aimed to systematically review the evidence for safety and effectiveness of high-dose VA supplementation (VAS) in treatment of children with SAM. A comprehensive literature review was undertaken for all relevant randomized controlled trials (RCT) and observational studies from 1950 to 2012. Studies identified for full review were evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology using a set of pre-defined criteria: indirectness; inconsistency; imprecision; and study limitations. A quality rating of high, moderate, or low was then assigned to each study, and only those attaining moderate to high were considered in making recommendations. Of the 2072 abstracts screened, 38 met criteria for full review, and 20 were rated moderate to high quality. Only one study replicated the WHO VA protocol in children with SAM. Indirectness was a critical limitation, as studies were not exclusive to children with SAM. There was inconsistency across trials for definitions of malnutrition, morbidities, and ages studied; and imprecision arising from sub-group analyses and small sample sizes. Evidence showed improved outcomes associated with low-dose compared to high-dose VAS, except in cases presenting with signs of VAD, measles, and severe diarrhea or shigellosis. Adverse outcomes related to respiratory infection, diarrhea, and growth were associated with high-dose VAS in children who were predominantly adequately nourished. No adverse effects of the high dose were found in children with SAM in the trial that replicated the WHO VA guideline. This is the first systematic review of the safety and efficacy of high-dose VAS in treatment of SAM. We recommend a low-dose VAS regimen for children with SAM, except in cases presenting with measles, severe diarrhea (shigellosis), and any indication of VAD. Further research is needed in exclusively malnourished children and to explore alternate delivery strategies.

Soil contamination standards for protection of personnel

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

Rittmann, P.D.

1998-04-16

The objective of this report is to recommend soil contamination levels that will ensure that radionuclide intakes by unprotected workers are likely to give internal doses below selected dose limits during the working year. The three internal dose limits are 1, 100, and 500 mrem per year. In addition, photon, beta, and alpha instrument readings are estimated for these soil concentration limits. Two exposure pathways are considered: the first is inhalation of resuspended dust and the second is ingestion of trace amounts of soil. In addition, radioactive decay and ingrowth of progeny during the year of exposure is included. Externalmore » dose from the soil contamination is not included because monitoring and control of external exposures is carried out independently from internal exposures, which are the focus of this report. The methods used are similar to those used by Carbaugh and Bihl (1993) to set bioassay criteria for such workers.« less

Canadian supportive care recommendations for the management of neutropenia in patients with cancer.

PubMed

Kouroukis, C T; Chia, S; Verma, S; Robson, D; Desbiens, C; Cripps, C; Mikhael, J

2008-01-01

Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest risk of neutropenic complications. Colony-stimulating factors (csfs) such as filgrastim and pegfilgrastim can effectively attenuate most of the neutropenic consequences of chemotherapy, improve the ability to continue chemotherapy on the planned schedule, and minimize the risk of febrile neutropenia and infectious morbidity and mortality. The present consensus statement reviews the use of csfs in the management of neutropenia in patients with cancer and sets out specific recommendations based on published international guidelines tailored to the specifics of the Canadian practice landscape. We review existing international guidelines, the indications for primary and secondary prophylaxis, the importance of maintaining dose intensity, and the use of csfs in leukemia, stem-cell transplantation, and radiotherapy. Specific disease-related recommendations are provided related to breast cancer, non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancer. Finally, csf dosing and schedules, duration of therapy, and associated acute and potential chronic toxicities are examined.

Occupational radiation dose to eyes from endoscopic retrograde cholangiopancreatography procedures in light of the revised eye lens dose limit from the International Commission on Radiological Protection.

PubMed

O'Connor, U; Gallagher, A; Malone, L; O'Reilly, G

2013-02-01

Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure that combines the use of X-ray fluoroscopy and endoscopy for examination of the bile duct. Published data on ERCP doses are limited, including staff eye dose from ERCP. Occupational eye doses are of particular interest now as the International Commission on Radiological Protection (ICRP) has recommended a reduction in the dose limit to the lens of the eye. The aim of this study was to measure occupational eye doses obtained from ERCP procedures. A new eye lens dosemeter (EYE-D(™), Radcard, Krakow, Poland) was used to measure the ERCP eye dose, H(p)(3), at two endoscopy departments in Ireland. A review of radiation protection practice at the two facilities was also carried out. The mean equivalent dose to the lens of the eye of a gastroenterologist is 0.01 mSv per ERCP procedure with an undercouch X-ray tube and 0.09 mSv per ERCP procedure with an overcouch X-ray tube. Staff eye dose normalised to patient kerma area product is also presented. Staff eye doses in ERCP have the potential to exceed the revised ICRP limit of 20 mSv per annum when an overcouch X-ray tube is used. The EYE-D dosemeter was found to be a convenient method for measuring lens dose. Eye doses in areas outside of radiology departments should be kept under review, particularly in light of the new ICRP eye dose limit. Occupational eye lens doses from ERCP procedures have been established using a new commercially available dedicated H(p)(3) dosemeter.

Phase I clinical and pharmacokinetic study of kahalalide F administered weekly as a 1-hour infusion to patients with advanced solid tumors.

PubMed

Pardo, Beatriz; Paz-Ares, Luis; Tabernero, Josep; Ciruelos, Eva; García, Margarita; Salazar, Ramón; López, Ana; Blanco, María; Nieto, Antonio; Jimeno, José; Izquierdo, Miguel Angel; Trigo, José Manuel

2008-02-15

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available. Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 microg/m(2), and dose escalation proceeded based on the worst toxicity found in the previous cohort. Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 microg/m(2). Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 microg/m(2), and the recommended dose for phase II studies was 650 microg/m(2). No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent. The maximum tolerated dose was 800 microg/m(2). Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 microg/m(2) was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.

Emergency department patient knowledge concerning acetaminophen (paracetamol) in over-the-counter and prescription analgesics.

PubMed

Fosnocht, D; Taylor, J R; Caravati, E M

2008-04-01

This study was designed to evaluate patient knowledge of the acetaminophen (paracetamol) content of commonly used pain medications and the maximum daily recommended dose of acetaminophen. A prospective, convenience sample of emergency department patients were enrolled. Data were recorded using a standardised questionnaire over 4 months. 1009 patients were enrolled. 492 patients (49%) did not know if Tylenol contained acetaminophen (paracetamol). The majority (66-90%) of patients did not know if Lortab, Vicodin, Percocet, non-aspirin pain reliever, ibuprofen, Motrin, or Advil contained acetaminophen. 568 patients (56%) reported not knowing the maximum daily dose of acetaminophen and only 71 patients (7%) reported the correct daily dose. Patient knowledge of the acetaminophen content of commonly used analgesic medications and its maximum recommended daily dose is limited. This may contribute to unintentional repeated supratherapeutic ingestion (RSTI) of acetaminophen, or overdose.

Dose estimation of eye lens for interventional procedures in diagnosis

NASA Astrophysics Data System (ADS)

Liu, Yu-Rong; Huang, Chia-Yu; Hsu, Ching-Han; Hsu, Fang-Yuh

2017-11-01

The International Commission on Radiological Protection (ICRP) recommended that the equivalent dose limit for the lens of the eye be decreased from 150 mSv/y (ICRP, 2007) to 20 mSv/y averaged over five years (ICRP, 2011). How to accurately measure the eye-lens dose has, therefore, been an issue of interest recently. Interventional radiologists are at a higher risk of radiation-induced eye injury, such as cataracts, than all other occupational radiation workers. The main objective of this study is to investigate the relationship between the doses to the eye lenses of interventional radiologists measured by different commercial eye-lens dosimeters. This study measured a reference eye-lens dose, which involved placing thermoluminescent dosimeter (TLD) chips at the surface of the eye of the Rando Phantom, and the TLD chips were covered by a 3-mm-thick tissue-equivalent bolus. Commercial eye-lens dosimeters, such as a headband dosimeter and standard personnel dose badges, were placed at the positions recommended by the manufacturers. The results show that the personnel dose badge is not an appropriate dosimeter for evaluating eye-lens dose. Dose deviations for different dosimeters are discussed and presented in this study.

Estimation of eye lens doses received by pediatric interventional cardiologists.

PubMed

Alejo, L; Koren, C; Ferrer, C; Corredoira, E; Serrada, A

2015-09-01

Maximum Hp(0.07) dose to the eye lens received in a year by the pediatric interventional cardiologists has been estimated. Optically stimulated luminescence dosimeters were placed on the eyes of an anthropomorphic phantom, whose position in the room simulates the most common irradiation conditions. Maximum workload was considered with data collected from procedures performed in the Hospital. None of the maximum values obtained exceed the dose limit of 20 mSv recommended by ICRP. Copyright © 2015 Elsevier Ltd. All rights reserved.

Occupational radiation dose to eyes from interventional radiology procedures in light of the new eye lens dose limit from the International Commission on Radiological Protection

PubMed Central

Walsh, C; Gallagher, A; Dowling, A; Guiney, M; Ryan, J M; McEniff, N; O'Reilly, G

2015-01-01

Objective: In 2011, the International Commission on Radiological Protection (ICRP) recommended a substantial reduction in the equivalent dose limit for the lens of the eye, in line with a reduced threshold of absorbed dose for radiation-induced cataracts. This is of particular relevance in interventional radiology (IR) where it is well established that staff doses can be significant, however, there is a lack of data on IR eye doses in terms of Hp(3). Hp(3) is the personal dose equivalent at a depth of 3 mm in soft tissue and is used for measuring lens dose. We aimed to obtain a reliable estimate of eye dose to IR operators. Methods: Lens doses were measured for four interventional radiologists over a 3-month period using dosemeters specifically designed to measure Hp(3). Results: Based on their typical workloads, two of the four interventional radiologists would exceed the new ICRP dose limit with annual estimated doses of 31 and 45 mSv to their left eye. These results are for an “unprotected” eye, and for IR staff who routinely wear lead glasses, the dose beneath the glasses is likely to be significantly lower. Staff eye dose normalized to patient kerma–area product and eye dose per procedure have been included in the analysis. Conclusion: Eye doses to IR operators have been established using a dedicated Hp(3) dosemeter. Estimated annual doses have the potential to exceed the new ICRP limit. Advances in knowledge: We have estimated lens dose to interventional radiologists in terms of Hp(3) for the first time in an Irish hospital setting. PMID:25761211

Development of a point-of-care HIV/AIDS medication dosing support system using the Android mobile platform.

PubMed

Sadasivam, Rajani S; Gathibandhe, Vaibhav; Tanik, Murat M; Willig, James H

2012-06-01

Medication dosing errors can greatly reduce HIV treatment effectiveness as incorrect dosing leads to drug resistance and non-adherence. In order to dose correctly, HIV therapy providers must balance several patient characteristics such as renal functions and weight. In developing countries and other resource-limited settings, dosing errors are more likely because treatment is provided by mid-level providers with only basic training in HIV therapy. These providers also typically lack electronic tools informing medical decisions. Widespread adoption of mobile phones in developing nations offers an opportunity to implement a point-of-care system to help providers reduce dosing errors. We discuss the development of the mHIV-Dr system prototype using the new Android mobile platform. mHIV-Dr is being designed to provide dosing recommendations for front-line providers in developing countries. We also discuss the additional challenges in the implementation of the mHIV-Dr system in a resource limited setting.

Canadian guideline for safe and effective use of opioids for chronic noncancer pain

PubMed Central

Kahan, Meldon; Mailis-Gagnon, Angela; Wilson, Lynn; Srivastava, Anita

2011-01-01

Abstract Objective To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group. Quality of evidence Researchers for the guideline conducted a systematic review of the literature on the effectiveness and safety of opioids for chronic noncancer pain, and drafted a series of recommendations. A panel of 49 clinicians from across Canada reviewed the draft and achieved consensus on 24 recommendations. Main message Screening for addiction risk is recommended before prescribing opioids. Weak opioids (codeine and tramadol) are recommended for mild to moderate pain that has not responded to first-line treatments. Oxycodone, hydromorphone, and morphine can be tried in patients who have not responded to weaker opioids. A low initial dose and slow upward titration is recommended, with patient education and close monitoring. Physicians should watch for the development of complications such as sleep apnea. The optimal dose is one which improves function or decreases pain ratings by at least 30%. For by far most patients, the optimal dose will be well below a 200-mg morphine equivalent dose per day. Tapering is recommended for patients who have not responded to an adequate opioid trial. Conclusion Opioids play an important role in the management of chronic noncancer pain, but careful prescribing is needed to limit potential harms. The new Canadian guideline provides much-needed guidance to help physicians achieve a balance between optimal pain control and safety. PMID:22084455

Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 1: general population.

PubMed

Kahan, Meldon; Mailis-Gagnon, Angela; Wilson, Lynn; Srivastava, Anita

2011-11-01

To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group. Researchers for the guideline conducted a systematic review of the literature on the effectiveness and safety of opioids for chronic noncancer pain, and drafted a series of recommendations. A panel of 49 clinicians from across Canada reviewed the draft and achieved consensus on 24 recommendations. Screening for addiction risk is recommended before prescribing opioids. Weak opioids (codeine and tramadol) are recommended for mild to moderate pain that has not responded to first-line treatments. Oxycodone, hydromorphone, and morphine can be tried in patients who have not responded to weaker opioids. A low initial dose and slow upward titration is recommended, with patient education and close monitoring. Physicians should watch for the development of complications such as sleep apnea. The optimal dose is one which improves function or decreases pain ratings by at least 30%. For by far most patients, the optimal dose will be well below a 200-mg morphine equivalent dose per day. Tapering is recommended for patients who have not responded to an adequate opioid trial. Opioids play an important role in the management of chronic noncancer pain, but careful prescribing is needed to limit potential harms. The new Canadian guideline provides much-needed guidance to help physicians achieve a balance between optimal pain control and safety.

Implications of the implementation of the revised dose limit to the lens of the eye: the view of IRPA professionals.

PubMed

Broughton, J; Cantone, M C; Ginjaume, M; Shah, B; Czarwinski, R

2015-06-01

In April 2011, the International Commission on Radiological Protection issued a statement on reduction of the equivalent dose limits for the lens of the eye, and strongly recommended its consideration in the revision of the International Atomic Energy Agency's International Basic Safety Standards on Radiation Protection. The reduced dose limit was incorporated in the final version of the Basic Safety Standards. As significant concern was expressed by radiation protection professionals worldwide, the International Radiation Protection Association (IRPA) established a task group to assess the impact of implementation of the revised dose limit for the lens of the eye for occupational exposure. IRPA Associate Societies (ASs) were asked for their views using a questionnaire addressing three topics: implications for dosimetry, implications for methods of protection, and wider implications. The responses received indicate various methods of approach and express different points of view, reflecting nuances of particular ASs or specific professional groups. Topic experts nominated by ASs were selected to assist with collation of responses, and a report was produced by the task group. Conclusions were drawn on the three issues, including potential cost implications. A number of recommendations were drawn from the responses received including: the request for more understanding about the relationship between exposure of the lens of the eye and cataract formation, and further guidance to assist implementation; the importance of economic and social considerations when introducing the limits into national regulations; the need to propose or define procedures related to employment of people with existing or pre-cataract conditions; and the practical aspects relating to dosimetry and protective equipment. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Comparison of selected dose calculation algorithms in radiotherapy treatment planning for tissues with inhomogeneities

NASA Astrophysics Data System (ADS)

Woon, Y. L.; Heng, S. P.; Wong, J. H. D.; Ung, N. M.

2016-03-01

Inhomogeneity correction is recommended for accurate dose calculation in radiotherapy treatment planning since human body are highly inhomogeneous with the presence of bones and air cavities. However, each dose calculation algorithm has its own limitations. This study is to assess the accuracy of five algorithms that are currently implemented for treatment planning, including pencil beam convolution (PBC), superposition (SP), anisotropic analytical algorithm (AAA), Monte Carlo (MC) and Acuros XB (AXB). The calculated dose was compared with the measured dose using radiochromic film (Gafchromic EBT2) in inhomogeneous phantoms. In addition, the dosimetric impact of different algorithms on intensity modulated radiotherapy (IMRT) was studied for head and neck region. MC had the best agreement with the measured percentage depth dose (PDD) within the inhomogeneous region. This was followed by AXB, AAA, SP and PBC. For IMRT planning, MC algorithm is recommended for treatment planning in preference to PBC and SP. The MC and AXB algorithms were found to have better accuracy in terms of inhomogeneity correction and should be used for tumour volume within the proximity of inhomogeneous structures.

Radiation and cataract.

PubMed

Rehani, Madan M; Vano, Eliseo; Ciraj-Bjelac, Olivera; Kleiman, Norman J

2011-09-01

When this paper was about to go to press, the International Commission on Radiological Protection released a statement recommending a change in the threshold dose for the eye lens and dose limits for eye for occupationally exposed persons. It is clear that the earlier published threshold for radiation cataract is no longer valid. Epidemiological studies among Chernobyl clean-up workers, A bomb survivors, astronauts, residents of contaminated buildings, radiological technicians and recent surveys of staff in interventional rooms indicate that there is an increased incidence of lens opacities at doses below 1 Gy. Nevertheless, eye lens dosimetry is at a primitive stage and needs to be developed further. Despite uncertainties concerning dose threshold and dosimetry, it is possible to significantly reduce the risk of radiation cataract through the use of appropriate eye protection. By increasing awareness among those at risk and better adoption and increased usage of protective measures, radiation cataract can become preventable despite lowering of dose limits.

Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer.

PubMed

Marshall, John; Shapiro, Geoffrey I; Uttenreuther-Fischer, Martina; Ould-Kaci, Mahmoud; Stopfer, Peter; Gordon, Michael S

2013-02-01

To determine the maximum tolerated dose (MTD), safety and anti-tumor activity of afatinib combined with docetaxel in advanced cancer. The MTD was determined from dose-limiting toxicities in the first cycle. Thirty-one patients received 10, 20 and 30 mg oral afatinib, plus 60 and 75 mg/m(2) intravenous docetaxel (six cohorts; 3-week cycles). The MTD of afatinib was 20 mg/day (days 2-21) with 75 mg/m(2) docetaxel (day 1). Dose-limiting toxicities were grade 3/4 diarrhea (n = 3) and febrile neutropenia (n = 6). Most frequently occurring adverse events were diarrhea, neutropenia and rash. Disease stabilization occurred in 14 patients. Afatinib 20 mg/day plus docetaxel was suboptimal and the study could not yield Phase II dose recommendations. The combination resulted in a manageable safety profile.

Regulating exposure of the lens of the eye to ionising radiations.

PubMed

Thorne, M C

2012-06-01

The International Commission on Radiological Protection (ICRP) has reviewed recent epidemiological evidence suggesting that, for the lens of the eye, the threshold in absorbed dose for the induction of deleterious health effects is about 0.5 Gy. On this basis, the Commission recommends that for occupational exposure in planned exposure situations, the equivalent dose limit for the lens of the eye should be 20 mSv in a year, averaged over defined periods of 5 yr, with exposure not exceeding 50 mSv in any single year. This paper summarises the data that have been taken into account by the ICRP and critically examines whether the proposed downward revision of the dose limit is justified. Overall, it is concluded that the accumulating radiobiological and epidemiological evidence makes it more appropriate to treat cataract induction as a stochastic rather than a deterministic effect. Within this framework, it is illogical to have the same dose limit for the lens of the eye as for the whole body irradiated uniformly. This could be addressed either by removing the special dose limit for the lens of the eye, assigning it an appropriate tissue weighting factor and including it in the computation of the effective dose, or through a composite approach involving the use of a tissue weighting factor for effective dose computations together with a special limit on the equivalent dose to the lens of the eye to ensure that no individual was subject to an unacceptably high risk of induction of clinically significant cataracts.

Phase I trial of S-1 every other day in combination with gemcitabine/cisplatin for inoperable biliary tract cancer.

PubMed

Uwagawa, Tadashi; Sakamoto, Taro; Abe, Kyohei; Okui, Norimitsu; Hata, Daigo; Shiba, Hiroaki; Futagawa, Yasuro; Aiba, Keisuke; Yanaga, Katsuhiko

2015-01-01

To date, gemcitabine-based or fluoropyrimidine-based regimens are recommended for unresectable advanced biliary tract cancer. Then, we conducted a phase I study of gemcitabine/cisplatin and S-1 that is an oral fluoropyrimidine. The aim of this study was to determine the dose-limiting toxicity (DLT), maximum-tolerated dose, and a recommended phase II dose of S-1. Response was assessed as a secondary endpoint. Patients who have been diagnosed with unresectable or postoperative recurrent biliary tract cancer received cisplatin (25 mg/m² i.v. for 120 min) followed by gemcitabine (1,000 mg/m² i.v. for 30 min) on days 1 and 8, and oral S-1 on alternate days; this regimen was repeated at 21-day intervals. A standard '3 + 3' phase I dose-escalation design was adopted. This study was registered with University hospital Medical Information Network (UMIN) Center in Japan, number UMIN000008415. Twelve patients were evaluable in this study. No patients developed DLTs. Recommended dose of S-1 was 80 (<1.25 m²), 100 (1.25 ≤ 1.5 m²), and 120 mg (1.5 m²≥) per day. One patient could achieve conversion to curative surgery. This phase I study was performed safely and demonstrated encouraging response.

Pediatric patient and staff dose measurements in barium meal fluoroscopic procedures

NASA Astrophysics Data System (ADS)

Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Porto, L. E.; Ledesma, J. A.; Nascimento, E. X.; Legnani, A.; Andrade, M. E. A.; Khoury, H. J.

2015-11-01

This study investigates patient and staff dose measurements in pediatric barium meal series fluoroscopic procedures. It aims to analyze radiographic techniques, measure the air kerma-area product (PKA), and estimate the staff's eye lens, thyroid and hands equivalent doses. The procedures of 41 patients were studied, and PKA values were calculated using LiF:Mg,Ti thermoluminescent dosimeters (TLDs) positioned at the center of the patient's upper chest. Furthermore, LiF:Mg,Cu,P TLDs were used to estimate the equivalent doses. The results showed a discrepancy in the radiographic techniques when compared to the European Commission recommendations. Half of the results of the analyzed literature presented lower PKA and dose reference level values than the present study. The staff's equivalent doses strongly depends on the distance from the beam. A 55-cm distance can be considered satisfactory. However, a distance decrease of ~20% leads to, at least, two times higher equivalent doses. For eye lenses this dose is significantly greater than the annual limit set by the International Commission on Radiological Protection. In addition, the occupational doses were found to be much higher than in the literature. Changing the used radiographic techniques to the ones recommended by the European Communities, it is expected to achieve lower PKA values ​​and occupational doses.

Dosimetric quality, accuracy, and deliverability of modulated radiotherapy treatments for spinal metastases

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

Kairn, Tanya, E-mail: t.kairn@gmail.com; School of Chemistry, Physics, and Mechanical Engineering, Queensland University of Technology, Brisbane; Papworth, Daniel

2016-10-01

Cancer often metastasizes to the vertebra, and such metastases can be treated successfully using simple, static posterior or opposed-pair radiation fields. However, in some cases, including when re-irradiation is required, spinal cord avoidance becomes necessary and more complex treatment plans must be used. This study evaluated 16 sample intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans designed to treat 6 typical vertebral and paraspinal volumes using a standard prescription, with the aim of investigating the advantages and limitations of these treatment techniques and providing recommendations for their optimal use in vertebral treatments. Treatment plan quality and beammore » complexity metrics were evaluated using the Treatment And Dose Assessor (TADA) code. A portal-imaging–based quality assurance (QA) system was used to evaluate treatment delivery accuracy, and radiochromic film measurements were used to provide high-resolution verification of treatment plan dose accuracy, especially in the steep dose gradient regions between each vertebral target and spinal cord. All treatment modalities delivered approximately the same doses and the same levels of dose heterogeneity to each planning target volume (PTV), although the minimum PTV doses in the vertebral plans were substantially lower than the prescription, because of the requirement that the plans meet a strict constraint on the dose to the spinal cord and cord planning risk volume (PRV). All plans met required dose constraints on all organs at risk, and all measured PTV-cord dose gradients were steeper than planned. Beam complexity analysis suggested that the IMRT treatment plans were more deliverable (less complex, leading to greater QA success) than the VMAT treatment plans, although the IMRT plans also took more time to deliver. The accuracy and deliverability of VMAT treatment plans were found to be substantially increased by limiting the number of monitor units (MU) per beam at the optimization stage, and thereby limiting beam modulation complexity. The VMAT arcs that were optimized with MU limitation had higher QA pass rates as well as higher modulation complexity scores (less complexity), lower modulation indices (less modulation), lower MU per beam, larger beam segments, and fewer small apertures than the VMAT arcs that were optimized without MU limitation. It is recommended that VMAT treatments for vertebral volumes, where the PTV abuts or surrounds the spinal cord, should be optimized with MU limitation. IMRT treatments may be preferable to the VMAT treatments, for dosimetry and deliverability reasons, but may be inappropriate for some patients because of their increased treatment delivery time.« less

Low-molecular-weight heparin use in the obese, elderly, and in renal insufficiency.

PubMed

Clark, N P

2008-01-01

Superior bioavailability and simple weight-based dosing have made low-molecular-weight heparins (LMWH) the preferred agents for treatment and prevention of venous thromboembolism (VTE) for most indications. Despite improved pharmacokinetics, there remain populations where appropriate LMWH dose intensity and frequency are open to question. Obese patients have a lower proportion of lean body mass as a percentage of total body weight. As a result, LMWH dosing based on total body weight could cause supra-therapeutic anticoagulation. Elderly patients also have less lean body mass in addition to a higher incidence of age-related renal disease and increased risk of bleeding. Renal insufficiency presents a risk of LMWH accumulation as well as increased risk of bleeding. Among LMWH products, only dalteparin labeling recommends a maximum dose. Prospective data call into question the validity of this dose limitation. Additionally, because obese patients are already at higher risk of VTE recurrence, they may be particularly sensitive to subtherapeutic anticoagulation. Prospective data evaluating LMWH use in elderly patients have been limited to in-patient treatment. Few recommendations can be made in this population other than close monitoring. Renal insufficiency is a risk for bleeding during LMWH use. Available evidence supports the potential for enoxaparin accumulation, but not tinzaparin. Enoxaparin dose adjustment, either empiric or based on anti-Xa monitoring, has insufficient data to support widespread implementation. Unfractionated heparin is not reliant on renal elimination and is a sensible option for VTE treatment in patients with a creatinine clearance<30 ml/min.

Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?

PubMed

Oztekin, Osman; Kalay, Salih; Tezel, Gonul; Akcakus, Mustafa; Oygur, Nihal

2013-08-01

We investigated whether the recommended phenobarbital loading dose of 15-20 mg/kg with maintenance of 3-4 mg/kg/day can safely be administered to very low birth weight preterm newborns with seizures. Twenty-four convulsive preterms of <1,500 g were enrolled in the study. Phenobarbital was administered intravenously with a loading dose of 15 mg/kg in approximately 10-15 min. After 24 h, the maintenance dose of 3 mg/kg/day was administered as a single injection. Blood samples were obtained 2, 24, 48, 72, and 96 h after the phenobarbital loading dose was administered, immediately before the next phenobarbital dose was injected. None of the cases had plasma phenobarbital concentrations above the therapeutic upper limit of 40 μg/mL on the 2nd hour; one case (4.7%), on the 24th; 11 cases (45.8%), on the 48th; 15 cases (62.5%), on the 72nd; and 17 cases (70.8%), on the 96th hour. A negative correlation was detected between the serum concentrations of phenobarbital and gestational age on the 72th (p, 0.036; r, -0.608) and 96th hour (p, 0.043; r, -0.769). We suggest that particular attention should be done while administering phenobarbital in preterms, as blood levels of phenobarbital are higher than the reference ranges that those are often reached with the recommended doses in these groups of babies.

Assessment of the occupational eye lens dose for clinical staff in interventional radiology, cardiology and neuroradiology.

PubMed

Omar, Artur; Kadesjö, Nils; Palmgren, Charlotta; Marteinsdottir, Maria; Segerdahl, Tony; Fransson, Annette

2017-03-20

In accordance with recommendations by the International Commission on Radiological Protection, the current European Basic Safety Standards has adopted a reduced occupational eye lens dose limit of 20 mSv yr -1 . The radiation safety implications of this dose limit is of concern for clinical staff that work with relatively high dose x-ray angiography and interventional radiology. Presented in this work is a thorough assessment of the occupational eye lens dose based on clinical measurements with active personal dosimeters worn by staff during various types of procedures in interventional radiology, cardiology and neuroradiology. Results are presented in terms of the estimated equivalent eye lens dose for various medical professions. In order to compare the risk of exceeding the regulatory annual eye lens dose limit for the widely different clinical situations investigated in this work, the different medical professions were separated into categories based on their distinct work pattern: staff that work (a) regularly beside the patient, (b) in proximity to the patient and (c) typically at a distance from the patient. The results demonstrate that the risk of exceeding the annual eye lens dose limit is of concern for staff category (a), i.e. mainly the primary radiologist/cardiologist. However, the results also demonstrate that the risk can be greatly mitigated if radiation protection shields are used in the clinical routine. The results presented in this work cover a wide range of clinical situations, and can be used as a first indication of the risk of exceeding the annual eye lens dose limit for staff at other medical centres.

Radiation Protection Quantities for Near Earth Environments

NASA Technical Reports Server (NTRS)

Clowdsley, Martha S.; Wilson, John W.; Kim, Myung-Hee; Anderson, Brooke M.; Nealy, John E.

2004-01-01

As humans travel beyond the protection of the Earth's magnetic field and mission durations grow, risk due to radiation exposure will increase and may become the limiting factor for such missions. Here, the dosimetric quantities recommended by the National Council on Radiation Protection and Measurements (NCRP) for the evaluation of health risk due to radiation exposure, effective dose and gray-equivalent to eyes, skin, and blood forming organs (BFO), are calculated for several near Earth environments. These radiation protection quantities are evaluated behind two different shielding materials, aluminum and polyethylene. Since exposure limits for missions beyond low Earth orbit (LEO) have not yet been defined, results are compared to limits recommended by the NCRP for LEO operations.

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits

PubMed Central

Cox, Daniel T. C.; Shanahan, Danielle F.; Hudson, Hannah L.; Fuller, Richard A.; Anderson, Karen; Hancock, Steven; Gaston, Kevin J.

2017-01-01

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare. PMID:28208789

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits.

PubMed

Cox, Daniel T C; Shanahan, Danielle F; Hudson, Hannah L; Fuller, Richard A; Anderson, Karen; Hancock, Steven; Gaston, Kevin J

2017-02-09

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare.

Status of NCRP Scientific Committee 1-23 Commentary on Guidance on Radiation Dose Limits for the Lens of the Eye.

PubMed

Dauer, Lawrence T; Ainsbury, Elizabeth A; Dynlacht, Joseph; Hoel, David; Klein, Barbara E K; Mayer, Don; Prescott, Christina R; Thornton, Raymond H; Vano, Eliseo; Woloschak, Gayle E; Flannery, Cynthia M; Goldstein, Lee E; Hamada, Nobuyuki; Tran, Phung K; Grissom, Michael P; Blakely, Eleanor A

2016-02-01

Previous National Council on Radiation Protection and Measurements (NCRP) publications have addressed the issues of risk and dose limitation in radiation protection and included guidance on specific organs and the lens of the eye. NCRP decided to prepare an updated commentary intended to enhance the previous recommendations provided in earlier reports. The NCRP Scientific Committee 1-23 (SC 1-23) is charged with preparing a commentary that will evaluate recent studies on the radiation dose response for the development of cataracts and also consider the type and severity of the cataracts as well as the dose rate; provide guidance on whether existing dose limits to the lens of the eye should be changed in the United States; and suggest research needs regarding radiation effects on and dose limits to the lens of the eye. A status of the ongoing work of SC 1-23 was presented at the Annual Meeting, "Changing Regulations and Radiation Guidance: What Does the Future Hold?" The following represents a synopsis of a few main points in the current draft commentary. It is likely that several changes will be forthcoming as SC 1-23 responds to subject matter expert review and develops a final document, expected by mid 2016.

Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors.

PubMed

Moore, Kathleen N; Borghaei, Hossein; O'Malley, David M; Jeong, Woondong; Seward, Shelly M; Bauer, Todd M; Perez, Raymond P; Matulonis, Ursula A; Running, Kelli L; Zhang, Xiaoyan; Ponte, Jose F; Ruiz-Soto, Rodrigo; Birrer, Michael J

2017-08-15

Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate that selectively targets folate receptor α (FRα). In this phase 1 dose-escalation study, the authors investigated IMGN853 in patients with FRα-positive solid tumors. Patients received IMGN853 on day 1 of a 21-day cycle (once every 3 weeks dosing), with cycles repeated until patients experienced dose-limiting toxicity or progression. Dose escalation commenced in single-patient cohorts for the first 4 planned dose levels and then followed a standard 3 + 3 scheme. The primary objectives were to determine the maximum tolerated dose and the recommended phase 2 dose. Secondary objectives were to determine safety and tolerability, to characterize the pharmacokinetic profile, and to describe preliminary clinical activity. In total, 44 patients received treatment at doses escalating from 0.15 to 7.0 mg/kg. No meaningful drug accumulation was observed with the dosing regimen of once every 3 weeks. The most common treatment-related adverse events were fatigue, blurred vision, and diarrhea, the majority of which were grade 1 or 2. The dose-limiting toxicities observed were grade 3 hypophosphatemia (5.0 mg/kg) and grade 3 punctate keratitis (7.0 mg/kg). Two patients, both of whom were individuals with epithelial ovarian cancer, achieved confirmed tumor responses according to Response Evaluation Criteria in Solid Tumors 1.1, and each was a partial response. IMGN853 demonstrated a manageable safety profile and encouraging preliminary clinical activity, particularly in patients with ovarian cancer. The results establish a recommended phase 2 dosing of 6.0 mg/kg (based on adjusted ideal body weight) once every 3 weeks. Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:3080-7. © 2017 American Cancer Society. © 2017 American Cancer Society.

Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose (MTD) in Future Studies.

PubMed

Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

2015-07-01

High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum tolerated dose (MTD), although this dose selection strategy has not been critically evaluated. We analyzed the body weight gains (BWGs), mortality, and tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at BioReliance. Based on our analysis, it is evident that the MTD was exceeded at the high and/or mid-doses in several studies. The incidence of tumors in high doses was lower when compared to the low and mid-doses of both sexes. Thus, we recommend that the high dose in male mice should not exceed one-half of the estimated MTD (EMTD), as it is currently chosen, and the next dose should be one-fourth of the EMTD. Because females were less sensitive to decrements in BWG, the high dose in female mice should not exceed two-third of EMTD and the next dose group should be one-third of EMTD. If needed, a third dose group should be set at one-eighth EMTD in males and one-sixth EMTD in females. In addition, for compounds that do not show toxicity in the range finding studies, a limit dose should be applied for the 26-week carcinogenicity studies. © 2014 by The Author(s).

Phase I study of 6-diazo-5-oxo-L-norleucine (DON).

PubMed

Sklaroff, R B; Casper, E S; Magill, G B; Young, C W

1980-01-01

We conducted a phase I study of 6-diazo-5-oxo-L-norleucine given iv on a twice weekly schedule. Twenty-six evaluable patients received 31 courses of the drug. Doses ranged from 100 to 500 mg/m2. Nausea with vomiting was the dose-limiting toxic effect, transient thrombocytopenia was seen frequently, and mucositis occurred in 39% of the patients. No definite therapeutic responses were observed in 18 patients with measurable lesions. The recommended dose for phase II studies is 200-300 mg/m2 iv twice weekly.

Determination of naturally radioactive elements in chalk sticks by means of gamma spectroscopy

NASA Astrophysics Data System (ADS)

Abd El-Wahab, Magda; Morsy, Zeinab; El-Faramawy, Nabil

2010-04-01

The radiation hazards due to ingestion of chalkboard dust were investigated. Sixteen samples from three different origin fabricates were used. The estimation of radiation hazard indices were based on the evaluation of the concentration activities of the natural radionuclides 238U, 232Th and 40K. The radium equivalent activity, external hazard index, internal hazard index and the annual dose equivalent associated with the radionuclides were calculated and compared with international recommended values to assess the radiation hazard. The values of internal and external radiation hazard indices were found to be less than unity. The annual effective dose rate obtained, E eff, and the annual gonadal dose equivalent (AGDE) are found to be less than the limit of the doses recommended by the International Commission on Radiological Protection for the general public. The analytical results show that besides the main calcium content, some toxic elements, S, Mo and Pb and Ni and Pb, in the Egyptian and imported chalk stocks, respectively, existed.

Determination of naturally radioactive elements in chalk sticks by means of gamma spectroscopy

NASA Astrophysics Data System (ADS)

El-Wahab, Magda Abd; Morsy, Zeinab; El-Faramawy, Nabil

The radiation hazards due to ingestion of chalkboard dust were investigated. Sixteen samples from three different origin fabricates were used. The estimation of radiation hazard indices were based on the evaluation of the concentration activities of the natural radionuclides 238U, 232Th and 40K. The radium equivalent activity, external hazard index, internal hazard index and the annual dose equivalent associated with the radionuclides were calculated and compared with international recommended values to assess the radiation hazard. The values of internal and external radiation hazard indices were found to be less than unity. The annual effective dose rate obtained, Eeff, and the annual gonadal dose equivalent (AGDE) are found to be less than the limit of the doses recommended by the International Commission on Radiological Protection for the general public. The analytical results show that besides the main calcium content, some toxic elements, S, Mo and Pb and Ni and Pb, in the Egyptian and imported chalk stocks, respectively, existed.

A Phase I Trial and Pharmacokinetic Study of Aflibercept (VEGF Trap) in Children with Refractory Solid Tumors: A Children’s Oncology Group Phase I Consortium Report

PubMed Central

Bender, Julia Glade; Blaney, Susan M.; Borinstein, Scott; Reid, Joel M.; Baruchel, Sylvain; Ahern, Charlotte; Ingle, Ashish M.; Yamashiro, Darrell J.; Chen, Alice; Weigel, Brenda; Adamson, Peter C.; Park, Julie R.

2012-01-01

Background Aflibercept is a novel decoy receptor that efficiently neutralizes circulating vascular endothelial growth factor (VEGF). A pediatric phase 1 trial was performed to define the dose limiting toxicities (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of aflibercept. Methods Cohorts of 3–6 children with refractory solid tumors received aflibercept intravenously over 60 minutes every 14 days, at 2.0, 2.5 or 3.0 mg/kg/dose. PK sampling and analysis of peripheral blood biomarkers were performed with the initial dose. Results 21 eligible patients were enrolled; 18 were fully evaluable for toxicity. One of 6 patients receiving 2.0 mg/kg/dose developed dose-limiting intra-tumoral hemorrhage and 2 of 6 receiving 3.0 mg/kg/dose developed either dose-limiting tumor pain or tissue necrosis. None of the 6 patients receiving 2.5 mg/kg/dose developed DLT, defining this as the MTD. The most common non-dose limiting toxicities were hypertension and fatigue. Three patients with hepatocellular carcinoma, hepatoblastoma and clear cell sarcoma had stable disease for >13 weeks. At the MTD, the ratio of free to bound aflibercept serum concentration was 2.10 on day 8, but only 0.44 by day 15. A rapid decrease in VEGF (p<0.05) and increase in PlGF (p<0.05) from baseline was observed in response to aflibercept by day 2. Conclusion The aflibercept MTD in children of 2.5 mg/kg/dose every 14 days is lower that the adult recommended dose of 4.0 mg/kg. This dose achieves, but does not sustain, free aflibercept concentrations in excess of bound. Tumor pain and hemorrhage may be evidence of anti-tumor activity, but were dose-limiting. PMID:22791883

Uptake and timeliness of rotavirus vaccination in Norway: The first year post-introduction.

PubMed

Valcarcel Salamanca, Beatriz; Hagerup-Jenssen, Maria Elisabeth; Flem, Elmira

2016-09-07

To minimise vaccine-associated risk of intussusception following rotavirus vaccination, Norway adopted very strict age limits for initiating and completing the vaccine series at the time rotavirus vaccination was included in the national immunisation programme, October 2014. Although Norway has a high coverage for routine childhood vaccines, these stringent age limits could negatively affect rotavirus coverage. We documented the status and impact of rotavirus vaccination on other infant vaccines during the first year after its introduction. We used individual vaccination data from the national immunisation register to calculate coverage for rotavirus and other vaccines and examine adherence with the recommended schedules. We identified factors associated with completing the full rotavirus series by performing multiple logistic regression analyses. We also evaluated potential changes in uptake and timeliness of other routine vaccines after the introduction of rotavirus vaccine using the Kaplan-Meier method. The national coverage for rotavirus vaccine achieved a year after the introduction was 89% for one dose and 82% for two doses, respectively. Among fully rotavirus-vaccinated children, 98% received both doses within the upper age limit and 90% received both doses according to the recommended schedule. The child's age at the initiation of rotavirus series and being vaccinated with diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (DTaP/IPV/Hib) and pneumococcal vaccines were the strongest predictors of completing the full rotavirus series. No major changes in uptake and timeliness of other paediatric vaccines were observed after introduction of rotavirus vaccine. Norway achieved a high national coverage and excellent adherence with the strict age limits for rotavirus vaccine administration during the first year of introduction, indicating robustness of the national immunisation programme. Rotavirus vaccination did not impact coverage or timeliness of other infant vaccines. Copyright © 2016. Published by Elsevier Ltd.

Pertussis control in the Asia-Pacific region: a report from the Global Pertussis Initiative.

PubMed

Forsyth, Kevin; Thisyakorn, Usa; von König, Carl Heinz Wirsing; Tan, Tina; Plotkin, Stanley

2012-05-01

The Global Pertussis Initiative (GPI) is an expert, scientific forum that seeks to address the worldwide burden of pertussis. To reduce the global incidence of pertussis, the GPI recommends reinforcing and/or improving current infant and toddler immunization strategies, universal booster dosing of pre-school children, universal booster dosing of adolescents and adults (where appropriate), and cocooning to protect infants. To tailor these global recommendations to local needs, the GPI has hosted two meetings in Asia-Pacific. Pertussis vaccination practices differ across Asia-Pacific, with only some countries recommending booster dosing. Given the limited use of laboratory diagnostics, disease surveillance was considered inadequate. To make informed health policy decisions on pertussis prevention, more robust epidemiological data are needed. Because of its unique clinical presentation, adolescent and adult pertussis is under-recognized by lay and medical communities. Consequently, adolescent and adult disease likely exists even in Asian-Pacific countries where epidemiological data are presently lacking. In Asia-Pacific, there exist issues with health care access and costs. Fragmented health care will negatively impact the effectiveness of any proposed immunization strategies. The GPI recommends-in Asia-Pacific and elsewhere-that countries first educate lay and medical communities on pertussis, while simultaneously implementing robust surveillance practices. Once armed with sufficient epidemiological evidence, the prevention strategies recommended by the GPI can then be appropriately (and more effectively) introduced.

Evaluation and optimization of occupational eye lens dosimetry during positron emission tomography (PET) procedures.

PubMed

Guiu-Souto, Jacobo; Sánchez-García, Manuel; Vázquez-Vázquez, Rubén; Otero, Carlos; Luna, Victor; Mosquera, Javier; Busto, Ramón Lobato; Aguiar, Pablo; Ruibal, Álvaro; Pardo-Montero, Juan; Pombar-Cameán, Miguel

2016-06-01

The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded.

On the feasibility of utilizing active personal dosimeters worn on the chest to estimate occupational eye lens dose in x-ray angiography.

PubMed

Omar, Artur; Marteinsdottir, Maria; Kadesjö, Nils; Fransson, Annette

2015-06-01

The International Commission on Radiological Protection (ICRP) has recommended that the occupational dose limit to the eye lens be substantially reduced. To ensure compliance with these recommendations, monitoring of the occupational eye lens dose is essential in certain hospital work environments. For assessment of the eye lens dose it is recommended to use a supplementary dosimeter placed at a position adjacent to the eye(s). Wearing a dosimeter at eye level can, however, be impractical and distributing and managing additional dosimeters over long periods of time is cumbersome and costly for large clinical sites. An attractive alternative is to utilize active personal dosimeters (APDs), which are routinely used by clinical staff for real-time monitoring of the personal dose equivalent rate (H(p)(10)). In this work, a formalism for the determination of eye lens dose from the response of such APD's worn on the chest is proposed and evaluated. The evaluation is based on both phantom and clinical measurements performed in an x-ray angiography suite for interventional cardiology. The main results show that the eye lens dose to the primary operator and to the assisting clinical staff can be conservatively estimated from the APD response as D(eye)(conductor) = 2.0 APD chest and D(eye)(assisting) = 1.0 APD chest, respectively. However, care should be exercised for particularly short assisting staff and if radiation protection shields are misused. These concerns can be greatly mitigated if the clinical staff are provided with adequate radiation protection training.

Phase I/II Trial and Pharmacokinetic Study of Cixutumumab in Pediatric Patients With Refractory Solid Tumors and Ewing Sarcoma: A Report From the Children's Oncology Group

PubMed Central

Malempati, Suman; Weigel, Brenda; Ingle, Ashish M.; Ahern, Charlotte H.; Carroll, Julie M.; Roberts, Charles T.; Reid, Joel M.; Schmechel, Stephen; Voss, Stephan D.; Cho, Steven Y.; Chen, Helen X.; Krailo, Mark D.; Adamson, Peter C.; Blaney, Susan M.

2012-01-01

Purpose A phase I/II study of cixutumumab (IMC-A12) in children with refractory solid tumors was conducted. This study was designed to assess the toxicities, pharmacokinetics, and pharmacodynamics of cixutumumab in children to determine a recommended phase II dose and to assess antitumor activity in Ewing sarcoma (ES). Patients and Methods Pediatric patients with relapsed or refractory solid tumors were treated with cixutumumab as a 1-hour intravenous infusion once per week. Two dose levels—6 and 9 mg/kg—were evaluated using a standard three-plus-three cohort design. Patients with refractory ES were treated in an expanded phase II cohort at each dose level. Results Forty-seven eligible patients with a median age of 15 years (range, 4 to 28 years) were enrolled. Twelve patients were treated in the dose-finding phase. Hematologic and nonhematologic toxicities were generally mild and infrequent. Dose-limiting toxicities included grade 4 thrombocytopenia at 6 mg/kg and grade 3 dehydration at 9 mg/kg. Mean trough concentration (± standard deviation) at 9 mg/kg was 106 ± 57 μg/mL, which exceeded the effective trough concentration of 60 μg/mL observed in xenograft models. Three patients with ES had confirmed partial responses: one of 10 at 6 mg/kg and two of 20 at 9 mg/kg. Serum insulin-like growth factor I (IGF-I) levels consistently increased after one dose of cixutumumab. Tumor IGF-I receptor expression by immunohistochemistry did not correlate with response in patients with ES. Conclusion Cixutumumab is well tolerated in children with refractory solid tumors. The recommended phase II dose is 9 mg/kg. Limited single-agent activity of cixutumumab was seen in ES. PMID:22184397

Quality and efficiency of statin prescribing across countries with a special focus on South Africa: findings and future implications.

PubMed

Godman, Brian; Bishop, Iain; Campbell, Stephen M; Malmström, Rickard E; Truter, Ilse

2015-04-01

Statins are recommended first-line treatment for hyperlipidemia, with published studies suggesting limited differences between them. However, there are reports of under-dosing. South Africa has introduced measures to enhance generic utilization. Part one documents prescribed doses of statins in 2011. Part two determines the extent of generics versus originator and single-sourced statins in 2011 and their costs. Underdosing of simvastatin in 2011 with average prescribed dose of 23.7 mg; however, not for atorvastatin (20.91 mg) or rosuvastatin (15.02 mg). High utilization of generics versus originators at 93-99% for atorvastatin and simvastatin, with limited utilization of single-sourced statins (22% of total statins - defined daily dose basis), mirroring Netherlands, Sweden and UK. Generics priced 33-51% below originator prices. Opportunity to increase simvastatin dosing through education, prescribing targets and incentives. Opportunity to lower generic prices with generic simvastatin 96-98% below single-sourced prices in some European countries.

Radiation exposure and risk assessment for critical female body organs

NASA Technical Reports Server (NTRS)

Atwell, William; Weyland, Mark D.; Hardy, Alva C.

1991-01-01

Space radiation exposure limits for astronauts are based on recommendations of the National Council on Radiation Protection and Measurements. These limits now include the age at exposure and sex of the astronaut. A recently-developed computerized anatomical female (CAF) model is discussed in detail. Computer-generated, cross-sectional data are presented to illustrate the completeness of the CAF model. By applying ray-tracing techniques, shield distribution functions have been computed to calculate absorbed dose and dose equivalent values for a variety of critical body organs (e.g., breasts, lungs, thyroid gland, etc.) and mission scenarios. Specific risk assessments, i.e., cancer induction and mortality, are reviewed.

[Brachytherapy for head and neck cancers].

PubMed

Peiffert, D; Coche-Dequéant, B; Lapeyre, M; Renard, S

2018-05-29

The main indications of the brachytherapy of head and neck cancers are the limited tumours of the lip, the nose, the oral cavity and the oropharynx. Nasopharynx tumours are nowadays treated by intensity-modulated radiotherapy. This technique can be exclusive, associated with external radiotherapy or postoperative. It can also be a salvage treatment for the second primaries in previously irradiated areas. If the low dose rate brachytherapy rules remain the reference, the pulse dose rate technique allows the prescription of the dose rate and the optimisation of the dose distribution. Results of high dose rate brachytherapy are now published. This paper reports the recommendations of the Gec-ESTRO, published in 2017, and takes into account the data of the historical low dose rate series, and is upgraded with the pulsed-dose rate and high dose rate series. Copyright © 2018. Published by Elsevier SAS.

Clinical Application and Pharmacodynamic Monitoring of Apixaban in a Patient with End-Stage Renal Disease Requiring Chronic Hemodialysis.

PubMed

Kufel, Wesley D; Zayac, Adam S; Lehmann, David F; Miller, Christopher D

2016-11-01

Despite prescribing guidance, limited data exist to describe the use of apixaban in patients with end-stage renal disease (ESRD) requiring hemodialysis (HD). Current apixaban dosing recommendations for this patient population are based largely on a single-dose pharmacokinetic study of eight patients. We describe the clinical application and pharmacodynamic monitoring of apixaban in a 62-year-old 156-kg African-American woman with nonvalvular atrial fibrillation and ESRD requiring hemodialysis who developed calciphylaxis while receiving warfarin therapy. Based on a multidisciplinary clinical judgment decision due to concern for drug accumulation after multiple doses in patients with ESRD receiving HD, she was anticoagulated with apixaban 2.5 mg twice/day, as opposed to 5 mg twice/day as recommended by the package insert. Antifactor Xa monitoring was used, and resultant peak and trough apixaban concentrations were above the upper limit of detection for our clinical laboratory (more than 2.00 IU/ml). On day 7 of her hospitalization, the patient developed gastrointestinal bleeding, and apixaban was discontinued; no further clinical signs of bleeding occurred during her subsequent hospitalization course. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between apixaban exposure and the manifestation of gastrointestinal bleeding. The patient ultimately died 44 days after the acute bleeding event; however, coagulation concerns were not implicated in the patient's death. To our knowledge, this is the first case report that describes apixaban use and associated antifactor Xa monitoring in a patient with ESRD receiving HD, and it provides concern for current apixaban dosing recommendations in this patient population. Further pharmacokinetic and clinical data are likely necessary to better characterize apixaban use in these patients to optimize safety and efficacy. © 2016 Pharmacotherapy Publications, Inc.

Dose Transition Pathways: The Missing Link Between Complex Dose-Finding Designs and Simple Decision-Making.

PubMed

Yap, Christina; Billingham, Lucinda J; Cheung, Ying Kuen; Craddock, Charlie; O'Quigley, John

2017-12-15

The ever-increasing pace of development of novel therapies mandates efficient methodologies for assessment of their tolerability and activity. Evidence increasingly support the merits of model-based dose-finding designs in identifying the recommended phase II dose compared with conventional rule-based designs such as the 3 + 3 but despite this, their use remains limited. Here, we propose a useful tool, dose transition pathways (DTP), which helps overcome several commonly faced practical and methodologic challenges in the implementation of model-based designs. DTP projects in advance the doses recommended by a model-based design for subsequent patients (stay, escalate, de-escalate, or stop early), using all the accumulated information. After specifying a model with favorable statistical properties, we utilize the DTP to fine-tune the model to tailor it to the trial's specific requirements that reflect important clinical judgments. In particular, it can help to determine how stringent the stopping rules should be if the investigated therapy is too toxic. Its use to design and implement a modified continual reassessment method is illustrated in an acute myeloid leukemia trial. DTP removes the fears of model-based designs as unknown, complex systems and can serve as a handbook, guiding decision-making for each dose update. In the illustrated trial, the seamless, clear transition for each dose recommendation aided the investigators' understanding of the design and facilitated decision-making to enable finer calibration of a tailored model. We advocate the use of the DTP as an integral procedure in the co-development and successful implementation of practical model-based designs by statisticians and investigators. Clin Cancer Res; 23(24); 7440-7. ©2017 AACR . ©2017 American Association for Cancer Research.

Ethical issues related to professional exposure of pregnant women in the medical field: monitoring and limiting effective dose.

PubMed

Santos, J A M; Nunes, R

2011-03-01

The International Commission on Radiological Protection recommendations for occupational exposed pregnant women do not imply necessarily the complete avoidance of work with radiation or radioactive materials. Instead, a careful review of the exposure conditions, once the pregnancy is declared, as part of the exercise of the ICRP optimisation principle (based in a teleological ethics point of view) is suggested. The dose limitation (following a deontological ethics point of view) of the fetus/embryo is, however, not clearly well established as happens in the case of workers or members of the public. Also, the justification of practices (to continue to work or not with radiation or radioactive materials) is not clearly addressed in most national or international recommendations. An analysis of this justification (bearing in mind both teleological and deontological ethics) is examined in this work having in mind the best interest of the child-to-be as well as other existing social and economical factors.

Embracing model-based designs for dose-finding trials

PubMed Central

Love, Sharon B; Brown, Sarah; Weir, Christopher J; Harbron, Chris; Yap, Christina; Gaschler-Markefski, Birgit; Matcham, James; Caffrey, Louise; McKevitt, Christopher; Clive, Sally; Craddock, Charlie; Spicer, James; Cornelius, Victoria

2017-01-01

Background: Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). Methods: We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. Results: We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators’ preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. Conclusions: There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia. PMID:28664918

Eye lens monitoring for interventional radiology personnel: dosemeters, calibration and practical aspects of H p (3) monitoring. A 2015 review.

PubMed

Carinou, Eleftheria; Ferrari, Paolo; Bjelac, Olivera Ciraj; Gingaume, Merce; Merce, Marta Sans; O'Connor, Una

2015-09-01

A thorough literature review about the current situation on the implementation of eye lens monitoring has been performed in order to provide recommendations regarding dosemeter types, calibration procedures and practical aspects of eye lens monitoring for interventional radiology personnel. Most relevant data and recommendations from about 100 papers have been analysed and classified in the following topics: challenges of today in eye lens monitoring; conversion coefficients, phantoms and calibration procedures for eye lens dose evaluation; correction factors and dosemeters for eye lens dose measurements; dosemeter position and influence of protective devices. The major findings of the review can be summarised as follows: the recommended operational quantity for the eye lens monitoring is H p (3). At present, several dosemeters are available for eye lens monitoring and calibration procedures are being developed. However, in practice, very often, alternative methods are used to assess the dose to the eye lens. A summary of correction factors found in the literature for the assessment of the eye lens dose is provided. These factors can give an estimation of the eye lens dose when alternative methods, such as the use of a whole body dosemeter, are used. A wide range of values is found, thus indicating the large uncertainty associated with these simplified methods. Reduction factors from most common protective devices obtained experimentally and using Monte Carlo calculations are presented. The paper concludes that the use of a dosemeter placed at collar level outside the lead apron can provide a useful first estimate of the eye lens exposure. However, for workplaces with estimated annual equivalent dose to the eye lens close to the dose limit, specific eye lens monitoring should be performed. Finally, training of the involved medical staff on the risks of ionising radiation for the eye lens and on the correct use of protective systems is strongly recommended.

Performance Characteristics of an Independent Dose Verification Program for Helical Tomotherapy

PubMed Central

Chang, Isaac C. F.; Chen, Jeff; Yartsev, Slav

2017-01-01

Helical tomotherapy with its advanced method of intensity-modulated radiation therapy delivery has been used clinically for over 20 years. The standard delivery quality assurance procedure to measure the accuracy of delivered radiation dose from each treatment plan to a phantom is time-consuming. RadCalc®, a radiotherapy dose verification software, has released specifically for beta testing a module for tomotherapy plan dose calculations. RadCalc®'s accuracy for tomotherapy dose calculations was evaluated through examination of point doses in ten lung and ten prostate clinical plans. Doses calculated by the TomoHDA™ tomotherapy treatment planning system were used as the baseline. For lung cases, RadCalc® overestimated point doses in the lung by an average of 13%. Doses within the spinal cord and esophagus were overestimated by 10%. Prostate plans showed better agreement, with overestimations of 6% in the prostate, bladder, and rectum. The systematic overestimation likely resulted from limitations of the pencil beam dose calculation algorithm implemented by RadCalc®. Limitations were more severe in areas of greater inhomogeneity and less prominent in regions of homogeneity with densities closer to 1 g/cm3. Recommendations for RadCalc® dose calculation algorithms and anatomical representation were provided based on the results of the study. PMID:28974862

Assessment of Natural Radioactivity Levels and Potential Radiological Risks of Common Building Materials Used in Bangladeshi Dwellings.

PubMed

Asaduzzaman, Khandoker; Mannan, Farhana; Khandaker, Mayeen Uddin; Farook, Mohideen Salihu; Elkezza, Aeman; Amin, Yusoff Bin Mohd; Sharma, Sailesh; Abu Kassim, Hasan Bin

2015-01-01

The concentrations of primordial radionuclides (226Ra, 232Th and 40K) in commonly used building materials (brick, cement and sand), the raw materials of cement and the by-products of coal-fired power plants (fly ash) collected from various manufacturers and suppliers in Bangladesh were determined via gamma-ray spectrometry using an HPGe detector. The results showed that the mean concentrations of 226Ra, 232Th and 40K in all studied samples slightly exceeded the typical world average values of 50 Bq kg(-1), 50 Bq kg(-1) and 500 Bq kg(-1), respectively. The activity concentrations (especially 226Ra) of fly-ash-containing cement in this study were found to be higher than those of fly-ash-free cement. To evaluate the potential radiological risk to individuals associated with these building materials, various radiological hazard indicators were calculated. The radium equivalent activity values for all samples were found to be lower than the recommended limit for building materials of 370 Bq kg(-1), with the exception of the fly ash. For most samples, the values of the alpha index and the radiological hazard (external and internal) indices were found to be within the safe limit of 1. The mean indoor absorbed dose rate was observed to be higher than the population-weighted world average of 84 nGy h(-1), and the corresponding annual effective dose for most samples fell below the recommended upper dose limit of 1 mSv y(-1). For all investigated materials, the values of the gamma index were found to be greater than 0.5 but less than 1, indicating that the gamma dose contribution from the studied building materials exceeds the exemption dose criterion of 0.3 mSv y(-1) but complies with the upper dose principle of 1 mSv y(-1).

Assessment of Natural Radioactivity Levels and Potential Radiological Risks of Common Building Materials Used in Bangladeshi Dwellings

PubMed Central

Asaduzzaman, Khandoker; Mannan, Farhana; Khandaker, Mayeen Uddin; Farook, Mohideen Salihu; Elkezza, Aeman; Amin, Yusoff Bin Mohd; Sharma, Sailesh; Abu Kassim, Hasan Bin

2015-01-01

The concentrations of primordial radionuclides (226Ra, 232Th and 40K) in commonly used building materials (brick, cement and sand), the raw materials of cement and the by-products of coal-fired power plants (fly ash) collected from various manufacturers and suppliers in Bangladesh were determined via gamma-ray spectrometry using an HPGe detector. The results showed that the mean concentrations of 226Ra, 232Th and 40K in all studied samples slightly exceeded the typical world average values of 50 Bq kg−1, 50 Bq kg−1 and 500 Bq kg−1, respectively. The activity concentrations (especially 226Ra) of fly-ash-containing cement in this study were found to be higher than those of fly-ash-free cement. To evaluate the potential radiological risk to individuals associated with these building materials, various radiological hazard indicators were calculated. The radium equivalent activity values for all samples were found to be lower than the recommended limit for building materials of 370 Bq kg-1, with the exception of the fly ash. For most samples, the values of the alpha index and the radiological hazard (external and internal) indices were found to be within the safe limit of 1. The mean indoor absorbed dose rate was observed to be higher than the population-weighted world average of 84 nGy h–1, and the corresponding annual effective dose for most samples fell below the recommended upper dose limit of 1 mSv y–1. For all investigated materials, the values of the gamma index were found to be greater than 0.5 but less than 1, indicating that the gamma dose contribution from the studied building materials exceeds the exemption dose criterion of 0.3 mSv y-1 but complies with the upper dose principle of 1 mSv y−1. PMID:26473957

Randomized Trial of 2 Versus 1 Dose of Measles Vaccine: Effect on Hospital Admission of Children After 9 Months of Age.

PubMed

Brønd, Marie; Martins, Cesario L; Byberg, Stine; Benn, Christine S; Whittle, Hilton; Garly, May-Lill; Aaby, Peter; Fisker, Ane B

2017-06-15

Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investigated the effect on hospital admissions. Children were randomly assigned 1:2 to receive MV at 4.5 and 9 months of age or the currently recommended dose at 9 months. We compared hospital admission rates among children between 9 and 18 months of age in a Cox regression model with age as the underlying time scale. Half of the children had received neonatal vitamin A supplementation (NVAS) in another trial. The beneficial effect of MV at 4.5 and 9 months on mortality was limited to children who had not received NVAS; therefore, we investigated the interaction of MV with NVAS on admission rates. Among 5626 children (2 doses of MV, 1960 children; 1 dose of MV, 3666), we identified 311 hospital admissions of children between 9 and 18 months of age. Overall, compared to 1 dose of MV, 2 doses reduced the risk of hospital admission for children who had not received NVAS (hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.47-0.93]), but we found no effect among NVAS recipients (HR, 1.16 [95% CI, 0.82-1.63]) (P = .02 for interaction). The benefit of 2 doses of MV was limited to children who had not received NVAS. NVAS is not generally recommended; hence, an early 2-dose measles vaccination policy might reduce hospital admissions more than the current policy of providing the first MV at 9 months of age. ClinicalTrials.gov identifier NCT00168558. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparison of current recommended regimens of atropinization in organophosphate poisoning.

PubMed

Connors, Nicholas J; Harnett, Zachary H; Hoffman, Robert S

2014-06-01

Atropine is the mainstay of therapy in organophosphate (OP) toxicity, though research and consensus on dosing is lacking. In 2004, as reported by Eddleston et al. (J Toxicol Clin Toxicol 42(6):865-75, 2004), they noted variation in recommended regimens. We assessed revisions of original references, additional citations, and electronic sources to determine the current variability in atropine dosing recommendations. Updated editions of references from Eddleston et al.'s work, texts of Internal and Emergency Medicine, and electronic resources were reviewed for atropine dosing recommendations. For comparison, recommendations were assessed using the same mean dose (23.4 mg) and the highest dose (75 mg) of atropine as used in the original paper. Recommendations were also compared with the dosing regimen from the World Health Organization (WHO). Thirteen of the original recommendations were updated and 15 additional references were added giving a convenience sample of 28. Sufficient information to calculate time to targeted dose was provided by 24 of these samples. Compared to 2004, current recommendations have greatly increased the speed of atropinization with 13/24 able to reach the mean and high atropine dose within 30 min compared to 1/36 in 2004. In 2004, there were 13 regimens where the maximum time to reach 75 mg was over 18 h, whereas now, there are 2. While only one recommendation called for doubling the dose for faster escalation in 2004, 15 of the 24 current works include dose doubling. In 2004, Eddleston et al. called for an evidence-based guideline for the treatment of OP poisoning that could be disseminated worldwide. Many current recommendations can adequately treat patients within 1 h. While the WHO recommendations remain slow to treat patients with OP poisoning, other authorities are close to a consensus on rapid atropinization.

[Determination of vaccination quotas for pneumococcal conjugate vaccine in children on the basis of routine data of the statutory health insurance].

PubMed

Theidel, U; Braem, A; Rückinger, S

2013-05-01

The pneumococcal conjugate vaccine is recommended since July 2006 for all children up to 24 months by the Standing Committee on Vaccination (STIKO) in Germany. Immunisation includes 4 doses; a single dose should be administered at completed 2, 3, 4 months and 11-14 months of age. To analyse the immunization coverage, timeliness and completeness of vaccinations, a claims data analysis was conducted. The evaluation was based on routine claims data of a statutory health insurance covering the period from May 2008-September 2009. Overall, 81.2% (5 484/6 755) of all live births of mothers and fathers of the insurance received at least one vaccination dose. In 91.3% and 72.0% of these cases, the second and third dose was administered, respectively. A vaccination cycle of 4 doses was often not completed and the recommended time points for vaccination were not met in two-thirds of all children. Due to the limited and relatively short observation period, a conclusion about the rate of fully completed vaccination cycles was not possible. © Georg Thieme Verlag KG Stuttgart · New York.

The opioid epidemic and national guidelines for opioid therapy for chronic noncancer pain: a perspective from different continents.

PubMed

Häuser, Winfried; Schug, Stephan; Furlan, Andrea D

2017-05-01

A marked rise in opioid prescriptions for patients with chronic noncancer pain (CNCP) with a parallel increase in opioid abuse/misuse, and resulting deaths was noted in the Unites states in the past decade (opioid epidemic). In response, the US Center of Diseases Control (CDC) developed a guideline for prescribing of opioids for patients with CNCP. To assess (1) if there is an opioid epidemic in Australia, Canada, and Germany (2) to compare Australian, Canadian, German, and Center of Diseases Control guidelines recommendations for long-term opioid therapy for CNCP. National evidence-based guidelines and PubMed were searched for recommendations for opioid prescriptions for CNCP. There are signs of an opioid epidemic in Australia and Canada, but not in Germany. Guidelines in all 4 countries provide similar recommendations: opioids are not the first-line therapy for patients with CNCP; regular clinical assessments of benefits and harms are necessary; excessive doses should be avoided (recommended morphine equivalent daily doses range from 50 to 200 mg/d); stopping rules should be followed. All guidelines do not recommend the use of opioids in chronic pain conditions without an established nociceptive or neuropathic cause such as fibromyalgia and primary headache. Implementation of opioid prescribing guidelines should ensure that physicians prescribe opioids only for appropriate indications in limited doses for selected patients and advice patients on their safe use. These measures could contribute to reduce prescription opioid misuse/abuse and deaths.

[Omega-3 fatty acids, fish, fish oil and cardiovascular disease--a review with implications to Israeli nutritional guidelines].

PubMed

Eilat-Adar, Sigal; Lipovetzky, Nestor; Goldbourt, Uri; Henkin, Yaakov

2004-08-01

Evidence from epidemiological and randomized controlled trials shows beneficial effects of omega-3 (n-3) fatty acids from fish and plant sources on cardiovascular disease (CVD), especially in patients with preexisting CVD. The optimal dose of n-3 is not yet determined, but prospective secondary prevention studies suggest that the addition of 0.5-1.8 grams/day of marine-derived eicosapentaenoic acid and docosahexaenoic acid, or plant derived alpha-linolenic acid at a dose of 1.5-3 grams/day significantly reduce subsequent cardiac events and mortality. These data have led the American Heart Association Dietary Guidelines committee to recommend to the general population the consumption of at least two servings of fatty fish per week, in addition to vegetable oils high in alpha-linolenic acid. The risk of adverse effects and toxicity from contaminants at this dose is low. The amount of daily n-3 fatty acids recommended for patients with coronary heart disease is 1 gram/day. In patients who cannot consume this dose of n-3 fatty acids through diet alone, addition of n-3 supplements should be considered. Higher doses of contaminant-free n-3 supplements, 2-4 grams/day, can be used in the treatment of hypertriglyceridemia. Data on the content of n-3 fatty acids and contaminants in Israeli bred fish is limited. Thus, caution should be exercised when applying these recommendations to the Israeli fish market.

21 CFR 340.50 - Labeling of stimulant drug products.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the heading “Warnings”: (1) “The recommended dose of this product contains about as much caffeine as a cup of coffee. Limit the use of caffeine-containing medications, foods, or beverages while taking this product because too much caffeine may cause nervousness, irritability, sleeplessness, and, occasionally...

21 CFR 340.50 - Labeling of stimulant drug products.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the heading “Warnings”: (1) “The recommended dose of this product contains about as much caffeine as a cup of coffee. Limit the use of caffeine-containing medications, foods, or beverages while taking this product because too much caffeine may cause nervousness, irritability, sleeplessness, and, occasionally...

21 CFR 340.50 - Labeling of stimulant drug products.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the heading “Warnings”: (1) “The recommended dose of this product contains about as much caffeine as a cup of coffee. Limit the use of caffeine-containing medications, foods, or beverages while taking this product because too much caffeine may cause nervousness, irritability, sleeplessness, and, occasionally...

21 CFR 340.50 - Labeling of stimulant drug products.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the heading “Warnings”: (1) “The recommended dose of this product contains about as much caffeine as a cup of coffee. Limit the use of caffeine-containing medications, foods, or beverages while taking this product because too much caffeine may cause nervousness, irritability, sleeplessness, and, occasionally...

Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy.

PubMed

Mourad, Waleed F; Young, Brett M; Young, Rebekah; Blakaj, Dukagjin M; Ohri, Nitin; Shourbaji, Rania A; Manolidis, Spiros; Gámez, Mauricio; Kumar, Mahesh; Khorsandi, Azita; Khan, Majid A; Shasha, Daniel; Blakaj, Adriana; Glanzman, Jonathan; Garg, Madhur K; Hu, Kenneth S; Kalnicki, Shalom; Harrison, Louis B

2013-09-01

Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs. Published by Elsevier Ltd.

Incidental irradiation of mediastinal and hilar lymph node stations during 3D-conformal radiotherapy for non-small cell lung cancer.

PubMed

Kepka, Lucyna; Bujko, Krzysztof; Zolciak-Siwinska, Agnieszka; Garmol, Dariusz

2008-01-01

To estimate the doses of incidental irradiation in particular lymph node stations (LNS) in different extents of elective nodal irradiation (ENI) in 3D-conformal radiotherapy (3D-CRT) for non-small cell lung cancer (NSCLC). METHODS; Doses of radiotherapy were estimated for particular LNS delineated according to the recommendations of the University of Michigan in 220 patients treated using 3D-CRT with different (extended, limited and omitted) extents of ENI. Minimum doses and volumes of LNS receiving 40 Gy or more (V40) were compared for omitted vs. limited+ extended ENI and limited vs. extended ENI. For omission of the ENI the minimum doses and V40 for particular LNS were significantly lower than for patients treated with ENI. For the limited ENI group, the minimum doses for LNS 5, 6 lower parts of 3A and 3P (not included in the elective area) did not differ significantly from doses given to respective LNS for extended ENI group. When the V40 values for extended and limited ENI were compared, no significant differences were seen for any LNS, except for group 1/2R, 1/2L. Incidental irradiation of untreated LNS seems play a part in case of limited ENI, but not in cases without ENI. For subclinical disease the delineation of uninvolved LNS 5, 6, and lower parts of 3A, 3P may be not necessary, because these stations receive the substantial part of irradiation incidentally, if LNS 4R, 4L, 7, and ipsilateral hilum are included in the elective area while this is not case for stations 1 and 2.

Estimating age-based antiretroviral therapy costs for HIV-infected children in resource-limited settings based on World Health Organization weight-based dosing recommendations.

PubMed

Doherty, Kathleen; Essajee, Shaffiq; Penazzato, Martina; Holmes, Charles; Resch, Stephen; Ciaranello, Andrea

2014-05-02

Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0-13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments.

ICRP PUBLICATION 122: radiological protection in geological disposal of long-lived solid radioactive waste.

PubMed

Weiss, W; Larsson, C-M; McKenney, C; Minon, J-P; Mobbs, S; Schneider, T; Umeki, H; Hilden, W; Pescatore, C; Vesterlind, M

2013-06-01

This report updates and consolidates previous recommendations of the International Commission on Radiological Protection (ICRP) related to solid waste disposal (ICRP, 1985, 1997b, 1998). The recommendations given apply specifically to geological disposal of long-lived solid radioactive waste. The report explains how the ICRP system of radiological protection described in Publication 103 (ICRP, 2007) can be applied in the context of the geological disposal of long-lived solid radioactive waste. Although the report is written as a standalone document, previous ICRP recommendations not dealt with in depth in the report are still valid. The 2007 ICRP system of radiological protection evolves from the previous process-based protection approach relying on the distinction between practices and interventions by moving to an approach based on the distinction between three types of exposure situation: planned, emergency and existing. The Recommendations maintains the Commission's three fundamental principles of radiological protection namely: justification, optimisation of protection and the application of dose limits. They also maintain the current individual dose limits for effective dose and equivalent dose from all regulated sources in planned exposure situations. They re-enforce the principle of optimisation of radiological protection, which applies in a similar way to all exposure situations, subject to restrictions on individual doses: constraints for planned exposure situations, and reference levels for emergency and existing exposure situations. The Recommendations also include an approach for developing a framework to demonstrate radiological protection of the environment. This report describes the different stages in the life time of a geological disposal facility, and addresses the application of relevant radiological protection principles for each stage depending on the various exposure situations that can be encountered. In particular, the crucial factor that influences the application of the protection system over the different phases in the life time of a disposal facility is the level of oversight or 'watchful care' that is present. The level of oversight affects the capability to control the source, i.e. the waste and the repository, and to avoid or reduce potential exposures. Three main time frames are considered: time of direct oversight, when the disposal facility is being implemented and is under active supervision; time of indirect oversight, when the disposal facility is sealed and oversight is being exercised by regulators or special administrative bodies or society at large to provide additional assurance on behalf of society; and time of no oversight, when oversight is no longer exercised in case memory of the disposal facility is lost. Copyright © 2013. Published by Elsevier Ltd.

Treatment of chancroid, 1997.

PubMed

Schmid, G P

1999-01-01

Since the 1993 treatment guidelines for sexually transmitted diseases were published by the Centers for Disease Control and Prevention, experience has indicated that the regimens recommended then remain largely effective. The recommended therapies--with azithromycin (1 g orally, once), ceftriaxone (250 mg intramuscularly, once), or erythromycin (500 mg orally, four times a day for 7 days)--appear highly effective in the United States; limited data from Kenya suggest that the ceftriaxone regimen may not be as effective there as it once was. The alternative regimen of ciprofloxacin proposed in 1993 (500 mg orally, twice a day for 3 days) is as effective as the recommended therapies, but new information indicates that single-dose therapy with 500 mg orally is not as effective as the use of either larger single doses or more prolonged therapy. Persons who are infected with human immunodeficiency virus (HIV) do not respond as well as those who are not HIV-infected, and males who are uncircumcised appear not to respond as well as those who are circumcised.

Impact of the Revised 10 CFR 835 on the Neutron Dose Rates at LLNL

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

Radev, R

2009-01-13

In June 2007, 10 CFR 835 [1] was revised to include new radiation weighting factors for neutrons, updated dosimetric models, and dose terms consistent with the newer ICRP recommendations. A significant aspect of the revised 10 CFR 835 is the adoption of the recommendations outlined in ICRP-60 [2]. The recommended new quantities demand a review of much of the basic data used in protection against exposure to sources of ionizing radiation. The International Commission on Radiation Units and Measurements has defined a number of quantities for use in personnel and area monitoring [3,4,5] including the ambient dose equivalent H*(d) tomore » be used for area monitoring and instrument calibrations. These quantities are used in ICRP-60 and ICRP-74. This report deals only with the changes in the ambient dose equivalent and ambient dose rate equivalent for neutrons as a result of the implementation of the revised 10 CFR 835. In the report, the terms neutron dose and neutron dose rate will be used for convenience for ambient neutron dose and ambient neutron dose rate unless otherwise stated. This report provides a qualitative and quantitative estimate of how much the neutron dose rates at LLNL will change with the implementation of the revised 10 CFR 835. Neutron spectra and dose rates from selected locations at the LLNL were measured with a high resolution spectroscopic neutron dose rate system (ROSPEC) as well as with a standard neutron rem meter (a.k.a., a remball). The spectra obtained at these locations compare well with the spectra from the Radiation Calibration Laboratory's (RCL) bare californium source that is currently used to calibrate neutron dose rate instruments. The measurements obtained from the high resolution neutron spectrometer and dose meter ROSPEC and the NRD dose meter compare within the range of {+-}25%. When the new radiation weighting factors are adopted with the implementation of the revised 10 CFR 835, the measured dose rates will increase by up to 22%. The health physicists should consider this increase for any areas that have dose rates near a posting limit, such as near the 100 mrem/hr for a high radiation area, as this increase in measured dose rate may result in some changes to postings and consequent radiological controls.« less

An Eye Model for Computational Dosimetry Using A Multi-Scale Voxel Phantom

NASA Astrophysics Data System (ADS)

Caracappa, Peter F.; Rhodes, Ashley; Fiedler, Derek

2014-06-01

The lens of the eye is a radiosensitive tissue with cataract formation being the major concern. Recently reduced recommended dose limits to the lens of the eye have made understanding the dose to this tissue of increased importance. Due to memory limitations, the voxel resolution of computational phantoms used for radiation dose calculations is too large to accurately represent the dimensions of the eye. A revised eye model is constructed using physiological data for the dimensions of radiosensitive tissues, and is then transformed into a high-resolution voxel model. This eye model is combined with an existing set of whole body models to form a multi-scale voxel phantom, which is used with the MCNPX code to calculate radiation dose from various exposure types. This phantom provides an accurate representation of the radiation transport through the structures of the eye. Two alternate methods of including a high-resolution eye model within an existing whole body model are developed. The accuracy and performance of each method is compared against existing computational phantoms.

Review article: Efficacy and safety of methoxyflurane analgesia in the emergency department and prehospital setting.

PubMed

Grindlay, Joanne; Babl, Franz E

2009-02-01

This article reviews the evidence for the analgesic efficacy of methoxyflurane in both prehospital and ED settings, as well as the adverse event profile associated with methoxyflurane use. Although there are no published controlled trials of methoxyflurane in sub-anaesthetic doses, available data indicate that it is an efficacious analgesic. There is inadequate evidence regarding its use as an agent for procedural pain. Despite the potential for renal impairment evident when it was used in anaesthetic doses, no significant adverse effects have been reported in the literature, neither in patients nor occupationally, when the dose used is limited to that currently recommended.

Point-of-use chlorination of turbid water: results from a field study in Tanzania.

PubMed

Mohamed, Hussein; Brown, Joe; Njee, Robert M; Clasen, Thomas; Malebo, Hamisi M; Mbuligwe, Steven

2015-06-01

Household-based chlorine disinfection is widely effective against waterborne bacteria and viruses, and may be among the most inexpensive and accessible options for household water treatment. The microbiological effectiveness of chlorine is limited, however, by turbidity. In Tanzania, there are no guidelines on water chlorination at household level, and limited data on whether dosing guidelines for higher turbidity waters are sufficient to produce potable water. This study was designed to assess the effectiveness of chlorination across a range of turbidities found in rural water sources, following local dosing guidelines that recommend a 'double dose' for water that is visibly turbid. We chlorinated water from 43 sources representing a range of turbidities using two locally available chlorine-based disinfectants: WaterGuard and Aquatabs. We determined free available chlorine at 30 min and 24 h contact time. Our data suggest that water chlorination with WaterGuard or Aquatabs can be effective using both single and double doses up to 20 nephelometric turbidity units (NTU), or using a double dose of Aquatabs up to 100 NTU, but neither was effective at turbidities greater than 100 NTU.

Assessing dose of the representative person for the purpose of radiation protection of the public. ICRP publication 101. Approved by the Commission in September 2005.

PubMed

2006-01-01

The Commission intended that its revised recommendations should be based on a simple, but widely applicable, system of protection that would clarify its objectives and provide a basis for the more formal systems needed by operating managers and regulators. The recommendations would establish quantified constraints, or limits, on individual dose from specified sources. These dose constraints apply to actual or representative people who encounter occupational, medical, and public exposures. This report updates the previous guidance for estimating dose to the public. Dose to the public cannot be measured directly and, in some cases, it cannot be measured at all. Therefore, for the purpose of protection of the public, it is necessary to characterise an individual, either hypothetical or specific, whose dose can be used for determining compliance with the relevant dose constraint. This individual is defined as the 'representative person'. The Commission's goal of protection of the public is achieved if the relevant dose constraint for this individual for a single source is met and radiological protection is optimised. This report explains the process of estimating annual dose and recognises that a number of different methods are available for this purpose. These methods range from deterministic calculations to more complex probabilistic techniques. In addition, a mixture of these techniques may be applied. In selecting characteristics of the representative person, three important concepts should be borne in mind: reasonableness, sustainability, and homogeneity. Each concept is explained and examples are provided to illustrate their roles. Doses to the public are prospective (may occur in the future) or retrospective (occurred in the past). Prospective doses are for hypothetical individuals who may or may not exist in the future, while retrospective doses are generally calculated for specific individuals. The Commission recognises that the level of detail afforded by its provision of dose coefficients for six age categories is not necessary in making prospective assessments of dose, given the inherent uncertainties usually associated with estimating dose to the public and with identification of the representative person. It now recommends the use of three age categories for estimating annual dose to the representative person for prospective assessments. These categories are 0-5 years (infant), 6-15 years (child), and 16-70 years (adult). For practical implementation of this recommendation, dose coefficients and habit data for a 1-year-old infant, a 10-year-old child, and an adult should be used to represent the three age categories. In a probabilistic assessment of dose, whether from a planned facility or an existing situation, the Commission recommends that the representative person should be defined such that the probability is less than about 5% that a person drawn at random from the population will receive a greater dose. If such an assessment indicates that a few tens of people or more could receive doses above the relevant constraint, the characteristics of these people need to be explored. If, following further analysis, it is shown that doses to a few tens of people are indeed likely to exceed the relevant dose constraint, actions to modify the exposure should be considered. The Commission recognises the role that stakeholders can play in identifying characteristics of the representative person. Involvement of stakeholders can significantly improve the quality, understanding, and acceptability of the characteristics of the representative person and the resulting estimated dose.

Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy Through Science – Addressing the ODWAC New Recommendation

PubMed Central

Dingwall, S.; Mills, C.E.; Phan, N.; Taylor, K.; Boreham, D.R.

2011-01-01

Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered. The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from tritium exposure at 20 Bq/L would be orders of magnitude less than that from exposure to natural background sources of radiation. The new proposed standard would set the radiation dose limit for drinking water to 0.0003 mSv/year, which is equivalent to approximately three times the dose from naturally occurring tritium in drinking water. This new standard is incongruent with national and international standards for safe levels of radiation exposure, currently set at 1 mSv/year for the general public. Scientific research from leading authorities on the carcinogenic health effects of tritium exposure supports the notion that the current standard of 7,000 Bq/L (annual dose of 0.1 mSv) is a safe standard for human health. Policy-making for the purpose of regulating tritium levels in drinking water is a dynamic multi-stage process that is influenced by more than science alone. Ethics, economics, and public perception also play important roles in policy development; however, these factors sometimes undermine the scientific evidence that should form the basis of informed decision making. Consequently, implementing a new standard without a scientific basis may lead the public to perceive that risks from tritium have been historically underestimated. It was concluded that the new recommendation is not supported by any new scientific insight regarding negative consequences of low dose effects, and may be contrary to new data on the potential benefits of low dose effects. Given the lack of cost versus benefit analysis, this type of dramatic policy change could have detrimental effects to society from an ethical, economical, and public perception perspective. PMID:21431084

Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy Through Science - Addressing the ODWAC New Recommendation.

PubMed

Dingwall, S; Mills, C E; Phan, N; Taylor, K; Boreham, D R

2011-02-22

Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered.The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from tritium exposure at 20 Bq/L would be orders of magnitude less than that from exposure to natural background sources of radiation. The new proposed standard would set the radiation dose limit for drinking water to 0.0003 mSv/year, which is equivalent to approximately three times the dose from naturally occurring tritium in drinking water. This new standard is incongruent with national and international standards for safe levels of radiation exposure, currently set at 1 mSv/year for the general public. Scientific research from leading authorities on the carcinogenic health effects of tritium exposure supports the notion that the current standard of 7,000 Bq/L (annual dose of 0.1 mSv) is a safe standard for human health.Policy-making for the purpose of regulating tritium levels in drinking water is a dynamic multi-stage process that is influenced by more than science alone. Ethics, economics, and public perception also play important roles in policy development; however, these factors sometimes undermine the scientific evidence that should form the basis of informed decision making. Consequently, implementing a new standard without a scientific basis may lead the public to perceive that risks from tritium have been historically underestimated. It was concluded that the new recommendation is not supported by any new scientific insight regarding negative consequences of low dose effects, and may be contrary to new data on the potential benefits of low dose effects. Given the lack of cost versus benefit analysis, this type of dramatic policy change could have detrimental effects to society from an ethical, economical, and public perception perspective.

Dissipation of Pendimethalin in Soybean Crop Under Field Conditions.

PubMed

Tandon, Shishir

2016-05-01

Persistence of pendimethalin was studied in soil, soybean pods, straw and water under field conditions. Pendimethalin was applied at 1 and 2 kg a.i. ha(-1). Residues in soil were detected up to 60 and 90 days at the recommended and double dose, respectively. Dissipation followed first order kinetics and was accounted for by a biphasic pattern. The half-life for the initial phase and later phase was 12.73 and 26.60 days, respectively, for recommended and 7.25 and 37.91 days, respectively, for double dose. The limit of quantification was 0.005 µg g(-1) of sample. Percent recovery from soil, oil, defatted cake, straw and water samples fortified with 0.01-1.0 mg kg(-1) varied from 84.5 %-89.6 %, 84.6 %-88.7 %, 79.4 %-86.0 %, 78.2 %-85.6 % and 90.2 %-93.0 %, respectively. At harvest, pendimethalin residue in soybean pods, straw, and soil were below detectable limits. No residues of pendimethalin were detected in ground water. Current application of pendimethalin in the environment is not expected to cause adverse health effects form the consumption of soybeans.

Impact of the introduction of rotavirus vaccine on the timeliness of other scheduled vaccines: the Australian experience.

PubMed

Hull, Brynley P; Menzies, Robert; Macartney, Kristine; McIntyre, Peter B

2013-04-08

Strict age limits for receipt of rotavirus vaccines and simultaneous use of vaccines requiring two (Rotarix(®)) and three (RotaTeq(®)) doses in Australia may impact on coverage and timeliness of other vaccines in the infant schedule. Using data from the Australian Childhood Immunisation Register (ACIR), coverage and timeliness of rotavirus vaccines and changes in timeliness of other infant vaccines following rotavirus vaccine introduction was examined, with particular emphasis on Indigenous infants in whom coverage is less optimal. Final dose rotavirus coverage reached 83% within 21 months of program commencement but remained 7% lower than other vaccines due in infancy. Coverage was 11-17% lower in Indigenous infants. Adherence to the first dose upper age limits for rotavirus vaccine was high with >97% of children vaccinated by the recommended age, but for subsequent rotavirus doses, receipt beyond the upper age limits was more common, especially in Indigenous children. Following rotavirus vaccine introduction, there were improvements in timeliness of receipt of all doses of DTPa-containing and 7-valent pneumococcal conjugate vaccines. High population coverage can be attained with rotavirus vaccines, even with adherence to strict upper age restrictions for vaccine dose administration. Rotavirus vaccine introduction appears to have impacted upon the timeliness of other concomitantly scheduled vaccines. These factors should be considered when rotavirus programs are introduced. Copyright © 2013 Elsevier Ltd. All rights reserved.

TU-D-201-05: Validation of Treatment Planning Dose Calculations: Experience Working with MPPG 5.a

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

Xue, J; Park, J; Kim, L

2016-06-15

Purpose: Newly published medical physics practice guideline (MPPG 5.a.) has set the minimum requirements for commissioning and QA of treatment planning dose calculations. We present our experience in the validation of a commercial treatment planning system based on MPPG 5.a. Methods: In addition to tests traditionally performed to commission a model-based dose calculation algorithm, extensive tests were carried out at short and extended SSDs, various depths, oblique gantry angles and off-axis conditions to verify the robustness and limitations of a dose calculation algorithm. A comparison between measured and calculated dose was performed based on validation tests and evaluation criteria recommendedmore » by MPPG 5.a. An ion chamber was used for the measurement of dose at points of interest, and diodes were used for photon IMRT/VMAT validations. Dose profiles were measured with a three-dimensional scanning system and calculated in the TPS using a virtual water phantom. Results: Calculated and measured absolute dose profiles were compared at each specified SSD and depth for open fields. The disagreement is easily identifiable with the difference curve. Subtle discrepancy has revealed the limitation of the measurement, e.g., a spike at the high dose region and an asymmetrical penumbra observed on the tests with an oblique MLC beam. The excellent results we had (> 98% pass rate on 3%/3mm gamma index) on the end-to-end tests for both IMRT and VMAT are attributed to the quality beam data and the good understanding of the modeling. The limitation of the model and the uncertainty of measurement were considered when comparing the results. Conclusion: The extensive tests recommended by the MPPG encourage us to understand the accuracy and limitations of a dose algorithm as well as the uncertainty of measurement. Our experience has shown how the suggested tests can be performed effectively to validate dose calculation models.« less

Occupational dose constraints for the lens of the eye for interventional radiologists and interventional cardiologists in the UK.

PubMed

Mairs, William DA

2016-06-01

The International Commission on Radiological Protection (ICRP) has recommended a 20 mSv year(-1) dose limit for the lens of the eye, which has been adopted in the European Union Basic Safety Standards. Interventional radiologists (IRs) and interventional cardiologists (ICs) are likely to be affected by this. The effects of radiation in the lens are somewhat uncertain, and the ICRP explicitly recommend optimization. Occupational dose constraints are part of the optimization process and define a level of dose which ought to be achievable in a well-managed practice. This commentary calls on the professional bodies to review a need for national constraints to guide local decisions. Consideration is given to developing such constraints using maximum expected doses in high-workload facilities with good radiation protection practices and application of a factor allowing for attenuation by lead glasses (LG). Doses are based on a Public Health England survey of eye dose in the UK. Maximum expected doses for ICs are approximately 21 mSv year(-1), neglecting LG. However, the extent of IR exposure is not yet fully known, and further evidence is required before conclusions are drawn. A Health and Safety Laboratory review of LG established a conservative dose reduction factor of 3 for models available in 2012. Application of this factor provides a dose constraint of 7 mSv year(-1) to the eye for ICs. To achieve this constraint, those employers with the most exposed ICs will have to provide and ensure the correct use of a ceiling-suspended eye shield and LG.

Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours

PubMed Central

2013-01-01

Background Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. Methods Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5–12 mg/m2 doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. Results Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m2, which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in Cmax and AUC0–t were dose proportional for the 6–12 mg/m2 doses. Conclusion The MTD of weekly cabazitaxel was 12 mg/m2 and the recommended weekly dose was 10 mg/m2. The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. Trial registration The study was registered with ClinicalTrials.gov as NCT01755390. PMID:24099585

A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia

PubMed Central

Walter, Roland B.; Erba, Harry P.; Fathi, Amir T.; Advani, Anjali S.; Lancet, Jeffrey E.; Ravandi, Farhad; Kovacsovics, Tibor; DeAngelo, Daniel J.; Bixby, Dale; Faderl, Stefan; Jillella, Anand P.; O’Meara, Megan M.; Zhao, Baiteng; Biddle-Snead, Charles; Stein, Anthony S.

2018-01-01

Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33, which is expressed in the majority of acute myeloid leukemia (AML) patients. This phase 1 study evaluated the safety, pharmacokinetics, and preliminary activity of vadastuximab talirine and determined the recommended monotherapy dose in patients with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab talirine in specific subpopulations of relapsed AML, and in a cohort of older, treatment-naive patients. Patients received vadastuximab talirine IV on day 1 (5-60 µg/kg) or on days 1 and 4 (20 µg/kg) of 21-day cycles. A total of 131 patients (median age, 73 years [range, 26-89 years]) had intermediate I-II (48%) or adverse (34%) risk by European LeukemiaNet classification; 50% of patients had underlying myelodysplasia. Two dose-limiting toxicities (grade 2 pulmonary embolism and grade 4 hypocellular marrow) occurred during dose finding. Most adverse events (AEs) were consistent with myelosuppression; nonhematologic AEs included fatigue, nausea, and diarrhea. The 30-day mortality was 8%. At the recommended monotherapy dose of 40 µg/kg, the complete remission + CRi rate was 28% (5 of 18 patients); 50% of patients who responded achieved minimal residual disease negativity. In patients across dose levels who achieved CR or CRi, the median time to full count recovery was 6.4 weeks for neutrophils (≥1000/µL) and 10.6 weeks for platelets (≥100 × 109/L). Vadastuximab talirine demonstrates activity and a tolerable safety profile as a single agent in patients with AML. The recommended monotherapy dose of vadastuximab talirine is 40 µg/kg. This trial was registered at www.clinicaltrials.gov as # NCT01902329. PMID:29196412

Oral penicillin prescribing for children in the UK: a comparison with BNF for Children age-band recommendations

PubMed Central

Saxena, Sonia; Ismael, Zareen; Murray, Macey L; Barker, Charlotte; Wong, Ian CK; Sharland, Mike; Long, Paul F

2014-01-01

Background The British National Formulary for Children (BNFC) recommends dosing oral penicillins according to age-bands, weight-bands, or weight-based calculations. Because of the rising prevalence of childhood obesity, age-band-based prescribing could lead to subtherapeutic dosing. Aim To investigate actual oral penicillin prescribing by GPs in the UK with reference to the current BNFC age-band recommendations. Design and setting Descriptive analysis of UK prescriptions in the 2010 IMS Disease-Analyzer database (IMS-DA). Method A detailed database analysis was undertaken of oral penicillin prescriptions for 0–18 year olds from the 2010 IMS-DA. The prescription analysis included all available data on formulation, strength (mg), prescription quantity unit, package size, prescribed quantity, and volume. Results Considering amoxicillin alone, no infants (aged <1 year) were prescribed the BNFC 2011 edition recommended unit dose (62.5 mg), while the majority received double the dose (125 mg); among children aged 1–5 years, 96% were prescribed the recommended unit dose (125 mg), but 40% of 6–12 year olds and 70% of 12–18 year olds were prescribed unit doses below the BNFC recommendations. For otitis media, only those children aged <1 year received the recommended dose of amoxicillin (40–90 mg/kg/day). Similar variations in dosing across age-bands were observed for phenoxymethylpenicillin and flucloxacillin. Conclusion There is wide variation in the dosing of penicillins for children in UK primary care, with very few children being prescribed the current national recommended doses. There is an urgent need to review dosing guidelines, in relation to the weights of children today. PMID:24686886

Mumps Postexposure Prophylaxis with a Third Dose of Measles-Mumps-Rubella Vaccine, Orange County, New York, USA

PubMed Central

Lawler, Jacqueline; Curns, Aaron T.; Brandeburg, Christina; Wallace, Gregory S.

2013-01-01

Although the measles-mumps-rubella (MMR) vaccine is not recommended for mumps postexposure prophylaxis (PEP), data on its effectiveness are limited. During the 2009–2010 mumps outbreak in the northeastern United States, we assessed effectiveness of PEP with a third dose of MMR vaccine among contacts in Orthodox Jewish households who were given a third dose within 5 days of mumps onset in the household’s index patient. We compared mumps attack rates between persons who received a third MMR dose during the first incubation period after onset in the index patient and 2-dose vaccinated persons who had not. Twenty-eight (11.7%) of 239 eligible household members received a third MMR dose as PEP. Mumps attack rates were 0% among third-dose recipients versus 5.2% among 2-dose recipients without PEP (p = 0.57). Although a third MMR dose administered as PEP did not have a significant effect, it may offer some benefits in specific outbreak contexts. PMID:23965729

Modification of Enrofloxacin Treatment Regimens for Poultry Experimentally Infected with Salmonella enterica Serovar Typhimurium DT104 To Minimize Selection of Resistance▿

PubMed Central

Randall, Luke P.; Cooles, Sue W.; Coldham, Nick C.; Stapleton, Ken S.; Piddock, Laura J. V.; Woodward, Martin J.

2006-01-01

We hypothesized that higher doses of fluoroquinolones for a shorter duration could maintain efficacy (as measured by reduction in bacterial count) while reducing selection in chickens of bacteria with reduced susceptibility. Chicks were infected with Salmonella enterica serovar Typhimurium DT104 and treated 1 week later with enrofloxacin at the recommended dose for 5 days (water dose adjusted to give 10 mg/kg of body weight of birds or equivalence, i.e., water at 50 ppm) or at 2.5 or 5 times the recommended dose for 2 days or 1 day, respectively. The dose was delivered continuously (ppm) or pulsed in the water (mg/kg) or by gavage (mg/kg). In vitro in sera, increasing concentrations of 0.5 to 8 μg/ml enrofloxacin correlated with increased activity. In vivo, the efficacy of the 1-day treatment was significantly less than that of the 2- and 5-day treatments. The 2-day treatments showed efficacy similar to that of the 5-day treatment in all but one repeat treatment group and significantly (P < 0.01) reduced the Salmonella counts. Dosing at 2.5× the recommended dose and pulsed dosing both increased the peak antibiotic concentrations in cecal contents, liver, lung, and sera as determined by high-pressure liquid chromatography. There was limited evidence that shorter treatment regimens (in particular the 1-day regimen) selected for fewer strains with reduced susceptibility. In conclusion, the 2-day treatment would overall require a shorter withholding time than the 5-day treatment and, in view of the increased peak antibiotic concentrations, may give rise to improved efficacy, in particular for treating respiratory and systemic infections. However, it would be necessary to validate the 2-day regimen in a field situation and in particular against respiratory and systemic infections to validate or refute this hypothesis. PMID:17030564

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

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

Shinoto, Makoto, E-mail: shinoto@saga-himat.jp; Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions undermore » the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.« less

Assessment of national dosimetry quality audits results for teletherapy machines from 1989 to 2015.

PubMed

Muhammad, Wazir; Ullah, Asad; Mahmood, Khalid; Matiullah

2016-01-01

The purpose of this study was to ensure accuracy in radiation dose delivery, external dosimetry quality audit has an equal importance with routine dosimetry performed at clinics. To do so, dosimetry quality audit was organized by the Secondary Standard Dosimetry Laboratory (SSDL) of Pakistan Institute of Nuclear Science and Technology (PINSTECH) at the national level to investigate and minimize uncertainties involved in the measurement of absorbed dose, and to improve the accuracy of dose measurement at different radiotherapy hospitals. A total of 181 dosimetry quality audits (i.e., 102 of Co-60 and 79 of linear accelerators) for teletherapy units installed at 22 different sites were performed from 1989 to 2015. The percent deviation between users’ calculated/stated dose and evaluated dose (in the result of on-site dosimetry visits) were calculated and the results were analyzed with respect to the limits of ± 2.5% (ICRU "optimal model") ± 3.0% (IAEA on-site dosimetry visits limit) and ± 5.0% (ICRU minimal or "lowest acceptable" model). The results showed that out of 181 total on-site dosimetry visits, 20.44%, 16.02%, and 4.42% were out of acceptable limits of ± 2.5% ± 3.0%, and ± 5.0%, respectively. The importance of a proper ongoing quality assurance program, recommendations of the followed protocols, and properly calibrated thermometers, pressure gauges, and humidity meters at radiotherapy hospitals are essential in maintaining consistency and uniformity of absorbed dose measurements for precision in dose delivery.

Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement.

PubMed

Moyer, Virginia A

2014-03-04

Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for lung cancer. The USPSTF reviewed the evidence on the efficacy of low-dose computed tomography, chest radiography, and sputum cytologic evaluation for lung cancer screening in asymptomatic persons who are at average or high risk for lung cancer (current or former smokers) and the benefits and harms of these screening tests and of surgical resection of early-stage non-small cell lung cancer. The USPSTF also commissioned modeling studies to provide information about the optimum age at which to begin and end screening, the optimum screening interval, and the relative benefits and harms of different screening strategies. This recommendation applies to asymptomatic adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. The USPSTF recommends annual screening for lung cancer with low-dose computed tomography in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation).

Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship.

PubMed

Arem, Hannah; Moore, Steven C; Patel, Alpa; Hartge, Patricia; Berrington de Gonzalez, Amy; Visvanathan, Kala; Campbell, Peter T; Freedman, Michal; Weiderpass, Elisabete; Adami, Hans Olov; Linet, Martha S; Lee, I-Min; Matthews, Charles E

2015-06-01

The 2008 Physical Activity Guidelines for Americans recommended a minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5 metabolic-equivalent hours per week) of aerobic activity for substantial health benefit and suggested additional benefits by doing more than double this amount. However, the upper limit of longevity benefit or possible harm with more physical activity is unclear. To quantify the dose-response association between leisure time physical activity and mortality and define the upper limit of benefit or harm associated with increased levels of physical activity. We pooled data from 6 studies in the National Cancer Institute Cohort Consortium (baseline 1992-2003). Population-based prospective cohorts in the United States and Europe with self-reported physical activity were analyzed in 2014. A total of 661,137 men and women (median age, 62 years; range, 21-98 years) and 116,686 deaths were included. We used Cox proportional hazards regression with cohort stratification to generate multivariable-adjusted hazard ratios (HRs) and 95% CIs. Median follow-up time was 14.2 years. Leisure time moderate- to vigorous-intensity physical activity. The upper limit of mortality benefit from high levels of leisure time physical activity. Compared with individuals reporting no leisure time physical activity, we observed a 20% lower mortality risk among those performing less than the recommended minimum of 7.5 metabolic-equivalent hours per week (HR, 0.80 [95% CI, 0.78-0.82]), a 31% lower risk at 1 to 2 times the recommended minimum (HR, 0.69 [95% CI, 0.67-0.70]), and a 37% lower risk at 2 to 3 times the minimum (HR, 0.63 [95% CI, 0.62-0.65]). An upper threshold for mortality benefit occurred at 3 to 5 times the physical activity recommendation (HR, 0.61 [95% CI, 0.59-0.62]); however, compared with the recommended minimum, the additional benefit was modest (31% vs 39%). There was no evidence of harm at 10 or more times the recommended minimum (HR, 0.69 [95% CI, 0.59-0.78]). A similar dose-response relationship was observed for mortality due to cardiovascular disease and to cancer. Meeting the 2008 Physical Activity Guidelines for Americans minimum by either moderate- or vigorous-intensity activities was associated with nearly the maximum longevity benefit. We observed a benefit threshold at approximately 3 to 5 times the recommended leisure time physical activity minimum and no excess risk at 10 or more times the minimum. In regard to mortality, health care professionals should encourage inactive adults to perform leisure time physical activity and do not need to discourage adults who already participate in high-activity levels.

MEASUREMENT OF RADIATION DOSES TO THE EYE LENS DURING ORTHOPEDIC SURGERY USING AN C-ARM X-RAY SYSTEM.

PubMed

Suzuki, Akira; Matsubara, Kosuke; Sasa, Yuko

2018-04-01

The present study aimed to determine doses delivered to the eye lenses of surgeons while using the inverted-C-arm technique and the protective effect of leaded spectacles during orthopedic surgery. The kerma in air was measured at five positions on leaded glasses positioned near the eye lens and on the neck using small optically stimulated luminescence (OSL) dosemeters. The lens equivalent dose was also measured at the neck using an OSL dosemeter. The maximum equivalent dose to the eye lens and the maximum kerma were 0.8 mSv/month and 0.66 mGy/month, respectively. The leaded glasses reduced the exposure by ~60%. Even if the surgeons are exposed to the maximum dose of X-ray radiation for 5 years, the equivalent doses to the eye lens will not exceed the present limit recommended by the ICRP.

Impact of inadequate doses of rituximab in the treatment of diffuse large B cell lymphoma in Malaysian patients.

PubMed

Gan, Gin Gin; Subramaniam, Rajaletchumy; Bee, Ping Chong; Chin, Edmund Fui Min; Abdul-Halim, Habibah; Tai, Mei Chee

2014-01-01

The current standard treatment for patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) is rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). A significant number of patients were not treated with recommended dose of rituximab due to limited financial resources in Malaysia. This study evaluates the efficacy of R-CHOP like chemotherapy in Malaysian patients with DLBCL. The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome. A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ≤ 2 had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001). The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.

Pharmacokinetic Dashboard-Recommended Dosing Is Different than Standard of Care Dosing in Infliximab-Treated Pediatric IBD Patients.

PubMed

Dubinsky, Marla C; Phan, Becky L; Singh, Namita; Rabizadeh, Shervin; Mould, Diane R

2017-01-01

Standard of care (SOC; combination of 5-10 mg/kg and an interval every 6-8 weeks) dosing of infliximab (IFX) is associated with significant loss of response. Dashboards using covariates that influence IFX pharmacokinetics (PK) may be a more precise way of optimizing anti-TNF dosing. We tested a prototype dashboard to compare forecasted dosing regimens with actual administered regimens and SOC. Fifty IBD patients completing IFX induction were monitored during maintenance (weeks 14-54). Clinical and laboratory data were collected at each infusion; serum was analyzed for IFX concentrations and anti-drug antibodies (ADA) at weeks 14 and 54 (Prometheus Labs, San Diego). Dosing was blinded to PK data. Dashboard-based assessments were conducted on de-identified clinical, laboratory, and PK data. Bayesian algorithms were used to forecast individualized troughs and determine optimal dosing to maintain target trough concentrations (3 μg/mL). Dashboard forecasted dosing post-week 14 was compared to actual administered dose and frequency and SOC. Using week 14 clinical data only, the dashboard recommended either a dose or an interval change (<0.5 mg/kg or <1 week difference) in 43/50 patients; only 44% recommended to have SOC dosing. When IFX14 concentration and ADA status were added to clinical data, dose and/or interval changes based on actual dosing were recommended in 48/50 (96%) patients; SOC dosing was recommended in only 11/50 (22%). Dashboard recommended SOC IFX dosing in a minority of patients. Dashboards will be an important tool to individualize IFX dosing to improve treatment durability.

Organ biodistribution of Germanium-68 in rat in the presence and absence of [68Ga]Ga-DOTA-TOC for the extrapolation to the human organ and whole-body radiation dosimetry

PubMed Central

Velikyan, Irina; Antoni, Gunnar; Sörensen, Jens; Estrada, Sergio

2013-01-01

Positron Emission Tomography (PET) and in particular gallium-68 (68Ga) applications are growing exponentially worldwide contributing to the expansion of nuclear medicine and personalized management of patients. The significance of 68Ga utility is reflected in the implementation of European Pharmacopoeia monographs. However, there is one crucial point in the monographs that might limit the use of the generators and consequently expansion of 68Ga applications and that is the limit of 0.001% of Germanium-68 (68Ge(IV)) radioactivity content in a radiopharmaceutical. We have investigated the organ distribution of 68Ge(IV) in rat and estimated human dosimetry parameters in order to provide experimental evidence for the determination and justification of the 68Ge(IV) limit. Male and female rats were injected in the tail vein with formulated [68Ge]GeCl4 in the absence or presence of [68Ga]Ga-DOTA-TOC. The tissue radioactivity distribution data was extrapolated for the estimation of human organ equivalent doses and total effective dose using Organ Level Internal Dose Assessment Code software (OLINDA/EXM). 68Ge(IV) was evenly distributed among the rat organs and fast renal excretion prevailed. Human organ equivalent dose and total effective dose estimates indicated that the kidneys were the dose-limiting organs (185±54 μSv/MBq for female and 171±38 μSv/MBq for male) and the total effective dose was 15.5±0.1 and 10.7±1.2 μSv/MBq, respectively for female and male. The results of this dosimetry study conclude that the 68Ge(IV) limit currently recommended by monographs could be increased considerably (>100 times) without exposing the patient to harm given the small absorbed doses to normal organs and fast excretion. PMID:23526484

The current status of eye lens dose measurement in interventional cardiology personnel in Thailand.

PubMed

Krisanachinda, Anchali; Srimahachota, Suphot; Matsubara, Kosuke

2017-06-01

Workers involved in interventional cardiology procedures receive high eye lens doses if radiation protection tools are not properly utilized. Currently, there is no suitable method for routine measurement of eye dose. In Thailand, the eye lens equivalent doses in terms of Hp(3) of the interventional cardiologists, nurses, and radiographers participating in interventional cardiology procedures have been measured at 12 centers since 2015 in the pilot study. The optically stimulated luminescence (OSL) dosimeter was used for measurement of the occupational exposure and the eye lens dose of 42 interventional cardiology personnel at King Chulalongkorn Memorial Hospital as one of the pilot centers. For all personnel, it is recommended that a first In Light OSL badge is placed at waist level and under the lead apron for determination of Hp(10); a second badge is placed at the collar for determination of Hp(0.07) and estimation of Hp(3). Nano Dots OSL dosimeter has been used as an eye lens dosimeter for 16 interventional cardiology personnel, both with and without lead-glass eyewear. The mean effective dose at the body, equivalent dose at the collar, and estimated eye lens dose were 0.801, 5.88, and 5.70 mSv per year, respectively. The mean eye lens dose measured by the Nano Dots dosimeter was 8.059 mSv per year on the left eye and 3.552 mSv per year on the right eye. Two of 16 interventional cardiologists received annual eye lens doses on the left side without lead glass that were higher than 20 mSv per year, the new eye lens dose limit as recommended by ICRP with the risk of eye lens opacity and cataract.

Ocular Toxicity Testing of Lunar Dust

NASA Technical Reports Server (NTRS)

Meyers, Valerie E.

2010-01-01

This slide presentation reviews the use of ocular testing to determine the toxicity of lunar dust. The OECD recommendations are reviewed. With these recommendations in mind the test methodology was to use EpiOcular, tissues derived from normal human epidermal keratinocytes, the cells of which have been differentiated on cell culture inserts to form a multi-layered structure, which closely parallels the corneal epithelium and to dose the tissue with 100 mg dust from various sources. The in-vitro study provides evidence that lunar dust is not severely corrosive or irritating, however, in vitro tests have limitations, and in vivo tests provides a more complete scenario, and information, it is recommended that in vivo tests be performed.

Estimating age-based antiretroviral therapy costs for HIV-infected children in resource-limited settings based on World Health Organization weight-based dosing recommendations

PubMed Central

2014-01-01

Background Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. Methods We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0–13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. Results The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. Conclusions The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments. PMID:24885453

Healthcare provider compliance with the 2013 ACC/AHA Adult Cholesterol Guideline recommendation for high-intensity dose statins for patients with coronary artery disease.

PubMed

Housholder-Hughes, Susan D; Martin, Melanie M; McFarland, Marilyn R; Creech, Constance J; Shea, Michael J

Atherosclerotic cardiovascular disease is the foremost cause of death for U.S. adults. The 2013 ACC/AHA Adult Cholesterol Guidelines recommend high-intensity dose statins for individuals with coronary artery disease (CAD). To determine healthcare provider compliance with the Cholesterol Guideline recommendation specific to high-intensity dose statins for patients with CAD. A retrospective chart review was conducted to determine compliance rate. A questionnaire was developed to evaluate healthcare provider beliefs, attitudes, and self-confidence toward this recommendation. Of the 473 patients with CAD, 67% were prescribed a high-intensity dose statin. Patients with non-ST segment myocardial infarction and ST segment myocardial infarction were more likely to be prescribed a high-intensity dose statin versus a moderate or low-intensity dose. Healthcare providers strongly agreed with this guideline recommendation. There exists a dichotomy between intention to prescribe and actual prescribing behaviors of high-intensity dose statin for patients with CAD. Copyright © 2017 Elsevier Inc. All rights reserved.

RADIATION DOSE DUE TO RADON AND HEAVY METAL ANALYSIS IN DRINKING WATER SAMPLES OF JAMMU DISTRICT, JAMMU & KASHMIR, INDIA.

PubMed

Kumar, A; Kaur, M; Sharma, S; Mehra, R; Sharma, D K; Mishra, R

2016-10-01

In the present investigation, radon concentration and heavy metal analysis were carried out in drinking water samples in Jammu district, Jammu & Kashmir, India. The radon concentration was measured by using RAD-7, portable alpha particle detector. The values of radon concentration in drinking water samples were also compared within the safe limit recommended by different health agencies. The total annual effective dose ranged from 53.04 to 197.29 µSv y -1 The annual effective dose from few locations from the studied area was found to be greater than the safe limit (100 µSv y -1 ) suggested by World Health Organisation (WHO) and EU Council. Heavy metal concentration was determined by atomic absorption spectrophotometer. A total of eight elements were analysed, viz. arsenic, mercury, zinc, iron, copper, chromium, manganese and cadmium. Heavy metals are considered to be the major pollutants of water sources. The results were compared with the limits of WHO, EU and Indian organisations. The trace metal analysis is not on the exceeding side of the permissible limit in all the samples. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Safe Handling of Radioactive Materials. Recommendations of the National Committee on Radiation Protection. Handbook 92.

ERIC Educational Resources Information Center

National Bureau of Standards (DOC), Washington, DC.

This handbook is designed to help users of radioactive materials to handle the radioactive material without exposing themselves or others to radiation doses in excess of maximum permissible limits. The discussion of radiation levels is in terms of readings from dosimeters and survey instruments. Safety in the handling of radioactive materials in…

Growth, yield and tuber quality of Solanum tuberosum L. under supplemental ultraviolet-B radiation at different NPK levels.

PubMed

Singh, S; Kumari, R; Agrawal, M; Agrawal, S B

2011-05-01

In many areas, decreases in the stratospheric ozone layer have resulted in an increase in ultraviolet-B (UV-B, 280-315 nm) radiation reaching the Earth's surface. The present study was conducted to evaluate the interactive effects of supplemental UV-B (sUV-B) and mineral nutrients on a tuber crop, potato (Solanum tuberosum L. var Kufri Badshah), under natural field conditions in a dry tropical environment. The nutrient treatments were the recommended dose of NPK (F(o)), 1.5 times the recommended dose of NPK (F(1)), 1.5 times the recommended dose of N (F(2)) and 1.5 times the recommended dose of K (F(3)). The response of potato plants to sUV-B varied with nutrient treatment and concentration. sUV-B adversely affected growth, yield and quality of tubers, causing an increase in reducing sugars in the tubers and thus reducing the economic value. Growth and fresh weight of tubers was maximal with sUV-B at 1.5 times recommended NPK, but the dry weight of tubers were highest with the recommended NPK dose. Reducing sugar content was lower in potato plants treated with sUV-B and the recommended NPK than with sUV-B and 1.5 times the recommended NPK. This study thus clearly shows that growing potato with 1.5 times the recommended NPK or 1.5 times the recommended dose of N/K does not alleviate the sUV-B induced changes in yield and quality of tubers compared to the recommended NPK dose. © 2010 German Botanical Society and The Royal Botanical Society of the Netherlands.

Impact of reduced dose limits on NRC licensed activities. Major issues in the implementation of ICRP/NCRP dose limit recommendations: Final report

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

Meinhold, C.B.

This report summarizes information required to estimate, at least qualitatively, the potential impacts of reducing occupational dose limits below those given in 10 CFR 20 (Revised). For this study, a questionnaire was developed and widely distributed to the radiation protection community. The resulting data together with data from existing surveys and sources were used to estimate the impact of three dose-limit options; 10 mSv yr{sup {minus}1} (1 rem yr{sup {minus}1}), 20 mSv yr{sup {minus}1} (2 rem yr{sup {minus}1}), and a combination of an annual limit of 50 mSv yr{sup {minus}1} (5 rem yr{sup {minus}1}) coupled with a cumulative limit, inmore » rem, equal to age in years. Due to the somewhat small number of responses and the lack of data in some specific areas, a working committee of radiation protection experts from a variety of licensees was employed to ensure the exposure data were representative. The following overall conclusions were reached: (1) although 10 mSv yr{sup {minus}1} is a reasonable limit for many licensees, such a limit could be extraordinarily difficult to achieve and potentially destructive to the continued operation of some licensees, such as nuclear power, fuel fabrication, and medicine; (2) twenty mSv yr{sup {minus}1} as a limit is possible for some of these groups, but for others it would prove difficult. (3) fifty mSv yr{sup {minus}1} and age in 10s of mSv appear reasonable for all licensees, both in terms of the lifetime risk of cancer and severe genetic effects to the most highly exposed workers, and the practicality of operation.« less

Overgrowth.

PubMed

Verge, Charles F; Mowat, David

2010-06-01

Overgrowth presenting at birth requires blood glucose monitoring while a cause is sought. Among older children presenting with tall stature, common causes such as familial tall stature and simple obesity must be distinguished from rarer endocrine and genetic causes. Several genetic overgrowth syndromes carry increased risk of malignancy and regular screening is recommended. The use of high-dose oestrogen or testosterone in an attempt to limit final stature has limited efficacy and carries a significant risk of side effects. Endocrine and genetic assessment ought to be considered for cases of unexplained overgrowth.

Radiation Exposure to Relatives of Patients Treated with Iodine-131 for Thyroid Cancer at Siriraj Hospital.

PubMed

Tonnonchiang, Siriporn; Sritongkul, Nopamon; Chaudakshetrin, Pachee; Tuntawiroon, Malulee

2016-02-01

Thyroid cancer patients treated with 1-131 are potential source of radiation exposure to relatives who are knowingly and willingly exposed to ionizing radiation as a result of providing comfort to patients undergoing I-131 therapy. This study aims to determine radiation dose received by relatives who care for non self-supporting 1-131 patients at Siriraj Hospital. Twenty caregivers of 20 patients underwent I-131 therapy for thyroid cancer with a standard protocol were given specific instructions with regard to radiation safety and provided with electronic digital dosimeter to continuously measure radiation dose received on daily basis, three days in the hospital. On the day patient is released, thyroid uptake estimates were performed to assess internal radiation dose received by caregivers. The 3-day accumulative doses to caregivers to patients receiving 150 mCi (n = 11) and 200 mCi (n = 9) of I-131 ranged from 37 to 333 uSv and 176 to 1,920 pSv respectively depending on the level of supports required. Thyroid uptake estimates in all caregivers were undetectable. Dosimeter indicated a maximum whole-body dose of1.92 mSv was more than the public dose limit of] mSv but within the dose constraint of 5 mSv for caregivers. Radiation dose to caregivers of a non self-supporting hospitalized patient undergoing 1-131 therapy were well below the limits recommended by the ICRP. The patients can be comforted with confidence that dose to caregivers will be less than the limit. This study provides guidance for medical practitioners to obtain practical radiation safety concerns associated with hospitalized patients receiving I-131 therapy especially when patient needs assistance.

Revisiting the definition of dose-limiting toxicities in paediatric oncology phase I clinical trials: An analysis from the Innovative Therapies for Children with Cancer Consortium.

PubMed

Bautista, Francisco; Moreno, Lucas; Marshall, Lynley; Pearson, Andrew D J; Geoerger, Birgit; Paoletti, Xavier

2017-11-01

Dose-escalation trials aim to identify the maximum tolerated dose and, importantly, the recommended phase II dose (RP2D) and rely on the occurrence of dose-limiting toxicities (DLTs) during the first treatment cycle. Molecularly targeted agents (MTAs) often follow continuous and prolonged administrations, displaying a distinct toxicity profile compared to conventional chemotherapeutics, and classical DLT criteria might not be appropriate to evaluate MTAs' toxicity. We investigated this issue in children. The Innovative Therapies for Children with Cancer Consortium (ITCC) phase I trials of novel anticancer agents between 2004 and 2015 were analysed. Data from investigational product, trial design, items defining DLT/RP2D were extracted. A survey on dose-escalation process, DLTs and RP2D definition was conducted among the ITCC clinical trials committee members. Thirteen phase I trials with 15 dose-escalation cohorts were analysed. They explored 11 MTAs and 2 novel cytotoxics; 12 evaluated DLT during cycle 1. Definition of DLT was heterogeneous: Grade III-IV haematologic toxicities that were transient or asymptomatic and grade III-IV non-haematological toxicities manageable with adequate supportive care were often excluded, whereas some included dose intensity or grade II toxicities into DLT. None of the studies considered delayed toxicity into the RP2D definition. DLTs should be homogeneously defined across trials, limiting the number of exceptions due to specific toxicities. Dose escalation should still be based on safety data from cycle 1, but delayed and overall toxicities, pharmacokinetic parameters and pharmacodynamic data should be considered to refine the final RP2D. The evaluation of long-term toxicity in the developing child cannot be adequately addressed in early trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparing Hp(3) evaluated from the conversion coefficients from air kerma to personal dose equivalent for eye lens dosimetry calibrated on a new cylindrical PMMA phantom

NASA Astrophysics Data System (ADS)

Esor, J.; Sudchai, W.; Monthonwattana, S.; Pungkun, V.; Intang, A.

2017-06-01

Based on a new occupational dose limit recommended by ICRP (2011), the annual dose limit for the lens of the eye for workers should be reduced from 150 mSv/y to 20 mSv/y averaged over 5 consecutive years in which no single year exceeding 50 mSv. This new dose limit directly affects radiologists and cardiologists whose work involves high radiation exposure over 20 mSv/y. Eye lens dosimetry (Hp(3)) has become increasingly important and should be evaluated directly based on dosimeters that are worn closely to the eye. Normally, Hp(3) dose algorithm was carried out by the combination of Hp(0.07) and Hp(10) values while dosimeters were calibrated on slab PMMA phantom. Recently, there were three reports from European Union that have shown the conversion coefficients from air kerma to Hp(3). These conversion coefficients carried out by ORAMED, PTB and CEA Saclay projects were performed by using a new cylindrical head phantom. In this study, various delivered doses were calculated using those three conversion coefficients while nanoDot, small OSL dosimeters, were used for Hp(3) measurement. These calibrations were performed with a standard X-ray generator at Secondary Standard Dosimetry Laboratory (SSDL). Delivered doses (Hp(3)) using those three conversion coefficients were compared with Hp(3) from nanoDot measurements. The results showed that percentage differences between delivered doses evaluated from the conversion coefficient of each project and Hp(3) doses evaluated from the nanoDots were found to be not exceeding -11.48 %, -8.85 % and -8.85 % for ORAMED, PTB and CEA Saclay project, respectively.

Decrease in varicella incidence after implementation of the 2-dose recommendation for varicella vaccine in New Hampshire.

PubMed

Daly, Elizabeth R; Anderson, Ludmila; Dreisig, John; Dionne-Odom, Jodie

2013-09-01

Varicella is a common infectious disease, for which 2-dose vaccination was recommended in 2006. Varicella case and vaccination data in New Hampshire were analyzed to assess impact of this recommendation on disease incidence and clinical characteristics. Varicella incidence decreased after the 2-dose recommendation, with greatest reductions in ages 5-19 years. Continued vaccination efforts should further reduce disease.

Phase I Trial Using Patupilone (Epothilone B) and Concurrent Radiotherapy for Central Nervous System Malignancies

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

Fogh, Shannon; Machtay, Mitchell; Werner-Wasik, Maria

Purpose: Based on preclinical data indicating the radiosensitizing potential of epothilone B, the present study was designed to evaluate the toxicity and response rate of patupilone, an epothilone B, with concurrent radiotherapy (RT) for the treatment of central nervous system malignancies. Methods and Materials: The present Phase I study evaluated the toxicities associated with patupilone combined with RT to establish the maximal tolerated dose. Eligible patients had recurrent gliomas (n = 10) primary (n = 5) or metastatic (n = 17) brain tumors. Dose escalation occurred if no dose-limiting toxicities, defined as any Grade 4-5 toxicity or Grade 3 toxicitymore » requiring hospitalization, occurred during treatment. Results: Of 14 patients, 5 were treated with weekly patupilone at 1.5 mg/m{sup 2}, 4 at 2.0 mg/m{sup 2}, 4 at 2.5 mg/m{sup 2}, and 1 at 4 mg/m{sup 2}. Of 18 patients, 7 were treated in the 6-mg/m{sup 2} group, 6 in the 8-mg/m{sup 2} group, and 5 in the 10-mg/m{sup 2} group. Primary central nervous system malignancies received RT to a median dose of 60 Gy. Central nervous system metastases received whole brain RT to a median dose of 37.4 Gy, and patients with recurrent gliomas underwent stereotactic RT to a median dose of 37.5 Gy. One dose-limiting toxicity (pneumonia) was observed in group receiving 8-mg/m{sup 2} every 3 weeks. At the subsequent dose level (10 mg/m{sup 2}), two Grade 4 dose-limiting toxicities occurred (renal failure and pulmonary hemorrhage); thus, 8 mg/m{sup 2} every 3 weeks was the maximal tolerated dose and the recommended Phase II dose. Conclusion: Combined with a variety of radiation doses and fractionation schedules, concurrent patupilone was well tolerated and safe, with a maximal tolerated dose of 8 mg/m{sup 2} every 3 weeks.« less

Designing Spacecraft and Mission Operations Plans to Meet Flight Crew Radiation Dose Requirements: Why is this an "Epic Challenge" for Long-Term Manned Interplanetary Flight

NASA Technical Reports Server (NTRS)

Koontz, Steven

2012-01-01

Outline of presentation: (1) Radiation Shielding Concepts and Performance - Galactic Cosmic Rays (GCRs) (1a) Some general considerations (1b) Galactic Cosmic Rays (2)GCR Shielding I: What material should I use and how much do I need? (2a) GCR shielding materials design and verification (2b) Spacecraft materials point dose cosmic ray shielding performance - hydrogen content and atomic number (2c) Accelerator point dose materials testing (2d) Material ranking and selection guidelines (2e) Development directions and return on investment (point dose metric) (2f) Secondary particle showers in the human body (2f-1) limited return of investment for low-Z, high-hydrogen content materials (3) GCR shielding II: How much will it cost? (3a) Spacecraft design and verification for mission radiation dose to the crew (3b) Habitat volume, shielding areal density, total weight, and launch cost for two habitat volumes (3c) It's All about the Money - Historical NASA budgets and budget limits (4) So, what can I do about all this? (4a) Program Design Architecture Trade Space (4b) The Vehicle Design Trade Space (4c) Some Near Term Recommendations

[Doses to organs at risk in conformational radiotherapy and stereotaxic irradiation: The heart].

PubMed

Vandendorpe, B; Servagi Vernat, S; Ramiandrisoa, F; Bazire, L; Kirova, Y M

2017-10-01

Radiation therapy of breast cancer, Hodgkin lymphoma, lung cancer and others thoracic irradiations induce an ionizing radiation dose to the heart. Irradiation of the heart, associated with patient cardiovascular risk and cancer treatment-induced cardiotoxicity, increase cardiovascular mortality. The long survival after breast or Hodgkin lymphoma irradiation requires watching carefully late treatment toxicity. The over-risk of cardiac events is related to the dose received by the heart and the irradiated cardiac volume. The limitation of cardiac irradiation should be a priority in the planning of thoracic irradiations. Practices have to be modified, using modern techniques to approach of the primary objective of radiotherapy which is to optimize the dose to the target volume, sparing healthy tissues, in this case the heart. We have reviewed the literature on cardiac toxicity induced by conformational tridimensional radiation therapy, intensity-modulated radiation therapy or stereotactic body radiation therapy, in order to evaluate the possibilities to limit cardiotoxicity. Finally, we summarise the recommendations on dose constraints to the heart and coronary arteries. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Multi-resolution voxel phantom modeling: a high-resolution eye model for computational dosimetry

NASA Astrophysics Data System (ADS)

Caracappa, Peter F.; Rhodes, Ashley; Fiedler, Derek

2014-09-01

Voxel models of the human body are commonly used for simulating radiation dose with a Monte Carlo radiation transport code. Due to memory limitations, the voxel resolution of these computational phantoms is typically too large to accurately represent the dimensions of small features such as the eye. Recently reduced recommended dose limits to the lens of the eye, which is a radiosensitive tissue with a significant concern for cataract formation, has lent increased importance to understanding the dose to this tissue. A high-resolution eye model is constructed using physiological data for the dimensions of radiosensitive tissues, and combined with an existing set of whole-body models to form a multi-resolution voxel phantom, which is used with the MCNPX code to calculate radiation dose from various exposure types. This phantom provides an accurate representation of the radiation transport through the structures of the eye. Two alternate methods of including a high-resolution eye model within an existing whole-body model are developed. The accuracy and performance of each method is compared against existing computational phantoms.

Doses to medical workers operating in a PET/CT department after the use of new dynamic techniques.

NASA Astrophysics Data System (ADS)

Dalianis, K.; Kollias, G.; Malamitsi, J.; Euthimiadou, R.; Andreou, J.; Georgiou, E.; Prassopoulos, V.

2015-09-01

Since new radiopharmaceuticals are used like [18F]-fluoro-3'-deoxy-3'-L- fluorothymidine and 18F fluoromethylcholine, also new dynamic techniques of imaging are used, measurements concerning the doses to medical staff are needed. The aim of this study was to measure the effective whole body dose of the personnel and compare them with the oldest. Estimation of equivalent dose for all members of the staff was monitored with the use of TLDs badges and electronic dosimeters. The duration of the study was year 2011 (983 patients).Concerning the nurses, we measured 10% increase in the wholebody doses and that is due to the longer time they spent near the patient (dynamic protocol). For technologist we measure 15-21% increase for they come near the patient immediately after administration. We can observe that there is an increase of the doses for technologists and nurses the numbers are significantly lower than the recommended annual dose limit by Euratrom 97/43.

Assessing endotoxins in equine-derived snake antivenoms: Comparison of the USP pyrogen test and the Limulus Amoebocyte Lysate assay (LAL).

PubMed

Solano, Gabriela; Gómez, Aarón; León, Guillermo

2015-10-01

Snake antivenoms are parenterally administered; therefore, endotoxin content must be strictly controlled. Following international indications to calculate endotoxin limits, it was determined that antivenom doses between 20 mL and 120 mL should not exceed 17.5 Endotoxin Units per milliliter (EU/mL) and 2.9 EU/mL, respectively. The rabbit pyrogen test (RPT) has been used to evaluate endotoxin contamination in antivenoms, but some laboratories have recently implemented the LAL assay. We compared the capability of both tests to evaluate endotoxin contamination in antivenoms, and we found that both methods can detect all endotoxin concentrations in the range of the antivenom specifications. The acceptance criteria of RPT and LAL must be harmonized by calculating the endotoxin limit as the quotient of the threshold pyrogenic dose and the therapeutic dose and the dose administered to rabbits as the quotient of the threshold pyrogenic dose and the endotoxin limit. Since endotoxins from Gram-negative bacteria exert different pyrogenicity, if contamination occurred, antivenom batches that induce pyrogenic reactions may be found in spite of passing LAL specifications. Although LAL assay can be used to assess endotoxin content throughout the antivenom manufacturing process, we recommend that the release of final products be based on the results of both methods. Copyright © 2015 Elsevier Ltd. All rights reserved.

Residues and dissipation kinetics of carbendazim and diethofencarb in tomato (Lycopersicon esculentum Mill.) and intake risk assessment.

PubMed

Li, Huidong; du, Hongxia; Fang, Liping; Dong, Zhan; Guan, Shuai; Fan, Wenjing; Chen, Zilei

2016-06-01

Dissipation behaviors and residues of carbendazim and diethofencarb in combination in tomato were investigated. The half-lives were 2.1-3.4 days for carbendazim, and 1.8-3.2 days for diethofencarb at a dose of 1.5 times of the recommended dosage. The residues of carbendazim and diethofencarb were below the maximum residue limits (MRLs) in China one day after application of the combination. The ultimate residues were significantly lower than the maximum permissible intake (MPI) in China at the recommended high dose for both child and adult. The values of the maximum dietary exposure for carbendazim and diethofencarb were 0.26 and 0.27 mg per person per day, respectively. The theoretical maximum daily intake (TMDI) values for carbendazim and diethofencarb were 1.5 and 0.5 mg/day, respectively. The dietary exposure was lower than the MPI, which indicates the harvested tomato samples under the experimental conditions (open field) are safe for human consumption at the recommended high dosage of the wettable powder. Copyright © 2016 Elsevier Inc. All rights reserved.

Insulin algorithms in the self-management of insulin-dependent diabetes: the interactive 'Apple Juice' program.

PubMed

Williams, A G

1996-01-01

The 'Apple Juice' program is an interactive diabetes self-management program which runs on a lap-top Macintosh Powerbook 100 computer. The dose-by-dose insulin advisory program was initially designed for children with insulin-dependent (type 1) diabetes mellitus. It utilizes several different insulin algorithms, measurement formulae, and compensation factors for meals, activity, medication and the dawn phenomenon. It was developed to assist the individual with diabetes and/or care providers, in determining specific insulin dosage recommendations throughout a 24 h period. Information technology functions include, but are not limited to automated record keeping, data recall, event reminders, data trend/pattern analyses and education. This paper highlights issues, observations and recommendations surrounding the use of the current version of the software, along with a detailed description of the insulin algorithms and measurement formulae applied successfully with the author's daughter over a six year period.

The new World Health Organization recommendation on the 2-dose measles vaccine schedule and the way forward in African Region

PubMed Central

Biellik, Robin Julian; Davis, Robert

2017-01-01

The new W.H.O. recommendation, which drops the coverage criterion for adoption of the 2-dose measles vaccine schedule, makes some African countries eligible for the 2-dose schedule which were previously ineligible. We look at the implications of the new recommendation for Ethiopia and Nigeria, the two largest African countries which are eligible under the new recommendation. PMID:29296149

Phase I/II Trial Evaluating Carbon Ion Radiotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma.

PubMed

Kong, Lin; Hu, Jiyi; Guan, Xiyin; Gao, Jing; Lu, Rong; Lu, Jiade J

2016-01-01

Radiation therapy is the mainstay strategy for the treatment of nasopharyngeal cancer (NPC). Intensity-modulated X-ray therapy (IMXT) alone is the current standard for stage I and II NPC. For stage III and IV A/B diseases, concurrent chemotherapy should be provided in addition to IMXT. However, optimal treatment for locally recurrent NPC after previous definitive dose of radiotherapy is lacking. Various techniques including brachytherapy, IMXT, stereotactic radiosurgery or radiotherapy (SRS or SBRT) have been used in the management of locally recurrent NPC. Due to the inherent limitation of these techniques, i.e., limited range of irradiation or over-irradiation to surrounding normal tissues, moderate efficacy has been observed at the cost of severe toxicities. Carbon ion radiotherapy (CIRT) offers potential physical and biological advantages over photon and proton radiotherapy. Due to the inverted dose profile of particle beams and their greater energy deposition within the Bragg peak, precise dose delivery to the target volume(s) without exposing the surrounding organs at risk to extra doses is possible. In addition, CIRT provides an increased relative biological effectiveness (RBE) as compared to photon and proton radiotherapy. Such advantages may translate to improved outcomes after irradiation in terms of disease control in radio-resistant and previously treated, recurrent malignancies. It is therefore reasonable to postulate that recurrent NPC after high-dose radiotherapy could be more resistant to re-irradiation using photons. Reports on the treatment of radio-resistant malignancies in the head and neck region such as melanoma, sarcoma, and adenoid cystic carcinoma (ACC) have demonstrated superior local control rates from CIRT as compared to photon irradiation. Thus patients with recurrent NPC are likely to benefit from the enhanced biological effectiveness of carbon ions. As effective retreatment strategy is lacking for locally recurrent NPC, carbon ion radiation therapy offers an ideal alternate to conventional X-ray irradiation. The recommended dose of re-irradiation using CIRT for locally recurrent NPC will be determined in the dose-escalating phase (Phase I) of the study. Efficacy in terms of local progression-free survival (LPFS) and overall survival (OS) will be studied in the second phase of the study. Increasing doses of CIRT using raster scanning technology from 55GyE (22×2.5 GyE) to 65 GyE (26× 2.5 GyE) will be delivered in the Phase I part of the study. The primary endpoint of the Phase I part of the study is acute and sub-acute toxicities; the primary endpoint in the Phase II part is local progression-free survival and overall survival. Using the historical 2-year OS rate of 50% in locally recurrent NPC patients treated with photon or proton, we hypothesize that CIRT can improve the 2-year OS rate to 70%. The utilization of conventional radiation techniques including IMXT, brachytherapy, or stereotactic radiation therapy provides moderate efficacy in the treatment of locally recurrent NPC due to the limitations in dose distribution and biological effectiveness. Improved outcome in terms of treatment-induced toxicity, LC, LPFS, and OS are expected using CIRT due to the physical and biological characteristics of carbon ion beam. However, the recommended dose of CIRT used in re-irradiation for the local NPC focus remain to be determined. The recommended dose as well as the efficacy of CIRT in the treatment of locally recurrent NPC will be evaluated in the present trial.

Feasibility of Implementing a Comprehensive Warfarin Pharmacogenetics Service

PubMed Central

Nutescu, Edith A.; Drozda, Katarzyna; Bress, Adam P.; Galanter, William L.; Stevenson, James; Stamos, Thomas D.; Desai, Ankit A.; Duarte, Julio D.; Gordeuk, Victor; Peace, David; Kadkol, ShriHari S.; Dodge, Carol; Saraf, Santosh; Garofalo, John; Krishnan, Jerry A.; Garcia, Joe G.N.; Cavallari, Larisa H.

2013-01-01

Objective To determine the procedural feasibility of a pharmacist-led interdisciplinary service for providing genotype-guided warfarin dosing for hospitalized patients newly starting warfarin. Design Prospective observational study Setting 483-bed hospital affiliated with a large academic institution Participants Eighty patients started on warfarin and managed by a newly implemented pharmacogenetics service. Intervention Routine warfarin genotyping and clinical pharmacogenetics consultation Measurements and Main Results The primary outcomes were percent of genotype-guided dose recommendations available prior to the second warfarin dose and adherence of the medical staff to doses recommended by the pharmacogenetics service. Of 436 genotype orders during the first 6 months of the service, 190 were deemed appropriate. For 80 patients on the service who consented to data collection, 77% of genotypes were available prior to the second warfarin dose. The median (range) time from the genotype order to the genotype result was 26 (7 to 80) hours, and the time to genotype-guided dosing recommendation was 30 (7 to 80) hours. Seventy-three percent of warfarin doses ordered by the medical staff were within 0.5 mg of the dose recommended by the pharmacogenetics consult service. Conclusions Providing routine genotype-guided warfarin dosing supported by a pharmacogenetics consult service is feasible from a procedural standpoint, with the majority of genotypes available prior to the second warfarin dose and good adherence to genotype-guided dose recommendations by the medical staff. PMID:23864527

Radiation dose to physicians’ eye lens during interventional radiology

NASA Astrophysics Data System (ADS)

Bahruddin, N. A.; Hashim, S.; Karim, M. K. A.; Sabarudin, A.; Ang, W. C.; Salehhon, N.; Bakar, K. A.

2016-03-01

The demand of interventional radiology has increased, leading to significant risk of radiation where eye lens dose assessment becomes a major concern. In this study, we investigate physicians' eye lens doses during interventional procedures. Measurement were made using TLD-100 (LiF: Mg, Ti) dosimeters and was recorded in equivalent dose at a depth of 0.07 mm, Hp(0.07). Annual Hp(0.07) and annual effective dose were estimated using workload estimation for a year and Von Boetticher algorithm. Our results showed the mean Hp(0.07) dose of 0.33 mSv and 0.20 mSv for left and right eye lens respectively. The highest estimated annual eye lens dose was 29.33 mSv per year, recorded on left eye lens during fistulogram procedure. Five physicians had exceeded 20 mSv dose limit as recommended by international commission of radiological protection (ICRP). It is suggested that frequent training and education on occupational radiation exposure are necessary to increase knowledge and awareness of the physicians’ thus reducing dose during the interventional procedure.

Recommendations to mitigate against human health risks incurred due to energetic particle irradiation beyond low earth orbit/BLEO

NASA Astrophysics Data System (ADS)

McKenna-Lawlor, Susan; Bhardwaj, Anil; Ferrari, Franco; Kuznetsov, Nikolay; Lal, Ajay K.; Li, Yinghui; Nagamatsu, Aiko; Nymmik, Rikho; Panasyuk, Michael; Petrov, Vladislav; Reitz, Günther; Pinsky, Lawrence; Shukor, Muszaphar (Sheikh); Singhvi, Ashok K.; Straube, Ulrich; Tomi, Leena; Lawrence, Townsend

2015-04-01

An account is provided of the main sources of energetic particle radiation in interplanetary space (Galactic Cosmic Radiation and Solar Energetic Particles) and career dose limits presently utilized by NASA to mitigate against the cancer and non-cancer effects potentially incurred by astronauts due to irradiation by these components are presented. Certain gaps in knowledge that presently militate against mounting viable human exploration in deep space due to the inherent health risks are identified and recommendations made as to how these gaps might be closed within a framework of global international cooperation.

Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer: a phase 1b study.

PubMed

Czito, Brian G; Deming, Dustin A; Jameson, Gayle S; Mulcahy, Mary F; Vaghefi, Houman; Dudley, Matthew W; Holen, Kyle D; DeLuca, Angela; Mittapalli, Rajendar K; Munasinghe, Wijith; He, Lei; Zalcberg, John R; Ngan, Samuel Y; Komarnitsky, Philip; Michael, Michael

2017-06-01

Further optimisation of present standard chemoradiation is needed in patients with locally advanced rectal cancer. Veliparib, an oral poly(ADP-ribose) polymerase inhibitor, has been shown to enhance the antitumour activity of chemotherapy and radiotherapy in preclinical models. We aimed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy. This phase 1b, open-label, multicentre, dose-escalation study was done at six hospitals (one in Australia and five in the USA). Patients were eligible if they were aged 18 years or more and were newly diagnosed with stage II to III locally advanced, resectable adenocarcinoma of the rectum with a distal tumour border of less than 12 cm from anal verge. Patients were ineligible if they had received anticancer therapy or surgery (except colostomy or ileostomy) 28 days or less before the first dose of study drug, previous pelvic radiotherapy, or previous treatment with poly (ADP-ribose) polymerase inhibitors. Enrolled patients received capecitabine (825 mg/m 2 orally twice daily) with radiotherapy (50·4 Gy in 1·8 Gy fractions daily, approximately 5 days consecutively per week for about 5·5 weeks). Veliparib (20-400 mg orally twice daily) was administered daily starting on day 2 of week 1 and continuing until 2 days after radiotherapy completion. Patients underwent total mesorectal excision 5-10 weeks after radiotherapy completion. The primary objectives were to establish the maximum tolerated dose and recommended phase 2 dose of veliparib plus capecitabine and radiotherapy, with an exposure-adjusted continual reassessment methodology. Efficacy and safety analyses were done per protocol. The reported study has completed accrual and all analyses are final. This trial is registered with ClinicalTrials.gov, number NCT01589419. Between June 12, 2012, and Jan 13, 2015, 32 patients received veliparib (22 in the dose-escalation group; ten in the safety expansion group); 31 were assessable for efficacy (<400 mg, n=16; 400 mg, n=15). During dose escalation, grade 2 dose-limiting toxic effects occurred in two patients; no grade 3-4 dose-limiting toxic effects were noted. Therefore, the maximum tolerated dose was not reached; the recommended phase 2 dose was selected as 400 mg twice daily. The most common treatment-emergent adverse events in all 32 patients were nausea (17 [53%]), diarrhoea (16 [50%]), and fatigue (16 [50%]). Grade 3 diarrhoea was noted in three (9%) of 32 patients; no grade 4 events were reported. Veliparib pharmacokinetics were dose proportional, with no effect on capecitabine pharmacokinetics. Tumour downstaging after surgery was noted in 22 (71%) of 31 patients; nine (29%) of 31 patients achieved a pathological complete response. Veliparib plus capecitabine and radiotherapy had an acceptable safety profile and showed a dose-proportional pharmacokinetic profile with no effect on the pharmacokinetics of capecitabine. Preliminary antitumour activity warrants further evaluation. AbbVie Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ionizing radiation sensitivity of the ocular lens and its dose rate dependence.

PubMed

Hamada, Nobuyuki

2017-10-01

In 2011, the International Commission on Radiological Protection reduced the threshold for the lens effects of low linear energy transfer (LET) radiation. On one hand, the revised threshold of 0.5 Gy is much lower than previously recommended thresholds, but mechanisms behind high radiosensitivity remain incompletely understood. On the other hand, such a threshold is independent of dose rate, in contrast to previously recommended separate thresholds each for single and fractionated/protracted exposures. Such a change was made predicated on epidemiological evidence suggesting that a threshold for fractionated/protracted exposures is not higher than an acute threshold, and that a chronic threshold is uncertain. Thus, the dose rate dependence is still unclear. This paper therefore reviews the current knowledge on the radiosensitivity of the lens and the dose rate dependence of radiation cataractogenesis, and discusses its mechanisms. Mounting biological evidence indicates that the lens cells are not necessarily radiosensitive to cell killing, and the high radiosensitivity of the lens thus appears to be attributable to other mechanisms (e.g., excessive proliferation, abnormal differentiation, a slow repair of DNA double-strand breaks, telomere, senescence, crystallin changes, non-targeted effects and inflammation). Both biological and epidemiological evidence generally supports the lack of dose rate effects. However, there is also biological evidence for the tissue sparing dose rate (or fractionation) effect of low-LET radiation and an enhancing inverse dose fractionation effect of high-LET radiation at a limited range of LET. Emerging epidemiological evidence in chronically exposed individuals implies the inverse dose rate effect. Further biological and epidemiological studies are warranted to gain deeper knowledge on the radiosensitivity of the lens and dose rate dependence of radiation cataractogenesis.

Radiation effects in space

NASA Astrophysics Data System (ADS)

Fry, R. J. M.

The radiation protection guidelines of the National Aeronautics and Space Administration (NASA) are under review by Scientific Committe 75 of the National Council on Radiation Protection and Measurements. The re-evaluation of the current guidelines is necessary, first, because of the increase in information about radiation risks since 1970 when the original recommendations were made and second, the population at risk has changed. For example, women have joined the ranks of the astronauts. Two types of radiation, protons and heavy ions, are of particular concern in space. Unfortunately, there is less information about the effects on tissues and the induction of cancer by these radiations than by other radiations. The choice of Quality Factors (Q) for obtaining dose equivalents for these radiations, is an important aspect of the risk estimate for space travel. There are not sufficient data for the induction of late effects by either protons or by heavy ions. The current information suggests a RBE for the relative protons of about 1, whereas, -a RBE of 20 for tumor induction by heavy ions, such as iron-56, appears appropriate. The recommendations for the dose equivalent career limits for skin and the lens of the eye have been reduced but the 30-day and annual limits have been raised.

Yellow Fever Vaccine Booster Doses: Recommendations of the Advisory Committee on Immunization Practices, 2015.

PubMed

Staples, J Erin; Bocchini, Joseph A; Rubin, Lorry; Fischer, Marc

2015-06-19

On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. ACIP also approved recommendations for at-risk laboratory personnel and certain travelers to receive additional doses of yellow fever vaccine (Box). The ACIP Japanese Encephalitis and Yellow Fever Vaccines Workgroup evaluated published and unpublished data on yellow fever vaccine immunogenicity and safety. The evidence for benefits and risks associated with yellow fever vaccine booster doses was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and provides the updated recommendations for yellow fever vaccine booster doses.

Radiation exposure to the eye lens of orthopaedic surgeons during various orthopaedic procedures.

PubMed

Romanova, K; Vassileva, J; Alyakov, M

2015-07-01

The aim of the present study was to assess the radiation dose to the eye lens of orthopaedic surgeons during various orthopaedic procedures and to make efforts to ensure that radiation protection is optimised. The study was performed for Fractura femoris and Fractura cruris procedures performed in orthopaedic operating theatres, as well as for fractures of wrist, ankle and hand/shoulder performed in the emergency trauma room. The highest mean value of the eye lens dose of 47.2 μSv and higher mean fluoroscopy time of 3 min, as well as the corresponding highest maximum values of 77.1 μSv and 5.0 min were observed for the Fractura femoris procedure performed with the Biplanar 500e fluoroscopy systems. At a normal workload, the estimated mean annual dose values do not exceed the annual occupational dose limit for the lens of eye, but at a heavy workload in the department, this dose limit could be achieved or exceeded. The use of protective lead glasses is recommended as they could reduce the radiation exposure of the lens of the eye. The phantom measurements demonstrated that the use of half-dose mode could additionally reduce dose to the operator's eye lens. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Treatment of subglottic laryngitis (pseudocroup): steroids instead of steam].

PubMed

Roorda, R J; Walhof, C M; Brand, P L

1998-07-18

Traditionally, steaming with warm moist air was recommended for the treatment of subglottic laryngitis (pseudocroup). However, no favourable effect has ever been demonstrated. Consequently, steaming is no longer to be advised. Systemic corticosteroids, already of proven effectiveness in severe croup, were shown to be also effective when administered in a single oral dose in moderately severe disease. Besides, in various studies, nebulisation of budesonide (2000 micrograms) with a jet nebuliser had a good effect on the clinical course of croup. However, dose-effect studies are still lacking. A single dose of corticosteroids, either systemic or inhaled via a jet nebuliser, should be the first line therapy in moderate and severe croup syndrome. In milder cases no specific treatment is needed as the disease is self-limiting.

Use of CroFab antivenin in the management of a very young pediatric copperhead envenomation.

PubMed

Trinh, Hai H; Hack, Jason B

2005-08-01

The use of crotalid Fab antivenin (CroFab) in the treatment of snake envenomations in the pediatric population is still an underexplored area. There are very limited data to confirm the efficacy and safety of dosing children the same as adults and even less information available to evaluate this antivenin use in copperhead snake bites in children. We report the first use of crotalid Fab antivenin in an adult dose for a copperhead snake envenomation in a 2-year-old child. She had rapid resolution of symptoms with no adverse effects. The report serves to increase the literature supporting the current dosing recommendations of crotalid Fab antivenin in very young pediatric patients evidenced by its effectiveness in this patient.

Potential impurities in drug substances: Compound-specific toxicology limits for 20 synthetic reagents and by-products, and a class-specific toxicology limit for alkyl bromides.

PubMed

Bercu, J P; Galloway, S M; Parris, P; Teasdale, A; Masuda-Herrera, M; Dobo, K; Heard, P; Kenyon, M; Nicolette, J; Vock, E; Ku, W; Harvey, J; White, A; Glowienke, S; Martin, E A; Custer, L; Jolly, R A; Thybaud, V

2018-04-01

This paper provides compound-specific toxicology limits for 20 widely used synthetic reagents and common by-products that are potential impurities in drug substances. In addition, a 15 μg/day class-specific limit was developed for monofunctional alkyl bromides, aligning this with the class-specific limit previously defined for monofunctional alkyl chlorides. Both the compound- and class-specific toxicology limits assume a lifetime chronic exposure for the general population (including sensitive subpopulations) by all routes of exposure for pharmaceuticals. Inhalation-specific toxicology limits were also derived for acrolein, formaldehyde, and methyl bromide because of their localized toxicity via that route. Mode of action was an important consideration for a compound-specific toxicology limit. Acceptable intake (AI) calculations for certain mutagenic carcinogens assumed a linear dose-response for tumor induction, and permissible daily exposure (PDE) determination assumed a non-linear dose-response. Several compounds evaluated have been previously incorrectly assumed to be mutagenic, or to be mutagenic carcinogens, but the evidence reported here for such compounds indicates a lack of mutagenicity, and a non-mutagenic mode of action for tumor induction. For non-mutagens with insufficient data to develop a toxicology limit, the ICH Q3A qualification thresholds are recommended. The compound- and class-specific toxicology limits described here may be adjusted for an individual drug substance based on treatment duration, dosing schedule, severity of the disease and therapeutic indication. Copyright © 2018. Published by Elsevier Inc.

SU-E-T-649: Quality Assurances for Proton Therapy Delivery Equipment

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

Arjomandy, B; Kase, Y; Flanz, J

2015-06-15

Purpose: The number of proton therapy centers has increased dramatically over the past decade. Currently, there is no comprehensive set of guidelines that addresses quality assurance (QA) procedures for the different technologies used for proton therapy. The AAPM has charged task group 224 (TG-224) to provide recommendations for QA required for accurate and safe dose delivery, using existing and next generation proton therapy delivery equipment. Methods: A database comprised of QA procedures and tolerance limits was generated from many existing proton therapy centers in and outside of the US. These consist of proton therapy centers that possessed double scattering, uniformmore » scanning, and pencil beams delivery systems. The diversity in beam delivery systems as well as the existing devices to perform QA checks for different beam parameters is the main subject of TG-224. Based on current practice at the clinically active proton centers participating in this task group, consensus QA recommendations were developed. The methodologies and requirements of the parameters that must be verified for consistency of the performance of the proton beam delivery systems are discussed. Results: TG-224 provides procedures and QA checks for mechanical, imaging, safety and dosimetry requirements for different proton equipment. These procedures are categorized based on their importance and their required frequencies in order to deliver a safe and consistent dose. The task group provides daily, weekly, monthly, and annual QA check procedures with their tolerance limits. Conclusions: The procedures outlined in this protocol provide sufficient information to qualified medical physicists to perform QA checks for any proton delivery system. Execution of these procedures should provide confidence that proton therapy equipment is functioning as commissioned for patient treatment and delivers dose safely and accurately within the established tolerance limits. The report will be published in late 2015.« less

Feasibility of implementing a comprehensive warfarin pharmacogenetics service.

PubMed

Nutescu, Edith A; Drozda, Katarzyna; Bress, Adam P; Galanter, William L; Stevenson, James; Stamos, Thomas D; Desai, Ankit A; Duarte, Julio D; Gordeuk, Victor; Peace, David; Kadkol, Shrihari S; Dodge, Carol; Saraf, Santosh; Garofalo, John; Krishnan, Jerry A; Garcia, Joe G N; Cavallari, Larisa H

2013-11-01

To determine the procedural feasibility of a pharmacist-led interdisciplinary service for providing genotype-guided warfarin dosing for hospitalized patients newly starting warfarin. Prospective observational study. A 438-bed tertiary care hospital affiliated with a large academic institution. Eighty patients who started warfarin therapy and were managed by a newly implemented pharmacogenetics service. All patients received routine warfarin genotyping and clinical pharmacogenetics consultation. The primary outcomes were percentage of genotype-guided dose recommendations available prior to the second warfarin dose and adherence of the medical staff to doses recommended by the pharmacogenetics service. Of 436 genotype orders placed during the first 6 months of the service, 190 (44%) were deemed appropriate. For the 80 patients on the service who consented to data collection, 76% of the genotypes were available prior to the second warfarin dose. The median (range) time from genotype order to genotype result was 26 hours (7-80 hrs), and the time to genotype-guided dose recommendation was 30 hours (7-80 hrs). A total of 73% of warfarin doses ordered by the medical staff were within 0.5 mg of the daily dose recommended by the pharmacogenetics consult service. Providing routine genotype-guided warfarin dosing supported by a pharmacogenetics consult service is feasible from a procedural standpoint, with most genotypes available prior to the second warfarin dose and good adherence to genotype-guided dose recommendations by the medical staff. © 2013 Pharmacotherapy Publications, Inc.

Phase I trial of combination chemotherapy with docetaxel, cisplatin and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer.

PubMed

Tahara, M; Araki, K; Okano, S; Kiyota, N; Fuse, N; Minashi, K; Yoshino, T; Doi, T; Zenda, S; Kawashima, M; Ogino, T; Hayashi, R; Minami, H; Ohtsu, A

2011-01-01

we investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer (HNC). treatment consisted of docetaxel (Taxotere) at doses of 50, 60, and 70 mg/m(2); cisplatin at 70 mg·m(2)/day on day 1; and S-1 twice daily on days 1-14 at doses of 40, 60, and 80 mg·m(2)/day, repeated every 3 or 4 weeks. forty patients were enrolled. MTD was not reached until level 4. Subjects at expanded dose were limited to patients with locally advanced disease. Two dose-limiting toxic effects (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg·m(2)/day, every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 patients treated at dose level 6 (TPS: 70/70/60 mg·m(2)/day, every 3 weeks), 2 DLTs were seen. Six achieved a complete response and 22 a partial response, giving a response rate of 70%. TPS was well tolerated. The recommended phase II dose as induction chemotherapy for locally advanced HNC was determined as 70/70/60 mg·m(2)/day every 3 weeks. Antitumor activity was highly promising and warrants further investigation.

Personal Dose Equivalent Conversion Coefficients For Photons To 1 GEV

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

Veinot, K. G.; Hertel, N. E.

2010-09-27

The personal dose equivalent, H{sub p}(d), is the quantity recommended by the International Commission on Radiation Units and Measurements (ICRU) to be used as an approximation of the protection quantity Effective Dose when performing personal dosemeter calibrations. The personal dose equivalent can be defined for any location and depth within the body. Typically, the location of interest is the trunk where personal dosemeters are usually worn and in this instance a suitable approximation is a 30 cm X 30 cm X 15 cm slab-type phantom. For this condition the personal dose equivalent is denoted as H{sub p,slab}(d) and the depths,more » d, are taken to be 0.007 cm for non-penetrating and 1 cm for penetrating radiation. In operational radiation protection a third depth, 0.3 cm, is used to approximate the dose to the lens of the eye. A number of conversion coefficients for photons are available for incident energies up to several MeV, however, data to higher energies are limited. In this work conversion coefficients up to 1 GeV have been calculated for H{sub p,slab}(10) and H{sub p,slab}(3) using both the kerma approximation and by tracking secondary charged particles. For H{sub p}(0.07) the conversion coefficients were calculated, but only to 10 MeV due to computational limitations. Additionally, conversions from air kerma to H{sub p,slab}(d) have been determined and are reported. The conversion coefficients were determined for discrete incident energies, but analytical fits of the coefficients over the energy range are provided. Since the inclusion of air can influence the production of secondary charged particles incident on the face of the phantom conversion coefficients have been determined both in vacuo and with the source and slab immersed within a sphere in air. The conversion coefficients for the personal dose equivalent are compared to the appropriate protection quantity, calculated according to the recommendations of the latest International Commission on Radiological Protection (ICRP) guidance.« less

LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer.

PubMed

Takahashi, Shunji; Kobayashi, Takayuki; Tomomatsu, Junichi; Ito, Yoshinori; Oda, Hisanobu; Kajitani, Tatsuhiro; Kakizume, Tomoyuki; Tajima, Takeshi; Takeuchi, Hiromi; Maacke, Heiko; Esaki, Taito

2017-01-01

Human epidermal growth factor receptor 3 (HER3) has been identified as an important component of many receptor tyrosine kinase-driven cancers. LJM716 is a human IgG monoclonal antibody that binds HER3, trapping it in an inactive conformation. In this study, a phase I dose escalation was performed with a primary objective to establish the maximum tolerated dose and/or the recommended dose of LJM716 in Japanese patients with selected advanced solid tumors. Secondary objectives included the evaluation of the safety and tolerability, preliminary antitumor activity, and pharmacokinetics of LJM716 in Japanese patients. LJM716 was administered intravenously at doses of 10, 20, or 40 mg/kg once weekly, in 28-day cycles, to 12 patients with HER2-amplified breast cancer or gastric cancer, or with esophageal squamous cell carcinoma or squamous cell carcinoma of the head and neck, regardless of HER2 status. The maximum tolerated dose was not reached, and the recommended dose was established at 40 mg/kg. No dose-limiting toxicities were observed in the first cycle. The most frequently reported adverse events were diarrhea, fatigue, stomatitis, pyrexia, and paronychia. One unconfirmed partial response was observed in a patient with breast cancer, and 50% of the patients achieved stable disease as the best overall response. Exposure increased with ascending dose, and half-life was estimated to be 11-14 days. No anti-LJM716 antibodies were detected. LJM716 was well tolerated in Japanese patients, and a degree of tumor shrinkage was observed. ClinicalTrials.gov NCT01911936.

A phase 1 and dose-finding study of LY2523355 (litronesib), an Eg5 inhibitor, in Japanese patients with advanced solid tumors.

PubMed

Wakui, Hiroshi; Yamamoto, Noboru; Kitazono, Satoru; Mizugaki, Hidenori; Nakamichi, Shinji; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamada, Yasuhide; Suzuki, Kohei; Kanda, Hironori; Akinaga, Shiro; Tamura, Tomohide

2014-07-01

Eg5, a mitotic motor kinesin protein, plays an essential role in bipolar spindle formation in the M phase of the cell cycle. LY2523355 (litronesib) is an allosteric inhibitor of Eg5. This phase 1 and dose-finding study aimed to assess the safety, pharmacokinetics (PK), recommended dose for further studies, and preliminary efficacy in Japanese patients with advanced solid tumors. LY2523355 was given on days 1, 2, and 3 every 3 weeks at one of three dose levels: 2, 4, and 5 mg/m²/day. Toxicity was assessed according to NCI-CTCAE version 4.0, and tumor response according to RECIST version 1.1. granulocyte colony-stimulating factor (G-CSF) was used only for grade 4 neutropenia or grade 3 febrile neutropenia. Twelve patients were treated at doses of 2 (n = 3), 4 (n = 3), and 5 (n = 6) mg/m²/day. Most frequent treatment-related adverse events were neutropenia and leukopenia (100 %). Grade 4 neutropenia was observed in 83 %, but all recovered to above 500 neutrophils/μl within 7 days. All patients at 4 and 5 mg/m²/day required G-CSF support. No dose-limiting toxicities were reported up to 5 mg/m²/day. In PK analysis, LY2523355 exposure increased in a dose-dependent manner. The PK parameters for LY2523355 were similar to those observed in Western populations. No objective tumor responses were observed. The recommended dose of LY2523355 with therapeutic G-CSF use for further studies was determined to be 5 mg/m²/day in Japanese patients with advanced solid tumors.

Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies

PubMed Central

2010-01-01

Background YN968D1 (Apatinib) selectively inhibits phosphorylation of VEGFR-2 and tumor angiogenesis in mice model. The study was conducted to determine the maximum tolerated dose (MTD), safety profile, pharmacokinetic variables, and antitumor activity in advanced solid malignancies. Methods This dose-escalation study was conducted according to the Chinese State Food and Drug Administration (SFDA) recommendations in patients with advanced solid tumors to determine the MTD for orally administered apatinib. Doses of continuously administered apatinib were escalated from 250 mg. Treatment continued after dose-escalation phase until withdrawal of consent, intolerable toxicities, disease progression or death. Results Forty-six patients were enrolled. Hypertension and hand-foot syndrome were the two dose-limiting toxicities noted at dose level of 1000 mg. MTD was determined to be 850 mg once daily. Pharmacokinetic analysis showed early absorption with a half-life of 9 hours. The mean half-life was constant over all dose groups. Steady-state conditions analysis suggested no accumulation during 56 days of once-daily administration. The most frequently observed drug-related adverse events were hypertension (69.5%, 29 grade 1-2 and 3 grade 3-4), proteinuria (47.8%, 16 grade 1-2 and 6 grade 3-4), and hand-foot syndrome (45.6%, 15 grade 1-2 and 6 grade 3-4). Among the thirty-seven evaluable patients, PR was noted in seven patients (18.9%), SD 24 (64.9%), with a disease control rate of 83.8% at 8 weeks. Conclusions The recommended dose of 750 mg once daily was well tolerated. Encouraging antitumor activity across a broad range of malignancies warrants further evaluation in selected populations. Trial registration ClinicalTrials.gov unique identifier: NCT00633490 PMID:20923544

European Society for Paediatric Infectious Diseases consensus recommendations for rotavirus vaccination in Europe: update 2014.

PubMed

Vesikari, Timo; Van Damme, Pierre; Giaquinto, Carlo; Dagan, Ron; Guarino, Alfredo; Szajewska, Hania; Usonis, Vytautas

2015-06-01

The first evidence-based recommendations for rotavirus (RV) vaccination in Europe were prepared at the time of licensure of 2 live oral RV vaccines (Rotarix, GlaxoSmithKline Biologicals, and RotaTeq, Sanofi Pasteur MSD) in 2006 and published in 2008. Since then several countries in Europe and more globally have adopted universal RV vaccination of all healthy infants as part of their national immunization programs (NIPs). The experience from these NIPs has produced a wealth of post-introduction effectiveness data that, together with the evidence from prelicensure efficacy trials presented in the 2008 Recommendations, support the case of RV vaccination in Europe. The prelicensure safety trials of Rotarix and RotaTeq, each in populations of more than 60,000 infants, did not reveal risk of intussusception (IS), but postvaccination surveillance in several countries, particularly Australia and Mexico, has established that the risk of IS for both vaccines after the first dose might be between 1:50,000 and 1:80,000. Although it may be argued that the risk is acceptable vis-à-vis the great benefits of RV vaccination, this argument alone may not suffice, and every effort should be made to reduce the risk of IS. Considerable evidence, including postvaccination surveillance data from Germany, suggests that the risk of IS can be reduced by early administration of the first dose of oral RV vaccine. The previous European Society for Paediatric Infectious Diseases/European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommendations held that the first dose of oral RV vaccine should be given between 6 and 12 weeks of age; this recommendation is sustained but with an emphasis toward the lower range of the recommended age, that is, preferably between 6 and 8 weeks of age. At the time of the earlier recommendations, experience of RV vaccination in premature infants and other special target groups was limited. It is now recommended with greater confidence than before that prematurely born infants should be vaccinated according to their calendar age as recommended for full-term infants. It is now strongly recommended that all HIV-infected or HIV-exposed infants should be vaccinated with oral RV vaccine. Although specific information on many immunodeficiencies is lacking, infants with known severe combined immunodeficiency should not receive live RV vaccine.

Fertilization with phosphorus increases soil nitrogen absorption in young plants of Eucalyptus grandis.

Treesearch

Corina Graciano; Juan F. Goya; Jorge L. Frangi; Juan J. Guiamet

2006-01-01

Nitrogen (N) and phosphorus (P) are the nutrients that most commonly limit tree growth. Interactions between fertilization and soil type are well known, and in soils with moderate or low N availability, N-fertilization is frequently recommended to improve tree nutrition. The aim of this paper was to analyze how different doses of P and N applied in three different...

Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods

PubMed Central

2009-01-01

Background The International Commission on Radiological Protection (ICRP) recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model. Methods Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa) methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR) and tests against the linear model. Results The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years), liver (36.9), lung (13.6), leukaemia (23.66), and pancreas (11.86) and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose) are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range. Conclusion Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of latency and risk from 10 mSv are obtained from the 0 - 20 mSv and 5 - 500 mSv subcohorts. Large and significant cancer risks for Japanese survivors exposed to less than 20 mSv external radiation from the atomic bombs in 1945 cast doubt on the ICRP recommended annual occupational dose limit. PMID:20003238

Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.

PubMed

Paoletti, X; Ezzalfani, M; Le Tourneau, C

2015-09-01

More than 95% of published phase I trials have used the 3 + 3 design to identify the dose to be recommended for phase II trials. However, the statistical community agrees on the limitations of the 3 + 3 design compared with model-based approaches. Moreover, the mechanisms of action of targeted agents strongly challenge the hypothesis that the maximum tolerated dose constitutes the optimal dose, and more outcomes including clinical and biological activity increasingly need to be taken into account to identify the optimal dose. We review key elements from clinical publications and from the statistical literature to show that the 3 + 3 design lacks the necessary flexibility to address the challenges of targeted agents. The design issues raised by expansion cohorts, new definitions of dose-limiting toxicity and trials of combinations are not easily addressed by the 3 + 3 design or its extensions. Alternative statistical proposals have been developed to make a better use of the complex data generated by phase I trials. Their applications require a close collaboration between all actors of early phase clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP)

PubMed Central

Tiwari, Tejpratap; Moro, Pedro; Messonnier, Nancy E.; Reingold, Arthur; Sawyer, Mark; Clark, Thomas A.

2018-01-01

Summary This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus, diphtheria, and pertussis in the United States. As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations and replaces all previously published reports and policy notes; it is intended for use by clinicians and public health providers as a resource. ACIP recommends routine vaccination for tetanus, diphtheria, and pertussis. Infants and young children are recommended to receive a 5-dose series of diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccines, with one adolescent booster dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Adults who have never received Tdap also are recommended to receive a booster dose of Tdap. Women are recommended to receive a dose of Tdap during each pregnancy, which should be administered from 27 through 36 weeks’ gestation, regardless of previous receipt of Tdap. After receipt of Tdap, adolescents and adults are recommended to receive a booster tetanus and diphtheria toxoids (Td) vaccine every 10 years to assure ongoing protection against tetanus and diphtheria. PMID:29702631

Implications of current recommendations for third-generation cephalosporin use in the WHO Western Pacific Region following the emergence of multiresistant gonococci.

PubMed

Tapsall, J W

2009-08-01

To ascertain recommendations for the treatment of gonorrhoea in the WHO Western Pacific Region (WPR) following the emergence of "cephalosporin-resistant" Neisseria gonorrhoeae and to relate these to clinical and laboratory measures directed towards disease and antibiotic resistance control. WHO WPR Gonococcal Antimicrobial Resistance Programme members provided data on the type, dose and source of third-generation cephalosporins recommended for the treatment of gonorrhoea. Ceftriaxone was recommended more widely (11/15 respondents) than cefixime (five centres). No cephalosporins were recommended in three jurisdictions. One other oral (ceftibuten) and injectable (cefodizime) agent was recommended. Uniform (400 mg) doses of cefixime were recommended but ceftriaxone regimens ranged between 125 mg and 1 g, with nine of 11 respondents using a 250 mg dose. Both generic and proprietary preparations were widely used. Third-generation cephalosporins are widely recommended for the treatment of gonorrhoea in the WPR, with injectable ceftriaxone more extensively so than oral cefixime and in an expanded dose range. Few other cephalosporins were recommended. Current knowledge suggests that the trend towards ceftriaxone treatment in higher doses may decrease the impact of the circulation of "cephalosporin-resistant" gonococci in the WPR. These recommendations represent public sector practice only and of themselves are unlikely to contain the further spread of "cephalosporin-resistant" gonococci because of the general clinical use of cephalosporins. Optimisation of strategies for laboratory detection of third-generation cephalosporin resistance can be simplified in the WPR because of the restricted spectrum of cephalosporins recommended. Additional efforts are urgently required for both disease and antibiotic resistance control in gonorrhoea.

Occupational radiation exposure in vascular interventional radiology: A complete evaluation of different body regions.

PubMed

Bacchim Neto, Fernando Antonio; Alves, Allan Felipe Fattori; Mascarenhas, Yvone Maria; Nicolucci, Patrícia; Pina, Diana Rodrigues de

2016-08-01

To perform a complete evaluation on radiation doses, received by primary and assistant medical staff, while performing different vascular interventional radiology procedures. We evaluated dose received in different body regions during three categories of vascular procedures: lower limb angiography (Angiography), lower limb percutaneous transluminal angioplasty (Angioplasty) and stent graft placement for abdominal aortic aneurysm treatment (A. A. A. Treatment). We positioned the dosimeters near the eye lens, thyroid, chest, abdomen, hands, and feet of the interventional physicians. Equivalent dose was compared with annual dose limits for workers in order to determine the maximum number of procedures per year that each physician could perform. We assessed 90 procedures. We found the highest equivalent doses in the A. A. A. Treatment, in which 90% of the evaluations indicated at least one region receiving more than 1mSv per procedure. Angioplasty was the only procedural modality that provided statistically different doses for different professionals, which is an important aspect on regards to radiological protection strategies. In comparison with the dose limits, the most critical region in all procedures was the eye lens. Since each body region of the interventionist is exposed to different radiation levels, dose distribution measurements are essential for radiological protection strategies. These results indicate that dosimeters placed in abdomen instead of chest may represent more accurately the whole body doses received by the medical staff. Additional dosimeters and a stationary shield for the eye lens are strongly recommended. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Rare problems with RhD immunoglobulin for postnatal prophylaxis after large fetomaternal haemorrhage

PubMed Central

Kidson-Gerber, Giselle

2015-01-01

We report a case of unusually large fetomaternal haemorrhage in a RhD- patient; of symptomatic non-sustained haemolysis of fetal red cells in the maternal circulation with infusion of intravenous high-dose RhD immunoglobulin; and of a failure to prevent RhD alloimmunisation. The haemolytic reaction is not previously reported in this patient group and we suggest would be limited to patients where the number of fetal red cells in the circulation is high. We advocate caution in treatment and spaced dosing of RhD immunoglobulin where the required dose is high, and refer readers to the WinRhoSDF™ RhD immunoglobulin product information for their updated dosing recommendations. There is a need for better understanding of pathophysiology and RhD immunoglobulin effects, to further reduce alloimmunisation rates, and we support the reporting of prophylaxis failures to haemovigilance programmes as is in place in the United Kingdom. PMID:27512480

The radiation protection problems of high altitude and space flight

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

Fry, R.J.M.

1993-04-01

This paper considers the radiation environment in aircraft at high altitudes and spacecraft in low earth orbit and in deep space and the factors that influence the dose equivalents. Altitude, latitude and solar cycle are the major influences for flights below the radiation belts. In deep space, solar cycle and the occurrence of solar particle events are the factors of influence. The major radiation effects of concern are cancer and infertility in males. In high altitude aircraft the radiation consists mainly of protons and neutrons, with neutrons contributing about half the equivalent dose. The average dose rate at altitudes ofmore » transcontinental flights that approach the polar regions are greater by a factor of about 2.5 than on routes at low latitudes. Current estimates of does to air crews suggest they are well within the ICRP (1990) recommended dose limits for radiation workers.« less

Combined autophagy and proteasome inhibition

PubMed Central

Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-01-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy. PMID:24991834

[Diagnostic and Therapeutic Approach of Chronic Spontaneous Urticaria: Recommendations in Portugal].

PubMed

Costa, Célia; Gonçalo, Margarida

2016-11-01

Chronic spontaneous urticaria is a complex disorder, of unclear etiology, easily diagnosed although often difficult to treat. It has a significant impact on the patients' quality of life and results in high direct and indirect costs. The diagnosis of chronic spontaneous urticaria is mainly clinical and a limited number of tests is recommended for differential diagnosis and/or for the investigation/exclusion of possible causes. In addition to the complete blood count and C-reactive protein, and/or erythrocyte sedimentation rate, additional tests must be selected according to clinical criteria. The aim of therapy is the complete clinical control of chronic spontaneous urticaria. Evolution should be documented by weekly symptom scoring - Weekly Urticaria Activity Score (UAS7) -, as well as the assessment of quality of life. The therapeutic approach is based on second-generation H1 antihistamines (anti-H1) administered continuously in the approved doses (first line), and, in the absence of a clinical response, up to four times the daily-approved dose (second line). First generation H1 antihistamines are not recommended. Approximately 30% of patients are not controlled with second line therapy, and it is recommended to add a third line therapy. Of the two options, omalizumab and cyclosporine, only omalizumab is approved for chronic spontaneous urticaria and has a better safety profile, thus being preferably recommended. In Portugal there are no national-based recommendations applicable to clinical practice. The elaboration of these recommendations is justified by the need to standardize both the diagnosis and the treatment approach of patients with chronic spontaneous urticaria in Portugal, and for the referral of patients to specialized centers, in the most severe cases.

Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation.

PubMed

Dumas, J L; Lorchel, F; Perrot, Y; Aletti, P; Noel, A; Wolf, D; Courvoisier, P; Bosset, J F

2007-03-01

The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

Solar particle dose rate buildup and distribution in critical body organs

NASA Technical Reports Server (NTRS)

Atwell, William; Weyland, Mark D.; Simonsen, Lisa C.

1993-01-01

Human body organs have varying degrees of radiosensitivity as evidenced by radioepidemiologic tables. The major critical organs for both the male and female that have been identified include the lung, thyroid, stomach, and breast (female). Using computerized anatomical models of the 50th percentile United States Air Force male and female, we present the self-shielding effects of these various body organs and how the shielding effects change as the location (dose point) in the body varies. Several major solar proton events from previous solar cycles and several events from the current 22nd solar cycle have been analyzed. The solar particle event rise time, peak intensity, and decay time vary considerably from event to event. Absorbed dose and dose equivalent rate calculations and organ risk assessment data are presented for each critical body organ. These data are compared with the current NASA astronaut dose limits as recommended by the National Council on Radiation Protection and Measurements.

Microbial quality evaluation and effective decontamination of nutraceutically valued lotus seeds by electron beams and gamma irradiation

NASA Astrophysics Data System (ADS)

Bhat, Rajeev; Sridhar, K. R.; Karim, A. A.

2010-09-01

Lotus seeds are nutraceutically valued natural plant produce, which succumbs to microbial contamination, predominantly to toxigenic moulds. Results of the present study revealed seed coat portion to harbor higher proportion of microbial load, particularly fungi than cotyledon portion. Among the mycotoxins analyzed, aflatoxins (B 1, B 2, G 1 and G 2) were below detectable limits, while the seeds were devoid of Ochratoxin-A (OTA). Application of different doses of electron beam and gamma irradiation (0, 2.5, 5, 7.5, 10, 15 and 30 kGy) for decontamination purpose revealed significant dose-dependent decrease in the fungal contaminants ( P<0.05). However, the contaminant yeasts could survive up to 10 kGy dose, which could be completely eliminated at 15 kGy. From the results obtained, a dose range between 10 and 15 kGy is recommended for complete decontamination, as these doses have also been shown earlier to have minimal effects on nutritional and functional properties of lotus seeds.

A first in human, safety, pharmacokinetics, and clinical activity phase I study of once weekly administration of the Hsp90 inhibitor ganetespib (STA-9090) in patients with solid malignancies

PubMed Central

2013-01-01

Background This phase I study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and antitumor activity of ganetespib in patients with solid malignancies. Methods Patients were enrolled in cohorts of escalating ganetespib doses, given as 1 hour IV infusion, once weekly for 3 weeks, followed by a 1-week rest until disease progression or unacceptable toxicity. Endpoints included safety, pharmacokinetic and pharmacodynamic parameters and preliminary clinical activity. Results Fifty-three patients were treated at doses escalating from 7 to 259 mg/m2. The most common adverse events were Grade 1 and 2 diarrhea, fatigue, nausea or vomiting. Dose-limiting toxicities (DLT) observed were: one Grade 3 amylase elevation (150 mg/m2), one Grade 3 diarrhea and one Grade 3 and one Grade 4 asthenia (259 mg/m2). The MTD was 216 mg/m2 and the recommended phase 2 dose was established at 200 mg/m2 given IV at Days 1, 8, and 15 every 4 weeks. There was a linear relationship between dose and exposure. Plasma HSP70 protein levels remained elevated for over a week post treatment. Disease control rate (objective response and stable disease at ≥ 16 weeks) was 24.4%. Conclusions Ganetespib is well tolerated as a weekly infusion for 3 of every 4 weeks cycle. The recommended phase II dose is 200 mg/m2, and is associated with an acceptable tolerability profile. Trial registration NCT00687934 PMID:23530663

Inhibition of Mutated, Activated BRAF in Metastatic Melanoma

PubMed Central

Flaherty, Keith T.; Puzanov, Igor; Kim, Kevin B.; Ribas, Antoni; McArthur, Grant A.; Sosman, Jeffrey A.; O'Dwyer, Peter J.; Lee, Richard J.; Grippo, Joseph F.; Nolop, Keith; Chapman, Paul B.

2013-01-01

Background The identification of somatic mutations in the gene encoding the serine–threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for this disease. Methods We conducted a multicenter, phase 1, dose-escalation trial of PLX4032 (also known as RG7204), an orally available inhibitor of mutated BRAF, followed by an extension phase involving the maximum dose that could be administered without adverse effects (the recommended phase 2 dose). Patients received PLX4032 twice daily until they had disease progression. Pharmacokinetic analysis and tumor-response assessments were conducted in all patients. In selected patients, tumor biopsy was performed before and during treatment to validate BRAF inhibition. Results A total of 55 patients (49 of whom had melanoma) were enrolled in the dose-escalation phase, and 32 additional patients with metastatic melanoma who had BRAF with the V600E mutation were enrolled in the extension phase. The recommended phase 2 dose was 960 mg twice daily, with increases in the dose limited by grade 2 or 3 rash, fatigue, and arthralgia. In the dose-escalation cohort, among the 16 patients with melanoma whose tumors carried the V600E BRAF mutation and who were receiving 240 mg or more of PLX4032 twice daily, 10 had a partial response and 1 had a complete response. Among the 32 patients in the extension cohort, 24 had a partial response and 2 had a complete response. The estimated median progression-free survival among all patients was more than 7 months. Conclusions Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients. (Funded by Plexxikon and Roche Pharmaceuticals.) PMID:20818844

Determinants of antipyretic misuse in children up to 5 years of age: a cross-sectional study.

PubMed

Bilenko, Natalya; Tessler, Hedva; Okbe, Ranya; Press, Joseph; Gorodischer, Rafael

2006-05-01

Fever in children is a common and usually benign symptom. It is known that antipyretic treatment is ineffective in the prevention of simple febrile seizures. Caregivers' administration of antipyretic medications to children has been reported, but data concerning the formulations used, actual doses administered, and effects of ethnicity and socioeconomic status on administration practices are incomplete. The aim of this study was to identify the factors affecting antipyretic administration (higher-than-recommended doses in particular) by caregivers to their febrile children in 2 differing cultural-ethnic backgrounds. This cross-sectional survey study, conducted from January to March 2002, was part of a larger, ongoing survey study of the differences in care givers' knowledge, beliefs, and attitudes concerning children's fever in the 2 major cultural-ethnic groups in the Negev District in Israel: Jews and Bedouin Moslems. It was conducted at the Pediatric Emergency Department (PED), Soroka Medical Center, Beer-Sheva, Israel. A structured questionnaire was administered to Jewish and Bedouin Moslem parents or usual caregivers of young (age, 0-60 months) children attending the PED due to fever. Each child's weight was obtained from the PED medical record. After completion of the interview, the reported antipyretic dose per kilogram of body weight was calculated. Less-than-recommended dose was defined as <9 mg/kg for acetaminophen and <4.5 mg/kg for ibuprofen. Higher-than-recommended dose was defined as >16.5 mg/kg for acetaminophen and >11 mg/kg for ibuprofen. The caregivers of a total of 201 children (mean [SD] age, 20 [17] months; mean [SD] weight, 10.4 [4.0] kg) were included in the study. The study included 101 Jewish and 100 Bedouin Moslem caregivers. The proportion of people surveyed who were parents was 98%; grandmothers, 2%. Differences existed between the 2 cultural-ethnic groups in the source of knowledge regarding antipyretic use in children (a significantly larger proportion of Jewish caregivers received their knowledge concerning antipyretic use from package inserts compared with Bedouin caregivers [25.7% vs 6.0%; P < 0.001], and a significantly lower proportion of Jewish caregivers used "other" sources [15.8% vs 39.0%; P < 0.001]). Most (65.2%) caregivers indicated that they administered antipyretics for no or minimal elevations in body temperature (<-38 degrees C); 52.7% administered individual acetaminophen doses within 10% of the recommended dose, 34.8 % administered a higher-than-recommended dose, and 21.4% repeated the dose at intervals of

Can UV radiation-blocking soft contact lenses attenuate UV radiation to safe levels during summer months in the southern United States?

PubMed

Walsh, James E; Bergmanson, Jan P G; Saldana, Gerardo; Gaume, Amber

2003-01-01

Peak solar UV radiation (UVR) intensities are typically experienced in summer months. People living in the southern states of the United States, where the UVR frequently exceeds the recommended minimum erythema dose (MED), are at particular risk, especially outdoor workers. The present study analyzed summertime MED readings in Houston, TX, to assess the frequency of intensities regarded as unhealthy. The study also sought to assess whether UV-blocking hydrogel contact lenses provide ocular protection from these high doses. Readings, taken at midday using a UVR biometer, were analyzed to assess the potential UVR risk. The spectral response of the meter, modified by the spectral transmission curves of the contact lenses, allowed us to mathematically assess the ocular protection provided. In addition, ambient UVR measurements were taken at midday, using a portable UVR radiometer. The detector was adapted so that a standard diameter hydrogel contact lens could be placed over it to quantify the UV-blocking capabilities of the lens. The MED readings showed that the recommended safety standards were exceeded approximately at local midday 90% of the time. Model calculations and empirical data demonstrated that contact lenses attenuated the MED readings by up to 90%, bringing them well within the recommended Environmental Protection Agency safety standards. The efficacy of the model used in this study was verified through direct comparison of the modeled and measured data. UV-blocking hydrogel soft contact lenses reduce the MED to the human eye and therefore limit the lifetime ocular dose. These lenses are highly recommended to prevent the development of UVR-related ocular pathologic conditions.

Sound exposure during outdoor music festivals.

PubMed

Tronstad, Tron V; Gelderblom, Femke B

2016-01-01

Most countries have guidelines to regulate sound exposure at concerts and music festivals. These guidelines limit the allowed sound pressure levels and the concert/festival's duration. In Norway, where there is such a guideline, it is up to the local authorities to impose the regulations. The need to prevent hearing-loss among festival participants is self-explanatory, but knowledge of the actual dose received by visitors is extremely scarce. This study looks at two Norwegian music festivals where only one was regulated by the Norwegian guideline for concert and music festivals. At each festival the sound exposure of four participants was monitored with noise dose meters. This study compared the exposures experienced at the two festivals, and tested them against the Norwegian guideline and the World Health Organization's recommendations. Sound levels during the concerts were higher at the festival not regulated by any guideline, and levels there exceeded both the national and the Worlds Health Organization's recommendations. The results also show that front-of-house measurements reliably predict participant exposure.

Occurrence of 222Rn in irrigation water from Wadi Al-Rummah Qassim province, Saudi Arabia

NASA Astrophysics Data System (ADS)

El-Taher, Atef; Alashrah, Saleh

2015-08-01

Naturally accruing radioactive materials in the environment have received attention since they may be present in high level and pose risk to human health. The present work deals with measuring of 222Rn in irrigation water samples from Wadi Al-Rummah, Qassim province, in central of Saudi Arabia. 222Rn concentrations were measured by RAD7. It was found that the concentration of 222Rn ranged from 2.1 ± 1.2 to 7.2 ± 1.5 BqL-1. These values are below 11.1 BqL-1 the maximum contamination level recommended from the U.S. Environmental Protection Agency. The calculated annual effective dose (AED) ranging from 7.5 to 26.1 µSv/y. It was evident that the total annual effective dose resulting from radon in irrigation groundwater in Wadi Al-Rummah in Qassim area were significantly lower than the recommended limit 1 mSv/y for the public.

Updosing of Nonsedating Anti-histamines in Recalcitrant Chronic Urticaria

PubMed Central

Godse, Kiran; Bhattar, Prachi; Patil, Sharmila; Nadkarni, Nitin; Gautam, Manjyot

2016-01-01

Chronic urticaria (CU) is a persistent, debiliating condition that causes severe impairment on the quality of life (QoL) of patient by interrupting work productivity. Current guidelines recommend second-generation (nonsedating) anti-histamines for the treatment for all forms of urticaria. In patients who do not respond adequately to conventional doses of anti-histamines, it is recommended to increase the dose to up to four times to obtain control. But there are only few controlled studies that have assessed the efficacy and safety of nonsedating anti-histamines. Though sedating histamines are frequently used as an add-on therapy in severe cases, they have a negative impact on QoL by compromising sleep and performance. The use of other suggested therapeutic options (omalizumab, cyclosporine A, montelukast and dapsone) is also limited by paucity of data on their efficacy and adverse effect profile. Second-generation anti-histamines which are relatively safer require more proven data to support their judicious use to improve disease in patients with CU. PMID:27293247

Sound Exposure During Outdoor Music Festivals

PubMed Central

Tronstad, Tron V.; Gelderblom, Femke B.

2016-01-01

Most countries have guidelines to regulate sound exposure at concerts and music festivals. These guidelines limit the allowed sound pressure levels and the concert/festival's duration. In Norway, where there is such a guideline, it is up to the local authorities to impose the regulations. The need to prevent hearing-loss among festival participants is self-explanatory, but knowledge of the actual dose received by visitors is extremely scarce. This study looks at two Norwegian music festivals where only one was regulated by the Norwegian guideline for concert and music festivals. At each festival the sound exposure of four participants was monitored with noise dose meters. This study compared the exposures experienced at the two festivals, and tested them against the Norwegian guideline and the World Health Organization's recommendations. Sound levels during the concerts were higher at the festival not regulated by any guideline, and levels there exceeded both the national and the Worlds Health Organization's recommendations. The results also show that front-of-house measurements reliably predict participant exposure. PMID:27569410

Occurrence of {sup 222}Rn in irrigation water from Wadi Al-Rummah Qassim province, Saudi Arabia

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

El-Taher, Atef; Alashrah, Saleh

Naturally accruing radioactive materials in the environment have received attention since they may be present in high level and pose risk to human health. The present work deals with measuring of {sup 222}Rn in irrigation water samples from Wadi Al-Rummah, Qassim province, in central of Saudi Arabia. {sup 222}Rn concentrations were measured by RAD7. It was found that the concentration of {sup 222}Rn ranged from 2.1 ± 1.2 to 7.2 ± 1.5 BqL{sup −1}. These values are below 11.1 BqL{sup −1} the maximum contamination level recommended from the U.S. Environmental Protection Agency. The calculated annual effective dose (AED) ranging frommore » 7.5 to 26.1 µSv/y. It was evident that the total annual effective dose resulting from radon in irrigation groundwater in Wadi Al-Rummah in Qassim area were significantly lower than the recommended limit 1 mSv/y for the public.« less

HPV vaccination among lesbian and bisexual women: Findings from a national survey of young adults

PubMed Central

McRee, Annie-Laurie; Katz, Mira L.; Paskett, Electra D.; Reiter, Paul L.

2014-01-01

Background Human papillomavirus (HPV) infection and associated cervical disease are common among all women, regardless of sexual identity, yet limited research has examined HPV vaccination among lesbian and bisexual women. Methods A national sample of lesbian and bisexual women ages 18-26 (n=543) completed our online survey during Fall 2013. We used multivariable logistic regression to identify correlates of HPV vaccine initiation (receipt of at least 1 dose) and completion (receipt of all 3 recommended doses among initiators). Results Overall, 45% of respondents had initiated HPV vaccine, and 70% of initiators reported completing the series. HPV vaccine initiation was higher among respondents who: were students, had received a healthcare provider's recommendation, perceived greater positive social vaccination norms, or anticipated greater regret if they did not get vaccinated and later got HPV. Initiation was lower among those who perceived greater HPV vaccine harms or greater barriers to getting the vaccine (all p<.05). HPV vaccine completion was higher among initiators who had a college degree while it was lower among those who perceived a greater likelihood of acquiring HPV or who anticipated greater regret if they got the vaccine and fainted (all p<.05). Among HPV vaccine initiators who had not yet completed the series, about half (47%) intended to get the remaining doses. Conclusions Many lesbian and bisexual women are not getting vaccinated against HPV. Healthcare provider recommendations and women's health beliefs may be important leverage points for increasing vaccination among this population. PMID:25038312

An exposure indicator for digital radiography: AAPM Task Group 116 (executive summary).

PubMed

Shepard, S Jeff; Wang, Jihong; Flynn, Michael; Gingold, Eric; Goldman, Lee; Krugh, Kerry; Leong, David L; Mah, Eugene; Ogden, Kent; Peck, Donald; Samei, Ehsan; Wang, Jihong; Willis, Charles E

2009-07-01

Digital radiographic imaging systems, such as those using photostimulable storage phosphor, amorphous selenium, amorphous silicon, CCD, and MOSFET technology, can produce adequate image quality over a much broader range of exposure levels than that of screen/film imaging systems. In screen/film imaging, the final image brightness and contrast are indicative of over- and underexposure. In digital imaging, brightness and contrast are often determined entirely by digital postprocessing of the acquired image data. Overexposure and underexposures are not readily recognizable. As a result, patient dose has a tendency to gradually increase over time after a department converts from screen/film-based imaging to digital radiographic imaging. The purpose of this report is to recommend a standard indicator which reflects the radiation exposure that is incident on a detector after every exposure event and that reflects the noise levels present in the image data. The intent is to facilitate the production of consistent, high quality digital radiographic images at acceptable patient doses. This should be based not on image optical density or brightness but on feedback regarding the detector exposure provided and actively monitored by the imaging system. A standard beam calibration condition is recommended that is based on RQA5 but uses filtration materials that are commonly available and simple to use. Recommendations on clinical implementation of the indices to control image quality and patient dose are derived from historical tolerance limits and presented as guidelines.

An exposure indicator for digital radiography: AAPM Task Group 116 (Executive Summary)

PubMed Central

Shepard, S. Jeff; Wang, Jihong; Flynn, Michael; Gingold, Eric; Goldman, Lee; Krugh, Kerry; Leong, David L.; Mah, Eugene; Ogden, Kent; Peck, Donald; Samei, Ehsan; Wang, Jihong; Willis, Charles E.

2009-01-01

Digital radiographic imaging systems, such as those using photostimulable storage phosphor, amorphous selenium, amorphous silicon, CCD, and MOSFET technology, can produce adequate image quality over a much broader range of exposure levels than that of screen/film imaging systems. In screen/film imaging, the final image brightness and contrast are indicative of over- and underexposure. In digital imaging, brightness and contrast are often determined entirely by digital postprocessing of the acquired image data. Overexposure and underexposures are not readily recognizable. As a result, patient dose has a tendency to gradually increase over time after a department converts from screen/film-based imaging to digital radiographic imaging. The purpose of this report is to recommend a standard indicator which reflects the radiation exposure that is incident on a detector after every exposure event and that reflects the noise levels present in the image data. The intent is to facilitate the production of consistent, high quality digital radiographic images at acceptable patient doses. This should be based not on image optical density or brightness but on feedback regarding the detector exposure provided and actively monitored by the imaging system. A standard beam calibration condition is recommended that is based on RQA5 but uses filtration materials that are commonly available and simple to use. Recommendations on clinical implementation of the indices to control image quality and patient dose are derived from historical tolerance limits and presented as guidelines. PMID:19673189

The evaluation the magnitude radiation exposure dose rate in digital radiography room design

NASA Astrophysics Data System (ADS)

Dwiyanto, Agung; Setia Budi, Wahyu; Hardiman, Gagoek

2017-12-01

This study discusses the dose rate in digital radiography room, buit according to meet the provisions of KEMENKES No.1014 / Menkes / SK / XI / 2008 and Regulation of BAPETEN No. 8 / 2011. The provisions primary concern of radiation safety, not comfort, by considering the space design. There are five aspects to consider in designing the space: functionality, comfort, security, movement activities and aesthetics. However provisions only met three aspects of the design, which are a function, security and movement activity. Therefore, it is necessary to evaluate digital radiography room in terms of its ability to control external radiation exposure to be safe and comfortable The dose rate is measured by the range of primary and secondary radiation in the observation points by using Surveymeter. All data are obtained by the preliminary survey prior to the study. Furthermore, the review of digital radiography room is done based on architectural design theory. The dose rate for recommended improvement room is recalculated using the same method as the actual room with the help of computer modeling. The result of dose rate calculation at the inner and outer part of digital radiography observation room shows that in-room dose for a week at each measuring point exceeds the allowable dose limit both for staff and public. During a week of observation, the outdoor dose at some measuring points exceeds the dose limit set by the KEMENKES No.1014 / Menkes / SK / XI / 2008 and Regulation BEPETEN No 8/2011. Meanwhile, the result of dose rate calculation in the inner and outer part of the improved digital radiography room can meet the applicable regulations better.

A Phase I and Pharmacokinetic Study of the Oral Histone Deacetylase Inhibitor, MS-275, in Patients with Refractory Solid Tumors and Lymphomas

PubMed Central

Gore, Lia; Rothenberg, Mace L.; O'Bryant, Cindy L.; Schultz, Mary Kay; Sandler, Alan B.; Coffin, Denise; McCoy, Candice; Schott, Astrid; Scholz, Catherine; Eckhardt, S. Gail

2010-01-01

Purpose To evaluate the toxicity profile, pharmacologic, and biological properties of 3-pyridylmethyl N-{4-[(2-aminophenyl)carbamoyl]benzyl}carbamate (MS-275), a histone deacetylase inhibitor, when administered orally on three different dosing schedules. Experimental Design Patients with advanced solid malignancies and lymphomas were treated on three dose schedules: once every other week, twice weekly for 3 weeks every 28 days, and once weekly for 3 weeks every 28 days. First-cycle plasma pharmacokinetics and peripheral blood mononuclear cell histone acetylation were determined. Results Twenty-seven patients received ≥149 courses of treatment. Hypophosphatemia and asthenia were dose limiting on the weekly and twice-weekly dosing schedules; there was no dose-limiting toxicity on the every other week schedule. Pharmacokinetic variables revealed dose-dependent and dose-proportional increases. Two of 27 patients showed partial remissions, including one patient with metastatic melanoma who had a partial response and has remained on study for >5 years. Six patients showed prolonged disease stabilization. Levels of histone H3 and H4 acetylation in peripheral blood mononuclear cells increased qualitatively but with a high degree of interpatient variation. Conclusions MS-275 is well tolerated at doses up to 6 mg/m2 every other week or 4 mg/m2 weekly for 3 weeks followed by 1 week of rest and results in biologically relevant plasma concentrations and antitumor activity. Twice-weekly dosing was not tolerable due to asthenia, and further evaluation of this schedule was halted. The recommended dose for further disease-focused studies is 4 mg/m2 given weekly for 3 weeks every 28 days or 2 to 6 mg/m2 given once every other week. PMID:18579665

Measurement of dose equivalent distribution on-board commercial jet aircraft.

PubMed

Kubančák, J; Ambrožová, I; Ploc, O; Pachnerová Brabcová, K; Štěpán, V; Uchihori, Y

2014-12-01

The annual effective doses of aircrew members often exceed the limit of 1 mSv for the public due to the increased level of cosmic radiation at the flight altitudes, and thus, it is recommended to monitor them [International Commission on Radiation Protection. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60. Ann. ICRP 21: (1-3), (1991)]. According to the Monte Carlo simulations [Battistoni, G., Ferrari, A., Pelliccioni, M. and Villari, R. Evaluation of the doses to aircrew members taking into consideration the aircraft structures. Adv. Space Res. 36: , 1645-1652 (2005) and Ferrari, A., Pelliccioni, M. and Villari, R. Evaluation of the influence of aircraft shielding on the aircrew exposure through an aircraft mathematical model. Radiat. Prot. Dosim. 108: (2), 91-105 (2004)], the ambient dose equivalent rate Ḣ*(10) depends on the location in the aircraft. The aim of this article is to experimentally evaluate Ḣ*(10) on-board selected types of aircraft. The authors found that Ḣ*(10) values are higher in the front and the back of the cabin and lesser in the middle of the cabin. Moreover, total dosimetry characteristics obtained in this way are in a reasonable agreement with other data, in particular with the above-mentioned simulations. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Survey of patient knowledge related to acetaminophen recognition, dosing, and toxicity.

PubMed

Hornsby, Lori B; Whitley, Heather P; Hester, E Kelly; Thompson, Melissa; Donaldson, Amy

2010-01-01

To assess patient knowledge regarding acetaminophen dosing, toxicity, and recognition of acetaminophen-containing products. Descriptive, nonexperimental, cross-sectional study. Alabama, January 2007 to February 2008. 284 patients at four outpatient medical facilities. 12-item investigator-administered questionnaire. Degree of patient knowledge regarding acetaminophen safety, dosing recommendations, toxicity, alternative names and abbreviations, and products. Two-thirds of the 284 patients completing the survey reported current or recent use of pain, cold, or allergy medication. Of these, 25% reported knowing the active ingredient. Of patients, 46% and 13% knew that "acetaminophen" and "APAP," respectively, were synonymous with "Tylenol." Several patients (12%) believed that ingesting a harmful amount of acetaminophen was difficult or impossible. One-third of patients correctly identified the maximum daily dose, 10% reported a dose greater than 4 g, 25% were unsure of the dose, and 7% were unsure whether a maximum dose existed. One-half recognized liver damage as the primary toxicity. Results were similar between acetaminophen users and nonusers. Deficiencies were found in patient knowledge regarding acetaminophen recognition, dosing, and potential for toxicity. The development of effective educational initiatives is warranted to ensure patient awareness and limit the potential for acetaminophen overdose.

Test of ring, eye lens and whole body dosemeters for the dose quantity Hp(3) to be used in interventional radiology

NASA Astrophysics Data System (ADS)

Szumska, A.; Budzanowski, M.; Kopeć, R.

2017-11-01

In its statement on tissue reactions approved on 21st April 2011, the International Commission on Radiological Protection (ICRP, 2012) reviewed its recommendation concerning the equivalent dose limit for the eye lens and reduced the dose limits for occupationally exposed persons to 20 mSv in a year, averaged over defined periods of 5 years, with no single year exceeding 50 mSv. This limit was approved and written down in the new EURATOM (European Atomic Energy Community) directive 2013/59 and in the IAEA (International Atomic Energy Agency) BSS (Basic Safety Standard) of July 2014. For that reason, the necessity to monitor the eye lens may become more important than it was before. However, specially dedicated dosemeters for the dose quantity Hp(3) are using very rarely. Commonly use are only whole body personal dosemeters for the personal dose equivalent quantities Hp(10) worn on the trunk and ring dosemeters worn on finger to measure the quantity Hp(0.07). Therefore, in this work it was investigated whether dosemeters from routine use calibrated in terms of Hp(10) and Hp(0.07) and worn on thyroid collar and protective apron could deliver similar results like dedicated eye lens dosemeter worn close to the eyes. The results show that the best method if dedicated eye lens dosimeters is not used is to measure doses in terms of Hp(0.07) on the thyroid collar (Pearson product, r=0.85). Obtained results shows also importance of proper localization of eye lens dosimeter (close to the eye, from side of the X-ray source).

Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

PubMed Central

Chou, Roger; Fanciullo, Gilbert J.; Fine, Perry G.; Adler, Jeremy A.; Ballantyne, Jane C.; Davies, Pamela; Donovan, Marilee I.; Fishbain, David A.; Foley, Kathy M.; Fudin, Jeffrey; Gilson, Aaron M.; Kelter, Alexander; Mauskop, Alexander; O'Connor, Patrick G.; Passik, Steven D.; Pasternak, Gavril W.; Portenoy, Russell K.; Rich, Ben A.; Roberts, Richard G.; Todd, Knox H.; Miaskowski, Christine

2014-01-01

Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices. Perspective: Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel following a systematic review of the evidence. PMID:19187889

[Gradation in the level of vitamin consumption: possible risk of excessive consumption].

PubMed

Kodentsova, V M

2014-01-01

The ratio between the levels of consumption of certain vitamins and minerals [recommended daily allowance for labelling purposes < maximum supplement levels < tolerable upper intake level (UL) < safe level (limit) of consumption < or = therapeutic dose has been characterized. Vitamin A and beta-carotene maximum supplement levels coincides with UL, and recommended daily allowance for these micronutrients coincides with the maximal level of consumption through dietary supplements and/or multivitamins. Except for vitamin A and beta-carotene recommended daily allowance for other vitamins adopted in Russia are considerably lower than the upper safe level of consumption. For vitamin A and beta-carotene there is a potential risk for excess consumption. According to the literature data (meta-analysis) prolonged intake of high doses of antioxidant vitamins (above the RDA) both alone and in combination with two other vitamins or vitamin C [> 800 microg (R.E.) of vitamin A, > 9.6 mg of beta-carotene, > 15 mg (T.E.) of vitamin E] do not possess preventive effects and may be harmful with unwanted consequences to health, especially in well-nourished populations, persons having risk of lung cancer (smokers, workers exposed to asbestos), in certain conditions (in the atmosphere with high oxygen content, hyperoxia, oxygen therapy). Proposed mechanisms of such action may be due to the manifestation of prooxidant action when taken in high doses, shifting balance with other important natural antioxidants, their displacement (substitution), interference with the natural defense mechanisms. Athletes are the population group that requires attention as used antioxidant vitamins A, C, E, both individually and in combination in extremely high doses. In summary, it should be noted that intake of physiological doses which are equivalent to the needs of the human organism, as well as diet inclusion of fortified foods not only pose no threat to health, but will bring undoubted benefits, filling the existing lack of vitamins in the ration.

Benefit-harm analysis and charts for individualized and preference-sensitive prevention: example of low dose aspirin for primary prevention of cardiovascular disease and cancer.

PubMed

Puhan, Milo A; Yu, Tsung; Stegeman, Inge; Varadhan, Ravi; Singh, Sonal; Boyd, Cynthia M

2015-10-01

Clinical practice guidelines provide separate recommendations for different diseases that may be prevented or treated by the same intervention. Also, they commonly provide recommendations for entire populations but not for individuals. To address these two limitations, our aim was to conduct benefit-harm analyses for a wide range of individuals using the example of low dose aspirin for primary prevention of cardiovascular disease and cancer and to develop Benefit-Harm Charts that show the overall benefit-harm balance for individuals. We used quantitative benefit-harm modeling that included 16 outcomes to estimate the probability that low dose aspirin provides more benefits than harms for a wide range of men and women between 45 and 84 years of age and without a previous myocardial infarction, severe ischemic stroke, or cancer. We repeated the quantitative benefit-harm modeling for different combinations of age, sex, and outcome risks for severe ischemic and hemorrhagic stroke, myocardial infarction, cancers, and severe gastrointestinal bleeds. The analyses considered weights for the outcomes, statistical uncertainty of the effects of aspirin, and death as a competing risk. We constructed Benefit-Harm Charts that show the benefit-harm balance for different combinations of outcome risks. The Benefit-Harm Charts ( http://www.benefit-harm-balance.com ) we have created show that the benefit-harm balance differs largely across a primary prevention population. Low dose aspirin is likely to provide more benefits than harms in men, elderly people, and in those at low risk for severe gastrointestinal bleeds. Individual preferences have a major impact on the benefit-harm balance. If, for example, it is a high priority for individuals to prevent stroke and severe cancers while severe gastrointestinal bleeds are deemed to be of little importance, the benefit-harm balance is likely to favor low dose aspirin for most individuals. Instead, if severe gastrointestinal bleeds are judged to be similarly important compared to the benefit outcomes, low dose aspirin is unlikely to provide more benefits than harms. Benefit-Harm Charts support individualized benefit-harm assessments and decision making. Similarly, individualized benefit-harm assessments may allow guideline developers to issue more finely granulated recommendations that reduce the risk of over- and underuse of interventions. The example of low dose aspirin for primary prevention of cardiovascular disease and cancer shows that it may be time for guideline developers to provide combined recommendations for different diseases that may be prevented or treated by the same intervention.

A Methodology to Compare Insulin Dosing Recommendations in Real-Life Settings.

PubMed

Groat, Danielle; Grando, Maria A; Thompson, Bithika; Neto, Pedro; Soni, Hiral; Boyle, Mary E; Bailey, Marilyn; Cook, Curtiss B

2017-11-01

We propose a methodology to analyze complex real-life glucose data in insulin pump users. Patients with type 1 diabetes (T1D) on insulin pumps were recruited from an academic endocrinology practice. Glucose data, insulin bolus (IB) amounts, and self-reported alcohol consumption and exercise events were collected for 30 days. Rules were developed to retrospectively compare IB recommendations from the insulin pump bolus calculator (IPBC) against recommendations from a proposed decision aid (PDA) and for assessing the PDA's recommendation for exercise and alcohol. Data from 15 participants were analyzed. When considering instances where glucose was below target, the PDA recommended a smaller dose in 14%, but a larger dose in 13% and an equivalent IB in 73%. For glucose levels at target, the PDA suggested an equivalent IB in 58% compared to the subject's IPBC, but higher doses in 20% and lower in 22%. In events where postprandial glucose was higher than target, the PDA suggested higher doses in 25%, lower doses in 13%, and equivalent doses in 62%. In 64% of all alcohol events the PDA would have provided appropriate advice. In 75% of exercise events, the PDA appropriately advised an IB, a carbohydrate snack, or neither. This study provides a methodology to systematically analyze real-life data generated by insulin pumps and allowed a preliminary analysis of the performance of the PDA for insulin dosing. Further testing of the methodological approach in a broader diabetes population and prospective testing of the PDA are needed.

Phase I Study of LY2606368, a Checkpoint Kinase 1 Inhibitor, in Patients With Advanced Cancer

PubMed Central

Infante, Jeffrey; Janku, Filip; Jones, Suzanne; Nguyen, Ly M.; Burris, Howard; Naing, Aung; Bauer, Todd M.; Piha-Paul, Sarina; Johnson, Faye M.; Kurzrock, Razelle; Golden, Lisa; Hynes, Scott; Lin, Ji; Lin, Aimee Bence; Bendell, Johanna

2016-01-01

Purpose The primary objective was to determine safety, toxicity, and a recommended phase II dose regimen of LY2606368, an inhibitor of checkpoint kinase 1, as monotherapy. Patients and Methods This phase I, nonrandomized, open-label, dose-escalation trial used a 3 + 3 dose-escalation scheme and included patients with advanced solid tumors. Intravenous LY2606368 was dose escalated from 10 to 50 mg/m2 on schedule 1 (days 1 to 3 every 14 days) or from 40 to 130 mg/m2 on schedule 2 (day 1 every 14 days). Safety measures and pharmacokinetics were assessed, and pharmacodynamics were measured in blood, hair follicles, and circulating tumor cells. Results Forty-five patients were treated; seven experienced dose-limiting toxicities (all hematologic). The maximum-tolerated doses (MTDs) were 40 mg/m2 (schedule 1) and 105 mg/m2 (schedule 2). The most common related grade 3 or 4 treatment-emergent adverse events were neutropenia, leukopenia, anemia, thrombocytopenia, and fatigue. Grade 4 neutropenia occurred in 73.3% of patients and was transient (typically < 5 days). Febrile neutropenia incidence was low (7%). The LY2606368 exposure over the first 72 hours (area under the curve from 0 to 72 hours) at the MTD for each schedule coincided with the exposure in mouse xenografts that resulted in maximal tumor responses. Minor intra- and intercycle accumulation of LY2606368 was observed at the MTDs for both schedules. Two patients (4.4%) had a partial response; one had squamous cell carcinoma (SCC) of the anus and one had SCC of the head and neck. Fifteen patients (33.3%) had a best overall response of stable disease (range, 1.2 to 6.7 months), six of whom had SCC. Conclusion An LY2606368 dose of 105 mg/m2 once every 14 days is being evaluated as the recommended phase II dose in dose-expansion cohorts for patients with SCC. PMID:27044938

Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors.

PubMed

Lewin, Jeremy; Soria, Jean-Charles; Stathis, Anastasios; Delord, Jean-Pierre; Peters, Solange; Awada, Ahmad; Aftimos, Philippe G; Bekradda, Mohamed; Rezai, Keyvan; Zeng, Zhen; Hussain, Azher; Perez, Susan; Siu, Lillian L; Massard, Christophe

2018-05-07

Purpose Birabresib (MK-8628/OTX015) is a first-in-class bromodomain inhibitor with activity in select hematologic tumors. Safety, efficacy, and pharmacokinetics of birabresib were evaluated in patients with castrate-resistant prostate cancer, nuclear protein in testis midline carcinoma (NMC), and non-small-cell lung cancer in this phase Ib study. Patients and Methods Forty-seven patients were enrolled to receive birabresib once daily at starting doses of 80 mg continuously (cohort A) or 100 mg for 7 consecutive days (cohort B) in 21-day cycles using a parallel dose escalation 3 + 3 design. The primary objective was occurrence of dose-limiting toxicities (DLTs) and determination of the recommended phase II dose. Results Of 46 treated patients, 26 had castrate-resistant prostate cancer, 10 NMC, and 10 non-small-cell lung cancer. For cohort A, four of 19 (21%) evaluable patients had DLTs at 80 mg once daily (grade 3 thrombocytopenia [n = 3], ALT/hyperbilirubinemia [n = 1]) and two of three had DLTs at 100 mg once daily (grade 2 anorexia and nausea with treatment delay > 7 days [n = 1], grade 4 thrombocytopenia [n = 1]). No DLTs occurred in cohort B. Of 46 patients, 38 (83%) had treatment-related adverse events (diarrhea, 17 [37%]; nausea, 17 [37%]; anorexia, 14 [30%]; vomiting, 12 [26%]; thrombocytopenia 10 [22%]). Three patients with NMC (80 mg once daily) had a partial response (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) with duration of 1.4 to 8.4 months. Pharmacokinetic analysis indicated a dose-proportional increase in birabresib exposure and rapid absorption. Conclusion The recommended phase II dose of birabresib in patients with select solid tumors is 80 mg once daily with continuous dosing. Birabresib has dose-proportional exposure and a favorable safety profile, with clinical activity observed in NMC. Future studies of birabresib must consider intermittent scheduling to possibly mitigate the toxicities of chronic dosing.

Ultra-Low-Dose Fetal CT With Model-Based Iterative Reconstruction: A Prospective Pilot Study.

PubMed

Imai, Rumi; Miyazaki, Osamu; Horiuchi, Tetsuya; Asano, Keisuke; Nishimura, Gen; Sago, Haruhiko; Nosaka, Shunsuke

2017-06-01

Prenatal diagnosis of skeletal dysplasia by means of 3D skeletal CT examination is highly accurate. However, it carries a risk of fetal exposure to radiation. Model-based iterative reconstruction (MBIR) technology can reduce radiation exposure; however, to our knowledge, the lower limit of an optimal dose is currently unknown. The objectives of this study are to establish ultra-low-dose fetal CT as a method for prenatal diagnosis of skeletal dysplasia and to evaluate the appropriate radiation dose for ultra-low-dose fetal CT. Relationships between tube current and image noise in adaptive statistical iterative reconstruction and MBIR were examined using a 32-cm CT dose index (CTDI) phantom. On the basis of the results of this examination and the recommended methods for the MBIR option and the known relationship between noise and tube current for filtered back projection, as represented by the expression SD = (milliamperes) -0.5 , the lower limit of the optimal dose in ultra-low-dose fetal CT with MBIR was set. The diagnostic power of the CT images obtained using the aforementioned scanning conditions was evaluated, and the radiation exposure associated with ultra-low-dose fetal CT was compared with that noted in previous reports. Noise increased in nearly inverse proportion to the square root of the dose in adaptive statistical iterative reconstruction and in inverse proportion to the fourth root of the dose in MBIR. Ultra-low-dose fetal CT was found to have a volume CTDI of 0.5 mGy. Prenatal diagnosis was accurately performed on the basis of ultra-low-dose fetal CT images that were obtained using this protocol. The level of fetal exposure to radiation was 0.7 mSv. The use of ultra-low-dose fetal CT with MBIR led to a substantial reduction in radiation exposure, compared with the CT imaging method currently used at our institution, but it still enabled diagnosis of skeletal dysplasia without reducing diagnostic power.

Is eye lens dosimetry needed in nuclear medicine?

PubMed

Wrzesień, M; Królicki, L; Albiniak, Ł; Olszewski, J

2018-06-01

The exact level of exposure experienced by nuclear medicine personnel, whose work often requires performing manual procedures involving radioactive isotopes, is associated with the form of radiation source used. The variety of radionuclides and medical procedures, and the yearly increase in the number of patients, as well as the change of the individual dose limit for the lens of the eye from a value of 150 mSv yr -1 to 20 mSv yr -1 , mean that issues of eye lens routine dosimetry become interesting from the radiation protection point of view. This paper presents an analysis of the exposure of the eye lenses of nuclear medicine department personnel, as well as those of personnel in the facilities that produce radiopharmaceuticals for the purpose of diagnosis by positron emission tomography, from the viewpoint of the advisability of routine eye lens exposure monitoring, taking into account changes in the dose limit for the lens of the eye. The paper considers the two most commonly used radionuclides for diagnostic purposes 99m Tc, 18 F, and-for therapeutic purposes- 131 I. Dose measurements were made using thermoluminescent detectors. The estimated exposure analysis identifies the cases when the maximum annual value of the personal dose equivalent, in terms of Hp(3), exceeds threefold the new limit value (20 mSv yr -1 ). It is recommended that Hp(3) doses be routinely monitored in the group of radiopharmacists who label pharmaceuticals with the radionuclide 99m Tc and in chemists working in 18 F-FDG quality control departments in production units, where this is carried out manually.

Some Considerations for Chelation Treatment and Surgical Excision Following Incorporation of Plutonium in Wounds

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

Poudel, Deepesh; Bertelli, Luiz; Klumpp, John A.

After a plutonium-contaminated wound, the role of an internal dosimetrist is to inform the patient and the physician of the dosimetric considerations. The doses averted due to medical treatments (excision or chelation) are higher if the treatments are administered early; therefore, the internal dosimetrist needs to rely on limited information on wound counts and process knowledge for advising the physician. For this study, several wound cases in the literature were reviewed to obtain estimates of the efficacies of surgical excision and chelation treatment after plutonium-contaminated wounds. The dose coefficients calculated by coupling the NCRP 156 wound model with the systemicmore » model were used to derive the decision guidelines that may indicate medical treatment based on 1) the concept of saved doses proposed by the NCRP 156 wound model, 2) the limits recommended by the CEC/DOE guidebook, and 3) the Clinical Decision Guidelines proposed in NCRP Report No. 161. These guidelines by themselves, however, are of limited use for several reasons, including 1) large uncertainties associated with wound measurements, 2) exposure to forms of radionuclides that cannot be assigned to a single category in the NCRP 156 framework, 3) inability of the NCRP 156 model to explain some of the wound cases in the literature, 4) neglect of the local doses to the wound site and the pathophysiological response of the tissue, 5) poorly understood relationship between effective doses and risks of late health effects, and 6) disregard of the psychological aspects of radionuclide intake.« less

Some Considerations for Chelation Treatment and Surgical Excision Following Incorporation of Plutonium in Wounds

DOE PAGES

Poudel, Deepesh; Bertelli, Luiz; Klumpp, John A.; ...

2018-03-01

After a plutonium-contaminated wound, the role of an internal dosimetrist is to inform the patient and the physician of the dosimetric considerations. The doses averted due to medical treatments (excision or chelation) are higher if the treatments are administered early; therefore, the internal dosimetrist needs to rely on limited information on wound counts and process knowledge for advising the physician. For this study, several wound cases in the literature were reviewed to obtain estimates of the efficacies of surgical excision and chelation treatment after plutonium-contaminated wounds. The dose coefficients calculated by coupling the NCRP 156 wound model with the systemicmore » model were used to derive the decision guidelines that may indicate medical treatment based on 1) the concept of saved doses proposed by the NCRP 156 wound model, 2) the limits recommended by the CEC/DOE guidebook, and 3) the Clinical Decision Guidelines proposed in NCRP Report No. 161. These guidelines by themselves, however, are of limited use for several reasons, including 1) large uncertainties associated with wound measurements, 2) exposure to forms of radionuclides that cannot be assigned to a single category in the NCRP 156 framework, 3) inability of the NCRP 156 model to explain some of the wound cases in the literature, 4) neglect of the local doses to the wound site and the pathophysiological response of the tissue, 5) poorly understood relationship between effective doses and risks of late health effects, and 6) disregard of the psychological aspects of radionuclide intake.« less

Meeting report: Estimating the benefits of reducing hazardous air pollutants--summary of 2009 workshop and future considerations.

PubMed

Gwinn, Maureen R; Craig, Jeneva; Axelrad, Daniel A; Cook, Rich; Dockins, Chris; Fann, Neal; Fegley, Robert; Guinnup, David E; Helfand, Gloria; Hubbell, Bryan; Mazur, Sarah L; Palma, Ted; Smith, Roy L; Vandenberg, John; Sonawane, Babasaheb

2011-01-01

Quantifying the benefits of reducing hazardous air pollutants (HAPs, or air toxics) has been limited by gaps in toxicological data, uncertainties in extrapolating results from high-dose animal experiments to estimate human effects at lower doses, limited ambient and personal exposure monitoring data, and insufficient economic research to support valuation of the health impacts often associated with exposure to individual air toxics. To address some of these issues, the U.S. Environmental Protection Agency held the Workshop on Estimating the Benefits of Reducing Hazardous Air Pollutants (HAPs) in Washington, DC, from 30 April to 1 May 2009. Experts from multiple disciplines discussed how best to move forward on air toxics benefits assessment, with a focus on developing near-term capability to conduct quantitative benefits assessment. Proposed methodologies involved analysis of data-rich pollutants and application of this analysis to other pollutants, using dose-response modeling of animal data for estimating benefits to humans, determining dose-equivalence relationships for different chemicals with similar health effects, and analysis similar to that used for criteria pollutants. Limitations and uncertainties in economic valuation of benefits assessment for HAPS were discussed as well. These discussions highlighted the complexities in estimating the benefits of reducing air toxics, and participants agreed that alternative methods for benefits assessment of HAPs are needed. Recommendations included clearly defining the key priorities of the Clean Air Act air toxics program to identify the most effective approaches for HAPs benefits analysis, focusing on susceptible and vulnerable populations, and improving dose-response estimation for quantification of benefits.

Human papillomavirus vaccination coverage using two-dose or three-dose schedule criteria.

PubMed

Lin, Xia; Rodgers, Loren; Zhu, Liping; Stokley, Shannon; Meites, Elissa; Markowitz, Lauri E

2017-10-13

In October 2016, the Advisory Committee on Immunization Practices (ACIP) updated the human papillomavirus (HPV) vaccination recommendation to include a 2-dose schedule for U.S. adolescents initiating the vaccine series before their 15th birthday. We analyzed records for >4million persons aged 9-17years receiving any HPV vaccine by the end of each quarter during January 1, 2014-September 30, 2016 from six Immunization Information Systems Sentinel Sites, and reclassified HPV vaccination up-to-date coverage according to the updated recommendations. Compared with HPV vaccination up-to-date coverage by the 3-dose schedule only, including criteria for either a 2-dose or 3-dose schedule increased up-to-date coverage in 11-12, 13-14, and 15-17 year-olds by 4.5-8.5 percentage points. The difference between 3-dose up-to-date coverage and 2- or 3-dose up-to-date coverage was greatest in late 2016. These data provide baseline HPV vaccination coverage using current ACIP recommendations. Published by Elsevier Ltd.

Measurement of 131I activity in thyroid of nuclear medical staff and internal dose assessment in a Polish nuclear medical hospital.

PubMed

Brudecki, K; Kowalska, A; Zagrodzki, P; Szczodry, A; Mroz, T; Janowski, P; Mietelski, J W

2017-03-01

This paper presents results of 131 I thyroid activity measurements in 30 members of the nuclear medicine personnel of the Department of Endocrinology and Nuclear Medicine Holy Cross Cancer Centre in Kielce, Poland. A whole-body spectrometer equipped with two semiconductor gamma radiation detectors served as the basic research instrument. In ten out of 30 examined staff members, the determined 131 I activity was found to be above the detection limit (DL = 5 Bq of 131 I in the thyroid). The measured activities ranged from (5 ± 2) Bq to (217 ± 56) Bq. The highest activities in thyroids were detected for technical and cleaning personnel, whereas the lowest values were recorded for medical doctors. Having measured the activities, an attempt has been made to estimate the corresponding annual effective doses, which were found to range from 0.02 to 0.8 mSv. The highest annual equivalent doses have been found for thyroid, ranging from 0.4 to 15.4 mSv, detected for a cleaner and a technician, respectively. The maximum estimated effective dose corresponds to 32% of the annual background dose in Poland, and to circa 4% of the annual limit for the effective dose due to occupational exposure of 20 mSv per year, which is in compliance with the value recommended by the International Commission on Radiological Protection.

Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.

PubMed

Wright, Jennifer Gordon; Quinn, Conrad P; Shadomy, Sean; Messonnier, Nancy

2010-07-23

These recommendations from the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations for anthrax vaccine adsorbed (AVA) (CDC. Use of anthrax vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2000;49:1-20; CDC. Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2002;51:1024-6) and reflect the status of anthrax vaccine supplies in the United States. This statement 1) provides updated information on anthrax epidemiology; 2) summarizes the evidence regarding the effectiveness and efficacy, immunogenicity, and safety of AVA; 3) provides recommendations for pre-event and preexposure use of AVA; and 4) provides recommendations for postexposure use of AVA. In certain instances, recommendations that did not change were clarified. No new licensed anthrax vaccines are presented. Substantial changes to these recommendations include the following: 1) reducing the number of doses required to complete the pre-event and preexposure primary series from 6 doses to 5 doses, 2) recommending intramuscular rather than subcutaneous AVA administration for preexposure use, 3) recommending AVA as a component of postexposure prophylaxis in pregnant women exposed to aerosolized Bacillus anthracis spores, 4) providing guidance regarding preexposure vaccination of emergency and other responder organizations under the direction of an occupational health program, and 5) recommending 60 days of antimicrobial prophylaxis in conjunction with 3 doses of AVA for optimal protection of previously unvaccinated persons after exposure to aerosolized B. anthracis spores.

Weighted concentration of sup 137 Cs equivalent in foodstuffs in Kuwait from June 1986 to December 1988

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

Bakir, Y.Y.; Sayed, A.M.; Salem, M.S.

1990-06-01

The weighted monthly concentration of {sup 137}Cs equivalent (WMC) for various types of foodstuffs imported from June 1986 to December 1988 are discussed. The data presented are based on total concentration of {sup 137}Cs equivalent. The concentration was found below the disqualifying level applied in Kuwait. The radioactive contamination was higher in milk and baby milk relative to other types of foodstuffs. The calculation of Kuwait's disqualifying levels are based on the annual dose equivalent of 1 mSv (100 mrem). The measured WMC for most types of foodstuffs represents a small fraction to the annual dose limit recommended for themore » general public.« less

Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study.

PubMed

Palanca-Wessels, Maria Corinna A; Czuczman, Myron; Salles, Gilles; Assouline, Sarit; Sehn, Laurie H; Flinn, Ian; Patel, Manish R; Sangha, Randeep; Hagenbeek, Anton; Advani, Ranjana; Tilly, Herve; Casasnovas, Olivier; Press, Oliver W; Yalamanchili, Sreeni; Kahn, Robert; Dere, Randall C; Lu, Dan; Jones, Surai; Jones, Cheryl; Chu, Yu-Waye; Morschhauser, Franck

2015-06-01

Patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) have an unfavourable prognosis with few treatment options. Polatuzumab vedotin is an antibody-drug conjugate containing an anti-CD79B monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the safety and clinical activity of polatuzumab vedotin in relapsed or refractory B-cell NHL and chronic lymphocytic leukaemia (CLL). In this phase 1, multicentre, open-label study, we enrolled patients with documented NHL or CLL expected to express CD79B (confirmation of CD79B expression was not required) and for whom no suitable therapy of curative intent or higher priority existed from 13 centres. The primary endpoints of the study were to assess safety and tolerability, determine the maximum tolerated dose, and identify the recommended phase 2 dose of polatuzumab vedotin as a single agent and in combination with rituximab. A 3 + 3 dose-escalation design was used in which we treated patients with polatuzumab vedotin (0·1-2·4 mg/kg every 21 days) in separate dose-escalation cohorts for NHL and CLL. After determination of the recommended phase 2 dose, we enrolled patients with relapsed or refractory diffuse large B-cell lymphoma and relapsed or refractory indolent NHL into indication-specific cohorts. We also enrolled patients with relapsed or refractory NHL into an additional cohort to assess the feasibility of the combination of polatuzumab vedotin and rituximab 375 mg/m(2). Patients who received any dose of polatuzumab vedotin were available for safety analyses. This study is registered with ClinicalTrials.gov, number NCT01290549. Between March 21, 2011, and Nov 30, 2012, we enrolled 95 patients (34 to the NHL dose-escalation cohort, 18 to the CLL dose-escalation cohort, 34 with NHL to the expansion cohort at the recommended phase 2 dose, and nine with NHL to the rituximab combination cohort; no expansion cohort of CLL was started due to lack of activity in the dose-escalation cohort). The recommended phase 2 dose in NHL was 2·4 mg/kg as a single agent and in combination with rituximab; the maximum tolerated dose in CLL was 1·0 mg/kg as a result of dose-limiting toxic effects reported in two of five patients given 1·8 mg/kg. Grade 3-4 adverse events were reported in 26 (58%) of 45 patients with NHL treated at the single-agent recommended phase 2 dose, and the most common grade 3-4 adverse events were neutropenia (18 [40%] of 45), anaemia (five [11%]), and peripheral sensory neuropathy (four [9%]). Serious adverse events were reported in 17 (38%) of 45 patients, and included diarrhoea (two patients), lung infection (two patients), disease progression (two patients), and lung disorder (two patients). Seven (77%) of nine patients in the rituximab combination cohort had a grade 3-4 adverse event, with neutropenia (five [56%]), anaemia (two [22%]), and febrile neutropenia (two [22%]) reported in more than one patient. 11 (12%) of 95 patients died during the study: eight with relapsed or refractory diffuse large B-cell lymphoma (due to progressive disease in four patients, infections in three patients [two treatment related], and treatment-related worsening ascites in one patient) and three with relapsed or refractory CLL (due to progressive disease, pulmonary infection, and pneumonia; none thought to be treatment-related). At the recommended phase 2 dose, objective responses were noted in 23 of 42 activity-evaluable patients with NHL given single-agent polatuzumab vedotin (14 of 25 with diffuse large B-cell lymphoma, seven of 15 with indolent NHL, and two with mantle-cell lymphoma) and seven of nine patients treated with polatuzumab vedotin combined with rituximab. No objective responses were observed in patients with CLL. Polatuzumab vedotin has an acceptable safety and tolerability profile in patients with NHL but not in those with CLL. Its clinical activity should be further assessed in NHL. Genentech. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recommendation of the Advisory Committee on Immunization Practices for Use of a Third Dose of Mumps Virus-Containing Vaccine in Persons at Increased Risk for Mumps During an Outbreak.

PubMed

Marin, Mona; Marlow, Mariel; Moore, Kelly L; Patel, Manisha

2018-01-12

A substantial increase in the number of mumps outbreaks and outbreak-associated cases has occurred in the United States since late 2015 (1,2). To address this public health problem, the Advisory Committee on Immunization Practices (ACIP) reviewed the available evidence and determined that a third dose of measles, mumps, rubella (MMR) vaccine is safe and effective at preventing mumps. During its October 2017 meeting, ACIP recommended a third dose of a mumps virus-containing vaccine* for persons previously vaccinated with 2 doses who are identified by public health authorities as being part of a group or population at increased risk for acquiring mumps because of an outbreak. The purpose of the recommendation is to improve protection of persons in outbreak settings against mumps disease and mumps-related complications. This recommendation supplements the existing ACIP recommendations for mumps vaccination (3).

Phase I safety, pharmacokinetic and pharmacodynamic evaluation of the vascular disrupting agent ombrabulin (AVE8062) in patients with advanced solid tumors.

PubMed

Sessa, Cristiana; Lorusso, Patricia; Tolcher, Anthony; Farace, Françoise; Lassau, Nathalie; Delmonte, Angelo; Braghetti, Antonio; Bahleda, Rastislav; Cohen, Patrick; Hospitel, Marie; Veyrat-Follet, Christine; Soria, Jean-Charles

2013-09-01

The vascular disrupting agent ombrabulin rapidly reduces tumor blood flow and causes necrosis in vivo. A phase I dose-escalation study was designed to determine the recommended phase II dose (RP2D) of single-agent ombrabulin administered once every three weeks in patients with advanced solid malignancies. Ombrabulin (30-minute infusion) was escalated from 6 to 60 mg/m2, with RP2D cohort expansion. Safety, tumor response, pharmacokinetics, and pharmacodynamic biomarkers were evaluated. Eleven dose levels were evaluated in 105 patients. Two patients had dose-limiting toxicities in cycle 1 during escalation: grade 3 abdominal pain at 50 mg/m2, grade 3 tumor pain/grade 3 hypertension at 60 mg/m2, and the RP2D was 50 mg/m2 (39 patients). Common toxicities were headache, asthenia, abdominal pain, nausea, diarrhea, transient hypertension, anemia, and lymphopenia. No clinically significant QTc prolongations or left ventricular ejection fraction (LVEF) decreases occurred. Ombrabulin was rapidly converted to its active metabolite RPR258063 (half-life 17 minutes and 8.7 hours, respectively), both having dose-proportional exposure. Weak inhibition of CYP2C19-mediated metabolism occurred at the clinical doses used and there was no effect on CYP1A2 and CYP3A4. A patient with rectal cancer had a partial response and eight patients had stable disease lasting four months or more. Circulating endothelial cells (CEC), VEGF, and matrix metalloproteinase (MMP)-9 levels increased significantly six to 10 hours postinfusion in a subset of patients. The recommended schedule for single-agent ombrabulin is 50 mg/m2 every 3 weeks. CECs, VEGF, and MMP-9 are potential biomarkers of ombrabulin activity. ©2013 AACR.

Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia.

PubMed

Fathi, Amir T; Wander, Seth A; Blonquist, Traci M; Brunner, Andrew M; Amrein, Philip C; Supko, Jeffrey; Hermance, Nicole M; Manning, Amity L; Sadrzadeh, Hossein; Ballen, Karen K; Attar, Eyal C; Graubert, Timothy A; Hobbs, Gabriela; Joseph, Christelle; Perry, Ashley M; Burke, Meghan; Silver, Regina; Foster, Julia; Bergeron, Meghan; Ramos, Aura Y; Som, Tina T; Fishman, Kaitlyn M; McGregor, Kristin L; Connolly, Christine; Neuberg, Donna S; Chen, Yi-Bin

2017-04-01

Aberrant expression of aurora kinase A is implicated in the genesis of various neoplasms, including acute myeloid leukemia. Alisertib, an aurora A kinase inhibitor, has demonstrated efficacy as monotherapy in trials of myeloid malignancy, and this efficacy appears enhanced in combination with conventional chemotherapies. In this phase I, dose-escalation study, newly diagnosed patients received conventional induction with cytarabine and idarubicin, after which alisertib was administered for 7 days. Dose escalation occurred via cohorts. Patients could then receive up to four cycles of consolidation, incorporating alisertib, and thereafter alisertib maintenance for up to 12 months. Twenty-two patients were enrolled. One dose limiting toxicity occurred at dose level 2 (prolonged thrombocytopenia), and the recommended phase 2 dose was established at 30mg twice daily. Common therapy-related toxicities included cytopenias and mucositis. Only three (14%) patients had persistent disease at mid-cycle, requiring "5+2" reinduction. The composite remission rate (complete remission and complete remission with incomplete neutrophil recovery) was 86% (nineteen of twenty-two patients; 90% CI 68-96%). Among those over age 65 and those with high-risk disease (secondary acute leukemia or cytogenetically high-risk disease), the composite remission rate was 88% and 100%, respectively. The median follow up was 13.5 months. Of those treated at the recommended phase 2 dose, the 12-month overall survival and progression-free survival were 62% (90% CI 33-81%) and 42% (90% CI 17-65%), respectively. Alisertib is well tolerated when combined with induction chemotherapy in acute myeloid leukemia, with a promising suggestion of efficacy. ( clinicaltrials.gov Identifier:01779843 ). Copyright© Ferrata Storti Foundation.

A Phase I Study of Zoledronic Acid and Low Dose Cyclophosphamide in Recurrent/Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) Study

PubMed Central

Russell, Heidi V.; Groshen, Susan G.; Ara, Tasnim; DeClerck, Yves A.; Hawkins, Randy; Jackson, Hollie A.; Daldrup-Link, Heike E.; Marachelian, Araz; Skerjanec, Andrej; Park, Julie R.; Katzenstein, Howard; Matthay, Katherine K.; Blaney, Susan M.; Villablanca, Judith G.

2010-01-01

Background Zoledronic acid, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone is a common metastatic site of advanced neuroblastoma. We previously reported efficacy of zoledronic acid in a murine model of neuroblastoma bone invasion prompting this Phase I trial of zoledronic acid with cyclophosphamide in children with neuroblastoma and bone metastases. The primary objective was to determine recommended dosing of zoledronic acid for future trials. Procedure Escalating doses of intravenous zoledronic acid were given every 28 days with oral metronomic cyclophosphamide (25 mg/m2/day). Toxicity, response, zoledronic acid pharmacokinetics, bone turnover markers, serum IL-6, and sIL-6R were evaluated. Results Twenty-one patients, median age 7.5 (range 0.8 - 25.6) years were treated with 2 mg/m2 (n=4), 3 mg/m2 (n=3), or 4 mg/m2 (n=14) zoledronic acid. Fourteen patients were evaluable for dose escalation. A median of one (range 1-18) courses was given. Two dose limiting toxicities (Grade 3 hypophosphatemia) occurred at 4 mg/m2 zoledronic acid. Other Grade 3-4 toxicities included hypocalcemia (n=2), elevated transaminases (n=1), neutropenia (n=2), anemia (n=1), lymphopenia (n=1), and hypokalemia (n=1). Osteosclerosis contributed to fractures in one patient after 18 courses. Responses in evaluable patients included 1 partial response, 9 stable disease (median 4.5 courses, range 3-18), and 10 progressions. Zoledronic acid pharmacokinetics were similar to adults. Markers of osteoclast activity and serum IL-6 levels decreased with therapy. Conclusions Zoledronic acid with metronomic cyclophosphamide is well tolerated with clinical and biologic responses in recurrent/refractory neuroblastoma. The recommended dose of zoledronic acid is 4 mg/m2 every 28 days. PMID:21671363

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

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

Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu; Schipper, Mathew; Francis, Isaac R.

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) wasmore » given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.« less

Dose‐finding methods for Phase I clinical trials using pharmacokinetics in small populations

PubMed Central

Zohar, Sarah; Lentz, Frederike; Alberti, Corinne; Friede, Tim; Stallard, Nigel; Comets, Emmanuelle

2017-01-01

The aim of phase I clinical trials is to obtain reliable information on safety, tolerability, pharmacokinetics (PK), and mechanism of action of drugs with the objective of determining the maximum tolerated dose (MTD). In most phase I studies, dose‐finding and PK analysis are done separately and no attempt is made to combine them during dose allocation. In cases such as rare diseases, paediatrics, and studies in a biomarker‐defined subgroup of a defined population, the available population size will limit the number of possible clinical trials that can be conducted. Combining dose‐finding and PK analyses to allow better estimation of the dose‐toxicity curve should then be considered. In this work, we propose, study, and compare methods to incorporate PK measures in the dose allocation process during a phase I clinical trial. These methods do this in different ways, including using PK observations as a covariate, as the dependent variable or in a hierarchical model. We conducted a large simulation study that showed that adding PK measurements as a covariate only does not improve the efficiency of dose‐finding trials either in terms of the number of observed dose limiting toxicities or the probability of correct dose selection. However, incorporating PK measures does allow better estimation of the dose‐toxicity curve while maintaining the performance in terms of MTD selection compared to dose‐finding designs that do not incorporate PK information. In conclusion, using PK information in the dose allocation process enriches the knowledge of the dose‐toxicity relationship, facilitating better dose recommendation for subsequent trials. PMID:28321893

Patritumab plus trastuzumab and paclitaxel in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer.

PubMed

Mukai, Hirofumi; Saeki, Toshiaki; Aogi, Kenjiro; Naito, Yoichi; Matsubara, Nobuaki; Shigekawa, Takashi; Ueda, Shigeto; Takashima, Seiki; Hara, Fumikata; Yamashita, Tomonari; Ohwada, Shoichi; Sasaki, Yasutsuna

2016-10-01

Human epidermal growth factor receptor 3 (HER3) expression in lung and breast cancers has a negative impact on survival. Patritumab, a human anti-HER3 mAb, has shown anticancer activity in preclinical models. This study examined the safety and pharmacokinetics of patritumab in combination with trastuzumab and paclitaxel in patients with HER2-overexpressing metastatic breast cancer. In this open-label, multicenter, dose-escalation, phase Ib study, patients received patritumab 9 or 18 mg/kg plus trastuzumab and paclitaxel at known tolerated doses. Safety and tolerability were assessed based on dose-limiting toxicities and other non-life threatening adverse events. The pharmacokinetic profile for patritumab was determined based on the target trough level. Clinical efficacy was evaluated based on the overall response rate and progression-free survival. Six patients received patritumab 9 mg/kg and 12 received 18 mg/kg. The most common adverse events were diarrhea, alopecia, leukopenia, neutropenia, and maculopapular rash. No dose-limiting toxicities were observed. The target trough serum concentration was achieved in all patients at a dose of 18 mg/kg. Overall response rate was 38.9% and median progression-free survival was 274 days. In conclusion, patritumab plus trastuzumab and paclitaxel was tolerable and efficacious at both doses. We recommend the dose level of 18 mg/kg for future phase II studies. (Clinical trial registration: JapicCTI-121772.). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Dose-finding designs using a novel quasi-continuous endpoint for multiple toxicities

PubMed Central

Ezzalfani, Monia; Zohar, Sarah; Qin, Rui; Mandrekar, Sumithra J; Deley, Marie-Cécile Le

2013-01-01

The aim of a phase I oncology trial is to identify a dose with an acceptable safety profile. Most phase I designs use the dose-limiting toxicity, a binary endpoint, to assess the unacceptable level of toxicity. The dose-limiting toxicity might be incomplete for investigating molecularly targeted therapies as much useful toxicity information is discarded. In this work, we propose a quasi-continuous toxicity score, the total toxicity profile (TTP), to measure quantitatively and comprehensively the overall severity of multiple toxicities. We define the TTP as the Euclidean norm of the weights of toxicities experienced by a patient, where the weights reflect the relative clinical importance of each grade and toxicity type. We propose a dose-finding design, the quasi-likelihood continual reassessment method (CRM), incorporating the TTP score into the CRM, with a logistic model for the dose–toxicity relationship in a frequentist framework. Using simulations, we compared our design with three existing designs for quasi-continuous toxicity score (the Bayesian quasi-CRM with an empiric model and two nonparametric designs), all using the TTP score, under eight different scenarios. All designs using the TTP score to identify the recommended dose had good performance characteristics for most scenarios, with good overdosing control. For a sample size of 36, the percentage of correct selection for the quasi-likelihood CRM ranged from 80% to 90%, with similar results for the quasi-CRM design. These designs with TTP score present an appealing alternative to the conventional dose-finding designs, especially in the context of molecularly targeted agents. PMID:23335156

Comparison of optimized single and multifield irradiation plans of antiproton, proton and carbon ion beams.

PubMed

Bassler, Niels; Kantemiris, Ioannis; Karaiskos, Pantelis; Engelke, Julia; Holzscheiter, Michael H; Petersen, Jørgen B

2010-04-01

Antiprotons have been suggested as a possibly superior modality for radiotherapy, due to the energy released when antiprotons annihilate, which enhances the Bragg peak and introduces a high-LET component to the dose. However, concerns are expressed about the inferior lateral dose distribution caused by the annihilation products. We use the Monte Carlo code FLUKA to generate depth-dose kernels for protons, antiprotons, and carbon ions. Using these we then build virtual treatment plans optimized according to ICRU recommendations for the different beam modalities, which then are recalculated with FLUKA. Dose-volume histograms generated from these plans can be used to compare the different irradiations. The enhancement in physical and possibly biological dose from annihilating antiprotons can significantly lower the dose in the entrance channel; but only at the expense of a diffuse low dose background from long-range secondary particles. Lateral dose distributions are improved using active beam delivery methods, instead of flat fields. Dose-volume histograms for different treatment scenarios show that antiprotons have the potential to reduce the volume of normal tissue receiving medium to high dose, however, in the low dose region antiprotons are inferior to both protons and carbon ions. This limits the potential usage to situations where dose to normal tissue must be reduced as much as possible. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.

PubMed

Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-08-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.

Measurements of occupational exposure for a technologist performing 18F FDG PET scans.

PubMed

Biran, Talma; Weininger, Jolie; Malchi, Shalom; Marciano, Rami; Chisin, Roland

2004-11-01

Radiation doses to one PET technologist performing 100 18F FDG (18F fluorodeoxyglucose) imaging procedures were measured in a clinical setting using two types of thermoluminescent dosimeter (TLD) badges, one finger-ring TLD and one electronic pocket dosimeter (EPD). 18F FDG was handled either with unshielded or with viewing window tungsten shielded syringes. The resulting doses using unshielded syringes were 13.8 +/- 0.8 microSv/370 MBq and 14.3 +/- 0.4 microSv/370 MBq, measured with TLD 100 and with TLD 700H/600H, respectively. For the same series of measurements, the doses obtained using shielded syringes were 10.7 +/- 0.4 microSv/370 MBq and 7.2 +/- 2.1 microSv/370 MBq with TLD700H/600H and with EPD, respectively. The dose to the right hand from shielded syringes was 69.3 +/- 5.5 microSv/370 MBq. All these values are within the ICRP recommended dose limits. Extrapolated to 725 examinations per year, the resulting effective dose measured with TLD would be 10 mSv with unshielded and 7.5 mSv with shielded syringes, respectively (25% dose reduction). The doses measured by TLD were consistently higher than those measured by EPD, suggesting that EPD measurements might underestimate occupational doses.

42 CFR 82.31 - How can the public recommend changes to scientific elements underlying the dose reconstruction...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false How can the public recommend changes to scientific... ACTIVITIES METHODS FOR CONDUCTING DOSE RECONSTRUCTION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 Updating the Scientific Elements Underlying Dose Reconstructions § 82.31 How...

42 CFR 82.31 - How can the public recommend changes to scientific elements underlying the dose reconstruction...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false How can the public recommend changes to scientific... ACTIVITIES METHODS FOR CONDUCTING DOSE RECONSTRUCTION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 Updating the Scientific Elements Underlying Dose Reconstructions § 82.31 How...

42 CFR 82.31 - How can the public recommend changes to scientific elements underlying the dose reconstruction...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false How can the public recommend changes to scientific... ACTIVITIES METHODS FOR CONDUCTING DOSE RECONSTRUCTION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 Updating the Scientific Elements Underlying Dose Reconstructions § 82.31 How...

42 CFR 82.31 - How can the public recommend changes to scientific elements underlying the dose reconstruction...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false How can the public recommend changes to scientific... ACTIVITIES METHODS FOR CONDUCTING DOSE RECONSTRUCTION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000 Updating the Scientific Elements Underlying Dose Reconstructions § 82.31 How...

Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968)

PubMed Central

Joerger, M; Hess, D; Delmonte, A; Gallerani, E; Fasolo, A; Gianni, L; Cresta, S; Barbieri, P; Pace, S; Sessa, C

2015-01-01

Aims Namitecan is a new camptothecan compound undergoing early clinical development. This study was initiated to build an integrated pharmacokinetic (PK) and pharmacodynamic (PD) population model of namitecan to guide future clinical development. Methods Plasma concentration–time data, neutrophils and thrombocytes were pooled from two phase 1 studies in 90 patients with advanced solid tumours, receiving namitecan as a 2 h infusion on days 1 and 8 every 3 weeks (D1,8) (n = 34), once every 3 weeks (D1) (n = 29) and on 3 consecutive days (D1–3) (n = 27). A linear three compartment PK model was coupled to a semiphysiological PD-model for neutrophils and thrombocytes. Data simulations were used to interrogate various dosing regimens and give dosing recommendations. Results Clearance was estimated to be 0.15 l h–1, with a long terminal half-life of 48 h. Body surface area was not associated with clearance, supporting flat-dosing of namitecan. A significant and clinically relevant association was found between namitecan area under the concentration–time curve (AUC) and the percentage drop of neutrophils (r2 = 0.51, P < 10−4) or thrombocytes (r2 = 0.49, P < 10−4). With a target for haematological dose-limiting toxicity of <20%, the recommended dose was defined as 12.5 mg for the D1,8 regimen, 23 mg for the once every 3 week regimen and 7 mg for the D1–3 regimen. Conclusion This is the first integrated population PK–PD analysis of the new hydrophilic topoisomerase I inhibitor namitecan, that is currently undergoing early clinical development. A distinct relationship was found between drug exposure and haematological toxicity, supporting flat-dosing once every 3 weeks as the most adequate dosing regimen. PMID:25580946

Dissipation kinetics of beta-cyfluthrin and imidacloprid in tea and their transfer from processed tea to infusion.

PubMed

Paramasivam, M; Deepa, M; Selvi, C; Chandrasekaran, S

2017-10-01

Dissipation kinetics of mixed formulation consisting beta-cyfluthrin and imidacloprid in tea crop under an open field ecosystem was investigated. The mixed formulation was applied on tea plant at recommended (27 + 63) and double the recommended (54 + 126g a.i./ha) dose and residues were determined using gas chromatography-electron capture detector and high performance liquid chromatography-photodiode array detector for beta-cyfluthrin and imidacloprid, respectively. The limit of quantification of analytical method was 0.05µg/g and the average recoveries were ranged from 88.36% to 103.49% with relative standard deviations of less than 6% at three spiked levels. The experimental results showed that in the green tea leaves imidacloprid dissipated faster than beta-cyfluthrin with the half-life ranging between 1.20-1.39 and 2.89-3.15days, respectively. The beta-cyfluthrin residues present in the processed tea not transferred into the tea infusion during the infusion process and imidacloprid transferred in the range 43.12-49.7%. On the basis of the transfer of residues from processed tea to infusion, a waiting period of 17 days for tea plucking after pesticide application at recommended dose may be suggested. Copyright © 2017 Elsevier Inc. All rights reserved.

The use of paracetamol (acetaminophen) among a community sample of people with chronic non-cancer pain prescribed opioids.

PubMed

Hoban, B; Larance, B; Gisev, N; Nielsen, S; Cohen, M; Bruno, R; Shand, F; Lintzeris, N; Hall, W; Farrell, M; Degenhardt, L

2015-11-01

The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3-24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6-6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (χ(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). The majority of people with chronic non-cancer pain prescribed opioids report using paracetamol appropriately. High income, use of paracetamol/opioid combination analgesics and higher opioid dose were independently associated with paracetamol use above the recommended maximum daily dose. © 2015 John Wiley & Sons Ltd.

A triplet combination with capecitabine/oxaliplatin/irinotecan (XELOXIRI) plus cetuximab as first-line therapy for patients with metastatic colorectal cancer: a dose escalation study.

PubMed

Sato, Yasushi; Hirakawa, Masahiro; Ohnuma, Hiroyuki; Takahashi, Minoru; Okamoto, Tetsuro; Okamoto, Koichi; Miyamoto, Hiroshi; Muguruma, Naoki; Furuhata, Tomohisa; Takemasa, Ichiro; Kato, Junji; Takayama, Tetsuji

2017-12-01

The addition of cetuximab to triplet chemotherapy can increase treatment efficacy for patients with metastatic colorectal cancer (mCRC). We explored the dose-limiting toxicity and feasibility of a triweekly capecitabine, oxaliplatin, irinotecan, plus cetuximab (XELOXIRI plus cetuximab) regimen in patients with wild-type KRAS mCRC. Patients received oxaliplatin (100 mg/m 2 , day 1), capecitabine (1700 mg/m 2 per day from day 2 to 15), irinotecan (100, 120, and 150 mg/m 2 for dose levels 1, 2, 3, respectively, on day 1), and cetuximab (400 mg/m 2 , day 1 and, thereafter, 250 mg/m 2 every week), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first 2 treatment cycles to determine the maximum tolerated dose (MTD) and the recommended dose (RD). Twelve patients received a median of 7 cycles of therapy (range 2-10). The DLT was grade 4 neutropenia, observed in 1 of 6 patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m 2 . Most common grade ≥ 3 toxicities were neutropenia (50%), diarrhea (17%), and febrile neutropenia (8%). The response rate was 83% (complete and partial response: 1 and 9 patient(s), respectively), including 4 conversion cases. The combination of XELOXIRI and cetuximab is feasible and has an acceptable toxicity profile; neutropenia was the DLT. The RD of irinotecan is 150 mg/m 2 . The observed response rate was promising and warrants further investigation.

A Phase I Study of Chemoradiotherapy With Use of Involved-Field Conformal Radiotherapy and Accelerated Hyperfractionation for Stage III Non-Small Cell Lung Cancer: WJTOG 3305

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

Tada, Takuhito, E-mail: tada@msic.med.osaka-cu.ac.jp; Department of Radiology, Izumi Municipal Hospital, Izumi; Chiba, Yasutaka

2012-05-01

Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m{sup 2}) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m{sup 2}). Total doses were 54 Gy in 36 fractions, 60 Gymore » in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade {>=}4 esophagitis and neutropenic fever and Grade {>=}3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.« less

Measured occupational solar UVR exposures of lifeguards in pool settings.

PubMed

Gies, Peter; Glanz, Karen; O'Riordan, David; Elliott, Tom; Nehl, Eric

2009-08-01

The aim of this study was to measure ultraviolet radiation (UVR) exposures of lifeguards in pool settings and evaluate their personal UVR protective practices. Lifeguards (n = 168) wore UVR sensitive polysulfone (PS) film badges in wrist bracelets on 2 days and completed a survey and diary covering sun protection use. Analyses were used to describe sun exposure and sun protection practices, to compare UVR exposure across locations, and to compare findings with recommended threshold limits for occupational exposure. The measured UVR exposures varied with location, ranging from high median UVR exposures of 6.2 standard erythemal doses (SEDs) to the lowest median of 1.7 SEDs. More than 74% of the lifeguards' PS badges showed UVR above recommended threshold limits for occupational exposure. Thirty-nine percent received more than four times the limit and 65% of cases were sufficient to induce sunburn. The most common protective behaviors were wearing sunglasses and using sunscreen, but sun protection was often inadequate. At-risk individuals were exposed to high levels of UVR in excess of occupational limits and though appropriate types of sun protection were used, it was not used consistently and more than 50% of lifeguards reported being sunburnt at least twice during the previous year.

Role of belly board device in the age of intensity modulated radiotherapy for pelvic irradiation

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

Estabrook, Neil C.; Bartlett, Gregory K.; Compton, Julia J.

Small bowel dose often represents a limiting factor for radiation treatment of pelvic malignancies. To reduce small bowel toxicity, a belly board device (BBD) with a prone position is often recommended. Intensity modulated radiotherapy (IMRT) could reduce dose to small bowel based on the desired dose-volume constraints. We investigated the efficacy of BBD in conjunction with IMRT. A total of 11 consecutive patients with the diagnosis of rectal cancer, who were candidates for definitive therapy, were selected. Patients were immobilized with BBD in prone position for simulation and treatment. Supine position computed tomography (CT) data were either acquired at themore » same time or during a diagnostic scan, and if existed was used. Target volumes (TV) as well as organs at risk (OAR) were delineated in both studies. Three-dimensional conformal treatment (3DCRT) and IMRT plans were made for both scans. Thus for each patient, 4 plans were generated. Statistical analysis was conducted for maximum, minimum, and mean dose to each structure. When comparing the normalized mean Gross TV dose for the different plans, there was no statistical difference found between the planning types. There was a significant difference in small bowel sparing when using prone position on BBD comparing 3DCRT and IMRT plans, favoring IMRT with a 29.6% reduction in dose (p = 0.007). There was also a statistically significant difference in small bowel sparing when comparing supine position IMRT to prone-BBD IMRT favoring prone-BBD IMRT with a reduction of 30.3% (p = 0.002). For rectal cancer when small bowel could be a limiting factor, prone position using BBD along with IMRT provides the best sparing. We conclude that whenever a dose escalation in rectal cancer is desired where small bowel could be limiting factor, IMRT in conjunction with BBD should be selected.« less

Use of gastroprotective agents in recommended doses in hospitalized patients receiving NSAIDs: a drug utilization study.

PubMed

Erdeljic, Viktorija; Francetic, Igor; Macolic Sarinic, Viola; Bilusic, Marinko; Makar Ausperger, Ksenija; Huic, Mirjana; Mercep, Iveta

2006-10-01

In recent years, studies investigated to what extend recommendations for co-prescribing gastroprotective agents in prevention of NSAID-induced gastrointestinal complications are followed in clinical practice. However, only a few studies have also taken into consideration the recommended dose of gastroprotectives prescribed in NSAID-induced ulcer prophylaxis. The aim of our study was to evaluate the prevalence of concomitant use of gastroprotectives with NSAIDs in hospitalized patients, with emphasis on the recommended dose of gastroprotectives for ulcer prophylaxis. This observational, cross-sectional, drug utilization study included all adult patients receiving NSAIDs hospitalized in the Clinical Hospital Center Zagreb on the day of the study. Data on age, sex, comorbidities, indications for NSAID use, type/dose of NSAIDs and gastroprotectives, history of gastrointestinal events, active gastrointestinal symptoms and risk factors were evaluated. Study outcomes were: (1) prevalence of prescription of gastroprotectives among NSAID-users at risk; (2) prevalence of prescription of gastroprotective in recommended dose; (3) association between risk factors and prescription of GPAs. The rates of gastroprotectives prescription were significantly higher in NSAID-users with concomitant risk factors as compared to patients without risk factors [47/70 (67.1%) and 8/22 (36.4%), respectively; p=0.01072]. However, gastroprotection in recommended ulcer-preventive dose was low in both groups [8/70 (11.4%) and 9/92 (9.8%), respectively]. The number of concomitant risk factors did not increase the odds of receiving anti-ulcer therapy (odds ratio 0.7279). Thirty-three percent of patients with concomitant risk factors were not prescribed gastroprotectives. Ibuprofen, NSAID with the lowest risk of inducing gastrointestinal complications, was prescribed in only two patients. The results indicate high awareness among hospital physicians about possible NSAID-induced gastrointestinal complications, but insufficient knowledge about risk factors related to NSAID-induced gastrointestinal toxicity, recommended dose of gastroprotectives in NSAID-induced ulcer prophylaxis and gastrointestinal toxicity of different types of NSAIDs.

Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen.

PubMed

Creaven, P J; Rustum, Y M; Petrelli, N J; Meropol, N J; Raghavan, D; Rodriguez-Bigas, M; Levine, E G; Frank, C; Udvary-Nagy, S; Proefrock, A

1994-01-01

A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m2 by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly x 6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m2 per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m2 developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with a t1/2 beta of approximately 2 h. Plasma clearance was high (> 200 1 h-1). No correlation between pharmacokinetic parameters and toxicity could be identified.

Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

PubMed

Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

2011-12-01

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

Therapeutic drug monitoring in pregnancy.

PubMed

Matsui, Doreen M

2012-10-01

Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review.

PubMed

Price, Laura C; Wort, Stephen J; Finney, Simon J; Marino, Philip S; Brett, Stephen J

2010-01-01

Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care. A systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method. Clinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy. This systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.

Lauriston S. Taylor Lecture: Yucca mountain radiation standards, dose/risk assessments, thinking outside the box, evaluations, and recommendations.

PubMed

Moeller, Dade W

2009-11-01

The Yucca Mountain high-level radioactive waste repository is designed to contain spent nuclear fuel and vitrified fission products. Due to the fact that it will be the first such facility constructed anywhere in the world, it has proved to be one in which multiple organizations, most prominently the U.S. Congress, are exercising a role. In addition to selecting a site for the facility, Congress specified that the U.S. Environmental Protection Agency (U.S. EPA) promulgate the associated Standards, the U.S. Nuclear Regulatory Commission establish applicable Regulations to implement the Standards, and the U.S. Department of Energy (U.S. DOE) design, construct, and operate the repository. Congress also specified that U.S. EPA request that the National Academy of Sciences (NAS) provide them guidance on the form and nature of the Standards. In so doing, Congress also stipulated that the Standards be expressed in terms of an "equivalent dose rate." As will be noted, this subsequently introduced serious complications. Due to the inputs of so many groups, and the fact that the NAS recommendations conflicted with the Congressional stipulation that the limits be expressed in terms of a dose rate, the outcome is a set of Standards that not only does not comply with the NAS recommendations, but also is neither integrated, nor consistent. The initial goals of this paper are to provide an independent risk/dose analysis for each of the eight radionuclides that are to be regulated, and to evaluate them in terms of the Standards. These efforts reveal that the Standards are neither workable nor capable of being implemented. The concluding portions of the paper provide guidance that, if successfully implemented, would enable U.S. DOE to complete the construction of the repository and operate it in accordance with the recommendations of NAS while, at the same time, provide a better, more accurate, understanding of its potential risks to the public. This facility is too important to the U.S. nuclear energy program to be impeded by inappropriate Standards and unnecessary regulatory restrictions. As will be noted, the sources of essentially all of the recommendations suggested in this paper were derived through applications of the principles of good science, and the benefits of "thinking outside the box."

NCRP Vision for the Future and Program Area Committee Activities.

PubMed

Boice, John D

2017-02-01

The National Council on Radiation Protection and Measurements (NCRP) believes that the most critical need for the nation in radiation protection is to train, engage, and retain radiation professionals for the future. Not only is the pipeline shrinking, but for some areas there is no longer a pipe! When the call comes to respond, there may be no one to answer the phone! The NCRP "Where are the Radiation Professionals?" initiative, Council Committee (CC) 2, and this year's annual meeting are to focus our efforts to find solutions and not just reiterate the problems. Our next major initiative is CC 1, where the NCRP is making recommendations for the United States on all things dealing with radiation protection. Our last publication was NCRP Report No. 116, Limitation of Exposure to Ionizing Radiation, in 1993-time for an update. NCRP has seven active Program Area Committees on biology and epidemiology, operational concerns, emergency response and preparedness, medicine, environmental issues and waste management, dosimetry, and communications. A major scientific research initiative is the Million Person Study of Low Dose Radiation Health Effects. It includes workers from the Manhattan Project, nuclear weapons test participants (atomic veterans), industrial radiographers, and early medical workers such as radiologists and technologists. This research will answer the one major gap in radiation risk evaluation: what are the health effects when the exposure occurs gradually over time? Other cutting edge initiatives include a re-evaluation of science behind recommendations for lens of the eye dose limits, recommendations for emergency responders on dosimetry after a major radiological incident, guidance to the National Aeronautics and Space Administration with regard to possible central nervous system effects from galactic cosmic rays (the high energy, high mass particles bounding through space), re-evaluating the population exposure to medical radiation (NCRP Report No. 160, Ionizing Radiation Exposure of the Population of the United States, is over 10 y old, and computed tomography exams have increased substantially since then), and concerning whether the linear no-, threshold model is still the best available for purposes of radiation protection (not for risk assessment). We believe evaluation of heart disease and cerebral vascular disease following low-dose and dose-rate exposure is important for assessments of possible detriment from such exposures. We continue to seek the necessary resources to follow our quest to improve radiation protection for the public!

Comparison of cosmic rays radiation detectors on-board commercial jet aircraft.

PubMed

Kubančák, Ján; Ambrožová, Iva; Brabcová, Kateřina Pachnerová; Jakůbek, Jan; Kyselová, Dagmar; Ploc, Ondřej; Bemš, Július; Štěpán, Václav; Uchihori, Yukio

2015-06-01

Aircrew members and passengers are exposed to increased rates of cosmic radiation on-board commercial jet aircraft. The annual effective doses of crew members often exceed limits for public, thus it is recommended to monitor them. In general, the doses are estimated via various computer codes and in some countries also verified by measurements. This paper describes a comparison of three cosmic rays detectors, namely of the (a) HAWK Tissue Equivalent Proportional Counter; (b) Liulin semiconductor energy deposit spectrometer and (c) TIMEPIX silicon semiconductor pixel detector, exposed to radiation fields on-board commercial Czech Airlines company jet aircraft. Measurements were performed during passenger flights from Prague to Madrid, Oslo, Tbilisi, Yekaterinburg and Almaty, and back in July and August 2011. For all flights, energy deposit spectra and absorbed doses are presented. Measured absorbed dose and dose equivalent are compared with the EPCARD code calculations. Finally, the advantages and disadvantages of all detectors are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Application of bioassay technique to determine onduty herbicide resistance in soil

NASA Astrophysics Data System (ADS)

Bakar, F. A. A.; Ismail, B. S.; Bajrai, F. S. M.

2016-11-01

A study was conducted to determine the resistance of OnDuty herbicide in paddy soil with different concentrations by using a broadleaf plant, Brassica juncea. The herbicide was used in the Clearfield® Production System that was adopted in Malaysia to overcome problems mainly caused by weedy rice. Evaluation of herbicide half-life was based on bioassay technique with different concentrations, i.e 0% (control), 50% (half dose), 100% (recommended dose) and 200% (double dose). The study was done in three replicates and followed the Complete Randomized Block Design (CRBD). Results showed that there was a correlation between the amount of herbicide doses and degradation period. The highest half-life value was shown by root inhibition in the double dose concentration of 33 days half-life, followed by the recommended dose with 23 days half-life. Meanwhile, the half dose treatment indicated a half-life value of 17 days for root and 11 days for shoot. Therefore, application of herbicides should follow the recommended dose as the degradation period will not be too long, hence providing maximum effectiveness of the herbicide to overcome weed infestation problems.

Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study.

PubMed

Ouwerkerk, W; Voors, A A; Anker, S D; Cleland, J G; Dickstein, K; Filippatos, G; van der Harst, P; Hillege, H L; Lang, C C; Ter Maaten, J M; Ng, L L; Ponikowski, P; Samani, N J; van Veldhuisen, D J; Zannad, F; Metra, M; Zwinderman, A H

2017-06-21

Despite clear guidelines recommendations, most patients with heart failure and reduced ejection-fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers. BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50-99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43-2.01; for beta-blocker: HR 1.70; 95% CI 1.36-2.05). Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Radon estimation in water resources of Mandi - Dharamshala region of Himachal Pradesh, India for health risk assessments

NASA Astrophysics Data System (ADS)

Kumar, Gulshan; Kumari, Punam; Kumar, Mukesh; Kumar, Arvind; Prasher, Sangeeta; Dhar, Sunil

2017-07-01

The present study deals with the radon estimation in 40 water samples collected from different natural resources and radium content in the soils of Mandi-Dharamshala Region. Radon concentration is determined by using RAD-7 detector and radium contents of the soil in vicinity of water resources is as well measured by using LR-115 type - II detector, which is further correlated with radon concentration in water samples. The potential health risks related with 222Rn have also been estimated. The results show that the radon concentrations within the range of 1.51 to 22.7Bq/l with an average value of 5.93 Bq/l for all type of water samples taken from study area. The radon concentration in water samples is found lower than 100Bq/l, the exposure limit of radon in water recommended by the World Health Organization. The calculated average effective dose of radon received by the people of study area is 0.022 mSv/y with maximum of 0.083 mSv/y and minimum 0.0056 mSv/y. The total effective dose in all sites of the studied area is found to be within the safe limit (0.1 mSv/year) recommended by World Health Organization. The average value of radium content in the soil of study area is 6.326 Bq/kg.

Phase I study of stereotactic body radiation therapy for centrally located stage IA non-small cell lung cancer (JROSG10-1).

PubMed

Kimura, Tomoki; Nagata, Yasushi; Harada, Hideyuki; Hayashi, Shinya; Matsuo, Yukinori; Takanaka, Tsuyoshi; Kokubo, Masaki; Takayama, Kenji; Onishi, Hiroshi; Hirakawa, Koichi; Shioyama, Yoshiyuki; Ehara, Takeshi

2017-10-01

To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC). Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1-2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT. Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy. The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions.

Radiation Exposure of Interventional Radiologists During Computed Tomography Fluoroscopy-Guided Renal Cryoablation and Lung Radiofrequency Ablation: Direct Measurement in a Clinical Setting.

PubMed

Matsui, Yusuke; Hiraki, Takao; Gobara, Hideo; Iguchi, Toshihiro; Fujiwara, Hiroyasu; Kawabata, Takahiro; Yamauchi, Takatsugu; Yamaguchi, Takuya; Kanazawa, Susumu

2016-06-01

Computed tomography (CT) fluoroscopy-guided renal cryoablation and lung radiofrequency ablation (RFA) have received increasing attention as promising cancer therapies. Although radiation exposure of interventional radiologists during these procedures is an important concern, data on operator exposure are lacking. Radiation dose to interventional radiologists during CT fluoroscopy-guided renal cryoablation (n = 20) and lung RFA (n = 20) was measured prospectively in a clinical setting. Effective dose to the operator was calculated from the 1-cm dose equivalent measured on the neck outside the lead apron, and on the left chest inside the lead apron, using electronic dosimeters. Equivalent dose to the operator's finger skin was measured using thermoluminescent dosimeter rings. The mean (median) effective dose to the operator per procedure was 6.05 (4.52) μSv during renal cryoablation and 0.74 (0.55) μSv during lung RFA. The mean (median) equivalent dose to the operator's finger skin per procedure was 2.1 (2.1) mSv during renal cryoablation, and 0.3 (0.3) mSv during lung RFA. Radiation dose to interventional radiologists during renal cryoablation and lung RFA were at an acceptable level, and in line with recommended dose limits for occupational radiation exposure.

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

Matsui, Yusuke, E-mail: wckyh140@yahoo.co.jp; Hiraki, Takao, E-mail: takaoh@tc4.so-net.ne.jp; Gobara, Hideo, E-mail: gobara@cc.okayama-u.ac.jp

IntroductionComputed tomography (CT) fluoroscopy-guided renal cryoablation and lung radiofrequency ablation (RFA) have received increasing attention as promising cancer therapies. Although radiation exposure of interventional radiologists during these procedures is an important concern, data on operator exposure are lacking.Materials and MethodsRadiation dose to interventional radiologists during CT fluoroscopy-guided renal cryoablation (n = 20) and lung RFA (n = 20) was measured prospectively in a clinical setting. Effective dose to the operator was calculated from the 1-cm dose equivalent measured on the neck outside the lead apron, and on the left chest inside the lead apron, using electronic dosimeters. Equivalent dose to the operator’s finger skinmore » was measured using thermoluminescent dosimeter rings.ResultsThe mean (median) effective dose to the operator per procedure was 6.05 (4.52) μSv during renal cryoablation and 0.74 (0.55) μSv during lung RFA. The mean (median) equivalent dose to the operator’s finger skin per procedure was 2.1 (2.1) mSv during renal cryoablation, and 0.3 (0.3) mSv during lung RFA.ConclusionRadiation dose to interventional radiologists during renal cryoablation and lung RFA were at an acceptable level, and in line with recommended dose limits for occupational radiation exposure.« less

Public member dose assessment of Bushehr Nuclear Power Plant under normal operation by modeling the fallout from stack using the HYSPLIT atmospheric dispersion model.

PubMed

Zali, A; Shamsaei Zafarghandi, M; Feghhi, S A; Taherian, A M

2017-05-01

In this work, public dose resulting from fission products released from Bushehr Nuclear Power Plant (BNPP) under normal operation is assessed. Due to the long range transport of radionuclides in this work (80 km) and considering terrain and meteorological data, HYbrid Single-Particle Lagrangian Integrated Trajectory (HYsplit) model, which uses three dimensional long-range numerical models, has been employed to calculate atmospheric dispersion. Annual effective dose calculation is carried out for inhalation, ingestion, and external exposure pathways in 16directions and within 80 km around the site for representative person. The results showed the maximum dose of inhalation and external exposure for adults is 3.8 × 10 -8 Sv/y in the SE direction and distance of 600 m from the BNPP site which is less than ICRP 103 recommended dose limit (1 mSv). Children and infants' doses are higher in comparison with adults, although they are less than 1 mSv. Ingestion dose percentage in the total dose is less than 0.1%. The results of this study underestimate the Final Safety Analysis Report ofBNPP-1 (FSAR)data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of the criteria used by the International Commission on Radiological Protection to justify the setting of numerical protection level values.

PubMed

2006-01-01

This report compiles the various numerical protection level values published by the International Commission on Radiological Protection (ICRP) since its 1990 Recommendations (Publication 60). Several terms are used to denominate the protection levels: individual dose limit, 'maximum' individual dose, dose constraint, exemption level, exclusion level, action level, or intervention level. The reasons provided by the Commission for selecting the associated numerical values is quoted as far as available. In some cases the rationale is not totally explicit in the original ICRP report concerned; in such cases the Task Group that prepared the present report have proposed their own interpretation. Originally, this report was prepared by a Task Group at CEPN, a French research and development center, in behalf of IRSN, a French public expert body engaged in radiological protection and nuclear safety. It is published here with kind permission by CEPN and IRSN.

A retrospective cohort study of long-term immediate-release hydrocodone/acetaminophen use and acetaminophen dosing above the Food and Drug Administration recommended maximum daily limit among commercially insured individuals in the United States (2008-2013).

PubMed

DeVeaugh-Geiss, Angela; Kadakia, Aditi; Chilcoat, Howard; Alexander, Louis; Coplan, Paul

2015-06-01

Immediate-release (IR) hydrocodone/acetaminophen is the most prescribed opioid in the United States; however, patterns of use, including long-term treatment and dose, are not well described. Duration of use, including the percentage of patients on long-term treatment (>90 days of continuous use), was assessed for patients newly prescribed IR hydrocodone/acetaminophen compared to other opioid analgesics in a national commercial insurance database (January 2008-September 2013). Though only a small percentage of IR hydrocodone/acetaminophen patients continued treatment long-term (1.7%), the number was large (104,839) and was nearly 5 times the number receiving extended-release (ER) morphine (n = 22,338) and nearly 4 times the number receiving ER oxycodone (n = 26,946) long-term. Using a less conservative allowable gap in treatment increased the number of patients meeting the criteria for long-term use (approximately 160,000 for IR hydrocodone/acetaminophen vs <30,000 for ER morphine and ER oxycodone). Most patients meeting these criteria received IR hydrocodone doses between >20 and ≤60 mg/d (n = 56,220, 53.6%) in month 4; 5.5% (n = 5,743) received doses >60 mg/d. Moreover, approximately 15% of IR hydrocodone/acetaminophen patients (n > 900,000) were prescribed total daily acetaminophen doses exceeding 4 g (the limit recommended by the U.S. Food and Drug Administration) at their initial IR hydrocodone/acetaminophen prescription or any time during therapy. Although most patients were prescribed IR hydrocodone/acetaminophen for acute pain, the number of patients prescribed long-term therapy exceeds the number of patients prescribed ER opioids. It is important to consider the benefits and risks inherent with long-term opioid therapy, whether with IR or ER opioids, to ensure safe use of these products. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Indian Academy of Pediatrics (IAP) recommended immunization schedule for children aged 0 through 18 years--India, 2014 and updates on immunization.

PubMed

Vashishtha, Vipin M; Choudhury, Panna; Kalra, Ajay; Bose, Anuradha; Thacker, Naveen; Yewale, Vijay N; Bansal, C P; Mehta, Pravin J

2014-10-01

There is a need to review/revise recommendations about existing vaccines in light of recent developments in the field of vaccinology. Following an IAP ACVIP meeting on April 19 and 20, 2014, a draft of revised recommendations for the year 2014 and updates on certain vaccine formulations was prepared and circulated among the meeting participants to arrive at a consensus. To review and revise recommendations for 2014 Immunization timetable for pediatricians in office practice and issue statements on certain new and existing vaccine formulations. The major changes in the 2014 Immunization Timetable include two doses of MMR vaccine at 9 and 15 months of age, single dose recommendation for administration of live attenuated H2 strain hepatitis A vaccine, inclusion of two new situations in high-risk category of children in context with pre-exposure prophylaxis of rabies, creation of a new slot at 9-12 months of age for typhoid conjugate vaccine for primary immunization, and recommendation of two doses of human papilloma virus vaccines with a minimum interval of 6 months between doses for primary schedule of adolescent/preadolescent girls aged 9-14 years. There would not be any change to the committee's last year's (2013) recommendations on pertussis vaccination and administration schedule of monovalent human rotavirus vaccine. There is no need of providing additional doses of whole-cell pertussis vaccine to children who have earlier completed their primary schedule with acellular pertussis vaccine-containing products. A brief update on the new Indian Rotavirus vaccine, 116E is also provided. The committee has reviewed and offered its recommendations on the currently available pentavalent vaccine (DTwP+Hib+Hepatitis-B) combinations in Indian market. The comments and footnotes for several vaccines are also updated and revised.

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

Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it; Cilla, Savino; Deodato, Francesco

Purpose: A prospective phase 1-2 clinical trial aimed at determining the recommended postoperative dose of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) in a large series of patients with high-risk and intermediate-risk endometrial cancer (HIR-EC) is presented. The study also evaluated the association between rate and severity of toxicity and comorbidities and the clinical outcomes. Methods and Materials: Two SIB-VMAT dose levels were investigated for boost to the vaginal vault, whereas the pelvic lymph nodes were always treated with 45 Gy. The first cohort received a SIB-VMAT dose of 55 Gy in 25 consecutive 2.2-Gy fractions, and the subsequent cohort receivedmore » higher doses (60 Gy in 2.4-Gy fractions). Results: Seventy consecutive HIR-EC patients, roughly half of whom were obese (47.1%) or overweight (37.1%), with Charlson Age-Comorbidity Index >2 (48.5%), were enrolled. Thirty-one patients (44.3%) were administered adjuvant chemotherapy before starting radiation therapy. All patients (n=35 per dose level) completed irradiation without any dose-limiting toxicity. Proctitis (any grade) was associated with radiation therapy dose (P=.001); not so enterocolitis. Grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity were recorded in 17 (24.3%) and 14 patients (20.0%), respectively, and were not associated with radiation dose. As for late toxicity, none of patients experienced late grade ≥3 GI or grade ≥2 GU toxicity. The 3-year late grade ≥2 GI and GU toxicity–free survival were 92.8% and 100%, respectively, with no difference between the 2 dose levels. With a median follow-up period of 25 months (range, 4-60 months), relapse/progression of disease was observed in 10 of 70 patients (14.2%). The 3-year cumulative incidence of recurrence was 1.5% (95% confidence interval (CI): 0.2-10.7), whereas the 3-year disease-free survival was 81.3% (95% CI: 65.0-90.0). Conclusions: This clinical study showed the feasibility of this technique and its good profile in terms of acute and late toxicity at the recommended doses even in aged and frail patients.« less

Integration of drug dosing data with physiological data streams using a cloud computing paradigm.

PubMed

Bressan, Nadja; James, Andrew; McGregor, Carolyn

2013-01-01

Many drugs are used during the provision of intensive care for the preterm newborn infant. Recommendations for drug dosing in newborns depend upon data from population based pharmacokinetic research. There is a need to be able to modify drug dosing in response to the preterm infant's response to the standard dosing recommendations. The real-time integration of physiological data with drug dosing data would facilitate individualised drug dosing for these immature infants. This paper proposes the use of a novel computational framework that employs real-time, temporal data analysis for this task. Deployment of the framework within the cloud computing paradigm will enable widespread distribution of individualized drug dosing for newborn infants.

Dose Modeling Evaluations and Technical Support Document For the Authorized Limits Request for the DOE-Owned Property Outside the Limited Area, Paducah Gaseous Diffusion Plant Paducah, Kentucky

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

Boerner, A. J.; Maldonado, D. G.; Hansen, Tom

2012-09-01

Environmental assessments and remediation activities are being conducted by the U.S. Department of Energy (DOE) at the Paducah Gaseous Diffusion Plant (PGDP), Paducah, Kentucky. The Oak Ridge Institute for Science and Education (ORISE), a DOE prime contractor, was contracted by the DOE Portsmouth/Paducah Project Office (DOE-PPPO) to conduct radiation dose modeling analyses and derive single radionuclide soil guidelines (soil guidelines) in support of the derivation of Authorized Limits (ALs) for 'DOE-Owned Property Outside the Limited Area' ('Property') at the PGDP. The ORISE evaluation specifically included the area identified by DOE restricted area postings (public use access restrictions) and areas licensedmore » by DOE to the West Kentucky Wildlife Management Area (WKWMA). The licensed areas are available without restriction to the general public for a variety of (primarily) recreational uses. Relevant receptors impacting current and reasonably anticipated future use activities were evaluated. In support of soil guideline derivation, a Conceptual Site Model (CSM) was developed. The CSM listed radiation and contamination sources, release mechanisms, transport media, representative exposure pathways from residual radioactivity, and a total of three receptors (under present and future use scenarios). Plausible receptors included a Resident Farmer, Recreational User, and Wildlife Worker. single radionuclide soil guidelines (outputs specified by the software modeling code) were generated for three receptors and thirteen targeted radionuclides. These soil guidelines were based on satisfying the project dose constraints. For comparison, soil guidelines applicable to the basic radiation public dose limit of 100 mrem/yr were generated. Single radionuclide soil guidelines from the most limiting (restrictive) receptor based on a target dose constraint of 25 mrem/yr were then rounded and identified as the derived soil guidelines. An additional evaluation using the derived soil guidelines as inputs into the code was also performed to determine the maximum (peak) dose for all receptors. This report contains the technical basis in support of the DOE?s derivation of ALs for the 'Property.' A complete description of the methodology, including an assessment of the input parameters, model inputs, and results is provided in this report. This report also provides initial recommendations on applying the derived soil guidelines.« less

Dissipation of Flonicamid in Honeysuckle and Its Transfer during Brewing Process.

PubMed

Wang, Yujie; Xue, Jian; Jin, Hongyu; Ma, Shuangcheng

2017-05-01

The dissipation of flonicamid in Honeysuckle and transfer pattern from Honeysuckle to its tea infusion were investigated. Flonicamid was applied on Honeysuckle crop at two dosages, 60 g of active gradient per hectare (g a.i. hm -2 ) and 180 g a.i. hm -2 (recommended and triple the recommended) in Fenqiu, Henan Province in 2015 and 2016. Gas Chromatography-Electron Capture Detector (GC-ECD) detection methods were developed for the analysis of flonicamid residues in honeysuckles and its infusion. The recoveries in both honeysuckles and its infusion ranged from 81.5 to 101.7% with relative standard deviations (RSDs) of 3.2-9.1%. The dissipations of flonicamid in Honeysuckle were found to follow the first order kinetics with half-life ranging between 2.8 and 3.2 d. After recommended dose pesticide application, contents of flonicamid residues were lower than theoretical maximum residue limit (tMRL). Flonicamid residues can easily transfer from Honeysuckle to its tea infusion and transfer rates of flonicamid decrease with the brewing temperature reduction or the brewing times increase. These results are helpful to establish maximum residue limit and develop guidance on the appropriate and secure use of flonicamid in Honeysuckle.

Occupational radiation exposure in nuclear medicine department in Kuwait

NASA Astrophysics Data System (ADS)

Alnaaimi, M.; Alkhorayef, M.; Omar, M.; Abughaith, N.; Alduaij, M.; Salahudin, T.; Alkandri, F.; Sulieman, A.; Bradley, D. A.

2017-11-01

Ionizing radiation exposure is associated with eye lens opacities and cataracts. Radiation workers with heavy workloads and poor protection measures are at risk for vision impairment or cataracts if suitable protection measures are not implemented. The aim of this study was to measure and evaluate the occupational radiation exposure in a nuclear medicine (NM) department. The annual average effective doses (Hp[10] and Hp[0.07]) were measured using calibrated thermos-luminescent dosimeters (TLDs; MCP-N [LiF:Mg,Cu,P]). Five categories of staff (hot lab staff, PET physicians, NM physicians, technologists, and nurses) were included. The average annual eye dose (Hp[3]) for NM staff, based on measurements for a typical yearly workload of >7000 patients, was 4.5 mSv. The annual whole body radiation (Hp[10]) and skin doses (Hp[0.07]) were 4.0 and 120 mSv, respectively. The measured Hp(3), Hp(10), and Hp(0.07) doses for all NM staff categories were below the dose limits described in ICRP 2014 in light of the current practice. The results provide baseline data for staff exposure in NM in Kuwait. Radiation dose optimization measures are recommended to reduce NM staff exposure to its minimal value.

Accuracy of dispersing tramadol capsules for oral administration in young children.

PubMed

Kluger, M; Penrose, S; Bjorksten, A R; Chalkiadis, G

2016-11-01

Tramadol is used in children aged <12 years for analgesia, particularly for those at risk of obstructive sleep apnoea undergoing adenotonsillectomy. The Australian Therapeutic Goods Administration have strongly recommended that oral tramadol drops (100 mg/ml) not be used in children <12 years because of the risk of inadvertent overdose. The total mass of drug in a 10 ml bottle is 1000 mg. The only alternative preparation available is a 50 mg capsule that requires dispersion of a capsule's contents should smaller doses be required. The accuracy of this preparation has not been assessed. Twenty surgical ward nurses were asked to prepare a 15 mg dose of tramadol from a 50 mg capsule. The dose was within ±5% of 15 mg in 13 cases (65%) and within ±10% in 19 cases (95%) (range 13.9-17.1 mg). Despite the dose variability of this method of preparing tramadol, we consider it sufficiently accurate for clinical use. We also consider it safe, as even at the highest dose prepared, the variability would be unlikely to contribute to clinically significant side-effects or toxicity. Moreover, the maximal dose that could be administered is limited to the size of the capsule (50 mg).

Consideration of the ICRP 2006 revised tissue weighting factors on age-dependent values of the effective dose for external photons

NASA Astrophysics Data System (ADS)

Lee, Choonsik; Lee, Choonik; Han, Eun Young; Bolch, Wesley E.

2007-01-01

The effective dose recommended by the International Commission on Radiological Protection (ICRP) is the sum of organ equivalent doses weighted by corresponding tissue weighting factors, wT. ICRP is in the process of revising its 1990 recommendations on the effective dose where new values of organs and tissue weighting factors have been proposed and published in draft form for consultation by the radiological protection community. In its 5 June 2006 draft recommendations, new organs and tissues have been introduced in the effective dose which do not exist within the 1987 Oak Ridge National Laboratory (ORNL) phantom series (e.g., salivary glands). Recently, the investigators at University of Florida have updated the series of ORNL phantoms by implementing new organ models and adopting organ-specific elemental composition and densities. In this study, the effective dose changes caused by the transition from the current recommendation of ICRP Publication 60 to the 2006 draft recommendations were investigated for external photon irradiation across the range of ICRP reference ages (newborn, 1-year, 5-year, 10-year, 15-year and adult) and for six idealized irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), left-lateral (LLAT), right-lateral (RLAT), rotational (ROT) and isotropic (ISO). Organ-absorbed doses were calculated by implementing the revised ORNL phantoms in the Monte Carlo radiation transport code, MCNPX2.5, after which effective doses were calculated under the 1990 and draft 2006 evaluation schemes of the ICRP. Effective doses calculated under the 2006 draft scheme were slightly higher than estimated under ICRP Publication 60 methods for all irradiation geometries exclusive of the AP geometry where an opposite trend was observed. The effective doses of the adult phantom were more greatly affected by the change in tissue weighting factors than that seen within the paediatric members of the phantom series. Additionally, dose conversion coefficients for newly identified radiosensitive organs—salivary glands, gall bladder, heart and prostate—were reported, as well as the brain, which was originally considered in ICRP Publication 60 as a member of the remainder category of the effective dose.

A Framework for "Fit for Purpose" Dose Response Assessment

EPA Science Inventory

The NRC report Science and Decisions: Advancing Risk Assessment made several recommendations to improve chemical risk assessment, with a focus on in-depth chronic dose-response assessments conducted by the U.S. Environmental Protection Agency. The recommendations addressed two ...

Measurement of natural radioactivity in Jordanian building materials and their contribution to the public indoor gamma dose rate.

PubMed

Sharaf, J M; Hamideen, M S

2013-10-01

This study is undertaken to determine the activity concentration of (226)Ra, (232)Th and (40)K in samples of commonly used building materials in Jordan. Samples of seven different materials were collected from construction sites and local agencies supplying raw construction materials and analyzed using a HPGe gamma-ray spectrometer, taking into account self-attenuation in bulk samples. The average specific activity concentrations of (226)Ra, (232)Th, and (40)K ranged from 2.84 to 41.52, 0.78 to 58.42. and 3.74 to 897 Bq/kg, respectively. All the samples had radium equivalent activities well below the limit of 370 Bq/kg set by the Organization for Economic Cooperation and Development (OECD, 1979). External and internal hazard indices, absorbed dose and annual effective dose rate associated with the radionuclides of interest were calculated and compared with the international legislation and guidance. In general, most of the activities did not exceed the recommended international limits, except for granite and ceramic samples which are usually used as secondary building materials in Jordan. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form.

PubMed

Agrawal, S; Kaul, C L; Panchagnula, R

2001-08-01

To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.

[CAS in rhino-surgical procedures in the growing age].

PubMed

Schipper, J; Maier, W; Gellrich, N-C; Arapakis, I; Hochmuth, A; Laszig, R

2005-01-01

Rhinosurgery in children and adolescents meets special requirements: Limited cooperation and reduced limits for the organ dose for ionizing radiological examinations aggravate diagnostics. On the other side, bone sutures and bone growth areas have to be respected intraoperatively, and regions of bones not yet calcified have to be distinguished from possible tumor infiltration. Computer assisted surgery (CAS) can help to identify these areas safely. 5 patients, from the first to the 20 (th) year of life, suffering from tumors, malformation syndromes or therapy resistant nasal polyposis were treated with CAS in rhinosurgery. In addition to radiological diagnostics, we performed 3D computed tomography of the skull for CAS. CAS enabled us to intraoperatively respect possible areas of bone growth, to identify regions with thin, not bonily developed cranial vault and to safely distinguish bone sutures from ethmoidal cells. CAS helped the surgeon to navigate in the not yet developed paranasal sinus system. CAS is a useful complementary method in rhinosurgery of the developing skull of the child. In spite of the additional 3D computed tomography, the calculated organ dose of the ocular lense amounted to 5 millisievert, so a recommended maximal organ dose for the ocular lense of 15 millisievert was not exceeded.

Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP).

PubMed

Marin, Mona; Broder, Karen R; Temte, Jonathan L; Snider, Dixie E; Seward, Jane F

2010-05-07

This report presents new recommendations adopted in June 2009 by CDC's Advisory Committee on Immunization Practices (ACIP) regarding use of the combination measles, mumps, rubella, and varicella vaccine (MMRV, ProQuad, Merck & Co., Inc.). MMRV vaccine was licensed in the United States in September 2005 and may be used instead of measles, mumps, rubella vaccine (MMR, M-M-RII, Merck & Co., Inc.) and varicella vaccine (VARIVAX, Merck & Co., Inc.) to implement the recommended 2-dose vaccine schedule for prevention of measles, mumps, rubella, and varicella among children aged 12 months-12 years. At the time of its licensure, use of MMRV vaccine was preferred for both the first and second doses over separate injections of equivalent component vaccines (MMR vaccine and varicella vaccine), which was consistent with ACIP's 2006 general recommendations on use of combination vaccines (CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2006;55;[No. RR-15]). Since July 2007, supplies of MMRV vaccine have been temporarily unavailable as a result of manufacturing constraints unrelated to efficacy or safety. MMRV vaccine is expected to be available again in the United States in May 2010. In February 2008, on the basis of preliminary data from two studies conducted postlicensure that suggested an increased risk for febrile seizures 5-12 days after vaccination among children aged 12-23 months who had received the first dose of MMRV vaccine compared with children the same age who had received the first dose of MMR vaccine and varicella vaccine administered as separate injections at the same visit, ACIP issued updated recommendations regarding MMRV vaccine use (CDC. Update: recommendations from the Advisory Committee on Immunization Practices [ACIP] regarding administration of combination MMRV vaccine. MMWR 2008;57:258-60). These updated recommendations expressed no preference for use of MMRV vaccine over separate injections of equivalent component vaccines for both the first and second doses. The final results of the two postlicensure studies indicated that among children aged 12--23 months, one additional febrile seizure occurred 5-12 days after vaccination per 2,300-2,600 children who had received the first dose of MMRV vaccine compared with children who had received the first dose of MMR vaccine and varicella vaccine administered as separate injections at the same visit. Data from postlicensure studies do not suggest that children aged 4--6 years who received the second dose of MMRV vaccine had an increased risk for febrile seizures after vaccination compared with children the same age who received MMR vaccine and varicella vaccine administered as separate injections at the same visit. In June 2009, after consideration of the postlicensure data and other evidence, ACIP adopted new recommendations regarding use of MMRV vaccine for the first and second doses and identified a personal or family (i.e., sibling or parent) history of seizure as a precaution for use of MMRV vaccine. For the first dose of measles, mumps, rubella, and varicella vaccines at age 12--47 months, either MMR vaccine and varicella vaccine or MMRV vaccine may be used. Providers who are considering administering MMRV vaccine should discuss the benefits and risks of both vaccination options with the parents or caregivers. Unless the parent or caregiver expresses a preference for MMRV vaccine, CDC recommends that MMR vaccine and varicella vaccine should be administered for the first dose in this age group. For the second dose of measles, mumps, rubella, and varicella vaccines at any age (15 months-12 years) and for the first dose at age >or=48 months, use of MMRV vaccine generally is preferred over separate injections of its equivalent component vaccines (i.e., MMR vaccine and varicella vaccine). This recommendation is consistent with ACIP's 2009 provisional general recommendations regarding use of combination vaccines (available at http://www.cdc.gov/vaccines/recs/provisional/downloads/combo-vax-Aug2009-508.pdf), which state that use of a combination vaccine generally is preferred over its equivalent component vaccines.

Review of high-dose intravenous vitamin C as an anticancer agent.

PubMed

Wilson, Michelle K; Baguley, Bruce C; Wall, Clare; Jameson, Michael B; Findlay, Michael P

2014-03-01

In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial. © 2014 Wiley Publishing Asia Pty Ltd.

Supra-recommendation Treatment of Super-refractory Status Epilepticus.

PubMed

Vyas, Devashish Dhiren; Dash, Gopal Krishna

2016-06-01

A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She required 3 cycles of midazolam and 2 cycles of thiopentone for complete cessation of seizures. She recovered with mild attentional and recent memory deficits on follow up. Treatment of super-refractory status epilepticus requires individualized regimens and may need doses beyond conventional limits. To the best of our knowledge, there is no such reported case from India.

The future of warfarin pharmacogenetics in under-represented minority groups

PubMed Central

Cavallari, Larisa H; Perera, Minoli A

2012-01-01

Genotype-based dosing recommendations are provided in the US FDA-approved warfarin labeling. However, data that informed these recommendations were from predominately Caucasian populations. Studies show that variants contributing to warfarin dose requirements in Caucasians provide similar contributions to dose requirements in US Hispanics, but significantly lesser contributions in African–Americans. Further data demonstrate that variants occurring commonly in individuals of African ancestry, but rarely in other racial groups, significantly influence dose requirements in African–Americans. These data suggest that it is important to consider variants specific for African–Americans when implementing genotype-guided warfarin dosing in this population. PMID:22871196

Safety of aquaflor (florfenicol, 50% type a medicated article), administered in feed to channel catfish, Ictalurus punctatus

USGS Publications Warehouse

Gaikowski, Mark P.; Wolf, Jeffery C.; Endris, Richard G.; Gingerich, William H.

2003-01-01

Aquaflor, a feed premix containing the broad spectrum antibacterial agent florfenicol (50% w/w), is being developed for use to control enteric septicemia (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative enterobacterium Edwardsiella ictaluri. The recommended dose of Aquaflor to control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was to determine the safety of Aquaflor administered in feed to channel catfish at doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days. Parameters evaluated included daily mortality, behavioral (appetite, distribution, flight/fright response), and water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Medicated feed consumption was 67-86% of target with group mean doses of 8.5 mg/kg BW/day, 24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically observable changes noted at any of the dose levels tested. Aquaflor-related changes were limited to the food consumption and histopathology data. Although Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg BW/day groups, there were no differences in fish growth among the treatment groups. Aquaflor-related histopathology findings were limited to a histomorphologically evident dose-dependent decrease in hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys, and spleens of channel catfish.

Safety of Aquaflor (Florfenicol, 50% Type A Medicated Article), Administered in Feed to Channel Catfish, Ictalurus punctatus

USGS Publications Warehouse

Gaikowski, M.P.; Wolf, J.C.; Endris, R.G.; Gingerich, W.H.

2003-01-01

Aquaflor, a feed premix containing the broad spectrum antibacterial agent florfenicol (50% w/w), is being developed for use to control enteric septicemia (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative enterobacterium Edwardsiella ictaluri. The recommended dose of Aquaflor to control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was to determine the safety of Aquaflor administered in feed to channel catfish at doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days. Parameters evaluated included daily mortality, behavioral (appetite, distribution, flight/fright response), and water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Medicated feed consumption was 67-86% of target with group mean doses of 8.5 mg/kg BW/day, 24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically observable changes noted at any of the dose levels tested. Aquaflor-related changes were limited to the food consumption and histopathology data. Although Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg BW/day groups, there were no differences in fish growth among the treatment groups. Aquaflor-related histopathology findings were limited to a histomorphologically evident dose-dependent decrease in hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys, and spleens of channel catfish.

A phase 1 study of eribulin mesylate (E7389), a novel microtubule-targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314).

PubMed

Schafer, Eric S; Rau, Rachel E; Berg, Stacey; Liu, Xiaowei; Minard, Charles G; D'Adamo, David; Scott, Rachael; Reyderman, Larisa; Martinez, Gresel; Devarajan, Sandhya; Reid, Joel M; Fox, Elizabeth; Weigel, Brenda J; Blaney, Susan M

2018-05-02

Eribulin mesylate is a novel anticancer agent that inhibits microtubule growth, without effects on shortening, and promotes nonproductive tubulin aggregate formation. We performed a phase 1 trial to determine the dose-limiting toxicities (DLTs), maximum tolerated or recommended phase 2 dose (MTD/RP2D), and pharmacokinetics (PK) of eribulin in children with refractory or recurrent solid (excluding central nervous system) tumors. Eribulin was administered intravenously on days 1 and 8 in 21-day cycles. Three dose levels (1.1, 1.4, and 1.8 mg/m 2 /dose) were evaluated using the rolling six design with additional patients enrolled into a PK expansion cohort at the MTD. PK samples were obtained following the day 1, cycle 1 dose. Twenty-three patients, ages 3-17 (median 14) years were enrolled; 20 were evaluable for toxicity. DLTs occurred in 0/6 and 1/6 subjects at the 1.1 and 1.4 mg/m 2 /dose, respectively. One subject at the 1.4 mg/m 2 /dose had grade 4 neutropenia and grade 3 fatigue. At the 1.8 mg/m 2 /dose, 2/5 subjects experienced dose-limiting (grade 4) neutropenia. Grade 3/4 non-DLTs included lymphopenia and hypokalemia, while low-grade toxicities included anorexia and nausea. No episodes of grade > 2 corrected QT interval prolongation or peripheral neuropathy were reported. Eribulin pharmacokinetic parameters were highly variable; the median elimination half-life was 39.6 (range 24.2-96.4) hr. A partial response was observed in one patient (Ewing sarcoma). Eribulin was well tolerated in children with refractory or recurrent solid tumors with neutropenia identified as the primary DLT. The RP2D of eribulin is 1.4 mg/m 2 /dose on days 1 and 8 of a 21-day cycle. © 2018 Wiley Periodicals, Inc.

Phase I trial of capecitabine rapidly disintegrating tablets and concomitant radiation therapy in children with newly diagnosed brainstem gliomas and high-grade gliomas

PubMed Central

Kilburn, Lindsay B.; Kocak, Mehmet; Schaedeli Stark, Franziska; Meneses-Lorente, Georgina; Brownstein, Carrie; Hussain, Sazzad; Chintagumpala, Murali; Thompson, Patrick A.; Gururangan, Sri; Banerjee, Anuradha; Paulino, Arnold C.; Kun, Larry; Boyett, James M.; Blaney, Susan M.

2013-01-01

Background We conducted a phase I study to estimate the maximum tolerated dose and describe the dose-limiting toxicities and pharmacokinetics of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy to children with newly diagnosed brainstem or high-grade gliomas. Methods Children 3–21 y with newly diagnosed intrinsic brainstem or high-grade gliomas were eligible for enrollment. The starting dose was 500 mg/m2, given twice daily, with subsequent cohorts enrolled at 650 mg/m2 and 850 mg/m2 using a 3 + 3 phase I design. Children received capecitabine at the assigned dose daily for 9 wks starting from the first day of radiation therapy (RT). Following a 2-wk break, patients received 3 courses of capecitabine 1250 mg/m2 twice daily for 14 days followed by a 7-day rest. Pharmacokinetic sampling was performed in consenting patients. Six additional patients with intrinsic brainstem gliomas were enrolled at the maximum tolerated dose to further characterize the pharmacokinetic and toxicity profiles. Results Twenty-four patients were enrolled. Twenty were fully assessable for toxicity. Dose-limiting toxicities were palmar plantar erythroderma (grades 2 and 3) and elevation of alanine aminotransferase (grades 2 and 3). Systemic exposure to capecitabine and metabolites was similar to or slightly lower than predicted based on adult data. Conclusions Capecitabine with concurrent RT was generally well tolerated. The recommended phase II capecitabine dose when given with concurrent RT is 650 mg/m2, administered twice daily. A phase II study to evaluate the efficacy of this regimen in children with intrinsic brainstem gliomas is in progress (PBTC-030). PMID:23592571

Human Papillomavirus (HPV) and Oropharyngeal Cancer

MedlinePlus

... CDC recommends that 11- to 12-year-old boys and girls get two doses of HPV vaccine. The second ... after the first dose. CDC also recommends that girls and women through age 26 years and boys and men through age 21 years get the ...

Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP).

PubMed

Watson, J C; Hadler, S C; Dykewicz, C A; Reef, S; Phillips, L

1998-05-22

These revised recommendations of the Advisory Committee on Immunization Practices (ACIP) on measles, mumps, and rubella prevention supersede recommendations published in 1989 and 1990. This statement summarizes the goals and current strategies for measles, rubella, and congenital rubella syndrome (CRS) elimination and for mumps reduction in the United States. Changes from previous recommendations include: Emphasis on the use of combined MMR vaccine for most indications; A change in the recommended age for routine vaccination to 12-15 months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A recommendation that all states take immediate steps to implement a two dose MMR requirement for school entry and any additional measures needed to ensure that all school-aged children are vaccinated with two doses of MMR by 2001; A clarification of the role of serologic screening to determine immunity; A change in the criteria for determining acceptable evidence of rubella immunity; A recommendation that all persons who work in health-care facilities have acceptable evidence of measles and rubella immunity; Changes in the recommended interval between administration of immune globulin and measles vaccination; and Updated information on adverse events and contraindications, particularly for persons with severe HIV infection, persons with a history of egg allergy or gelatin allergy, persons with a history of thrombocytopenia, and persons receiving steroid therapy.

Defined daily doses (DDD) do not accurately reflect opioid doses used in contemporary chronic pain treatment.

PubMed

Nielsen, Suzanne; Gisev, Natasa; Bruno, Raimondo; Hall, Wayne; Cohen, Milton; Larance, Briony; Campbell, Gabrielle; Shanahan, Marian; Blyth, Fiona; Lintzeris, Nicholas; Pearson, Sallie; Mattick, Richard; Degenhardt, Louisa

2017-05-01

To assess how well the defined daily dose (DDD) metric reflects opioid utilisation among chronic non-cancer pain patients. Descriptive, cross-sectional study, utilising a 7-day medication diary. Community-based treatment settings, Australia. A sample of 1101 people prescribed opioids for chronic non-cancer pain. Opioid dose data was collected via a self-completed 7-day medication diary capturing names, strengths and doses of each medication taken in the past week. Median daily dose was calculated for each opioid. Comparisons were made to the World Health Organization's (WHO) DDD metric. WHO DDDs ranged from 0.6 to 7.1 times the median opioid doses used by the sample. For transdermal fentanyl and oral hydromorphone, the median dose was comparable with the DDD. The DDD for methadone was 0.6 times lower than the median doses used by this sample of chronic pain patients. In contrast, the DDD for oxycodone and transdermal buprenorphine, the most commonly used strong opioids for chronic pain in Australia, was two to seven times higher than actual doses used. For many opioids, there are key differences between the actual doses used in clinical practice and the WHO's DDDs. The interpretation of opioid utilisation studies using population-level DDDs may be limited, and a recalibration of the DDD for many opioids or the reporting of opioid utilisation in oral morphine equivalent doses is recommended. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Dose Limits for Man do not Adequately Protect the Ecosystem

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

Higley, Kathryn A.; Alexakhin, Rudolf M.; McDonald, Joseph C.

2004-08-01

It has been known for quite some time that different organisms display differing degrees of sensitivity to the effects of ionizing radiations. Some microorganisms such as the bacterium Micrococcus radiodurans, along with many species of invertebrates, are extremely radio-resistant. Humans might be categorized as being relatively sensitive to radiation, and are a bit more resistant than some pine trees. Therefore, it could be argued that maintaining the dose limits necessary to protect humans will also result in the protection of most other species of flora and fauna. This concept is usually referred to as the anthropocentric approach. In other words,more » if man is protected then the environment is also adequately protected. The ecocentric approach might be stated as; the health of humans is effectively protected only when the environment is not unduly exposed to radiation. The ICRP is working on new recommendations dealing with the protection of the environment, and this debate should help to highlight a number of relevant issues concerning that topic.« less

Uses and Doses of Local Anesthetics in Fish, Amphibians, and Reptiles.

PubMed

Chatigny, Frederic; Kamunde, Collins; Creighton, Catherine M; Stevens, E Don

2017-05-01

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly benefit from those drugs. Some recommendations are currently available in the literature concerning analgesic use in these animals. However the pharmacological properties, safety and often efficacy of local anesthetic drugs have not been investigated yet in fish, amphibians, or reptiles. This review compiled current information concerning the use of those agents in fish, reptiles and amphibians to help clinicians make an informed decision as to which dose and drug to use. The resulting literature search showed that the literature concerning use of local analgesics in fish and amphibians is very limited while the literature for reptiles is more extensive. We found few experimental studies evaluating the efficacy of local anesthetics. Further studies would provide additional information for developing guidelines to improve the welfare of fish, amphibians and reptiles.

Uses and Doses of Local Anesthetics in Fish, Amphibians, and Reptiles

PubMed Central

Chatigny, Frederic; Kamunde, Collins; Creighton, Catherine M; Stevens, E Don

2017-01-01

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly benefit from those drugs. Some recommendations are currently available in the literature concerning analgesic use in these animals. However the pharmacological properties, safety and often efficacy of local anesthetic drugs have not been investigated yet in fish, amphibians, or reptiles. This review compiled current information concerning the use of those agents in fish, reptiles and amphibians to help clinicians make an informed decision as to which dose and drug to use. The resulting literature search showed that the literature concerning use of local analgesics in fish and amphibians is very limited while the literature for reptiles is more extensive. We found few experimental studies evaluating the efficacy of local anesthetics. Further studies would provide additional information for developing guidelines to improve the welfare of fish, amphibians and reptiles. PMID:28535859

Management of chronic spontaneous urticaria in routine clinical practice: A Delphi-method questionnaire among specialists to test agreement with current European guidelines statements.

PubMed

Giménez-Arnau, A; Ferrer, M; Bartra, J; Jáuregui, I; Labrador-Horrillo, M; Frutos, J Ortiz de; Silvestre, J F; Sastre, J; Velasco, M; Valero, A

Chronic spontaneous urticaria (CSU) is a frequent clinical entity that often presents a diagnostic and therapeutic challenge. To explore the degree of agreement that exists among the experts caring for patients with CSU diagnosis, evaluation, and management. An online survey was conducted to explore the opinions of experts in CSU, address controversial issues, and provide recommendations regarding its definition, natural history, diagnosis, and treatment. A modified Delphi method was used for the consensus. The questionnaire was answered by 68 experts (dermatologists, allergologists, and primary care physicians). A consensus was reached on 54 of the 65 items posed (96.4%). The experts concluded that CSU is a difficult-to-control disease of unpredictable evolution. Diagnostic tests should be limited and based on clinical history and should not be indiscriminate. Autoinflammatory syndromes and urticarial vasculitis must be ruled out in the differential diagnosis. A cutaneous biopsy is only recommended when wheals last more than 24h, to rule out urticarial vasculitis. The use of specific scales to assess the severity of the disease and the quality of life is recommended. In patients with severe and resistant CSU, second-generation H1-antihistamines could be used at doses up to four times the standard dose before giving second-line treatments. Omalizumab is a safe and effective treatment for CSU that is refractory to H1-antihistamines treatment. In general, diagnosis and treatment recommendations given for adults could be extrapolated to children. This work offers consensus recommendations that may be useful in the management of CSU. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Radiation protection guidelines for space missions

NASA Technical Reports Server (NTRS)

Fry, R. J.; Nachtwey, D. S.

1988-01-01

The current radiation protection guidelines of the National Aeronautics and Space Administration (NASA) were recommended in 1970. The career limit was set at 4.0 Sv (400 rem). Using the same approach as in 1970 but current risk estimates, a considerably lower career limit would obtain today. Also, there is now much more information about the radiation environments that will be experienced in different missions. Furthermore, since 1970 women have joined the ranks of the astronauts. For these and other reasons, it was considered necessary to re-examine the radiation protection guidelines. This task has been undertaken by the National Council on Radiation Protection and Measurements Scientific Committee 75. Within the magnetosphere, the radiation environment varies with altitude and inclination of the orbit. In outer space missions, galactic cosmic rays, with the small but important heavy-ion component, determine the radiation environment. The new recommendations for career dose limits, based on lifetime excess risk of cancer mortality, take into account age at first exposure and sex. The career limits range from 1.0 Sv (100 rem) for a 24-y-old female up to 4.0 Sv (400 rem) for a 55-y-old male, compared with the previous single limit of 4.0 Sv (400 rem). The career limit for the lens of the eye has been reduced from 6.0 Sv (600 rem) to 4.0 Sv (400 rem).

Experimental determination of the effective point of measurement of cylindrical ionization chambers for high-energy photon and electron beams.

PubMed

Huang, Yanxiao; Willomitzer, Christian; Zakaria, Golam Abu; Hartmann, Guenther H

2010-01-01

Measurements of depth-dose curves in water phantom using a cylindrical ionization chamber require that its effective point of measurement is located at the measuring depth. Recommendations for the position of the effective point of measurement with respect to the central axis valid for high-energy electron and photon beams are given in dosimetry protocols. According to these protocols, the use of a constant shift P(eff) is currently recommended. However, this is still based on a very limited set of experimental results. It is therefore expected that an improved knowledge of the exact position of the effective point of measurement will further improve the accuracy of dosimetry. Recent publications have revealed that the position of the effective point of measurement is indeed varying with beam energy, field size and also with chamber geometry. The aim of this study is to investigate whether the shift of P(eff) can be taken to be constant and independent from the beam energy. An experimental determination of the effective point of measurement is presented based on a comparison between cylindrical chambers and a plane-parallel chamber using conventional dosimetry equipment. For electron beams, the determination is based on the comparison of halfvalue depth R(50) between the cylindrical chamber of interest and a well guarded plane-parallel Roos chamber. For photon beams, the depth of dose maximum, d(max), the depth of 80% dose, d(80), and the dose parameter PDD(10) were used. It was again found that the effective point of measurement for both, electron and photon beams Dosimetry, depends on the beam energy. The deviation from a constant value remains very small for photons, whereas significant deviations were found for electrons. It is therefore concluded that use of a single upstream shift value from the centre of the cylindrical chamber as recommended in current dosimetry protocols is adequate for photons, however inadequate for accurate electron beam dosimetry.

A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study.

PubMed

Aparicio, Jorge; García-Mora, Carmen; Martín, Marta; Petriz, Ma Lourdes; Feliu, Jaime; Sánchez-Santos, Ma Elena; Ayuso, Juan Ramón; Fuster, David; Conill, Carlos; Maurel, Joan

2014-01-01

Sorafenib, an oral inhibitor of B-raf, VEGFR2, and PDGFR2-beta, acts against pancreatic cancer in preclinical models. Due to the radio-sensitization activity of both sorafenib and gemcitabine, we designed a multicenter, phase I trial to evaluate the safety profile and the recommended dose of this combination used with concomitant radiation therapy. Patients with biopsy-proven, unresectable pancreatic adenocarcinoma (based on vascular invasion detected by computed tomography) were treated with gemcitabine (300 mg/m2 i.v. weekly ×5 weeks) concurrently with radiation therapy (45 Gy in 25 fractions) and sorafenib (escalated doses in a 3+3 design, from 200 to 800 mg/day). Radiation portals included the primary tumor but not the regional lymph nodes. Patients with planning target volumes (PTV) over 500 cc were excluded. Cases not progressing during chemoradiation were allowed to continue with sorafenib until disease progression. Twelve patients were included. Three patients received 200 mg/day, 6 received 400 mg/day, and 3 received 800 mg/day; PTVs ranged from 105 to 500 cc. No dose-limiting toxicities occurred. The most common grade 2 toxicities were fatigue, neutropenia, nausea, and raised serum transaminases. Treatment was discontinued in one patient because of a reversible posterior leukoencephalopathy. There were no treatment-related deaths. The addition of sorafenib to concurrent gemcitabine and radiation therapy showed a favorable safety profile in unresectable pancreatic adenocarcinoma. A dose of 800 mg/day is recommended for phase II evaluation. EudraCT 2007-003211-31 ClinicalTrials.gov 00789763.

Dose finding and O6-alkylguanine-DNA alkyltransferase study of cisplatin combined with temozolomide in paediatric solid malignancies

PubMed Central

Geoerger, B; Vassal, G; Doz, F; O'Quigley, J; Wartelle, M; Watson, A J; Raquin, M-A; Frappaz, D; Chastagner, P; Gentet, J-C; Rubie, H; Couanet, D; Geoffray, A; Djafari, L; Margison, G P; Pein, F

2005-01-01

Cisplatin may have additive activity with temozolomide due to ablation of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (MGMT). This phase I/II study determined recommended combination doses using the Continual Reassessment Method, toxicities and antitumour activity in paediatric patients, and evaluated MGMT in peripheral blood mononuclear cells (PBMCs) in order to correlate with haematological toxicity. In total, 39 patients with refractory or recurrent solid tumours (median age ∼13 years; 14 pretreated with high-dose chemotherapy, craniospinal irradiation, or having bone marrow involvement) were treated with cisplatin, followed the next day by oral temozolomide for 5 days every 4 weeks at dose levels 80 mg m−2/150 mg m−2 day−1, 80/200, and 100/200, respectively. A total of 38 patients receiving 113 cycles (median 2, range 1–7) were evaluable for toxicity. Dose-limiting toxicity was haematological in all but one case. Treatment-related toxicities were thrombocytopenia, neutropenia, nausea-vomiting, asthenia. Hearing loss was experienced in five patients with prior irradiation to the brain stem or posterior fossa. Partial responses were observed in two malignant glioma, one brain stem glioma, and two neuroblastoma. Median MGMT activity in PBMCs decreased after 5 days of temozolomide treatment: low MGMT activity correlated with increased severity of thrombocytopenia. Cisplatin–temozolomide combinations are well tolerated without additional toxicity to single-agent treatments; the recommended phase II dosage is 80 mg m−2 cisplatin and 150 mg m−2 × 5 temozolomide in heavily treated, and 200 mg m−2 × 5 temozolomide in less-heavily pretreated children. PMID:16136028

Cone beam computed tomography in Endodontics - a review.

PubMed

Patel, S; Durack, C; Abella, F; Shemesh, H; Roig, M; Lemberg, K

2015-01-01

Cone beam computed tomography (CBCT) produces undistorted three-dimensional information of the maxillofacial skeleton, including the teeth and their surrounding tissues with a lower effective radiation dose than computed tomography. The aim of this paper is to: (i) review the current literature on the applications and limitations of CBCT; (ii) make recommendations for the use of CBCT in Endodontics; (iii) highlight areas of further research of CBCT in Endodontics. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study.

PubMed

Seto, Takashi; Kiura, Katsuyuki; Nishio, Makoto; Nakagawa, Kazuhiko; Maemondo, Makoto; Inoue, Akira; Hida, Toyoaki; Yamamoto, Nobuyuki; Yoshioka, Hiroshige; Harada, Masao; Ohe, Yuichiro; Nogami, Naoyuki; Takeuchi, Kengo; Shimada, Tadashi; Tanaka, Tomohiro; Tamura, Tomohide

2013-06-01

Currently, crizotinib is the only drug that has been approved for treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). We aimed to study the activity and safety of CH5424802, a potent, selective, and orally available ALK inhibitor. In this multicentre, single-arm, open-label, phase 1-2 study of CH5424802, we recruited ALK inhibitor-naive patients with ALK-rearranged advanced NSCLC from 13 hospitals in Japan. In the phase 1 portion of the study, patients received CH5424802 orally twice daily by dose escalation. The primary endpoints of the phase 1 were dose limiting toxicity (DLT), maximum tolerated dose (MTD), and pharmacokinetic parameters. In the phase 2 portion of the study, patients received CH5424802 at the recommended dose identified in the phase 1 portion of the study orally twice a day. The primary endpoint of the phase 2 was the proportion of patients who had an objective response. Treatment was continued in 21-day cycles until disease progression, intolerable adverse events, or withdrawal of consent. The analysis was done by intent to treat. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-101264. Patients were enrolled between Sept 10, 2010, and April 18, 2012. The data cutoff date was July 31, 2012. In the phase 1 portion, 24 patients were treated at doses of 20-300 mg twice daily. No DLTs or adverse events of grade 4 were noted up to the highest dose; thus 300 mg twice daily was the recommended phase 2 dose. In the phase 2 portion of the study, 46 patients were treated with the recommended dose, of whom 43 achieved an objective response (93.5%, 95% CI 82.1-98.6) including two complete responses (4.3%, 0.5-14.8) and 41 partial responses (89.1%, 76.4-96.4). Treatment-related adverse events of grade 3 were recorded in 12 (26%) of 46 patients, including two patients each experiencing decreased neutrophil count and increased blood creatine phosphokinase. Serious adverse events occurred in five patients (11%). No grade 4 adverse events or deaths were reported. The study is still ongoing, since 40 of the 46 patients in the phase 2 portion remain on treatment. CH5424802 is well tolerated and highly active in patients with advanced ALK-rearranged NSCLC. Chugai Pharmaceutical Co, Ltd. Copyright © 2013 Elsevier Ltd. All rights reserved.

SU-E-T-224: Considerations for the Proper Treatment of Multiple Cranial Metastases with Single Isocenter Volumetric Modulated Arc Therapy

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

Audet, C; Poffenbarger, B; Hwang, A

2015-06-15

Purpose: To investigate some limitations of single isocenter VMAT for cranial multiple met cases. Methods: A single isocenter VMAT plan (Varian, Eclipse AAA10 commissioned down to 1 cm) was designed for two 7mm diameter spherical targets in a rectangular Solid Water (Gammex) phantom. The targets were separated by a distance of 6cm and the isocenter was centered in one of the targets. The plan was delivered (Varian, Truebeam STx) three separate times with different artificial couch angle errors of 0, 0.5 and 1 degree. The coronal dose distributions were measured with calibrated EBT3 film placed at mid-phantom. EBT3 film dosimetrymore » was also performed on the delivery of separate multiple arc vmat plans to targets below 6mm in diameter. Results: Measurements of the sup/inf dose profiles through the high dose distributions show no movement of the central axis high dose region and shifts of the high dose region intended for the off-axis target. For the 1 degree rotation error, the high dose region was shifted 1.04mm from the target. This corresponds to the shift expected from triangulation (60mmxTan(1deg)=1.047mm). Furthermore, a streak of 10% interleaf leakage dose was observed and is likely a Result of the off axis target traveling a wide path such that a long length of MLC is exposed for the whole arc. The calculated dose was about 10% to 15% low compared to that measured on film for a 5mm diameter target. Conclusion: Judicious use of additional margin for off axis targets or limits on the span of multiple mets treated with one isocenter is recommended. The magnitude of the margin should be based on the rotational errors evaluated for the positioning system and the distance of the target from the isocenter. A lower limit of lesion size that can be accurately treated with VMAT should be determined.« less

Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis.

PubMed

Denti, Paolo; Garcia-Prats, Anthony J; Draper, Heather R; Wiesner, Lubbe; Winckler, Jana; Thee, Stephanie; Dooley, Kelly E; Savic, Rada M; McIlleron, Helen M; Schaaf, H Simon; Hesseling, Anneke C

2018-02-01

Levofloxacin is increasingly used in the treatment of multidrug-resistant tuberculosis (MDR-TB). There are limited pediatric pharmacokinetic data to inform dose selection for children. Children routinely receiving levofloxacin (250-mg adult tablets) for MDR-TB prophylaxis or disease in Cape Town, South Africa, underwent pharmacokinetic sampling following receipt of a dose of 15 or 20 mg/kg of body weight given as a whole or crushed tablet(s) orally or via a nasogastric tube. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Model-based simulations were performed to estimate the doses across weight bands that would achieve adult exposures with 750-mg once-daily dosing. One hundred nine children were included. The median age was 2.1 years (range, 0.3 to 8.7 years), and the median weight was 12 kg (range, 6 to 22 kg). Levofloxacin followed 2-compartment kinetics with first-order elimination and absorption with a lag time. After inclusion of allometric scaling, the model characterized the age-driven maturation of clearance (CL), with the effect reaching 50% of that at maturity at about 2 months after birth and 100% of that at maturity by 2 years of age. CL in a typical child (weight, 12 kg; age, 2 years) was 4.7 liters/h. HIV infection reduced CL by 16%. By use of the adult 250-mg formulation, levofloxacin exposures were substantially lower than those reported in adults receiving a similar dose on a milligram-per-kilogram basis. To achieve adult-equivalent exposures at a 750-mg daily dose, higher levofloxacin pediatric doses of from 18 mg/kg/day for younger children with weights of 3 to 4 kg (due to immature clearance) to 40 mg/kg/day for older children may be required. The doses of levofloxacin currently recommended for the treatment of MDR-TB in children result in exposures considerably lower than those in adults. The effects of different formulations and formulation manipulation require further investigation. We recommend age- and weight-banded doses of 250-mg tablets of the adult formulation most likely to achieve target concentrations for prospective evaluation. Copyright © 2018 American Society for Microbiology.

Vaccination coverage among foreign-born and U.S.-born adolescents in the United States: Successes and gaps - National Immunization Survey-Teen, 2012-2014.

PubMed

Healy, Jessica; Rodriguez-Lainz, Alfonso; Elam-Evans, Laurie D; Hill, Holly A; Reagan-Steiner, Sarah; Yankey, David

2018-03-20

An overall increase has been reported in vaccination rates among adolescents during the past decade. Studies of vaccination coverage have shown disparities when comparing foreign-born and U.S.-born populations among children and adults; however, limited information is available concerning potential disparities in adolescents. The National Immunization Survey-Teen is a random-digit-dialed telephone survey of caregivers of adolescents aged 13-17 years, followed by a mail survey to vaccination providers that is used to estimate vaccination coverage among the U.S. population of adolescents. Using the National Immunization Survey-Teen data, we assessed vaccination coverage during 2012-2014 among adolescents for routinely recommended vaccines for this age group (≥1 dose tetanus and diphtheria toxoids and acellular pertussis [Tdap] vaccine, ≥1 dose quadrivalent meningococcal conjugate [MenACWY] vaccine, ≥3 doses human papillomavirus [HPV] vaccine) and for routine childhood vaccination catch-up doses (≥2 doses measles, mumps, and rubella [MMR] vaccine, ≥2 doses varicella vaccine, and ≥3 doses hepatitis B [HepB] vaccine). Vaccination coverage prevalence and vaccination prevalence ratios were estimated. Of the 58,090 respondents included, 3.3% were foreign-born adolescents. Significant differences were observed between foreign-born and U.S.-born adolescents for insurance status, income-to-poverty ratio, education, interview language, and household size. Foreign-born adolescents had significantly lower unadjusted vaccination coverage for HepB (89% vs. 93%), and higher coverage for the recommended ≥3 doses of HPV vaccine among males, compared with U.S.-born adolescents (22% vs. 14%). Adjustment for demographic and socioeconomic factors accounted for the disparity in HPV but not HepB vaccination coverage. We report comparable unadjusted vaccination coverage among foreign-born and U.S.-born adolescents for Tdap, MenACWY, MMR, ≥2 varicella. Although coverage was high for HepB vaccine, it was significantly lower among foreign-born adolescents, compared with U.S.-born adolescents. HPV and ≥2-dose varicella vaccination coverage were low among both groups. Published by Elsevier Ltd.

Drug-Induced Nephrotoxicity and Dose Adjustment Recommendations: Agreement Among Four Drug Information Sources.

PubMed

Bicalho, Millena Drumond; Soares, Danielly Botelho; Botoni, Fernando Antonio; Reis, Adriano Max Moreira; Martins, Maria Auxiliadora Parreiras

2015-09-09

: Hospitalized patients require the use of a variety of drugs, many of which individually or in combination have the potential to cause kidney damage. The use of potentially nephrotoxic drugs is often unavoidable, and the need for dose adjustment should be evaluated. This study is aimed at assessing concordance in information on drug-induced nephrotoxicity and dose adjustment recommendations by comparing four drug information sources (DRUGDEX(®), UpToDate(®), Medscape(®) and the Brazilian Therapeutic Formulary) using the formulary of a Brazilian public hospital. A total of 218 drugs were investigated. The global Fleiss' kappa coefficient was 0.265 for nephrotoxicity (p < 0.001; CI 95%, 0.211-0.319) and 0.346 for recommendations (p < 0.001; CI 95%, 0.292-0.401), indicating fair concordance among the sources. Anti-infectives and anti-hypertensives were the main drugs cited as nephrotoxic by the different sources. There were no clear definitions for qualitative data or quantitative values for dose adjustments among the four information sources. There was no advice for dosing for a large number of the drugs in the international databases. The National Therapeutic Formulary offered imprecise dose adjustment recommendations for many nephrotoxic drugs. Discrepancies among information sources may have a clinical impact on patient care and contribute to drug-related morbidity and mortality.

Measurement of radiation exposure in relatives of thyroid cancer patients treated with (131)I.

PubMed

Ramírez-Garzón, Y T; Ávila, O; Medina, L A; Gamboa-deBuen, I; Rodríguez-Laguna, A; Buenfil, A E; Ruíz-Trejo, C; Estrada, E; Brandan, M E

2014-11-01

This work evaluates the radiological risk that patients treated with I for differentiated thyroid cancer could present to relatives and occupationally exposed workers. Recently, the International Atomic Energy Agency issued document K9010241, which recommends that patient discharge from the hospital must be based on the particular status of each patient. This work measures effective dose received by caregivers of patients treated with I at the Instituto Nacional de Cancerología, Mexico City. Thermoluminescent dosimeters were carried during a 15-d period by 40 family caregivers after patient release from hospital. Relatives were classified into two groups, ambulatory and hospitalized, according to the release mode of the patient, and three categories according to the individual patient home and transport facilities. Categories A, B, and C were defined going from most to least adequate concerning public exposure risk. Measurements were performed for 20 family caregivers in each group. The effective dose received by all caregivers participating in this study was found to be less than 5 mSv, the recommended limit per event for caregivers suggested by ICRP 103. In addition, 70 and 90% of ambulatory and hospitalized groups, respectively, received doses lower than 1 mSv. Caregivers belonging to category C, with home situations that are not appropriate for immediate release, received the highest average doses; i.e., 2.2 ± 1.3 and 3.1 ± 1.0 mSv for hospitalized and ambulatory patients, respectively. Results of this work have shown that the proper implementation of radiation protection instructions for relatives and patients can reduce significantly the risk that differentiated thyroid cancer patients treated with I can represent for surrounding individuals. The results also stress the relevance of the patient's particular lifestyle and transport conditions as the prevailing factors related to the dose received by the caregiver. Therefore, the patient's status should be the criterion used to decide his/her release modality. This work provides support to recommend the implementation of the "patient specific release criteria" in accordance with ICRP 94, IAEA Safety Report No. 63, and IAE document K9010241 A for patients treated with radiopharmaceuticals.

Implementing the birth dose of hepatitis B vaccine in rural Indonesia.

PubMed

Creati, Mick; Saleh, Asmaniar; Ruff, Tilman A; Stewart, Tony; Otto, Bradley; Sutanto, Agustinus; Clements, C John

2007-08-10

Reaching mothers and their newborn infants around the time of birth with adequate health services has long been a difficult problem in developing countries. In parallel, similar problems have arisen in attempting to deliver hepatitis B (HepB) vaccine to infants born at home in many countries where mother-to-infant transmission is common. It is logical, and supported by experience in Indonesia, to find a combined solution for both problems. The World Health Organization (WHO) recommends that a timely birth dose of HepB vaccine be given, particularly in areas of high vertical transmission of hepatitis B virus (HBV). This can be achieved relatively easily in situations where almost all births occur in health facilities. But where a significant proportion of births occur at home and without birth attendants able to give injections, this is much more difficult. Barriers to the timely administration of the birth dose of HepB vaccine include weakness in policy development and implementation, difficulties in reliably supplying potent vaccine to community level, limited transport, poor communication, limited cold chain capacity, lack of effective training, and lack of a clear delineation of responsibility between health care professionals. Demonstration projects, such as those in Indonesia, suggest that there are significant opportunities to improve the timely delivery of HepB vaccine birth dose in existing maternal and child health programmes where health workers are trained to provide home delivery care.

Evaluation of exposure-response relationships for health effects of microbial bioaerosols - A systematic review.

PubMed

Walser, Sandra M; Gerstner, Doris G; Brenner, Bernhard; Bünger, Jürgen; Eikmann, Thomas; Janssen, Barbara; Kolb, Stefanie; Kolk, Annette; Nowak, Dennis; Raulf, Monika; Sagunski, Helmut; Sedlmaier, Nadja; Suchenwirth, Roland; Wiesmüller, Gerhard; Wollin, Klaus-Michael; Tesseraux, Irene; Herr, Caroline E W

2015-10-01

Studies suggest adverse health effects following exposure to bioaerosols in the environment and in particular at workplaces. However, there is still a lack of health-related exposure limits based on toxicological or epidemiological studies from environmental health or from the working environment. The aim of this study was to derive health-based exposure limits for bioaerosols that can protect the general population as group "at risk" via environmental exposure using analysis of peer-reviewed studies related to occupational medicine, indoor air and environmental health. The derivation of exposure limits should be conducted by the members of a bioaerosol expert panel according to established toxicological criteria. A systematic review was performed in Medline (PubMed) including studies containing both data on exposure measurements and observed health outcomes. In addition, literature recommended by the experts was considered. A comprehensive search strategy was generated and resulted in a total of n=1569 studies in combination with the literature recommendations. Subsequently, abstracts were screened using defined exclusion criteria yielding a final number of n=44 studies. A standardized extraction sheet was used to combine data on health effects and exposure to different bioaerosols. After full-text screening and extraction according to the defined exclusion criteria n=20 studies were selected all related to occupational exposures comprising the working areas wood processing, farming, waste processing and others. These studies were analyzed in collaboration with the bioaerosol expert network in terms of suitability for derivation of health-related exposure limits. The bioaerosol expert network concluded that none of the analyzed studies provided suitable dose-response relationships for derivation of exposure limits. The main reasons were: (1) lack of studies with valid dose-response data; (2) diversity of employed measuring methods for microorganisms and bioaerosol-emitting facilities; (3) heterogeneity of health effects; (4) insufficient exposure assessment. However, several indicator parameters and exposure concentrations could be identified for different bioaerosol-emitting facilities. Nevertheless, health-related exposure limits are urgently needed especially in approval procedures of facilities like composting plants or livestock farms emitting bioaerosols in the neighbourhood of residents. In the regulatory toxicology framework, it is common to use animal experimental studies for derivation of general exposure limits if appropriate environmental epidemiological studies on harmful substances are lacking. This might be another possibility to obtain health-related exposure limits for specific bioaerosol parameters. Furthermore, we recommend to use suitable measurable outcome parameters related to bioaerosols; to measure bioaerosols according to a protocol representative for exposure pattern and duration at the particular work place; to develop standardized detection methods for indicator parameters; to combine different detection methods to compensate for the limitations of each method; to apply new analysis methods to identify the real risk potential. Copyright © 2015 Elsevier GmbH. All rights reserved.

The preteen visit: an opportunity for prevention.

PubMed

Campos-Outcalt, Doug

2006-12-01

All early adolescents should visit a physician at age 11 or 12 years to receive a set of recommended vaccines. Two vaccines are recommended for boys in this age group-quadrivalent meningococcal conjugate vaccine (MCV4) and tetanus toxoid, reduced diphtheria, and acellular pertussis vaccine (Tdap). Three vaccines are recommended for girls--MCV4, Tdap, and human papilloma virus (HPV) vaccine. In addition, 2 doses of varicella vaccine are now recommended before age 5 years; both boys and girls at age 11 or 12 who have received only 1 dose should be given a second.

Transferring Patients From Methadone to Buprenorphine: The Feasibility and Evaluation of Practice Guidelines.

PubMed

Lintzeris, Nicholas; Monds, Lauren A; Rivas, Consuelo; Leung, Stefanie; Dunlop, Adrian; Newcombe, David; Walters, Carina; Galea, Susanna; White, Nancy; Montebello, Mark; Demirkol, Apo; Swanson, Nicola; Ali, Robert

Transfer from methadone to buprenorphine is problematic for many opioid-dependent patients, with limited documented evidence or practical clinical guidance, particularly for the range of methadone doses routinely prescribed for most patients (>50 mg). This study aimed to implement and evaluate recent national Australian guidelines for transferring patients from methadone to buprenorphine. A multisite prospective cohort study. Participants were patients who transferred from methadone to buprenorphine-naloxone at 1 of 4 specialist addiction centers in Australia and New Zealand. Clinicians were trained in the guidelines, and medical records were reviewed to examine process (eg, transfer setting, doses, and guideline adherence) and safety (precipitated withdrawal) measures. Participants completed research interviews before and after transfer-assessing changes in substance use, health outcomes, and side effects. In all, 33 participants underwent transfer, 9 from low methadone doses (<30 mg), 9 from medium doses (30-50 mg), and 15 from high doses (>50 mg). The majority of high-dose transfers occurred in inpatient settings. There was reasonable guideline adherence, and no complications identified in the low and medium-dose transfers. Three high-dose transfers (20%) experienced precipitated withdrawal, and 7/33 participants (21%) returned to methadone within 1 week of attempted transfer. Transfer is feasible in outpatient settings for those transferring from methadone doses below 50 mg; however, inpatient settings and specialist supervision is recommended for higher-dose transfers. The Australian clinical guidelines appear safe and feasible, although further research is required to optimize high-dose transfer procedures.

[Immunisation schedule of the Spanish Association of Paediatrics: 2018 recommendations].

PubMed

Moreno-Pérez, David; Álvarez García, Francisco José; Álvarez Aldeán, Javier; Cilleruelo Ortega, María José; Garcés Sánchez, María; García Sánchez, Nuria; Hernández Merino, Ángel; Méndez Hernández, María; Merino Moína, Manuel; Montesdeoca Melián, Abián; Ruiz-Contreras, Jesús

2018-01-01

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics annually publishes the immunisation schedule considered optimal for children resident in Spain, according to available evidence on current vaccines. Regarding funded immunisations, 2+1 strategy (2, 4, 11-12 months) with hexavalent (DTPa-IPV-Hib-HB) and 13-valent pneumococcal vaccines are recommended. Administration of the 6-year booster dose with DTPa is recommended, and a poliomyelitis dose for children who had received the 2+1 scheme, as well as Tdap vaccine for adolescents and pregnant women in every pregnancy between 27 and 32 weeks' gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). MMRV vaccine could be applied as the second dose if available. Coverage of human papillomavirus vaccination in girls aged 12 with a two dose scheme (0, 6 months) should be improved. Information and recommendation for male adolescents about potential beneficial effects of this immunisation should be provided as well. The new 9 genotypes vaccine is now available, expanding the coverage for both gender. Regarding non-funded immunisations, Committee on Vaccines of the Spanish Association of Paediatrics recommends meningococcal B vaccination, with a 3+1 schedule, and requests to be included in the National Immunisation Program. Tetravalent meningococcal vaccine (MenACWY) is recommended to adolescents (14-18 years) who are going to live in countries with systematic vaccination against ACWY serogroups, and people >6 weeks of age with risk factors or travellers to countries with very high incidence. Vaccination against rotavirus is recommended in all infants. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Dose estimation to eye lens of industrial gamma radiography workers using the Monte Carlo method.

PubMed

de Lima, Alexandre Roza; Hunt, John Graham; Da Silva, Francisco Cesar Augusto

2017-12-01

The ICRP Statement on Tissue Reactions (2011), based on epidemiological evidence, recommended a reduction for the eye lens equivalent dose limit from 150 to 20 mSv per year. This paper presents mainly the dose estimations received by industrial gamma radiography workers, during planned or accidental exposure to the eye lens, Hp(10) and effective dose. A Brazilian Visual Monte Carlo Dose Calculation program was used and two relevant scenarios were considered. For the planned exposure situation, twelve radiographic exposures per day for 250 days per year, which leads to a direct exposure of 10 h per year, were considered. The simulation was carried out using a 192 Ir source with 1.0 TBq of activity; a source/operator distance between 5 and 10 m and placed at heights of 0.02 m, 1 m and 2 m, and an exposure time of 12 s. Using a standard height of 1 m, the eye lens doses were estimated as being between 16.3 and 60.3 mGy per year. For the accidental exposure situation, the same radionuclide and activity were used, but in this case the doses were calculated with and without a collimator. The heights above ground considered were 1.0 m, 1.5 m and 2.0 m; the source/operator distance was 40 cm, and the exposure time 74 s. The eye lens doses at 1.5 m were 12.3 and 0.28 mGy without and with a collimator, respectively. The conclusions were that: (1) the estimated doses show that the 20 mSv annual limit for eye lens equivalent dose can directly impact industrial gamma radiography activities, mainly in industries with high number of radiographic exposures per year; (2) the risk of lens opacity has a low probability for a single accident, but depending on the number of accidental exposures and the dose levels found in planned exposures, the threshold dose can easily be exceeded during the professional career of an industrial radiography operator, and; (3) in a first approximation, Hp(10) can be used to estimate the equivalent dose to the eye lens.

Meeting physical activity recommendations: self-regulatory efficacy characterizes differential adherence during arthritis flares.

PubMed

Gyurcsik, Nancy C; Brawley, Lawrence R; Spink, Kevin S; Sessford, James D

2013-02-01

Using social-cognitive theory, we examined whether adults who experienced an arthritis flare and met/did not meet the disease-specific public health recommended dose for physical activity differed in their self-regulatory efficacy beliefs, overall pain, and flare-related factors. Adults with arthritis (N = 56; M(age) = 49.41 ± 11.56 years) participated in this prospective study. Multivariate analysis of variance comparing groups who met or did not meet the recommended dose (n(met) = 24, ≥ 150 minutes/week vs. n(not met) = 32, < 150 min/week) on efficacy, overall pain, and flare-related factors was significant (p < .01; η(partial)² = .28). People meeting the dose had significantly greater self-regulatory efficacy to overcome arthritis barriers (M(met dose) = 7.33 ± 1.95 vs. M(did not meet dose) = 5.74 ± 2.08, η(partial)² = .14) and to schedule/plan (M(met dose) = 7.27 ± 1.80 vs. M(did not meet dose) = 5.72 ± 1.90, η(partial)² = .15). Overall pain and flare-related factors did not differ (ps > .05). During flares, individuals with greater self-regulatory efficacy to manage disease barriers and plan their physical activity were more adherent to disease-specific public health activity recommendations. This study was the first to demonstrate differences in social cognitions that characterize adherence to recommended activity among people challenged by arthritis flares. Findings support the theoretical position that self-regulatory efficacy is related to better adherence in the face of challenging disease-related circumstances. The importance of studying individual characteristics of people who succeed in being active despite such obstacles is stressed.

A prospective observational study to evaluate G-CSF usage in patients with solid tumors receiving myelosuppressive chemotherapy in Italian clinical oncology practice.

PubMed

Barni, S; Lorusso, V; Giordano, M; Sogno, G; Gamucci, T; Santoro, A; Passalacqua, R; Iaffaioli, V; Zilembo, N; Mencoboni, M; Roselli, M; Pappagallo, G; Pronzato, P

2014-01-01

Febrile neutropenia (FN) is a severe dose-limiting side effect of myelosuppressive chemotherapy in patients with solid tumors. Clinical practice guidelines recommend primary prophylaxis with G-CSF in patients with an overall ≥ 20 % risk of FN. AIOM Italian guidelines recommend starting G-CSF within 24-72 h after chemotherapy; for daily G-CSF, administration should continue until the absolute neutrophil count (ANC) is 1 × 10(9)/L post-nadir and should not be terminated after ANC increase in the early days of administration. The aim of this study was to assess guideline adherence in oncology practice in Italy. In this multicenter, prospective, observational study, patients were enrolled at the first G-CSF use in any cycle and were followed for two subsequent cycles (or until the end of chemotherapy if less than two additional cycles). Primary objective was to explore G-CSF use in Italian clinical practice; therefore, data were collected on the G-CSF type, timing of administration, and number of doses. 512 eligible patients were enrolled (median age, 62). The most common tumor types were breast (36 %), lung (18 %), and colorectal (13 %). A total of 1,164 G-CSF cycles (daily G-CSF, 718; pegfilgrastim, 446) were observed. Daily G-CSF was administered later than 72 h after chemotherapy in 42 % of cycles, and the median [range] number of doses was four [1, 10]. Pegfilgrastim was administered later than 72 h in 8 % of cycles. G-CSF prophylaxis in Italy is frequently administered in a manner which is not supported by evidence-based guidelines. As this practice may lead to poor outcomes, educational initiatives are recommended.

Uptake of oral rotavirus vaccine and timeliness of routine immunization in Brazil’s National Immunization Program

PubMed Central

Flannery, Brendan; Samad, Samia; de Moraes, José Cássio; Tate, Jacqueline E.; Danovaro-Holliday, M. Carolina; de Oliveira, Lúcia Helena; Rainey, Jeanette J.

2015-01-01

Introduction In March, 2006, oral rotavirus vaccine was added to Brazil’s infant immunization schedule with recommended upper age limits for initiating (by age 14 weeks) and completing (by age 24 weeks) the two-dose series to minimize age-specific risk of intussusception following rotavirus vaccination. Several years after introduction, estimated coverage with rotavirus vaccine (83%) was lower compared to coverage for other recommended childhood immunizations (≥94%). Methods We analyzed data from Brazil’s national immunization program on uptake of oral rotavirus vaccine by geographic region and compared administrative coverage estimates for first and second doses of oral rotavirus vaccine (Rota1 and Rota2) with first and second doses of diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP-Hib1 and DTP-Hib2). For 27 Brazilian cities, we compared differences between estimated rotavirus and DTP-Hib coverage in 2010 with delayed receipt of DTP-Hib vaccine among a cohort of children surveyed before rotavirus introduction. Results In 2010, infant vaccination coverage was 99.0% for DTP-Hib1 versus 95.2% for Rota1 (3.8% difference), and 98.4% for DTP-Hib2 versus 83.0% for Rota2 (15.4% difference), with substantial regional variation. Differences between DTP-Hib and rotavirus vaccination coverage in Brazilian cities correlated with delay in DTP-Hib vaccination among children surveyed. Age restrictions for initiating and completing the rotavirus vaccination series likely contributed to lower coverage with rotavirus vaccine in Brazil. Conclusion To maximize benefits of rotavirus vaccination, strategies are needed to improve timeliness of routine immunizations; monitoring rotavirus vaccine uptake and intussusception risk is needed to guide further recommendations for rotavirus vaccination. PMID:23313652

The Financial Burden of Public Health Responses to Hepatitis A Cases Among Food Handlers, 2012-2014.

PubMed

Morey, Rebecca J; Collier, Melissa G; Nelson, Noele P

When food handlers become ill with hepatitis A virus (HAV) infection, state and local health departments must assess the risk of HAV transmission through prepared food and recommend or provide postexposure prophylaxis (PEP) for those at risk for HAV infection. Providing PEP (eg, hepatitis A [HepA] vaccine or immunoglobulin), however, is costly. To describe the burden of these responses on state and local health departments, we determined the number of public health responses to HAV infections among food handlers by reviewing public internet sources of media articles. We then contacted each health department to collect data on whether PEP was recommended to food handlers or restaurant patrons, the number of PEP doses given, the number of HepA vaccine or immunoglobulin doses given as PEP, and the mean number of health department person-hours required for the response. Of 32 public health responses identified from Twitter, HealthMap, and Google alerts from January 1, 2012, to December 31, 2014, a total of 27 (84%) recommended PEP for other food handlers or restaurant patrons or both. Per public health response, the mean cost per dose of the HepA vaccine or immunoglobulin was $34 139; the mean personnel cost per response was $7329; and the total mean cost of each response was $41 468. PEP is expensive. Less aggressive approaches to PEP, such as limiting PEP to fellow food handlers in nonoutbreak situations, should be considered in the postvaccination era. HepA vaccine for PEP provides long-term immunity and can be used when immunoglobulin is unavailable or cannot be administered within 14 days of exposure to HAV.

Raspberry ketone in food supplements--High intake, few toxicity data--A cause for safety concern?

PubMed

Bredsdorff, Lea; Wedebye, Eva Bay; Nikolov, Nikolai Georgiev; Hallas-Møller, Torben; Pilegaard, Kirsten

2015-10-01

Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is marketed on the Internet as a food supplement. The recommended intake is between 100 and 1400 mg per day. The substance is naturally occurring in raspberries (up to 4.3 mg/kg) and is used as a flavouring substance. Toxicological studies on raspberry ketone are limited to acute and subchronic studies in rats. When the lowest recommended daily dose of raspberry ketone (100 mg) as a food supplement is consumed, it is 56 times the established threshold of toxicological concern (TTC) of 1800 μg/day for Class 1 substances. The margin of safety (MOS) based on a NOAEL of 280 mg/kg bw/day for lower weight gain in rats is 165 at 100 mg and 12 at 1400 mg. The recommended doses are a concern taking into account the TTC and MOS. Investigations of raspberry ketone in quantitative structure-activity relationship (QSAR) models indicated potential cardiotoxic effects and potential effects on reproduction/development. Taking into account the high intake via supplements, the compound's toxic potential should be clarified with further experimental studies. In UK the pure compound is regarded as novel food requiring authorisation prior to marketing but raspberry ketone is not withdrawn from Internet sites from this country. Copyright © 2015 Elsevier Inc. All rights reserved.

Regulatory responses to over-the-counter codeine analgesic misuse in Australia, New Zealand and the United Kingdom.

PubMed

Tobin, Claire L; Dobbin, Malcolm; McAvoy, Brian

2013-10-01

Analysis of the policy response by Australia's National Drugs and Poisons Schedule Committee (NDPSC) and comparison with recommendations by expert advisory committees in New Zealand and the United Kingdom. Analysis of public policy documents of relevant regulatory authorities was conducted. Data were extracted regarding changes to over-the-counter (OTC) codeine analgesic scheduling, indications, maximum unit dose, maximum daily dose, maximum pack size, warning labels, consumer medicine information and advertising. Where available, public submissions and other issues considered by the committees and rationale for their recommendations were recorded and thematically analysed. Expert advisory committees in Australia, NZ and the UK defined the policy problem of OTC codeine misuse and harm as small relative to total use and responded by restricting availability. Pharmacist supervision was required at the point-of-sale and pack sizes were reduced to short-term use. Comparison with recommendations by expert advisory committees in NZ and the UK suggests the NDPSC's actions in response to OTC codeine misuse were appropriate given the available evidence of misuse and harm, but highlights opportunities to utilise additional regulatory levers. Framing policy problems as matters of public health in the context of limited evidence may support decision makers to implement cautionary incremental policy change. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

Quality of life in a cohort of high-dose benzodiazepine dependent patients.

PubMed

Lugoboni, Fabio; Mirijello, Antonio; Faccini, Marco; Casari, Rebecca; Cossari, Anthony; Musi, Gessica; Bissoli, Giorgia; Quaglio, Gianluca; Addolorato, Giovanni

2014-09-01

Benzodiazepines (BZD) are among the most widely prescribed drugs in developed countries. Since BZD can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZD causes a number of serious side effects, i.e., cognitive impairment, falls, traffic accidents, dependence and tolerance. The aim of the present study was to evaluate quality of life (QoL) in a cohort of 62 consecutive high-dose BZD-dependent patients seeking a BZD detoxification. Patients seeking BZD detoxification were evaluated using the General Health Questionnaire (GHQ-12) and the short form-36 questionnaire (SF-36). Patients showed a significant reduction of QoL as measured by either SF-36 or GHQ-12. In particular, the greater impairment was observed in the items exploring physical and emotional status. Physical functioning was the item more influenced by the length of BZD abuse. Female patients showed a greater reduction of QoL compared to male, at least in some of the explored items. Social functioning scores were greatly reduced. The present study shows for the first time that high-doses BZD dependent patients have a reduced QoL and a reduced social functioning, along with high levels of psychological distress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Influence of oral polio vaccines on performance of the monovalent and pentavalent rotavirus vaccines.

PubMed

Patel, Manish; Steele, A Duncan; Parashar, Umesh D

2012-04-27

In recent years, two live, oral rotavirus vaccines have been successfully tested in developing and industrialized countries, and both vaccines are now recommended by the World Health Organization for all children worldwide. Both immunogenicity and efficacy of these rotavirus vaccines has been lower in developing compared to industrialized settings. We reviewed the data on the effect of trivalent OPV on the immunogenicity and efficacy of two rotavirus vaccines currently recommended by the WHO. While rotavirus vaccines have not affected immune responses to OPV, in general, the immune responses (i.e., antibody levels) to rotavirus vaccination were lower when rotavirus vaccines were co-administered with OPV. Limited data suggests that the interference is greater after the first dose of OPV, presumably because the first dose is associated with greatest intestinal replication of vaccine polio virus strains, and this interference is largely overcome with subsequent rotavirus vaccine doses. Despite the lower immunogenicity, one large efficacy study in middle income Latin American countries showed no decrease in protective efficacy of rotavirus vaccine in infants receiving concurrent OPV. While these data are encouraging and support simultaneous administration of rotavirus vaccines and OPV, additional evidence should be gathered as rotavirus vaccines are used more widely in developing country settings, where OPV is routinely used, rather than inactivated polio vaccine. Published by Elsevier Ltd.

Evidence-based treatment of frequent heartburn: the benefits and limitations of over-the-counter medications.

PubMed

McRorie, Johnson W; Gibb, Roger D; Miner, Philip B

2014-06-01

This review summarizes the pharmacological effects of over-the-counter (OTC) heartburn drugs, and the implications for treating frequent heartburn. PubMed and SCOPUS were searched across all years to identify well-controlled, randomized clinical studies that assessed mechanism of action and efficacy. Antacids can transiently neutralize acid in the esophagus, but do not significantly affect gastric pH or prevent subsequent heartburn episodes. Histamine-2 receptor antagonists (H2 RAs) rapidly develop tolerance with repeat dosing, and exhibit an analgesic effect that may provide heartburn relief while leaving the esophagus exposed to acid. Proton pump inhibitors (PPIs) provide a sustained inhibition of gastric acid production, and are superior to antacids and H2 RAs for control of gastric acid and treatment of frequent heartburn. When recommending therapies for frequent heartburn, it is of particular importance to understand the strengths and weaknesses of available OTC medications. Antacids and H2 RAs are not recommended for treatment of frequent heartburn, while OTC PPIs are both indicated for, and effective for, treatment of frequent heartburn. A PPI dose of 20 mg is optimal for empiric treatment of frequent heartburn, and consistent with the 2013 treatment guidelines established by the American College of Gastroenterology (ACG) for treatment with a minimum effective dose. ©2014 The Author(s) ©2014 American Association of Nurse Practitioners.

TH-EF-204-03: Determination of Small Field Output Factors, Advantages and Limitations of Monte Carlo Simulation

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

Vaque, J. Puxeu

2016-06-15

Joanna E. Cygler, Jan Seuntjens, J. Daniel Bourland, M. Saiful Huq, Josep Puxeu Vaque, Daniel Zucca Aparicio, Tatiana Krylova, Yuri Kirpichev, Eric Ford, Caridad Borras Stereotactic Radiation Therapy (SRT) utilizes small static and dynamic (IMRT) fields, to successfully treat malignant and benign diseases using techniques such as Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT). SRT is characterized by sharp dose gradients for individual fields and their resultant dose distributions. For appropriate targets, small field radiotherapy offers improved treatment quality by allowing better sparing of organs at risk while delivering the prescribed target dose. Specialized small field treatment deliverymore » systems, such as robotic-controlled linear accelerators, gamma radiosurgery units, and dynamic arc linear accelerators may utilize rigid fixation, image guidance, and tumor tracking, to insure precise dose delivery to static or moving targets. However, in addition to great advantages, small field delivery techniques present special technical challenges for dose calibration due to unique geometries and small field sizes not covered by existing reference dosimetry protocols such as AAPM TG-51 or IAEA TRS 398. In recent years extensive research has been performed to understand small field dosimetry and measurement instrumentation. AAPM, IAEA and ICRU task groups are expected to provide soon recommendations on the dosimetry of small radiation fields. In this symposium we will: 1] discuss the physics, instrumentation, methodologies and challenges for small field radiation dose measurements; 2] review IAEA and ICRU recommendations on prescribing, recording and reporting of small field radiation therapy; 3] discuss selected clinical applications and technical aspects for specialized image-guided, small field, linear accelerator based treatment techniques such as IMRT and SBRT. Learning Objectives: To learn the physics of small fields in contrast to dosimetry of conventional fields To learn about detectors suitable for small fields To learn about the role of Monte Carlo simulations in determination of small field output factors To provide an overview of the IAEA small field dosimetry recommendations To provide an overview of the content of the ICRU report on Prescribing, Reporting and Recording of Small Field Radiation Therapy. To learn about special technical considerations in delivering IMRT and SBRT treatments To appreciate specific challenges of IMRT implementation J. Seuntjens, Natural Sciences and Engineering Research Council; Canadian Institutes of Health Research.« less

Measured Occupational Solar UVR Exposures of Lifeguards in Pool Settings

PubMed Central

Gies, Peter; Glanz, Karen; O’Riordan, David; Elliott, Tom; Nehl, Eric

2013-01-01

Background The aim of this study was to measure ultraviolet radiation (UVR) exposures of lifeguards in pool settings and evaluate their personal UVR protective practices. Methods Lifeguards (n = 168) wore UVR sensitive polysulfone (PS) film badges in wrist bracelets on 2 days and completed a survey and diary covering sun protection use. Analyses were used to describe sun exposure and sun protection practices, to compare UVR exposure across locations, and to compare findings with recommended threshold limits for occupational exposure. Results The measured UVR exposures varied with location, ranging from high median UVR exposures of 6.2 standard erythemal doses (SEDs) to the lowest median of 1.7 SEDs. More than 74% of the lifeguards’ PS badges showed UVR above recommended threshold limits for occupational exposure. Thirty-nine percent received more than four times the limit and 65% of cases were sufficient to induce sunburn. The most common protective behaviors were wearing sunglasses and using sunscreen, but sun protection was often inadequate. Conclusions At-risk individuals were exposed to high levels of UVR in excess of occupational limits and though appropriate types of sun protection were used, it was not used consistently and more than 50% of lifeguards reported being sunburnt at least twice during the previous year. PMID:19572325

Prehospital Care for the Adult and Pediatric Seizure Patient: Current Evidence-based Recommendations.

PubMed

Silverman, Eric C; Sporer, Karl A; Lemieux, Justin M; Brown, John F; Koenig, Kristi L; Gausche-Hill, Marianne; Rudnick, Eric M; Salvucci, Angelo A; Gilbert, Greg H

2017-04-01

We sought to develop evidence-based recommendations for the prehospital evaluation and treatment of adult and pediatric patients with a seizure and to compare these recommendations against the current protocol used by the 33 emergency medical services (EMS) agencies in California. We performed a review of the evidence in the prehospital treatment of patients with a seizure, and then compared the seizure protocols of each of the 33 EMS agencies for consistency with these recommendations. We analyzed the type and route of medication administered, number of additional rescue doses permitted, and requirements for glucose testing prior to medication. The treatment for eclampsia and seizures in pediatric patients were analyzed separately. Protocols across EMS Agencies in California varied widely. We identified multiple drugs, dosages, routes of administration, re-dosing instructions, and requirement for blood glucose testing prior to medication delivery. Blood glucose testing prior to benzodiazepine administration is required by 61% (20/33) of agencies for adult patients and 76% (25/33) for pediatric patients. All agencies have protocols for giving intramuscular benzodiazepines and 76% (25/33) have protocols for intranasal benzodiazepines. Intramuscular midazolam dosages ranged from 2 to 10 mg per single adult dose, 2 to 8 mg per single pediatric dose, and 0.1 to 0.2 mg/kg as a weight-based dose. Intranasal midazolam dosages ranged from 2 to 10 mg per single adult or pediatric dose, and 0.1 to 0.2 mg/kg as a weight-based dose. Intravenous/intrasosseous midazolam dosages ranged from 1 to 6 mg per single adult dose, 1 to 5 mg per single pediatric dose, and 0.05 to 0.1 mg/kg as a weight-based dose. Eclampsia is specifically addressed by 85% (28/33) of agencies. Forty-two percent (14/33) have a protocol for administering magnesium sulfate, with intravenous dosages ranging from 2 to 6 mg, and 58% (19/33) allow benzodiazepines to be administered. Protocols for a patient with a seizure, including eclampsia and febrile seizures, vary widely across California. These recommendations for the prehospital diagnosis and treatment of seizures may be useful for EMS medical directors tasked with creating and revising these protocols.

A Single Dose of Intraoperative Antibiotics Is Sufficient to Prevent Urinary Tract Infection During Ureteroscopy.

PubMed

Chew, Ben H; Flannigan, Ryan; Kurtz, Michael; Gershman, Boris; Arsovska, Olga; Paterson, Ryan F; Eisner, Brian H; Lange, Dirk

2016-01-01

American Urology Association (AUA) Best Practice Guidelines for ureteroscopic stone treatment recommend antibiotic coverage for <24 hours following the procedure. The purpose of this study was to evaluate if the addition of postoperative antibiotics reduces urinary tract infections (UTIs) following ureteroscopic stone treatment beyond the recommended preoperative dose. A retrospective review was performed of consecutive patients at two institutions, University of British Columbia and Massachusetts General Hospital, Harvard. All patients received a single dose of antibiotics before ureteroscopic stone treatment. A subset of patients was also given postoperative antibiotics. The rate of UTI was compared in patients receiving only preoperative antibiotics (group 1) vs those who received pre- and postoperative antibiotics (group 2). Eighty-one patients underwent ureteroscopy for renal calculi. Mean time to follow up was 42 ± 88 days. Eight (9.9%) patients in total (two from group 1 and six from group 2, p = 0.1457) developed UTIs postoperatively. In group 1, both patients presented with pyelonephritis (n = 2); those patients with infections in group 2 presented with urosepsis (n = 2) and cystitis (n = 2) and two patients had asymptomatic bacteriuria. Risk factors such as preoperative stenting, nephrostomy tubes, and foley catheters neither differed between groups nor did they predispose patients to postoperative infections. The postoperative UTI rate in this study (9.9%) is consistent with previous reports. Our data suggest that a single preoperative dose of antibiotics is sufficient, and additional postoperative antibiotics do not decrease infection rates after ureteroscopic stone treatment. Risk for selection bias is a potential limitation.

Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory Drugs, Penicillins, and Proton Pump Inhibitors.

PubMed

Hall, Jill J; Bolina, Monika; Chatterley, Trish; Jamali, Fakhreddin

2017-02-01

To review the potential drug interactions between low-dose methotrexate (LD-MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, and proton-pump inhibitors (PPIs) given the disparity between interactions reported for high-dose and low-dose MTX to help guide clinicians. A literature search was performed in MEDLINE (1946 to September 2016), EMBASE (1974 to September 2016), and International Pharmaceutical Abstracts (1970 to January 2015) to identify reports describing potential drug interactions between LD-MTX and NSAIDS, penicillins, or PPIs. Reference lists of included articles were reviewed to find additional eligible articles. All English-language observational, randomized, and pharmacokinetic (PK) studies assessing LD-MTX interactions in humans were analyzed to determine clinical relevance in making recommendations to clinicians. Clinical case reports were assigned a Drug Interaction Probability Scale score. A total of 32 articles were included (28 with NSAIDs, 3 with penicillins, and 2 with PPIs [1 including both PPI and NSAID]). Although there are some PK data to describe increased LD-MTX concentrations when NSAIDs are used concomitantly, the clinical relevance remains unclear. Based on the limited data on LD-MTX with penicillins and PPIs, no clinically meaningful interaction was identified. Given the available evidence, the clinical importance of the interaction between LD-MTX and NSAIDs, penicillins, and PPIs cannot be substantiated. Health care providers should assess the benefit and risk of LD-MTX regardless of concomitant drug use, including factors known to predispose patients to MTX toxicity, and continue to monitor clinical and laboratory parameters per guideline recommendations.

Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels.

PubMed

Agrawal, Shrutidevi; Singh, Inderjit; Kaur, Kanwal Jit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2004-05-19

Fixed dose combination (FDC) formulations became popular in the treatment of tuberculosis (TB) because of the better patient compliance, reduced risk of monotherapy and emergence of drug resistance in contrast to treatment with separate formulations of two to four first-line drugs. However, its successful implementation in national programs is limited by probable bioinequivalency of rifampicin if present in FDC form. In this regard, World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. Hence, bioequivalence study of four drug FDC tablet was conducted using 22 healthy male volunteers according to WHO recommended protocol to determine bioavailability of rifampicin, isoniazid and pyrazinamide compared to standard separate combination at the same dose level. The study was designed as two period, two treatment crossover experiment with a washout period of 1 week. Bioequivalence of rifampicin was estimated by plasma and urinary method for both rifampicin and its active metabolite, des-acetyl rifampicin whereas isoniazid and pyrazinamide were estimated from plasma. Mean concentration time profiles and all the pharmacokinetic parameters of rifampicin, isoniazid and pyrazinamide from FDC tablet were comparable to individual formulations and passed the bioequivalence test with power of the test above 95%. Further, bioequivalence of both rifampicin and isoniazid shows that in vitro interaction of rifampicin and isoniazid is clinically insignificant. Thus, it was concluded that FDC formulation is bioequivalent for rifampicin, isoniazid and pyrazinamide and ensures the successful treatment of TB without compromising therapeutic efficacy of any of these components of anti-TB therapy.

The Elephant in the Room: Biomedical Challenges for Long Duration Lunar Habitation

NASA Technical Reports Server (NTRS)

Logan, James S.

2009-01-01

This slide presentation reviews 4 biomedical challenges that are involved in long duration lunar habitation: dust, radiation, hypogravity and synergistic effects. The first two of these challenges are reviewed with more in-depth information. The dangers of dust relate to the particle deposition in the lungs. The dangers of radiation are related to the permissible exposure limit (PEL) and the Risk of Exposure Induced Death (REID), a statistical approach pegged to a single radiation effect: Death from cancer directly attributable to the exposure. There has been a realization that radiation is more harmful than predicted. This is demonstrated by showing the change in the recommended career dose limits, have changed between 1989 and 2000.

Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study.

PubMed

Issa, Jean-Pierre J; Roboz, Gail; Rizzieri, David; Jabbour, Elias; Stock, Wendy; O'Connell, Casey; Yee, Karen; Tibes, Raoul; Griffiths, Elizabeth A; Walsh, Katherine; Daver, Naval; Chung, Woonbok; Naim, Sue; Taverna, Pietro; Oganesian, Aram; Hao, Yong; Lowder, James N; Azab, Mohammad; Kantarjian, Hagop

2015-09-01

Hypomethylating agents are used to treat cancers driven by aberrant DNA methylation, but their short half-life might limit their activity, particularly in patients with less proliferative diseases. Guadecitabine (SGI-110) is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine resistant to degradation by cytidine deaminase. We aimed to assess the safety and clinical activity of subcutaneously given guadecitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome. In this multicentre, open-label, phase 1 study, patients from nine North American medical centres with myelodysplastic syndrome or acute myeloid leukaemia that was refractory to or had relapsed after standard treatment were randomly assigned (1:1) to receive subcutaneous guadecitabine, either once-daily for 5 consecutive days (daily × 5), or once-weekly for 3 weeks, in a 28-day treatment cycle. Patients were stratified by disease. A 3 + 3 dose-escalation design was used in which we treated patients with guadecitabine doses of 3-125 mg/m(2) in separate dose-escalation cohorts. A twice-weekly treatment schedule was added to the study after a protocol amendment. The primary objective was to assess safety and tolerability of guadecitabine, determine the maximum tolerated and biologically effective dose, and identify the recommended phase 2 dose of guadecitabine. Safety analyses included all patients who received at least one dose of guadecitabine. Pharmacokinetic and pharmacodynamic analyses to determine the biologically effective dose included all patients for whom samples were available. This study is registered with ClinicalTrials.gov, number NCT01261312. Between Jan 4, 2011, and April 11, 2014, we enrolled and treated 93 patients: 35 patients with acute myeloid leukaemia and nine patients with myelodysplastic syndrome in the daily × 5 dose-escalation cohorts, 28 patients with acute myeloid leukaemia and six patients with myelodysplastic syndrome in the once-weekly dose-escalation cohorts, and 11 patients with acute myeloid leukaemia and four patients with myelodysplastic syndrome in the twice-weekly dose-escalation cohorts. The most common grade 3 or higher adverse events were febrile neutropenia (38 [41%] of 93 patients), pneumonia (27 [29%] of 93 patients), thrombocytopenia (23 [25%] of 93 patients), anaemia (23 [25%] of 93 patients), and sepsis (16 [17%] of 93 patients). The most common serious adverse events were febrile neutropenia (29 [31%] of 93 patients), pneumonia (26 [28%] of 93 patients), and sepsis (16 [17%] of 93 patients). Six of the 74 patients with acute myeloid leukaemia and six of the 19 patients with myelodysplastic syndrome had a clinical response to treatment. Two dose-limiting toxicities were noted in patients with myelodysplastic syndrome at 125 mg/m(2) daily × 5, thus the maximum tolerated dose in patients with myelodysplastic syndrome was 90 mg/m(2) daily × 5. The maximum tolerated dose was not reached in patients with acute myeloid leukaemia. Potent dose-related DNA demethylation occurred on the daily × 5 regimen, reaching a plateau at 60 mg/m(2) (designated as the biologically effective dose). Guadecitabine given subcutaneously at 60 mg/m(2) daily × 5 is well tolerated and is clinically and biologically active in patients with myelodysplastic syndrome and acute myeloid leukaemia. Guadecitabine 60 mg/m(2) daily × 5 is the recommended phase 2 dose, and these findings warrant further phase 2 studies. Astex Pharmaceuticals, Stand Up To Cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies.

PubMed

Bahleda, Rastislav; Grilley-Olson, Juneko E; Govindan, Ramaswamy; Barlesi, Fabrice; Greillier, Laurent; Perol, Maurice; Ray-Coquard, Isabelle; Strumberg, Dirk; Schultheis, Beate; Dy, Grace K; Zalcman, Gérard; Weiss, Glen J; Walter, Annette O; Kornacker, Martin; Rajagopalan, Prabhu; Henderson, David; Nogai, Hendrik; Ocker, Matthias; Soria, Jean-Charles

2017-06-06

To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway. Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6). Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.

Phase I study of icotinib, an EGFR tyrosine kinase inhibitor combined with IMRT in nasopharyngeal carcinoma.

PubMed

Hu, Wei; Wang, Wei; Yang, Peinong; Zhou, Chao; Yang, Weifang; Wu, Bo; Lu, Hongsheng; Yang, Haihua

2015-01-01

Epidermal growth factor receptor (EGFR) is a new target for nasopharyngeal carcinoma (NPC) therapy. This prospective phase I study sought to determine the safety and recommended phase II dose of icotinib, a novel highly selective oral EGFR tyrosine kinase inhibitor, in combination with intensity-modulated radiotherapy (IMRT) in patients with NPC. Eligible patients with NPC received escalating doses of icotinib during IMRT. We treated six patients at a particular dose level until the maximum tolerated dose (MTD) was determined. The starting dose was 125 mg, once-daily and the dose was escalated to another level 125 mg, twice- and thrice- daily, until dose-limiting toxicity (DLT) occurred in two or more patients at a dose level. Expression and mutation analysis of EGFR were performed in all cases. A total of twelve patients were enrolled. Three patients experienced DLT (250 mg/day cohort) and MTD was 125 mg/day. Mucositis toxicity appears to be the major DLT. While EGFR expression in tumor tissue was detected in 75% (9/12) patients, EGFR mutation was detected in 16.67% (1/6) patients in 125 mg/day cohort, and 50% (3/6) in 250 mg/day cohort. The combination of icotinib (125 mg/day) and IMRT in patients with locally NPC had an acceptable safety profile and was well tolerated.

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

Mwidu, U; Devic, S; Shehadeh, M

Purpose: A retrospective comparison of dose distributions achievable by High dose rate brachytherapy (HDRBT), Helical TomoTherapy (TOMO), CyberKnife (CK) and RapidArc (RA) in locally advanced inoperable cervical cancer patients is presented. Methods: Five patients with advanced stage cervical carcinoma were selected for this study after a full course of external beam radiotherapy (EBRT), chemotherapy and HDR Brachytherapy. To highlight any significant similarities/differences in dose distributions, high-risk clinical target volume (HRCTV) coverage, organs at risk (OAR) sparing, and machine specific delivery limitations, we used D90 (dose received by 90% of the volume) as the parameter for HRCTV coverage as recommended bymore » the GEC-ESTRO Working Group. We also compared both integral and differential dose volume histograms (DVH) between different dose distributions treatment modalities for HRCTV and OAR. Results: TOMO and RA provided the most conformal dose distributions to HRCTV. Median doses (in Gy) to organs at risk were; for rectal wall: 1.7±0.6, 2.5±0.6,1.2±0.3, and 1.5±0.6, and for bladder wall: 1.6±0.1, 2.4±0.4, 0.8±0.6, and 1.5±0.5, for HDRBT, TOMO, CK, and RA, respectively. Conclusion: Contemporary EBRT modalities might be able to replace brachytherapy treatments for cervix cancer. While brachytherapy dose distributions feature high dose gradients, EBRT modalities provide highly conformal dose distributions to the target. However, it is still not clear whether a highly conformal dose or high gradient dose is more clinically relevant for the HRCTV in cervix cancer patients.« less

Bridging the gap: a review of dose investigations in paediatric investigation plans

PubMed Central

Hampson, Lisa V; Herold, Ralf; Posch, Martin; Saperia, Julia; Whitehead, Anne

2014-01-01

Aims In the EU, development of new medicines for children should follow a prospectively agreed paediatric investigation plan (PIP). Finding the right dose for children is crucial but challenging due to the variability of pharmacokinetics across age groups and the limited sample sizes available. We examined strategies adopted in PIPs to support paediatric dosing recommendations to identify common assumptions underlying dose investigations and the attempts planned to verify them in children. Methods We extracted data from 73 PIP opinions recently adopted by the Paediatric Committee of the European Medicines Agency. These opinions represented 79 medicinal development programmes and comprised a total of 97 dose investigation studies. We identified the design of these dose investigation studies, recorded the analyses planned and determined the criteria used to define target doses. Results Most dose investigation studies are clinical trials (83 of 97) that evaluate a single dosing rule. Sample sizes used to investigate dose are highly variable across programmes, with smaller numbers used in younger children (< 2 years). Many studies (40 of 97) do not pre-specify a target dose criterion. Of those that do, most (33 of 57 studies) guide decisions using pharmacokinetic data alone. Conclusions Common assumptions underlying dose investigation strategies include dose proportionality and similar exposure−response relationships in adults and children. Few development programmes pre-specify steps to verify assumptions in children. There is scope for the use of Bayesian methods as a framework for synthesizing existing information to quantify prior uncertainty about assumptions. This process can inform the design of optimal drug development strategies. PMID:24720849

Single shot of 17D vaccine may not confer life-long protection against yellow fever.

PubMed

Vasconcelos, Pedro Fc

2018-02-01

The yellow fever (YF) vaccine has been used since the 1930s to prevent YF, which is a severe infectious disease caused by the yellow fever virus (YFV), and mainly transmitted by Culicidae mosquitoes from the genera Aedes and Haemagogus . Until 2013, the World Health Organization (WHO) recommended the administration of a vaccine dose every ten years. A new recommendation of a single vaccine dose to confer life-long protection against YFV infection has since been established. Recent evidence published elsewhere suggests that at least a second dose is needed to fully protect against YF disease. Here, we discuss the feasibility of administering multiple doses, the necessity for a new and modern vaccine, and recommend that the WHO conveys a meeting to discuss YFV vaccination strategies for people living in or travelling to endemic areas.

Exposure to Radioactive Emanations of Medical Personnel in Percutaneous Nephrolithotomy.

PubMed

Sierra-Diaz, E; Gaxiola-Perez, E; Beas-Ruiz Velasco, C; Sedano-Portillo, I; Gonzalez-Gonzalez, C A; Adel-Dominguez, M; Davila-Radilla, F

2018-01-01

The use of radioactive emanations has been of great importance for the performance of endourology procedures, such as percutaneous nephrolithotomy (NLP). The damage to health caused by radiation has been a sensitive issue. The objective of this work was to determine the dose received by the surgeon during NLP and the total dose generated by the fluoroscope. A cross-sectional study was conducted with data from a cohort study with a duration of 18 months that included 101 patients. Radiation was measured with dosimeter during the last 6 months. During the last 6 months of the study, 34 patients were submitted to surgery. The average age was 47 years. Average fluoroscopy time was 58.3 second (24-122 seconds) in both male and female groups, with 57.16 seconds and 58.95 seconds per case, respectively ( P = .6). Radiation emitted during 6 months for the 34 patients was 330.5 mGy. The total radiation measured by the dosimeter was 1 mSv, which is equivalent to 0.3% of the total radiation applied during the procedures. Doses measured by the dosimeter on the surgeon were within the recommended annual doses although dose received by the hands exceeds the authorized limits (500 mSv/y).

DETERMINATION AND DOSE CONTRIBUTION OF URANIUM ISOTOPES AND 210Po ACTIVITY CONCENTRATIONS OF NATURAL SPRING WATERS IN THE PROVINCE OF GRANADA, SPAIN.

PubMed

Milena-Pérez, A; Piñero-García, F; Expósito-Suárez, V M; Mantero, J; Benavente, J; Ferro-García, M A

2018-03-01

The activity concentrations of alpha-emitters comprising isotopes of uranium (238, 234, 235U) and polonium (210Po) were measured using alpha-particle spectrometry in natural spring waters in the province of Granada, Spain. These water are consumed by the population of the zone who live in villages. This is almost half of the population of the whole region. Mean values of activity concentrations found are 42.61 ± 2.66; 49.55 ± 3.03; 1.64 ± 0.28 and 1.74 ± 0.15 mBq L-1 for 238U, 234U, 235U and 210Po, respectively. Finally, the radiological impact of the analysed waters has been determined, in terms of the estimation of the committed annual effective dose due to the ingestion of the water. The assessment has been carried out for five age groups with the aim to cover all the population. The calculated annual effective doses are observed to be below the prescribed dose limit of 100 μSv y-1 recommended by WHO.

Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.

PubMed

Niesvizky, Ruben; Badros, Ashraf Z; Costa, Luciano J; Ely, Scott A; Singhal, Seema B; Stadtmauer, Edward A; Haideri, Nisreen A; Yacoub, Abdulraheem; Hess, Georg; Lentzsch, Suzanne; Spicka, Ivan; Chanan-Khan, Asher A; Raab, Marc S; Tarantolo, Stefano; Vij, Ravi; Zonder, Jeffrey A; Huang, Xiangao; Jayabalan, David; Di Liberto, Maurizio; Huang, Xin; Jiang, Yuqiu; Kim, Sindy T; Randolph, Sophia; Chen-Kiang, Selina

2015-01-01

This phase 1/2 study was the first to evaluate the safety and efficacy of the cyclin-dependent kinase (CDK) 4/6-specific inhibitor palbociclib (PD-0332991) in sequential combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. The recommended phase 2 dose was palbociclib 100 mg orally once daily on days 1-12 of a 21-day cycle with bortezomib 1.0 mg/m2 (intravenous) and dexamethasone 20 mg (orally 30 min pre-bortezomib dosing) on days 8 and 11 (early G1 arrest) and days 15 and 18 (cell cycle resumed). Dose-limiting toxicities were primarily cytopenias; most other treatment-related adverse events were grade≤3. At a bortezomib dose lower than that in other combination therapy studies, antitumor activity was observed (phase 1). In phase 2, objective responses were achieved in 5 (20%) patients; 11 (44%) achieved stable disease. Biomarker and pharmacodynamic assessments demonstrated that palbociclib inhibited CDK4/6 and the cell cycle initially in most patients.

Calibration of modified Liulin detector for cosmic radiation measurements on-board aircraft.

PubMed

Kyselová, D; Ambrožová, I; Krist, P; Kubančák, J; Uchihori, Y; Kitamura, H; Ploc, O

2015-06-01

The annual effective doses of aircrew members often exceed the limit of 1 mSv for the public due to the increased level of cosmic radiation at the flight altitudes, and thus, it is recommended to monitor them. Aircrew dosimetry is usually performed using special computer programs mostly based on results of Monte Carlo simulations. Contemporary, detectors are used mostly for validation of these computer codes, verification of effective dose calculations and for research purposes. One of such detectors is active silicon semiconductor deposited energy spectrometer Liulin. Output quantities of measurement with the Liulin detector are the absorbed dose in silicon D and the ambient dose equivalent H*(10); to determine it, two calibrations are necessary. The purpose of this work was to develop a calibration methodology that can be used to convert signal from the detector to D independently on calibration performed at Heavy Ion Medical Accelerator facility in Chiba, Japan. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Review of the Hypoglycemic Effects of Five Commonly Used Herbal Food Supplements

PubMed Central

Deng, Ruitang

2013-01-01

Hyperglycemia is a pathological condition associated with prediabetes and diabetes. The incidence of prediabetes and diabetes is increasing and imposes great burden on healthcare worldwide. Patients with prediabetes and diabetes have significantly increased risk for cardiovascular diseases and other complications. Currently, management of hyperglycemia includes pharmacological interventions, physical exercise, and change of life style and diet. Food supplements have increasingly become attractive alternatives to prevent or treat hyperglycemia, especially for subjects with mild hyperglycemia. This review summarized current patents and patent applications with relevant literature on five commonly used food supplements with claims of hypoglycemic effects, including emblica officinalis (gooseberry), fenugreek, green tea, momordica charantia (bitter melon) and cinnamon. The data from human clinical studies did not support a recommendation for all five supplements to manage hyperglycemia. Fenugreek and composite supplements containing emblica officinalis showed the most consistency in lowering fasting blood sugar (FBS) or glycated hemoglobin (HbA1c) levels in diabetic patients. The hypoglycemic effects of cinnamon and momordica charantia were demonstrated in most of the trials with some exceptions. However, green tea exhibited limited benefits in reducing FBS or HbA1c levels and should not be recommended for managing hyperglycemia. Certain limitations are noticed in a considerable number of clinical studies including small sample size, poor experimental design and considerable variations in participant population, preparation format, daily dose, and treatment duration. Future studies with more defined participants, standardized preparation and dose, and improved trial design and size are warranted. PMID:22329631

Radiation dose to the Malaysian populace via the consumption of bottled mineral water

NASA Astrophysics Data System (ADS)

Khandaker, Mayeen Uddin; Nasir, Noor Liyana Mohd; Zakirin, Nur Syahira; Kassim, Hasan Abu; Asaduzzaman, Khandoker; Bradley, D. A.; Zulkifli, M. Y.; Hayyan, Adeeb

2017-11-01

Due to the geological makeup of the various water bodies, mineral- and groundwater can be expected to contain levels of naturally occurring radioactive material (NORM) exceeding that of tap and surface water. Acknowledging mineral water to form a vital component of the intake in maintaining the healthy life of an individual, it nevertheless remains important to study the associated radiological implications of NORM content, especially in regard to the consumption of bottled mineral water, the presence of which is prevalent in modern urban society. In present study, various brands of bottled mineral waters that are commonly available in Malaysia were obtained from local markets, the presence of NORM subsequently being assessed by HPGe γ-ray spectrometry. The activity concentrations of the radionuclides of particular interest, 226Ra, 232Th and 40K, were found to be within the respective ranges of 1.45±0.28‒3.30±0.43, 0.65±0.18‒3.39±0.38 and 21.12±1.74‒25.31±1.84 Bq/L. The concentrations of 226Ra, of central importance in radiological risk assessment, exceed the World Health Organisation (WHO, 2011) recommended maximum permissible limit of 1.0 Bq/L; for all three radionuclides taken together, the annual effective doses are greater than the WHO recommended limit of 0.1 mSv/y, a matter of especial concern for those in the developmental stages of life.

Mumps Outbreak at a University and Recommendation for a Third Dose of Measles-Mumps-Rubella Vaccine - Illinois, 2015-2016.

PubMed

Albertson, Justin P; Clegg, Whitney J; Reid, Heather D; Arbise, Benjamin S; Pryde, Julie; Vaid, Awais; Thompson-Brown, Rachella; Echols, Fredrick

2016-07-29

Mumps is an acute viral disease characterized by fever and swelling of the parotid or other salivary glands. On May 1, 2015, the Illinois Department of Public Health (IDPH) confirmed a mumps outbreak at the University of Illinois at Urbana-Champaign. IDPH and the Champaign-Urbana Public Health District (C-UPHD) conducted an investigation and identified 317 cases of mumps during April 2015-May 2016. Because of sustained transmission in a population with high 2-dose coverage with measles-mumps-rubella (MMR) vaccine, a third MMR dose was recommended by IDPH, C-UPHD, and the university's McKinley Health Center. No formal recommendation for or against the use of a third MMR dose has been issued by the Advisory Committee on Immunization Practices (ACIP) (1). However, CDC has provided guidelines for use of a third dose as a control measure during mumps outbreaks in settings in which persons are in close contact with one another, where transmission is sustained despite high 2-dose MMR coverage, and when traditional control measures fail to slow transmission (2).

Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study

PubMed Central

Goldman, Stewart; Yamada, Tohru; Beattie, Craig W.; Bressler, Linda; Pacini, Michael; Pollack, Ian F.; Fisher, Paul Graham; Packer, Roger J.; Dunkel, Ira J.; Dhall, Girish; Wu, Shengjie; Onar, Arzu; Boyett, James M.; Fouladi, Maryam

2016-01-01

Background p53 is a promising target in human cancer. p28 is a cell-penetrating peptide that preferentially enters cancer cells and binds to both wild-type and mutant p53 protein, inhibiting COP1-mediated ubiquitination and proteasomal degradation. This results in increased levels of p53, which induces cell cycle arrest at G2/M. We conducted a phase I study to determine the maximum-tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) and pharmacokinetics (PKs) of p28 in children. Methods Children aged 3–21 years with recurrent or progressive central nervous system tumors were eligible. Intravenous p28 was administered 3 times weekly for 4 consecutive weeks of a 6-week cycle at 4.16 mg/kg/dose (the adult recommended phase II dose) using a rolling-6 study design. Expression status of p53 was characterized by immunohistochemistry, and serum PK parameters were established on the second dose. Results Of the 18 eligible patients enrolled in the study, 12 completed the DLT monitoring period and were evaluable for toxicity. p28 was well-tolerated; 7 participants received ≥2 courses, and the most common adverse event attributed to the drug was transient grade 1 infusion-related reaction. PK analysis revealed a profile similar to adults; however, an increased area under the curve was observed in pediatric patients. High p53 expression in tumor cell nuclei was observed in 6 of 12 available tissue samples. There were no objective responses; 2 participants remained stable on the study for >4 cycles. Conclusions This phase I study demonstrated that p28 is well-tolerated in children with recurrent CNS malignancies at the adult recommended phase II dose. PMID:27022131

Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors.

PubMed

Gandhi, Leena; Bahleda, Rastislav; Tolaney, Sara M; Kwak, Eunice L; Cleary, James M; Pandya, Shuchi S; Hollebecque, Antoine; Abbas, Richat; Ananthakrishnan, Revathi; Berkenblit, Anna; Krygowski, Mizue; Liang, Yali; Turnbull, Kathleen W; Shapiro, Geoffrey I; Soria, Jean-Charles

2014-01-10

Human epidermal growth factor (HER) -mediated signaling is critical in many cancers, including subsets of breast and lung cancer. HER family members signal via the phosphatidylinositide 3-kinase (PI3K) -AKT/protein kinase B-mammalian target of rapamycin (mTOR) cascade; mTOR activation is critical for the expression of multiple contributors to tumor growth and invasion. On the basis of preclinical data suggesting synergy of HER2 inhibition and mTOR inhibition in breast and lung cancer models, we conducted a phase I combination study of neratinib, a small-molecule irreversible pan-HER tyrosine kinase inhibitor, and temsirolimus, an mTOR inhibitor, in patients with advanced solid tumors. This study enrolled patients to dosing combinations of neratinib and temsirolimus. The primary objective was to estimate the toxicity contour of the combination and establish recommended phase II doses. Sixty patients were treated on 12 of 16 possible dosing combinations. Diarrhea was the most common drug-related (93%) and dose-limiting toxicity (DLT), constituting four of 10 DLTs. Dose-limiting grade 3 metabolic abnormalities were also observed. Other frequent drug-related toxicities included nausea, stomatitis (both 53%), and anemia (48%). Two maximum-tolerated dose combinations were identified: 200 mg of neratinib/25 mg of temsirolimus and 160 mg of neratinib/50 mg of temsirolimus. Responses were noted in patients with HER2-amplified breast cancer resistant to trastuzumab, HER2-mutant non-small-cell lung cancer, and tumor types without identified mutations in the HER-PI3K-mTOR pathway. The combination of neratinib and temsirolimus was tolerable and demonstrated antitumor activity in multiple tumor types, warranting further evaluation.

The influence of dosing on effect size of exercise therapy for musculoskeletal foot and ankle disorders: a systematic review.

PubMed

Young, Jodi L; Rhon, Daniel I; de Zoete, Rutger M J; Cleland, Joshua A; Snodgrass, Suzanne J

The purpose of this review was to identify doses of exercise therapy associated with greater treatment effect sizes in individuals with common musculoskeletal disorders of the foot and ankle, namely, achilles tendinopathy, ankle sprains and plantar heel pain. AMED, EMBASE and MEDLINE were searched from 2005 to August 2017 for randomized controlled trials related to exercise for these three diagnoses. The Physiotherapy Evidence Database scale was used for methodological quality assessment. Exercise dosing variables and outcome measures related to pain and function were extracted from the studies, and standardized mean differences were calculated for the exercise groups. Fourteen studies met the final inclusion. A majority of the studies showed large effects and two small trends were identified. Patients with plantar heel pain may benefit more from a daily home exercise program than two supervised visits per week (SMD=3.82), but this recommendation is based on weak evidence. In achilles tendinopathy, a relationship was also seen when sets and repetitions of eccentric exercise were performed as tolerated (SMD=1.08 for function, -1.29 for pain). Session duration, frequency, total number of visits, and overall length of care may all be dosing variables with limited value for determining effective exercise prescription. However, the limited number of studies prevents any definitive conclusions. Further investigation is warranted to improve our understanding of the influence exercise dosing has on treatment effect sizes. Future randomized controlled trials comparing specific exercise dose variables should be conducted to clarify the impact of these variables. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. All rights reserved.

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

Sarkaria, Jann N., E-mail: sarkaria.jann@mayo.edu; Galanis, Evanthia; Wu Wenting

Background: The mammalian target of rapamycin (mTOR) functions within the PI3K/Akt signaling pathway as a critical modulator of cell survival. On the basis of promising preclinical data, the safety and tolerability of therapy with the mTOR inhibitor RAD001 in combination with radiation (RT) and temozolomide (TMZ) was evaluated in this Phase I study. Methods and Materials: All patients received weekly oral RAD001 in combination with standard chemoradiotherapy, followed by RAD001 in combination with standard adjuvant temozolomide. RAD001 was dose escalated in cohorts of 6 patients. Dose-limiting toxicities were defined during RAD001 combination therapy with TMZ/RT. Results: Eighteen patients were enrolled,more » with a median follow-up of 8.4 months. Combined therapy was well tolerated at all dose levels, with 1 patient on each dose level experiencing a dose-limiting toxicity: Grade 3 fatigue, Grade 4 hematologic toxicity, and Grade 4 liver dysfunction. Throughout therapy, there were no Grade 5 events, 3 patients experienced Grade 4 toxicities, and 6 patients had Grade 3 toxicities attributable to treatment. On the basis of these results, the recommended Phase II dosage currently being tested is RAD001 70 mg/week in combination with standard chemoradiotherapy. Fluorodeoxyglucose (FDG) positron emission tomography scans also were obtained at baseline and after the second RAD001 dose before the initiation of TMZ/RT; the change in FDG uptake between scans was calculated for each patient. Fourteen patients had stable metabolic disease, and 4 patients had a partial metabolic response. Conclusions: RAD001 in combination with RT/TMZ and adjuvant TMZ was reasonably well tolerated. Changes in tumor metabolism can be detected by FDG positron emission tomography in a subset of patients within days of initiating RAD001 therapy.« less

Radiological protection issues arising during and after the Fukushima nuclear reactor accident.

PubMed

González, Abel J; Akashi, Makoto; Boice, John D; Chino, Masamichi; Homma, Toshimitsu; Ishigure, Nobuhito; Kai, Michiaki; Kusumi, Shizuyo; Lee, Jai-Ki; Menzel, Hans-Georg; Niwa, Ohtsura; Sakai, Kazuo; Weiss, Wolfgang; Yamashita, Shunichi; Yonekura, Yoshiharu

2013-09-01

Following the Fukushima accident, the International Commission on Radiological Protection (ICRP) convened a task group to compile lessons learned from the nuclear reactor accident at the Fukushima Daiichi nuclear power plant in Japan, with respect to the ICRP system of radiological protection. In this memorandum the members of the task group express their personal views on issues arising during and after the accident, without explicit endorsement of or approval by the ICRP. While the affected people were largely protected against radiation exposure and no one incurred a lethal dose of radiation (or a dose sufficiently large to cause radiation sickness), many radiological protection questions were raised. The following issues were identified: inferring radiation risks (and the misunderstanding of nominal risk coefficients); attributing radiation effects from low dose exposures; quantifying radiation exposure; assessing the importance of internal exposures; managing emergency crises; protecting rescuers and volunteers; responding with medical aid; justifying necessary but disruptive protective actions; transiting from an emergency to an existing situation; rehabilitating evacuated areas; restricting individual doses of members of the public; caring for infants and children; categorising public exposures due to an accident; considering pregnant women and their foetuses and embryos; monitoring public protection; dealing with 'contamination' of territories, rubble and residues and consumer products; recognising the importance of psychological consequences; and fostering the sharing of information. Relevant ICRP Recommendations were scrutinised, lessons were collected and suggestions were compiled. It was concluded that the radiological protection community has an ethical duty to learn from the lessons of Fukushima and resolve any identified challenges. Before another large accident occurs, it should be ensured that inter alia: radiation risk coefficients of potential health effects are properly interpreted; the limitations of epidemiological studies for attributing radiation effects following low exposures are understood; any confusion on protection quantities and units is resolved; the potential hazard from the intake of radionuclides into the body is elucidated; rescuers and volunteers are protected with an ad hoc system; clear recommendations on crisis management and medical care and on recovery and rehabilitation are available; recommendations on public protection levels (including infant, children and pregnant women and their expected offspring) and associated issues are consistent and understandable; updated recommendations on public monitoring policy are available; acceptable (or tolerable) 'contamination' levels are clearly stated and defined; strategies for mitigating the serious psychological consequences arising from radiological accidents are sought; and, last but not least, failures in fostering information sharing on radiological protection policy after an accident need to be addressed with recommendations to minimise such lapses in communication.

Real-World Dosing Patterns of Atomoxetine in Adults with Attention-Deficit/Hyperactivity Disorder.

PubMed

Kabul, Samaneh; Alatorre, Carlos; Montejano, Leslie B; Farr, Amanda M; Clemow, David B

2015-12-01

The aim was to investigate the dosing patterns of atomoxetine monotherapy in adult patients with attention-deficit/hyperactivity disorder (ADHD) in a retrospective analysis. Adult (≥ 18 years) patients with ADHD newly initiated on atomoxetine with ≥ 1 outpatient pharmacy claim for atomoxetine between January 2006 and December 2011 were selected from the Truven Health MarketScan(®) Commercial database. After a 30-day titration period, dosing patterns of atomoxetine monotherapy were analyzed in the 12 months following initiation. In addition, patient demographic and clinical characteristics were compared to identify characteristics associated with suboptimal versus recommended dosing. Of the 12,412 adult patients with ADHD newly initiated on atomoxetine, 4548 (36.6%) were suboptimally dosed, whereas 3323 (26.7%) were treated at recommended dose. Overall, study patients were treated at a mean (standard deviation [SD]) dose of 68.5 (44.9) mg/day. The suboptimal dosing cohort included significantly more females (54% vs. 44%, P < 0.001) and had fewer patients with pre-index use of other ADHD medications (17% vs. 20%, P < 0.001) compared with the recommended dosing cohort. Adult patients with ADHD receiving atomoxetine therapy in a real-world setting are often dosed suboptimally. Increasing the awareness on optimal dosing strategy among clinicians and patients is warranted to maximize the therapeutic benefits of atomoxetine among adult patients with ADHD. © 2015 Eli Lilly and Company. CNS Neuroscience and Therapeutics published by John Wiley & Sons Ltd.

Reconstruction of Absorbed Doses to Fibroglandular Tissue of the Breast of Women undergoing Mammography (1960 to the Present)

PubMed Central

Thierry-Chef, Isabelle; Simon, Steven L.; Weinstock, Robert M.; Kwon, Deukwoo; Linet, Martha S.

2013-01-01

The assessment of potential benefits versus harms from mammographic examinations as described in the controversial breast cancer screening recommendations of the U.S. Preventive Task Force included limited consideration of absorbed dose to the fibroglandular tissue of the breast (glandular tissue dose), the tissue at risk for breast cancer. Epidemiological studies on cancer risks associated with diagnostic radiological examinations often lack accurate information on glandular tissue dose, and there is a clear need for better estimates of these doses. Our objective was to develop a quantitative summary of glandular tissue doses from mammography by considering sources of variation over time in key parameters including imaging protocols, x-ray target materials, voltage, filtration, incident air kerma, compressed breast thickness, and breast composition. We estimated the minimum, maximum, and mean values for glandular tissue dose for populations of exposed women within 5-year periods from 1960 to the present, with the minimum to maximum range likely including 90% to 95% of the entirety of the dose range from mammography in North America and Europe. Glandular tissue dose from a single view in mammography is presently about 2 mGy, about one-sixth the dose in the 1960s. The ratio of our estimates of maximum to minimum glandular tissue doses for average-size breasts was about 100 in the 1960s compared to a ratio of about 5 in recent years. Findings from our analysis provide quantitative information on glandular tissue doses from mammographic examinations which can be used in epidemiologic studies of breast cancer. PMID:21988547

[Development of a perforated peptic ulcer in a child during high dose prednisolone treatment].

PubMed

Moll Harboe, Kirstine; Midtgaard, Helle; Wewer, Vibeke; Cortes, Dina

2012-09-24

Since perforated peptic ulcer is uncommon in children proton pump inhibitor prophylaxis is not routinely recommended when children are treated with high dose steroids. We describe a case of perforated ulcer in a six-year-old patient with nephrotic syndrome treated with high dose prednisolone. Initially, ulcer was not suspected due to uncharacteristic symptoms. The child developed peritoneal signs and surgery revealed a perforated peptic ulcer in the stomach. We recommend treatment with proton pump inhibitors if children, who are treated with high dose steroids develop abdominal symptoms, which can be caused by an ulcus.

Risk of radiation induced cataracts: investigation of radiation exposure to the eye lens during endourologic procedures.

PubMed

Hartmann, Josefin; Distler, Florian A; Baumueller, Martin; Guni, Ewald; Pahernik, Sascha A; Wucherer, Michael

2018-06-14

Due to new radiobiological data, the ICRP recommends a dose limit of 20mSv per year to the eye lens. Therefore, the IAEA International Basic Safety Standard and the EU council directive 2013/59/EURATOM requires a reduction of the annual dose limit from 150mSv to 20mSv. Urologists are exposed to an elevated radiation exposure in the head region during fluoroscopic interventions, due to the commonly used overtable X-ray tubes and the rarely used radiation protection for the head. Aim of the study was to analyze real radiation exposure to the eye lens of the urologist during various interventions during which the patient is in the lithotomy position. The partial body doses (forehead and apron collar) of the urologists and surgical staff were measured over a period of two months. 95 interventions were performed on Uroskop Omnia Max workplaces (Siemens Healthineers, Erlangen, Germany). Interventions were class-divided in less (stage I) and more complex (stage II) interventions. Two dosimeter-types were applied: well-calibrated electronic personal dosimeter EPD Mk2 and self-calibrated TLD-100H (both Thermo Fisher Scientific, Waltham, USA). The radiation exposure parameters were documented using the dose area product (DAP) and the fluoroscopy time (FT). The correlation between DAP and the apron dose of the urologist was in average 0.07µSv per 1µGym². The more experienced urologists yielded a mean DAP of 166µGym² for stage I and 415µGym² for stage II procedures. The interventionist was exposed with 10µSv in mean outside the lead apron collar. The mean dose value of the eye lenses per intervention was ascertained to 20µSv (mean DAP: 233µGym²). The study setup allows a differentiated and time-resolved measurement of the radiation exposure, which was found heterogeneous depending on intervention and surgeon. In this setting, approximately 1000 interventions can be performed until the annual eye lens dose limit is achieved.

[Dosimetric system for assessing doses received by people occupationally exposed to external sources of ionizing radiation].

PubMed

Brodecki, Marcin; Domienik, Joanna U; Zmyślony, Marek

2012-01-01

The current system of dosimetric quantities has been defined by the International Commission on Radiological Protection (ICRP) and the International Commission on Radiation Units and Measurements (ICRU). Complexity of the system implies the physical nature of ionizing radiation, resulting from the presence of different types of radiation of different ionization capabilities, as well as the individual radiation sensitivity of biological material exposed. According to the latest recommendations, there are three types of dosimeter quantities relevant to radiation protection and radiological assessment of occupational exposure. These are the basic quantities, safety quantities and operational quantities. Dose limits for occupational exposure relate directly to the protection quantities, i.e. the equivalent dose and effective dose, while these quantities are practically unmeasurable in real measurement conditions. For this reason, in the system of dosimetric quantities directly measurable operating volumes were defined. They represent equivalents of the protection quantities that allow for a reliable assessment of equivalent and effective dose by conducting routine monitoring of occupational exposure. This paper presents the characteristics of these quantities, their relationships and importance in assessing individual effects of radiation. Also the methods for their implementation in personal and environmental dosimetry were showcased. The material contained in the article is a compendium of essential information about dosimetric quantities with reference to the contemporary requirements of the law, including the changed annual occupational exposure limit for the lens of the eye. The material is especially addressed to those responsible for dosimetry monitoring in the workplace, radiation protection inspectors and occupational health physicians.

Verification of Dosimetric Commissioning Accuracy of Intensity Modulated Radiation Therapy and Volumetric Modulated Arc Therapy Delivery using Task Group-119 Guidelines.

PubMed

Kaviarasu, Karunakaran; Nambi Raj, N Arunai; Hamid, Misba; Giri Babu, A Ananda; Sreenivas, Lingampally; Murthy, Kammari Krishna

2017-01-01

The purpose of this study is to verify the accuracy of the commissioning of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) based on the recommendation of the American Association of Physicists in Medicine Task Group 119 (TG-119). TG-119 proposes a set of clinical test cases to verify the accuracy of IMRT planning and delivery system. For these test cases, we generated two sets of treatment plans, the first plan using 7-9 IMRT fields and a second plan utilizing two-arc VMAT technique for both 6 MV and 15 MV photon beams. The template plans of TG-119 were optimized and calculated by Varian Eclipse Treatment Planning System (version 13.5). Dose prescription and planning objectives were set according to the TG-119 goals. The point dose (mean dose to the contoured chamber volume) at the specified positions/locations was measured using compact (CC-13) ion chamber. The composite planar dose was measured with IMatriXX Evaluation 2D array with OmniPro IMRT Software (version 1.7b). The per-field relative gamma was measured using electronic portal imaging device in a way similar to the routine pretreatment patient-specific quality assurance. Our planning results are compared with the TG-119 data. Point dose and fluence comparison data where within the acceptable confident limit. From the obtained data in this study, we conclude that the commissioning of IMRT and VMAT delivery were found within the limits of TG-119.

Guidelines for exposure assessment in health risk studies following a nuclear reactor accident.

PubMed

Bouville, André; Linet, Martha S; Hatch, Maureen; Mabuchi, Kiyohiko; Simon, Steven L

2014-01-01

Worldwide concerns regarding health effects after the Chernobyl and Fukushima nuclear power plant accidents indicate a clear need to identify short- and long-term health impacts that might result from accidents in the future. Fundamental to addressing this problem are reliable and accurate radiation dose estimates for the affected populations. The available guidance for activities following nuclear accidents is limited with regard to strategies for dose assessment in health risk studies. Here we propose a comprehensive systematic approach to estimating radiation doses for the evaluation of health risks resulting from a nuclear power plant accident, reflected in a set of seven guidelines. Four major nuclear reactor accidents have occurred during the history of nuclear power production. The circumstances leading to these accidents were varied, as were the magnitude of the releases of radioactive materials, the pathways by which persons were exposed, the data collected afterward, and the lifestyle factors and dietary consumption that played an important role in the associated radiation exposure of the affected populations. Accidents involving nuclear reactors may occur in the future under a variety of conditions. The guidelines we recommend here are intended to facilitate obtaining reliable dose estimations for a range of different exposure conditions. We recognize that full implementation of the proposed approach may not always be feasible because of other priorities during the nuclear accident emergency and because of limited resources in manpower and equipment. The proposed approach can serve as a basis to optimize the value of radiation dose reconstruction following a nuclear reactor accident.

Verification of Dosimetric Commissioning Accuracy of Intensity Modulated Radiation Therapy and Volumetric Modulated Arc Therapy Delivery using Task Group-119 Guidelines

PubMed Central

Kaviarasu, Karunakaran; Nambi Raj, N. Arunai; Hamid, Misba; Giri Babu, A. Ananda; Sreenivas, Lingampally; Murthy, Kammari Krishna

2017-01-01

Aim: The purpose of this study is to verify the accuracy of the commissioning of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) based on the recommendation of the American Association of Physicists in Medicine Task Group 119 (TG-119). Materials and Methods: TG-119 proposes a set of clinical test cases to verify the accuracy of IMRT planning and delivery system. For these test cases, we generated two sets of treatment plans, the first plan using 7–9 IMRT fields and a second plan utilizing two-arc VMAT technique for both 6 MV and 15 MV photon beams. The template plans of TG-119 were optimized and calculated by Varian Eclipse Treatment Planning System (version 13.5). Dose prescription and planning objectives were set according to the TG-119 goals. The point dose (mean dose to the contoured chamber volume) at the specified positions/locations was measured using compact (CC-13) ion chamber. The composite planar dose was measured with IMatriXX Evaluation 2D array with OmniPro IMRT Software (version 1.7b). The per-field relative gamma was measured using electronic portal imaging device in a way similar to the routine pretreatment patient-specific quality assurance. Results: Our planning results are compared with the TG-119 data. Point dose and fluence comparison data where within the acceptable confident limit. Conclusion: From the obtained data in this study, we conclude that the commissioning of IMRT and VMAT delivery were found within the limits of TG-119. PMID:29296041

A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer.

PubMed

Masters, G A; Mauer, A M; Hoffman, P C; Wyka, D; Samuels, B L; Krauss, S A; Watson, S; Golomb, H; Vokes, E E

1998-06-01

We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.

A Phase I Dose-Escalation Study of Danusertib (PHA-739358) Administered as a 24-hour Infusion With and Without G-CSF in a 14-day Cycle in Patients with Advanced Solid Tumors

PubMed Central

Cohen, Roger B.; Jones, Suzanne F.; Aggarwal, Charu; von Mehren, Margaret; Cheng, Jonathan; Spigel, David R.; Greco, F. Anthony; Mariani, Mariangela; Rocchetti, Maurizio; Ceruti, Roberta; Comis, Silvia; Laffranchi, Bernard; Moll, Jurgen; Burris, Howard A.

2009-01-01

Purpose This study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of the intravenous pan-aurora kinase inhibitor PHA-739358, danusertib, in patients with advanced solid tumors. Experimental Design In Part 1, patients received escalating doses of danusertib (24-h infusion every 14 days) without filgrastim (G-CSF). Febrile neutropenia was the dose-limiting toxicity without G-CSF. Further dose escalation was performed in part 2 with G-CSF. Blood samples were collected for danusertib pharmacokinetics and pharmacodynamics. Skin biopsies were collected to assess histone H3 phosphorylation (pH3). Results Fifty-six patients were treated, 40 in part 1 and 16 in part 2. Febrile neutropenia was the dose limiting toxicity in Part 1 without G-CSF. Most other adverse events were grade 1–2, occurring at doses ≥360 mg/m2 with similar incidence in parts 1 and 2. The MTD without G-CSF is 500 mg/m2. The recommended phase 2 dose (RP2D) in Part 2 with G-CSF is 750 mg/m2. Danusertib demonstrated dose-proportional pharmacokinetics in parts 1 and 2 with a median half-life of 18–26 hours. pH3 modulation in skin biopsies was observed at ≥500 mg/m2. One patient with refractory small cell lung cancer (1000 mg/m2 with G-CSF) had an objective response lasting 23 weeks. One patient with refractory ovarian cancer had 27% tumor regression and 30% CA125 decline. Conclusions Danusertib was well tolerated with target inhibition in skin at ≥500 mg/m2. Preliminary evidence of anti-tumor activity, including a PR and several occurrences of prolonged stable disease (SD), was seen across a variety of advanced refractory cancers. Phase II studies are ongoing. PMID:19825950

An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma.

PubMed

von Tresckow, Bastian; Morschhauser, Franck; Ribrag, Vincent; Topp, Max S; Chien, Caly; Seetharam, Shobha; Aquino, Regina; Kotoulek, Sonja; de Boer, Carla J; Engert, Andreas

2015-04-15

This phase I/II study investigated JNJ-40346527, a selective inhibitor of the colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase as treatment for relapsed or refractory classical Hodgkin lymphoma (cHL). Patients ≥18 years with histopathologically confirmed initial diagnosis of cHL that had relapsed or was refractory after ≥1 appropriate therapies were assigned to sequential cohorts of oral daily doses of JNJ-40346527 (150, 300, 450, 600 mg every day, and 150 mg twice a day). For the dose-escalation phase, the primary endpoint was to establish the recommended phase II dose. Secondary endpoints included safety, pharmacokinetics, and pharmacodynamics. Twenty-one patients [(150 mg: 3; 300 mg: 5; 450 mg: 3, 600 mg: 3) every day, and 150 mg twice a day: 7] were enrolled, 10 men, median age 40 (range, 19-75) years, median number of prior systemic therapies 6 (range, 3-14). No dose-limiting toxicities were observed; maximum-tolerated dose was not established. Best overall response was complete remission in 1 patient (duration, +352 days) and stable disease in 11 patients: (duration, 1.5-8 months). Median number of cycles: 4 (range, 1-16). Most common (≥20% patients) possibly drug-related adverse events (per investigator assessment) were nausea (n = 6), headache, and pyrexia (n = 5 each). JNJ-40346527 exposure increased in near dose-proportional manner over a dose range of 150 to 450 mg every day, but plateaued at 600 mg every day. Target engagement was confirmed (>80% inhibition of CSF-1R phosphorylation, 4 hours after dosing). JNJ-40346527, a selective inhibitor of CSF-1R was well tolerated, and preliminary antitumor results suggested limited activity in monotherapy for the treatment of cHL. ©2015 American Association for Cancer Research.

Heavy construction equipment noise study using dosimetry and time-motion studies

NASA Astrophysics Data System (ADS)

Spencer, Ellsworth R.; Yantek, David S.

2005-09-01

Noise-induced hearing loss continues to afflict workers in many occupational settings despite longstanding recognition of the problems and well-known methods of prevention and regulations. Sound levels associated with heavy construction equipment range from 80 to 120 dB(A) and power tools commonly used in construction produce sound levels up to 115 dB(A). The focus of the research was to determine the noise exposures of heavy construction equipment operators while documenting the workers' tasks, (i.e., hauling, moving, and/or pushing construction material). Time-motion studies were performed at the construction sites and were used to correlate the noise dosage with the work performed by equipment operators. The cumulative dose for the operator was then plotted with references to work tasks, to identify the tasks that caused the greatest noise exposure. Three construction sites were examined and located in the western Pennsylvania and eastern Ohio areas. The types of construction equipment studied included asphalt pavers, backhoes, bulldozers, compaction equipment, excavators, haul trucks, telehandlers, and wheeled loaders. The results showed that bulldozer operators consistently had the highest noise exposures, ranging from a NIOSH REL (Recommended Exposure Limit) dose of 844% to 25836% and an OSHA PEL (Permissible Exposure Limit) dose of 139% to 1397%.

Preventing medication errors in cancer chemotherapy.

PubMed

Cohen, M R; Anderson, R W; Attilio, R M; Green, L; Muller, R J; Pruemer, J M

1996-04-01

Recommendations for preventing medication errors in cancer chemotherapy are made. Before a health care provider is granted privileges to prescribe, dispense, or administer antineoplastic agents, he or she should undergo a tailored educational program and possibly testing or certification. Appropriate reference materials should be developed. Each institution should develop a dose-verification process with as many independent checks as possible. A detailed checklist covering prescribing, transcribing, dispensing, and administration should be used. Oral orders are not acceptable. All doses should be calculated independently by the physician, the pharmacist, and the nurse. Dosage limits should be established and a review process set up for doses that exceed the limits. These limits should be entered into pharmacy computer systems, listed on preprinted order forms, stated on the product packaging, placed in strategic locations in the institution, and communicated to employees. The prescribing vocabulary must be standardized. Acronyms, abbreviations, and brand names must be avoided and steps taken to avoid other sources of confusion in the written orders, such as trailing zeros. Preprinted antineoplastic drug order forms containing checklists can help avoid errors. Manufacturers should be encouraged to avoid or eliminate ambiguities in drug names and dosing information. Patients must be educated about all aspects of their cancer chemotherapy, as patients represent a last line of defense against errors. An interdisciplinary team at each practice site should review every medication error reported. Pharmacists should be involved at all sites where antineoplastic agents are dispensed. Although it may not be possible to eliminate all medication errors in cancer chemotherapy, the risk can be minimized through specific steps. Because of their training and experience, pharmacists should take the lead in this effort.

Improving immunization approaches to cholera.

PubMed

Saha, Amit; Rosewell, Alexander; Hayen, Andrew; MacIntyre, C Raina; Qadri, Firdausi

2017-03-01

Cholera's impact is greatest in resource-limited countries. In the last decade several large epidemics have led to a global push to improve and implement the tools for cholera prevention and control. Areas covered: PubMed, Google Scholar and the WHO website were searched to review the literature and summarize the current status of cholera vaccines to make recommendations on improving immunization approaches to cholera. Oral cholera vaccines (OCVs) have demonstrated their effectiveness in endemic, outbreak response and emergency settings, highlighting their potential for wider adoption. While two doses of the currently available OCVs are recommended by manufacturers, a single dose would be easier to implement. Encouragingly, recent studies have shown that cold chain requirements may no longer be essential. The establishment of the global OCV stockpile in 2013 has been a major advance in cholera preparedness. New killed and live-attenuated vaccines are being actively explored as candidate vaccines for endemic settings and/or as a traveller's vaccine. The recent advances in cholera vaccination approaches should be considered in the global cholera control strategy. Expert commentary: The development of affordable cholera vaccines is a major success to improve cholera control. New vaccines and country specific interventions will further reduce the burden of this disease globally.

Organochlorines in urban soils from Central India: probabilistic health hazard and risk implications to human population.

PubMed

Kumar, Bhupander; Mishra, Meenu; Verma, V K; Rai, Premanjali; Kumar, Sanjay

2018-04-21

This study presents distribution of organochlorines (OCs) including HCH, DDT and PCBs in urban soils, and their environmental and human health risk. Forty-eight soil samples were extracted using ultrasonication, cleaned with modified silica gel chromatography and analyzed by GC-ECD. The observed concentrations of ∑HCH, ∑DDT and ∑PCBs in soils ranged between < 0.01-2.54, 1.30-27.41 and < 0.01-62.8 µg kg -1 , respectively, which were lower than the recommended soil quality guidelines. Human health risk was estimated following recommended guidelines. Lifetime average daily dose (LADD), non-cancer risk or hazard quotient (HQ) and incremental lifetime cancer risk (ILCR) for humans due to individual and total OCs were estimated and presented. Estimated LADD were lower than acceptable daily intake and reference dose. Human health risk estimates were lower than safe limit of non-cancer risk (HQ < 1.0) and the acceptable distribution range of ILCR (10 -6 -10 -4 ). Therefore, this study concluded that present levels of OCs (HCH, DDT and PCBs) in studied soils were low, and subsequently posed low health risk to human population in the study area.

Psychosocial, behavioural and health system barriers to delivery and uptake of intermittent preventive treatment of malaria in pregnancy in Tanzania – viewpoints of service providers in Mkuranga and Mufindi districts

PubMed Central

2014-01-01

Background Intermittent preventive treatment of malaria in pregnancy (IPTp) using sulphurdoxine-pyrimethamine (SP) is one of key malaria control strategies in Africa. Yet, IPTp coverage rates across Africa are still low due to several demand and supply constraints. Many countries implement the IPTp-SP strategy at antenatal care (ANC) clinics. This paper reports from a study on the knowledge and experience of health workers (HWs) at ANC clinics regarding psychosocial, behavioural and health system barriers to IPTp-SP delivery and uptake in Tanzania. Methods Data were collected through questionnaire-based interviews with 78 HWs at 28 ANC clinics supplemented with informal discussions with current and recent ANC users in Mkuranga and Mufindi districts. Qualitative data were analysed using a qualitative content analysis approach. Quantitative data derived from interviews with HWs were analysed using non-parametric statistical analysis. Results The majority of interviewed HWs were aware of the IPTp-SP strategy’s existence and of the recommended one month spacing of administration of SP doses. Some HWs were unsure of that it is not recommended to administer IPTp-SP and ferrous/folic acid concurrently. Others were administering three doses of SP per client following instruction from a non-governmental agency while believing that this was in conflict with national guidelines. About half of HWs did not find it appropriate for the government to recommend private ANC providers to provide IPTp-SP free of charge since doing so forces private providers to recover the costs elsewhere. HWs noted that pregnant women often register at clinics late and some do not comply with the regularity of appointments for revisits, hence miss IPTp and other ANC services. HWs also noted some amplified rumours among clients regarding health risks and treatment failures of SP used during pregnancy, and together with clients’ disappointment with waiting times and the sharing of cups at ANC clinics for SP, limit the uptake of IPTp-doses. Conclusion HWs still question SP’s treatment advantages and are confused about policy ambiguity on the recommended number of IPTp-SP doses and other IPTp-SP related guidelines. IPTp-SP uptake is further constrained by pregnant women’s perceived health risks of taking SP and of poor service quality. PMID:24410770

Psychosocial, behavioural and health system barriers to delivery and uptake of intermittent preventive treatment of malaria in pregnancy in Tanzania - viewpoints of service providers in Mkuranga and Mufindi districts.

PubMed

Mubyazi, Godfrey M; Bloch, Paul

2014-01-13

Intermittent preventive treatment of malaria in pregnancy (IPTp) using sulphurdoxine-pyrimethamine (SP) is one of key malaria control strategies in Africa. Yet, IPTp coverage rates across Africa are still low due to several demand and supply constraints. Many countries implement the IPTp-SP strategy at antenatal care (ANC) clinics. This paper reports from a study on the knowledge and experience of health workers (HWs) at ANC clinics regarding psychosocial, behavioural and health system barriers to IPTp-SP delivery and uptake in Tanzania. Data were collected through questionnaire-based interviews with 78 HWs at 28 ANC clinics supplemented with informal discussions with current and recent ANC users in Mkuranga and Mufindi districts. Qualitative data were analysed using a qualitative content analysis approach. Quantitative data derived from interviews with HWs were analysed using non-parametric statistical analysis. The majority of interviewed HWs were aware of the IPTp-SP strategy's existence and of the recommended one month spacing of administration of SP doses. Some HWs were unsure of that it is not recommended to administer IPTp-SP and ferrous/folic acid concurrently. Others were administering three doses of SP per client following instruction from a non-governmental agency while believing that this was in conflict with national guidelines. About half of HWs did not find it appropriate for the government to recommend private ANC providers to provide IPTp-SP free of charge since doing so forces private providers to recover the costs elsewhere. HWs noted that pregnant women often register at clinics late and some do not comply with the regularity of appointments for revisits, hence miss IPTp and other ANC services. HWs also noted some amplified rumours among clients regarding health risks and treatment failures of SP used during pregnancy, and together with clients' disappointment with waiting times and the sharing of cups at ANC clinics for SP, limit the uptake of IPTp-doses. HWs still question SP's treatment advantages and are confused about policy ambiguity on the recommended number of IPTp-SP doses and other IPTp-SP related guidelines. IPTp-SP uptake is further constrained by pregnant women's perceived health risks of taking SP and of poor service quality.

Systemic fluoroquinolone prescriptions for hospitalized children in Belgium, results of a multicenter retrospective drug utilization study.

PubMed

Meesters, Kevin; Mauel, Reiner; Dhont, Evelyn; Walle, Johan Vande; De Bruyne, Pauline

2018-02-23

Fluoroquinolones (FQ) are increasingly prescribed for children, despite being labeled for only a limited number of labeled pediatric indications. In this multicenter retrospective drug utilization study, we analyzed indications for systemic FQ prescriptions in hospitalized children and the appropriateness of the prescribed dose. Using data obtained from electronic medical files, the study included all children who received a systemic FQ prescription in two Belgian university children's hospitals between 2010 and 2013. Two authors reviewed prescribed daily doses. Univariate and multivariate logistic regression models were used to analyze risk factors for inadequately dosing. Results262 FQ prescriptions for individual patients were included for analysis. 16.8% of these prescriptions were for labeled indications, and 35.1% were guided by bacteriological findings. Prescribed daily dose was considered to be inappropriate in 79 prescriptions (30.2%). Other FQ than ciprofloxacin accounted for 9 prescriptions (3.4%), of which 8 were correctly dosed. Underdosing represented 45 (56.9%) dosing errors. Infants and preschool children were at particular risk for dosing errors, with associated adjusted OR of 0.263 (0.097-0.701) and 0.254 (0.106-0.588) respectively. FQ were often prescribed off-label and not guided by bacteriological findings in our study population. Dosing errors were common, particularly in infants and preschool children. FQ prescriptions for children should be improved by specific pediatric antimicrobial stewardship teams. Furthermore, pharmacokinetic studies should optimise dosing recommendations for children.

Limitations of silicon diodes for clinical electron dosimetry.

PubMed

Song, Haijun; Ahmad, Munir; Deng, Jun; Chen, Zhe; Yue, Ning J; Nath, Ravinder

2006-01-01

This work investigates the relevance of several factors affecting the response of silicon diode dosemeters in depth-dose scans of electron beams. These factors are electron energy, instantaneous dose rate, dose per pulse, photon/electron dose ratio and electron scattering angle (directional response). Data from the literature and our own experiments indicate that the impact of these factors may be up to +/-15%. Thus, the different factors would have to cancel out perfectly at all depths in order to produce true depth-dose curves. There are reports of good agreement between depth-doses measured with diodes and ionisation chambers. However, our measurements with a Scantronix electron field detector (EFD) diode and with a plane-parallel ionisation chamber show discrepancies both in the build-up and in the low-dose regions, with a ratio up to 1.4. Moreover, the absolute sensitivity of two diodes of the same EFD model was found to differ by a factor of 3, and this ratio was not constant but changed with depth between 5 and 15% in the low-dose regions of some clinical electron beams. Owing to these inhomogeneities among diodes even of the same model, corrections for each factor would have to be diode-specific and beam-specific. All these corrections would have to be determined using parallel plane chambers, as recommended by AAPM TG-25, which would be unrealistic in clinical practice. Our conclusion is that in general diodes are not reliable in the measurement of depth-dose curves of clinical electron beams.

Real-life GH dosing patterns in children with GHD, TS or born SGA: a report from the NordiNet® International Outcome Study

PubMed Central

Snajderova, Marta; Blair, Jo; Pournara, Effie; Pedersen, Birgitte Tønnes; Petit, Isabelle Oliver

2017-01-01

Objective To describe real-life dosing patterns in children with growth hormone deficiency (GHD), born small for gestational age (SGA) or with Turner syndrome (TS) receiving growth hormone (GH) and enrolled in the NordiNet International Outcome Study (IOS; Nbib960128) between 2006 and 2016. Design This non-interventional, multicentre study included paediatric patients diagnosed with GHD (isolated (IGHD) or multiple pituitary hormone deficiency (MPHD)), born SGA or with TS and treated according to everyday clinical practice from the Czech Republic (IGHD/MPHD/SGA/TS: n = 425/61/316/119), France (n = 1404/188/970/206), Germany (n = 2603/351/1387/411) and the UK (n = 259/60/87/35). Methods GH dosing was compared descriptively across countries and indications. Proportions of patients by GH dose group (low/medium/high) or GH dose change (decrease/increase/no change) during years 1 and 2 were also evaluated across countries and indications. Results In the Czech Republic, GH dosing was generally within recommended levels. In France, average GH doses were higher for patients with IGHD, MPHD and SGA than in other countries. GH doses in TS tended to be at the lower end of the recommended label range, especially in Germany and the UK; the majority of patients were in the low-dose group. A significant inverse association between baseline height standard deviation score and GH dose was shown (P < 0.05); shorter patients received higher doses. Changes in GH dose, particularly increases, were more common in the second (40%) than in the first year (25%). Conclusions GH dosing varies considerably across countries and indications. In particular, almost half of girls with TS received GH doses below practice guidelines and label recommendations. PMID:28522645

Design and operation of internal dosimetry programs

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

LaBone, T.R.

1991-01-01

The proposed revision to USNRC 10 CFR 20 and the USDOE Order 5480.11 require intakes of radioactive material to be evaluated. Radiation dose limits are based on the sum of effective dose equivalent from intakes and the whole body dose from external sources. These significant changes in the regulations will require, at a minimum, a complete review of personnel monitoring programs to determine their adequacy. In this session we will review a systematic method of designing a routine personnel monitoring program that will comply with the requirements of the new regulations. Specific questions discussed are: (a) What are the goalsmore » and objectives of a routine personnel monitoring program (b) When is a routine personnel monitoring program required (c) What are the required capabilities of the routine personnel monitoring program (d) What should be done with the information generated in a personnel monitoring program Specific recommendations and interpretations are given in the session. 5 refs., 3 figs., 33 tabs.« less

IMRT for head and neck cancer: reducing xerostomia and dysphagia.

PubMed

Wang, XiaoShen; Eisbruch, Avraham

2016-08-01

Dysphagia and xerostomia are the main sequellae of chemoradiotherapy for head and neck cancer, and the main factors in reducing long-term patient quality of life. IMRT uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of non-involved tissues. The decisions about sparing organs and tissues whose damage causes xerostomia and dysphagia depends on the evidence for dose-response relationships for the organs causing these sequellae. This paper discusses the evidence for the contribution of radiotherapy to xerostomia via damage of the major salivary glands (parotid and submandibular) and minor salivary glands within the oral cavity, and the contribution of radiotherapy-related effect on important swallowing structures causing dysphagia. Recommendations for dose limits to these organs, based on measurements of xerostomia and dysphagia following radiotherapy, are provided here. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

[Immunisation schedule of the Spanish Association of Paediatrics: 2017 recommendations].

PubMed

Moreno-Pérez, David; Álvarez García, Francisco José; Arístegui Fernández, Javier; Cilleruelo Ortega, María José; Corretger Rauet, José María; García Sánchez, Nuria; Hernández Merino, Ángel; Hernández-Sampelayo Matos, Teresa; Merino Moína, Manuel; Ortigosa Del Castillo, Luis; Ruiz-Contreras, Jesús

2017-02-01

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV- AEP) annually publishes the immunisation schedule which, in our opinion, is considered optimal for children resident in Spain, taking into account the evidence available on current vaccines. Pneumococcal and varicella immunisation in early childhood is already included in all funded vaccines present in the regional immunisation programmes. Furthermore, this committee establishes recommendations on vaccines not included in official calendars (non-funded immunisations), such as rotavirus, meningococcal B, and meningococcal ACWY. As regards funded immunisations, 2+1 strategy (2, 4, 11-12 months) with hexavalent (DTaP-IPV-Hib-HB) and 13-valent pneumococcal vaccines is recommended. Administration of the 6-year booster dose with DTaP is recommended, as well as a poliomyelitis dose for children who had received the 2+1 scheme, with the Tdap vaccine for adolescents and pregnant women between 27 and 32 weeks gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). Coverage of human papillomavirus vaccination in girls aged 12 with a two-dose scheme (0, 6 months) should be improved. Information and recommendations for male adolescents about potential beneficial effects of the tetravalent HPV vaccine should also be provided. ACWY meningococcal vaccine is the optimal choice in adolescents. For recommended unfunded immunisations, the CAV-AEP recommends the administration of meningococcal B vaccine, due to the current availability in Spanish community pharmacies, with a 3+1 scheme. CAV-AEP requests the incorporation of this vaccine in the funded unified schedule. Vaccination against rotavirus is recommended in all infants. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study.

PubMed

Doi, Toshihiko; Shitara, Kohei; Naito, Yoichi; Shimomura, Akihiko; Fujiwara, Yasuhiro; Yonemori, Kan; Shimizu, Chikako; Shimoi, Tatsunori; Kuboki, Yasutoshi; Matsubara, Nobuaki; Kitano, Atsuko; Jikoh, Takahiro; Lee, Caleb; Fujisaki, Yoshihiko; Ogitani, Yusuke; Yver, Antoine; Tamura, Kenji

2017-11-01

Antibody-drug conjugates have emerged as a powerful strategy in cancer therapy and combine the ability of monoclonal antibodies to specifically target tumour cells with the highly potent killing activity of drugs with payloads too toxic for systemic administration. Trastuzumab deruxtecan (also known as DS-8201) is an antibody-drug conjugate comprised of a humanised antibody against HER2, a novel enzyme-cleavable linker, and a topoisomerase I inhibitor payload. We assessed its safety and tolerability in patients with advanced breast and gastric or gastro-oesophageal tumours. This was an open-label, dose-escalation phase 1 trial done at two study sites in Japan. Eligible patients were at least 20 years old with breast or gastric or gastro-oesophageal carcinomas refractory to standard therapy regardless of HER2 status. Participants received initial intravenous doses of trastuzumab deruxtecan from 0·8 to 8·0 mg/kg and dose-limiting toxicities were assessed over a 21-day cycle; thereafter, dose reductions were implemented as needed and patients were treated once every 3 weeks until they had unacceptable toxic effects or their disease progressed. Primary endpoints included identification of safety and the maximum tolerated dose or recommended phase 2 dosing and were analysed in all participants who received at least one dose of study drug. The dose-escalation study is the first part of a two-part study with the second dose-expansion part ongoing and enrolling patients as of July 8, 2017, in Japan and the USA. This trial is registered at ClinicalTrials.gov, number NCT02564900. Between Aug 28, 2015, and Aug 26, 2016, 24 patients were enrolled and received trastuzumab deruxtecan (n=3 for each of 0·8, 1·6, 3·2, and 8·0 mg/kg doses; n=6 for each of 5·4 and 6·4 mg/kg). Up to the study cutoff date of Feb 1, 2017, no dose-limiting toxic effects, substantial cardiovascular toxic effects, or deaths occurred. One patient was removed from the activity analysis because they had insufficient target lesions for analysis. The most common grade 3 adverse events were decreased lymphocyte (n=3) and decreased neutrophil count (n=2); and grade 4 anaemia was reported by one patient. Three serious adverse events-febrile neutropenia, intestinal perforation, and cholangitis-were reported by one patient each. Overall, in 23 evaluable patients, including six patients with low HER2-expressing tumours, ten patients achieved an objective response (43%, 95% CI 23·2-65·5). Disease control was achieved in 21 (91%; 95% CI 72·0-98·9) of 23 patients. Median follow-up time was 6·7 months (IQR 4·4-10·2), with nine (90%) of ten responses seen at doses of 5·4 mg/kg or greater. The maximum tolerated dose of trastuzumab deruxtecan was not reached. In this small, heavily pretreated study population, trastuzumab deruxtecan showed antitumour activity, even in low HER2-expressing tumours. Based on safety and activity, the most likely recommended phase 2 dosing is 5·4 or 6·4 mg/kg. Daiichi Sankyo Co, Ltd. Copyright © 2017 Elsevier Ltd. All rights reserved.

Guided medication dosing for elderly emergency patients using real-time, computerized decision support.

PubMed

Griffey, Richard T; Lo, Helen G; Burdick, Elisabeth; Keohane, Carol; Bates, David W

2012-01-01

To evaluate the impact of a real-time computerized decision support tool in the emergency department that guides medication dosing for the elderly on physician ordering behavior and on adverse drug events (ADEs). A prospective controlled trial was conducted over 26 weeks. The status of the decision support tool alternated OFF (7/17/06-8/29/06), ON (8/29/06-10/10/06), OFF (10/10/06-11/28/06), and ON (11/28/06-1/16/07) in consecutive blocks during the study period. In patients ≥65 who were ordered certain benzodiazepines, opiates, non-steroidals, or sedative-hypnotics, the computer application either adjusted the dosing or suggested a different medication. Physicians could accept or reject recommendations. The primary outcome compared medication ordering consistent with recommendations during ON versus OFF periods. Secondary outcomes included the admission rate, emergency department length of stay for discharged patients, 10-fold dosing orders, use of a second drug to reverse the original medication, and rate of ADEs using previously validated explicit chart review. 2398 orders were placed for 1407 patients over 1548 visits. The majority (49/53; 92.5%) of recommendations for alternate medications were declined. More orders were consistent with dosing recommendations during ON (403/1283; 31.4%) than OFF (256/1115; 23%) periods (p≤0.0001). 673 (43%) visits were reviewed for ADEs. The rate of ADEs was lower during ON (8/237; 3.4%) compared with OFF (31/436; 7.1%) periods (p=0.02). The remaining secondary outcomes showed no difference. Single institution study, retrospective chart review for ADEs. Though overall agreement with recommendations was low, real-time computerized decision support resulted in greater acceptance of medication recommendations. Fewer ADEs were observed when computerized decision support was active.

Predictions of Leukemia Risks to Astronauts from Solar Particle Events

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Atwell, W.; Kim, M. Y.; George, K. A.; Ponomarev, A.; Nikjoo, H.; Wilson, J. W.

2006-01-01

Leukemias consisting of acute and chronic myeloid leukemia and acute lymphatic lymphomas represent the earliest cancers that appear after radiation exposure, have a high lethality fraction, and make up a significant fraction of the overall fatal cancer risk from radiation for adults. Several considerations impact the recommendation of a preferred model for the estimation of leukemia risks from solar particle events (SPE's): The BEIR VII report recommends several changes to the method of calculation of leukemia risk compared to the methods recommended by the NCRP Report No. 132 including the preference of a mixture model with additive and multiplicative components in BEIR VII compared to the additive transfer model recommended by NCRP Report No. 132. Proton fluences and doses vary considerably across marrow regions because of the characteristic spectra of primary solar protons making the use of an average dose suspect. Previous estimates of bone marrow doses from SPE's have used an average body-shielding distribution for marrow based on the computerized anatomical man model (CAM). We have developed an 82-point body-shielding distribution that faithfully reproduces the mean and variance of SPE doses in the active marrow regions (head and neck, chest, abdomen, pelvis and thighs) allowing for more accurate estimation of linear- and quadratic-dose components of the marrow response. SPE's have differential dose-rates and a pseudo-quadratic dose response term is possible in the peak-flux period of an event. Also, the mechanistic basis for leukemia risk continues to improve allowing for improved strategies in choosing dose-rate modulation factors and radiation quality descriptors. We make comparisons of the various choices of the components in leukemia risk estimates in formulating our preferred model. A major finding is that leukemia could be the dominant risk to astronauts for a major solar particle event.

Poor guideline adherence in the initiation of antidepressant treatment in children and adolescents in the Netherlands: choice of antidepressant and dose.

PubMed

de Vries, Ymkje Anna; de Jonge, Peter; Kalverdijk, Luuk; Bos, Jens H J; Schuiling-Veninga, Catharina C M; Hak, Eelko

2016-11-01

The Dutch guideline for the treatment of depression in young people recommends initiating antidepressant treatment with fluoxetine, as the evidence for its efficacy is strongest and the risk of suicidality may be lower than with other antidepressants. Furthermore, low starting doses are recommended. We aimed to determine whether antidepressant prescriptions are in accord with guidelines. A cohort of young people aged between 6 and 17 at the time of antidepressant initiation was selected from IABD, a Dutch pharmacy prescription database. The percentage of prescriptions for each antidepressant was determined. Starting and maintenance doses were determined and compared with recommendations for citalopram, fluoxetine, fluvoxamine, and sertraline. During the study period, 2942 patients initiated antidepressant treatment. The proportion of these young people who were prescribed fluoxetine increased from 10.1 % in 1994-2003 to 19.7 % in 2010-2014. However, the most commonly prescribed antidepressants were paroxetine in 1994-2003 and citalopram in 2004-2014. The median starting and maintenance doses were ≤0.5 DDD/day for tricyclic antidepressants and 0.5-1 DDD/day for SSRIs and other antidepressants. Starting doses were guideline-concordant 58 % of the time for children, 31 % for preteens, and 16 % for teens. Sixty percent of teens were prescribed an adult starting dose. In conclusion, guideline adherence was poor. Physicians preferred citalopram over fluoxetine, in contrast to the recommendations. Furthermore, although children were prescribed a low starting dose relatively frequently, teens were often prescribed an adult starting dose. These results suggest that dedicated effort may be necessary to improve guideline adherence.

Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

PubMed Central

Basu, Partha; Bhatla, Neerja; Ngoma, Twalib; Sankaranarayanan, Rengaswamy

2016-01-01

ABSTRACT World Health Organization (WHO) recommended 2 doses of the Human Papillomavirus (HPV) vaccine for girls below 15 y on the basis of the immune-bridging studies demonstrating non-inferior immune response of 2 doses in the adolescent girls compared to 3 doses in the young adult women in whom the efficacy against disease is established. The biological nature of the antigens (virus-like particles) constituting the HPV vaccine is responsible for the vigorous antibody response that may make the third dose redundant. The protection offered by 2 doses has been demonstrated in non-randomized clinical trials to be comparable to that offered by 3 doses against incident and persistent infections of vaccine targeted HPV types. However, results emerging from the ecological and nested case-control studies embedded in the population based screening programs of different countries indicate reduced efficacy of 2 doses against virological and disease end points. Some recent studies observed the protective effect of single dose of the vaccine against incident and persistent infections of the vaccine targeted HPV types to be similar to 3 doses in spite of immunological inferiority. The sample size, duration of follow-ups and number of events were limited in these studies. Longer follow ups of the less than 3 doses cohorts in the ongoing studies as well as appropriately designed and ethically justifiable randomized studies are needed to establish the protection offered by the alternative schedules at least beyond 10 y of vaccination. PMID:26933961

Prescribing patterns and the use of therapeutic drug monitoring of psychotropic medication in a psychiatric high-security unit.

PubMed

Castberg, Ingrid; Spigset, Olav

2008-10-01

The aim of this study was to investigate the use of psychotropic medication and therapeutic drug monitoring in a high-security psychiatric unit and to compare the doses and serum concentrations both with the recommended intervals and with the doses and serum concentrations in a control group. One hundred thirty-two patients were admitted in the period from January 2000 to December 2005. All available samples were used when comparing serum concentrations and doses with the recommended ranges. For the comparison of doses and serum concentration-to-dose (C:D) ratios with the control group only 1 sample from each patient was used. A total of 459 analyses of 27 different drugs in samples from 8 women and 73 men were included. The median number of therapeutic drug monitoring analyses per patient was 4 (range 1-29). Thirty-seven of the 81 patients (46%) used 2 or more antipsychotics at the same time. Clozapine, lamotrigine, olanzapine, quetiapine, ziprasidone, and zuclopenthixol were often given in doses above the recommended. The serum levels were frequently above those recommended for clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zuclopenthixol. The serum levels were significantly higher in the study group than in the control group for clozapine, lamotrigine, quetiapine, and zuclopenthixol. The given dose was significantly higher in the study group than in the control group for clozapine, lamotrigine and zuclopenthixol. The C:D ratio was significantly lower in the study group than in the control group for olanzapine but higher for quetiapine. The non-evidence based practice of high-dose polypharmacy with several antipsychotics is widely used in this unit. The use of higher doses in the study group than in the control group was not due to differences in metabolism or adherence to treatment between the 2 groups. The frequent use of therapeutic drug monitoring did not seem to have a great impact on the prescribed doses.

Phase I study of indicine N-oxide in patients with advanced cancer.

PubMed

Ohnuma, T; Sridhar, K S; Ratner, L H; Holland, J F

1982-07-01

Indicine N-oxide is a pyrrolizidine alkaloid isolated from Heliotropium indicum, one of the widely used herbs in Ayurvedic medicine. Thirty-seven patients with solid tumors received the drug: 15 men and 22 women (mean age, 53 years). All had had prior chemotherapy, and 25 had had prior radiotherapy. Eighty-four percent had a performance status of 0-3 (Cancer and Leukemia Group B criteria). The drug was given as a short infusion over 15 minutes and repeated with a median interval of 4 weeks. Doses were escalated from 1 to 9 g/m2. A total of 55 courses were evaluable. Dose-limiting toxic effects were leukopenia and thrombocytopenia, and the toxicity was cumulative with repeated doses. Other toxic effects included nausea and vomiting, anemia, and hepatic dysfunction. The hematologic toxicity tended to be more pronounced in patients with hepatic dysfunction, poor marrow reserve, and heavy prior chemotherapy and radiotherapy. There were no complete or partial responses. One patient with skin melanoma and another with ovarian carcinoma had improvement lasting 2 months. The maximally tolerated dose is 9 g/m2 in our population. A recommended dose for therapeutic study is 7 g/m2. High-risk patients should be started at a dose of 5 g/m2. The treatment may be repeated at 4-week intervals with close monitoring of wbc and platelet counts. Dose reductions may be necessary for repeated courses.

Cost-Effectiveness Analysis of Ixekizumab vs Etanercept and Their Manufacturer-Recommended Dosing Regimens in Moderate to Severe Plaque Psoriasis.

PubMed

Udkoff, Jeremy; Eichenfield, Lawrence F

2017-10-01

Biologic therapies have revolutionized the treatment of psoriasis; however, their use is limited by costs. Ixekizumab was more effective than etanercept in the UNCOVER trials, and the Food and Drug Administration (FDA) approved ixekizumab for treating psoriasis. Evaluating the cost-effectiveness of these therapies is crucial for medical decision making and our objective was to determine the cost-effectiveness of various ixekizumab dosing frequencies compared with etanercept. We utilized published data from the UNCOVER comparative efficacy trials, including transitional probabilities and treatment response rates, to create a Markov model simulating the clinical course and cost-effectiveness of three treatment algorithms for patients with moderate to severe plaque psoriasis over 60-weeks: (1) ixekizumab every 2 weeks for 12 weeks then every 4 weeks, (2) ixekizumab every 4 weeks throughout the treatment period, (3) biweekly etanercept for 12 weeks then once weekly. We utilized a standard willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) and Medicaid drug acquisition costs for our calculations. Ixekizumab every 4 weeks was $28,681 (USD) less expensive than biweekly etanercept, and $21,375 less expensive, and 0.006 QALY less effective, than ixekizumab every 2 weeks-- a savings of $28.7 and $21.4 million, respectively, per 1,000 patients. A 95.6% cost reduction to $197.83 per dose is required for ixekizumab every 2 weeks to be more cost-effective than every 4 weeks. Biweekly etanercept requires a 29.5% cost reduction ($743.82 per dose) to be competitive with ixekizumab every 4 weeks. This cost-effectiveness model utilizes strong input data but is a limited approximation of real-life scenarios. Treatment with ixekizumab every 2 weeks is unlikely to be cost-effective compared with ixekizumab every 4 weeks at current U.S. market prices. Yet, the U.S. FDA approval and manufacturer's recommendation are for ixekizumab every 2 weeks. Accordingly, we suggested selecting biologic therapies using cost-effectiveness analyses.

J Drugs Dermatol. 2017;16(10):964-970.

Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines.

PubMed

Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc

2016-04-01

The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor): For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation);For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation).For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin: The advice for warfarin is fundamentally unchanged from BSG 2008 guidance. Direct Oral Anticoagulants (DOAC): For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation). For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥ 48 hours before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30 - 50 mL/min we recommend that the last dose of DOAC be taken 72 hours before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). © Georg Thieme Verlag KG Stuttgart · New York.

An Updated Performance Assessment For A New Low-Level Radioactive Waste Disposal Facility In West Texas - 12192

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

Dornsife, William P.; Kirk, J. Scott; Shaw, Chris G.

2012-07-01

This Performance Assessment (PA) submittal is an update to the original PA that was developed to support the licensing of the Waste Control Specialists LLC Low-Level Radioactive Waste (LLRW) disposal facility. This update includes both the Compact Waste Facility (CWF) and the Federal Waste Facility (FWF), in accordance with Radioactive Material License (RML) No. R04100, License Condition (LC) 87. While many of the baseline assumptions supporting the initial license application PA were incorporated in this update, a new transport code, GoldSim, and new deterministic groundwater flow codes, including HYDRUS and MODFLOWSURFACT{sup TM}, were employed to demonstrate compliance with the performancemore » objectives codified in the regulations and RML No. R04100, LC 87. A revised source term, provided by the Texas Commission on Environmental Quality staff, was used to match the initial 15 year license term. This updated PA clearly confirms and demonstrates the robustness of the characteristics of the site's geology and the advanced engineering design of the disposal units. Based on the simulations from fate and transport models, the radiation doses to members of the general public and site workers predicted in the initial and updated PA were a small fraction of the criterion doses of 0.25 mSv and 50 mSv, respectively. In a comparison between the results of the updated PA against the one developed in support of the initial license, both clearly demonstrated the robustness of the characteristics of the site's geology and engineering design of the disposal units. Based on the simulations from fate and transport models, the radiation doses to members of the general public predicted in the initial and updated PA were a fraction of the allowable 25 mrem/yr (0.25 m sievert/yr) dose standard for tens-of-thousands of years into the future. Draft Texas guidance on performance assessment (TCEQ, 2004) recommends a period of analysis equal to 1,000 years or until peak doses from the more mobile radionuclides occur. The EPA National Emissions Standards for Hazardous Air Pollutants limits radionuclide doses through the air pathway to 10 mrem/yr. Gaseous radionuclide doses from the CWF and the FWF, due to decomposition gases, are a small fraction of the dose limit. The radon flux from the CWF and FWF were compared to the flux limit of 20 pCi/m{sup 2}-s from 40 CFR 192. Because of the thick cover system, the calculated radon flux was a very small fraction of the limit. (authors)« less

Older adults and high-risk medication administration in the emergency department.

PubMed

Kim, Mitchell; Mitchell, Steven H; Gatewood, Medley; Bennett, Katherine A; Sutton, Paul R; Crawford, Carol A; Bentov, Itay; Damodarasamy, Mamatha; Kaplan, Stephen J; Reed, May J

2017-01-01

Older adults are susceptible to adverse effects from opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and benzodiazepines (BZDs). We investigated factors associated with the administration of elevated doses of these medications of interest to older adults (≥65 years old) in the emergency department (ED). ED records were queried for the administration of medications of interest to older adults at two academic medical center EDs over a 6-month period. Frequency of recommended versus elevated ("High doses" were defined as doses that ranged between 1.5 and 3 times higher than the recommended starting doses; "very high doses" were defined as higher than high doses) starting doses of medications, as determined by geriatric pharmacy/medicine guidelines and expert consensus, was compared by age groups (65-69, 70-74, 75-79, 80-84, and ≥85 years), gender, and hospital. There were 17896 visits representing 11374 unique patients >65 years of age (55.3% men, 44.7% women). A total of 3394 doses of medications of interest including 1678 high doses and 684 very high doses were administered to 1364 different patients. Administration of elevated doses of medications was more common than that of recommended doses. Focusing on opioids and BZDs, the 65-69-year age group was much more likely to receive very high doses (1481 and 412 doses, respectively) than the ≥85-year age groups (relative risk [RR] 5.52, 95% CI 2.56-11.90), mainly reflecting elevated opioid dosing (RR 8.28, 95% CI 3.69-18.57). Men were more likely than women to receive very high doses (RR 1.47, 95% CI 1.26-1.72), primarily due to BZDs (RR 2.12, 95% CI 2.07-2.16). Administration of elevated doses of opioids and BZDs in the older population occurs frequently in the ED, especially to the 65-69-year age group and men. Further attention to potentially unsafe dosing of high-risk medications to older adults in the ED is warranted.

A Computer Prescribing Order Entry-Clinical Decision Support system designed for neonatal care: results of the 'preselected prescription' concept at the bedside.

PubMed

Gouyon, B; Iacobelli, S; Saliba, E; Quantin, C; Pignolet, A; Jacqz-Aigrain, E; Gouyon, J B

2017-02-01

The neonatal intensive care units (NICUs) are at the highest risk of drug dose error of all hospital wards. NICUs also have the most complicated prescription modalities. The computerization of the prescription process is currently recommended to decrease the risk of preventable adverse drug effects (pADEs) in NICUs. However, Computer Prescribing Order Entry-Clinical Decision Support (C.P.O.E./C.D.S.) systems have been poorly studied in NICUs, and their technical compatibility with neonatal specificities has been limited. We set up a performance study of the preselected prescription of drugs for neonates, which limited the role of the prescriber to choosing the drugs and their indications. A single 29 bed neonatal ward used this neonatal C.P.O.E./C.D.S. system for all prescriptions of all hospitalized newborns over an 18-month period. The preselected prescription of drugs was based on the indication, gestational age, body weight and post-natal age. The therapeutic protocols were provided by a formulary reference (330 drugs) that had been specifically designed for newborns. The preselected prescription also gave complete information about preparation and administration of drugs by nurses. The prescriber was allowed to modify the preselected prescription but alarms provided warning when the prescription was outside the recommended range. The main clinical characteristics and all items of each line of prescription were stored in a data warehouse, thus enabling this study to take place. Seven hundred and sixty successive newborns (from 24 to 42 weeks' gestation) were prescribed 52 392 lines of prescription corresponding to 65 drugs; About 30·4% of neonates had at least one out of licensed prescription; A prescription out of the recommended range for daily dose was recorded for 1·0% of all drug prescriptions. WHAT IS NEW?: The C.P.O.E./C.D.S. systems can currently provide a complete preselected prescription in NICUs according to dose rules, which are specific to newborns and also comply with local specificities (therapeutic protocols and formulation of drugs). The role of the prescriber is limited to the choice of drugs and their indications. The prescriber still retains the possibility of modifying each item of the prescription, with all other prescription items being calculated by the C.P.O.E. system. In these conditions, the prescribers rarely modified the preselected prescription and the rate of out of range prescription was low. A multicentric study is required to confirm and extend these observations. This study showed the feasibility of preselected prescription in NICUs and a low rate of out of range prescriptions. The preselected prescription could play a key role in lowering the dose error rate in NICUs. © 2016 John Wiley & Sons Ltd.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

PubMed

Dejaco, Christian; Singh, Yogesh P; Perel, Pablo; Hutchings, Andrew; Camellino, Dario; Mackie, Sarah; Abril, Andy; Bachta, Artur; Balint, Peter; Barraclough, Kevin; Bianconi, Lina; Buttgereit, Frank; Carsons, Steven; Ching, Daniel; Cid, Maria; Cimmino, Marco; Diamantopoulos, Andreas; Docken, William; Duftner, Christina; Fashanu, Billy; Gilbert, Kate; Hildreth, Pamela; Hollywood, Jane; Jayne, David; Lima, Manuella; Maharaj, Ajesh; Mallen, Christian; Martinez-Taboada, Victor; Maz, Mehrdad; Merry, Steven; Miller, Jean; Mori, Shunsuke; Neill, Lorna; Nordborg, Elisabeth; Nott, Jennifer; Padbury, Hannah; Pease, Colin; Salvarani, Carlo; Schirmer, Michael; Schmidt, Wolfgang; Spiera, Robert; Tronnier, David; Wagner, Alexandre; Whitlock, Madeline; Matteson, Eric L; Dasgupta, Bhaskar

2015-10-01

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Dose calculation for photon-emitting brachytherapy sources with average energy higher than 50 keV: report of the AAPM and ESTRO.

PubMed

Perez-Calatayud, Jose; Ballester, Facundo; Das, Rupak K; Dewerd, Larry A; Ibbott, Geoffrey S; Meigooni, Ali S; Ouhib, Zoubir; Rivard, Mark J; Sloboda, Ron S; Williamson, Jeffrey F

2012-05-01

Recommendations of the American Association of Physicists in Medicine (AAPM) and the European Society for Radiotherapy and Oncology (ESTRO) on dose calculations for high-energy (average energy higher than 50 keV) photon-emitting brachytherapy sources are presented, including the physical characteristics of specific (192)Ir, (137)Cs, and (60)Co source models. This report has been prepared by the High Energy Brachytherapy Source Dosimetry (HEBD) Working Group. This report includes considerations in the application of the TG-43U1 formalism to high-energy photon-emitting sources with particular attention to phantom size effects, interpolation accuracy dependence on dose calculation grid size, and dosimetry parameter dependence on source active length. Consensus datasets for commercially available high-energy photon sources are provided, along with recommended methods for evaluating these datasets. Recommendations on dosimetry characterization methods, mainly using experimental procedures and Monte Carlo, are established and discussed. Also included are methodological recommendations on detector choice, detector energy response characterization and phantom materials, and measurement specification methodology. Uncertainty analyses are discussed and recommendations for high-energy sources without consensus datasets are given. Recommended consensus datasets for high-energy sources have been derived for sources that were commercially available as of January 2010. Data are presented according to the AAPM TG-43U1 formalism, with modified interpolation and extrapolation techniques of the AAPM TG-43U1S1 report for the 2D anisotropy function and radial dose function.

Using Quality of Life Measures in a Phase I Clinical Trial of Noni in Patients with Advanced Cancer to Select a Phase II Dose

PubMed Central

Issell, Brian F.; Gotay, Carolyn C.; Pagano, Ian; Franke, A. Adrian

2015-01-01

Purpose We conducted a Phase I study of noni in patients with advanced cancer. Quality of life measures were examined as an alternate way to select a Phase II dose of this popular dietary supplement. Patients and Methods Starting at two capsules twice daily (2 grams), the dose suggested for marketed products, dose levels were escalated by 2 grams daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed QLQ-C30 Quality of Life, and the Brief Fatigue Inventory (BFI), questionnaires at baseline and at four week intervals. Scopoletin was measured in blood and urine collected at baseline and at approximately four week intervals. Results Fifty-one patients were enrolled at seven dose levels. Seven capsules four times daily (14 grams) was the maximum tolerated dose. No dose limiting toxicity was found but four of eight patients at this level withdrew from the study due to the challenges of ingesting so many capsules. There was a dose response for self reported physical functioning and the control of pain and fatigue. Patients taking four capsules four times daily experienced less fatigue than patients taking lower or higher doses. A relationship between noni dose and blood and urinary scopoletin concentrations was found. Conclusion Measuring quality of life to determine a dose for subsequent Phase II testing is feasible. A noni dose of four capsules four times daily (8 grams) is recommended for Phase II testing where controlling fatigue and maintaining physical function is the efficacy of interest. Scopoletin is a measurable noni ingredient for pharmacokinetic studies in patients with cancer. PMID:22435516

Dose Equivalents for Antipsychotic Drugs: The DDD Method.

PubMed

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Davis, John M

2016-07-01

Dose equivalents of antipsychotics are an important but difficult to define concept, because all methods have weaknesses and strongholds. We calculated dose equivalents based on defined daily doses (DDDs) presented by the World Health Organisation's Collaborative Center for Drug Statistics Methodology. Doses equivalent to 1mg olanzapine, 1mg risperidone, 1mg haloperidol, and 100mg chlorpromazine were presented and compared with the results of 3 other methods to define dose equivalence (the "minimum effective dose method," the "classical mean dose method," and an international consensus statement). We presented dose equivalents for 57 first-generation and second-generation antipsychotic drugs, available as oral, parenteral, or depot formulations. Overall, the identified equivalent doses were comparable with those of the other methods, but there were also outliers. The major strength of this method to define dose response is that DDDs are available for most drugs, including old antipsychotics, that they are based on a variety of sources, and that DDDs are an internationally accepted measure. The major limitations are that the information used to estimate DDDS is likely to differ between the drugs. Moreover, this information is not publicly available, so that it cannot be reviewed. The WHO stresses that DDDs are mainly a standardized measure of drug consumption, and their use as a measure of dose equivalence can therefore be misleading. We, therefore, recommend that if alternative, more "scientific" dose equivalence methods are available for a drug they should be preferred to DDDs. Moreover, our summary can be a useful resource for pharmacovigilance studies. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bridging the gap: a review of dose investigations in paediatric investigation plans.

PubMed

Hampson, Lisa V; Herold, Ralf; Posch, Martin; Saperia, Julia; Whitehead, Anne

2014-10-01

In the EU, development of new medicines for children should follow a prospectively agreed paediatric investigation plan (PIP). Finding the right dose for children is crucial but challenging due to the variability of pharmacokinetics across age groups and the limited sample sizes available. We examined strategies adopted in PIPs to support paediatric dosing recommendations to identify common assumptions underlying dose investigations and the attempts planned to verify them in children. We extracted data from 73 PIP opinions recently adopted by the Paediatric Committee of the European Medicines Agency. These opinions represented 79 medicinal development programmes and comprised a total of 97 dose investigation studies. We identified the design of these dose investigation studies, recorded the analyses planned and determined the criteria used to define target doses. Most dose investigation studies are clinical trials (83 of 97) that evaluate a single dosing rule. Sample sizes used to investigate dose are highly variable across programmes, with smaller numbers used in younger children (< 2 years). Many studies (40 of 97) do not pre-specify a target dose criterion. Of those that do, most (33 of 57 studies) guide decisions using pharmacokinetic data alone. Common assumptions underlying dose investigation strategies include dose proportionality and similar exposure-response relationships in adults and children. Few development programmes pre-specify steps to verify assumptions in children. There is scope for the use of Bayesian methods as a framework for synthesizing existing information to quantify prior uncertainty about assumptions. This process can inform the design of optimal drug development strategies. © 2014 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common

PubMed Central

2012-01-01

In areas of low malaria transmission, it is currently recommended that a single dose of primaquine (0.75 mg base/kg; 45 mg adult dose) be added to artemisinin combination treatment (ACT) in acute falciparum malaria to block malaria transmission. Review of studies of transmission-blocking activity based on the infectivity of patients or volunteers to anopheline mosquitoes, and of haemolytic toxicity in glucose 6-dehydrogenase (G6PD) deficient subjects, suggests that a lower primaquine dose (0.25 mg base/kg) would be safer and equally effective. This lower dose could be deployed together with ACTs without G6PD testing wherever use of a specific gametocytocide is indicated. PMID:23237606

Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common.

PubMed

White, Nicholas J; Qiao, Li Guo; Qi, Gao; Luzzatto, Lucio

2012-12-14

In areas of low malaria transmission, it is currently recommended that a single dose of primaquine (0.75 mg base/kg; 45 mg adult dose) be added to artemisinin combination treatment (ACT) in acute falciparum malaria to block malaria transmission. Review of studies of transmission-blocking activity based on the infectivity of patients or volunteers to anopheline mosquitoes, and of haemolytic toxicity in glucose 6-dehydrogenase (G6PD) deficient subjects, suggests that a lower primaquine dose (0.25 mg base/kg) would be safer and equally effective. This lower dose could be deployed together with ACTs without G6PD testing wherever use of a specific gametocytocide is indicated.

SU-E-T-581: Planning Evaluation of Step-And-Shoot IMRT, RapidArc and Helical TomoTherapy for Hippocampal-Avoidance Whole Brain Radiotherapy (HA-WBRT).

PubMed

Evans, J; Chen, Q; Wuthrick, E; Weldon, M; Rong, Y

2012-06-01

Several planning strategies are available for hippocampal- avoidance whole-brain radiotherapy (HA-WBRT) following RTOG protocol 0933, but have yet to be compared on a common set of patient data. In this inter-institutional investigation, we evaluate three modalities likely to be employed by protocol participants; step-and-shoot IMRT, volumetric modulated arc therapy, and helical tomotherapy. A common set of patients is used for comparison, including credentialing and successfully accrued patients. Eight patient datasets were selected and de-identified prior to planning. Structures were contoured by physicians per protocol using fused MRI datasets. Three plans were generated for each dataset: Philips Pinnacle 9-field non-coplanar IMRT using protocol recommended beam parameters, Varian's RapidArc using two coplanar arcs, and Accuray's TomoTherapy using a 1cm jaw width. With the goal of meeting the compliance criteria outlined in RTOG 0933 (target coverage and dose limits to the hippocampus and optic structures), three planners independently planned each modality without prior knowledge of the patient's other plans to reduce bias. The three plans for each patient were compared according to the protocol's dosimetric compliance criteria. A homogeneity index was also computed to compare target dose uniformity. All plans achieved the protocol dose criteria, except for one RapidArc plan with slightly inferior dose to the optic chiasm. TomoTherapy offered superior dose homogeneity for all patients. For the two linac based methods, RapidArc was found to provide dose homogeneity at least as good as, and in most cases superior to, 9-field step-and-shoot IMRT. Helical TomoTherapy offers superior dose homogeneity for HA-WBRT following RTOG 0933. Compared to step-and-shoot IMRT, volumetric modulated arc techniques, such as RapidArc, can offer improved homogeneity for HA- WBRT and are generally more efficient/expeditious to deliver than the noncoplanar 9-field arrangement recommended by the protocol, which uses 7 separate couch angles. © 2012 American Association of Physicists in Medicine.

Phase I Trial of Anti-MET Monoclonal Antibody in MET-Overexpressed Refractory Cancer.

PubMed

Lee, Jeeyun; Kim, Seung Tae; Park, Sungju; Lee, Sujin; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Ahn, Hongmo; Bok, Haesook; Kim, Kyoung-Mee; Ahn, Myung Ju; Kang, Won Ki; Park, Young Suk

2018-06-01

Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas. SAIT301 was administered intravenously once every 3 weeks in c-MET overexpressed solid tumor patients, focusing on metastatic colorectal cancer (CRC) according to common clinical phase I criteria. Dose escalation was performed according to a modified Fibonacci design, following the conventional 3+3 design. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose for clinical phase II studies and to assess potential anticancer activity of the compound. Sixteen patients with a median age of 56 (range, 39-69) years were enrolled in the study. The most common adverse events were decreased appetite (50.0%), hypophosphatemia, fatigue and dizziness (25.0%, respectively), and diarrhea, blood alkaline phosphatase increased and dyspnea (18.8%, respectively). For tumor response, no patients achieved complete response. One (9.1%) CRC patient had a partial response in the 1.23 mg/kg group, 4 (36.4%) patients achieved stable disease (2 in the 0.41 mg/kg group, 2 in the 1.23 mg/kg group, 0 in the 3.69 mg/kg group, and 1 in the 8.61 mg/kg group). Because of the increase in dose-limiting toxicities (DLTs) at 8.61 mg/kg, the 3.69 mg/kg dose was considered the maximum tolerated dose and selected for further assessment in phase II. We successfully completed a phase I trial with MET antibody in a MET-overexpressed patient population focusing on CRC, and found that the DLTs were alkaline phosphatase elevation or hypophosphatemia. The recommended dose of SAIT301 for phase II is the dose of 3.69 mg/kg. Copyright © 2018 Elsevier Inc. All rights reserved.

Use of Radiocontrast Agents in CKD and ESRD.

PubMed

Bahrainwala, Jehan Z; Leonberg-Yoo, Amanda K; Rudnick, Michael R

2017-07-01

Contrast exposure in a population with chronic kidney disease (CKD) requires additional consideration given the risk of contrast-induced nephropathy (CIN) after exposure to iodinated contrast as well as systemic injury with exposure to gadolinium-based contrast agents (GBCA). Strategies to avoid CIN, and manage patients after exposure, including extracorporeal removal of contrast media, may differ among an advanced CKD population as compared to a general population. There is strong evidence to support the use of isotonic volume expansion and the lowest dose of low-osmolar or iso-osmolar contrast media possible to decrease CIN. The current literature on other newer prophylactic strategies such as statins, remote ischemic preconditioning, discontinuation of renin angiotensin aldosterone system (RAAS) blockade, and RenalGuard is limited thus these strategies cannot currently be recommended as routine prophylaxis for CIN. The use of extracorporeal removal of contrast agents as prophylaxis to reduce CIN has been the subject of multiple studies; however, data do not support a beneficial effect in reduction in CIN. Immediate removal of contrast by dialysis in a maintenance dialysis population is also not recommended, unless an individual's cardiopulmonary status is dependent on strict volume management. In patients with reduced renal function, GCBA exposure increases the risk of NSF. In patients with AKI, CKD stage 3 or greater (eGFR <30 ml/minute/1.73 m 2 ), or patients on dialysis, we do not recommend the use of GBCA and alternative imaging modalities should be considered. If patients absolutely need magnetic resonance imaging with GBCA, we recommend the use of the lowest dose possible of the newer macrocylic, ionic agents (gadoterate meglumine) as well as immediate postprocedural HD in patients already on HD or peritoneal dialysis or with stage 5 CKD and with a functioning dialysis access already in place. © 2017 Wiley Periodicals, Inc.

Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older--United States, 2016.

PubMed

Kim, David K; Bridges, Carolyn B; Harriman, Kathleen H

2016-02-05

In October 2015, the Advisory Committee on Immunization Practices (ACIP)* approved the Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2016. This schedule provides a summary of ACIP recommendations for the use of vaccines routinely recommended for adults aged 19 years or older in two figures, footnotes for each vaccine, and a table that describes primary contraindications and precautions for commonly used vaccines for adults. Although the figures in the adult immunization schedule illustrate recommended vaccinations that begin at age 19 years, the footnotes contain information on vaccines that are recommended for adults that may begin at age younger than age 19 years. The footnotes also contain vaccine dosing, intervals between doses, and other important information and should be read with the figures.

Australasian Society for Parenteral and Enteral Nutrition guidelines for supplementation of trace elements during parenteral nutrition.

PubMed

Osland, Emma J; Ali, Azmat; Isenring, Elizabeth; Ball, Patrick; Davis, Melvyn; Gillanders, Lyn

2014-01-01

This work represents the first part of a progressive review of AuSPEN's 1999 Guidelines for Provision of Micronutrient Supplementation in Adult Patients receiving Parenteral Nutrition, in recognition of the developments in the literature on this topic since that time. A systematic literature review was undertaken and recommendations were made based on the available evidence and with consideration to specific elements of the Australian and New Zealand practice environment. The strength of evidence underpinning each recommendation was assessed. External reviewers provided feedback on the guidelines using the AGREE II tool. Reduced doses of manganese, copper, chromium and molybdenum, and an increased dose of selenium are recommended when compared with the 1999 guidelines. Currently the composition of available multi-trace element formulations is recognised as an obstacle to aligning these guidelines with practice. A paucity of available literature and limitations with currently available methods of monitoring trace element status are acknowledged. The currently unknown clinical impact of changes to trace element contamination of parenteral solutions with contemporary practices highlights need for research and clinical vigilance in this area of nutrition support practice. Trace elements are essential and should be provided daily to patients receiving parenteral nutrition. Monitoring is generally only required in longer term parenteral nutrition, however should be determined on an individual basis. Industry is encouraged to modify existing multi-trace element solutions available in Australia and New Zealand to reflect changes in the literature outlined in these guidelines. Areas requiring research are highlighted.

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

PubMed

Uchida, Mai; Spencer, Andrea E; Kenworthy, Tara; Chan, James; Fitzgerald, Maura; Rosales, Ana Maria; Kagan, Elana; Saunders, Alexandra; Biederman, Joseph

2017-06-01

Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

Pharmacogenetics-based personalized therapy: Levels of evidence and recommendations from the French Network of Pharmacogenetics (RNPGx).

PubMed

Picard, Nicolas; Boyer, Jean-Christophe; Etienne-Grimaldi, Marie-Christine; Barin-Le Guellec, Chantal; Thomas, Fabienne; Loriot, Marie-Anne

2017-04-01

More than 50 laboratories offer pharmacogenetic testing in France. These tests are restricted to a limited number of indications: prevention of serious adverse drug reactions; choice of most appropriate therapeutic option; dose adjustment for a specific drug. A very small proportion of these tests are mentioned in drug information labeling and the data provided (if any) are generally insufficient to ascertain whether a test is required and if it is useful. This article discusses the rationale for evaluating the performance and clinical usefulness of pharmacogenetics and provides, on behalf of the French national network of pharmacogenetics (RNPGx), three levels of recommendation for testing: essential, advisable, and possibly helpful. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

A phase I study of docetaxel as a radio-sensitizer for locally advanced squamous cell cervical cancer.

PubMed

Alvarez, Edwin A; Wolfson, Aaron H; Pearson, J Matt; Crisp, Meredith P; Mendez, Luis E; Lambrou, Nicholas C; Lucci, Joseph A

2009-05-01

This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy (RT) for the primary treatment of locally advanced squamous cell carcinoma of the cervix. Eligible patients included those with locally advanced squamous cell cervical cancer without para-aortic lymph node involvement. Docetaxel dose levels were 20 mg/m(2), 30 mg/m(2) and 40 mg/m(2) given intravenously weekly for 6 cycles. Three patients were to be treated at each dose level and 6 to receive the MTD. Fifteen patients completed 4-6 cycles of chemotherapy. One of three patients experienced 2 delayed grade 3 severe adverse events (SAE) at the 20 mg/m(2) dose level consisting of colonic and ureteral obstruction. At the 30 mg/m(2) dose level, 1/4 patients had a probable treatment-related celiotomy due to obstipation and a necrotic tumor. Of the 8 patients treated at the 40 mg/m(2) dose level, 1 experienced grade 3 pneumonitis, likely treatment related. Overall, 10/15 (67%) experienced grade 1 or 2 diarrhea, 6 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. 10 of 16 patients (67%) had no evidence of disease with follow-up ranging from 10-33 months (average 23 months). The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for locally advanced squamous cell carcinoma of the cervix is 40 mg/m(2).

Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study.

PubMed

Phuphanich, Surasak; Baker, Sharyn D; Grossman, Stuart A; Carson, Kathryn A; Gilbert, Mark R; Fisher, Joy D; Carducci, Michael A

2005-04-01

We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 muM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme-inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants.

Clinical Pharmacokinetics and Pharmacodynamics of Saxagliptin, a Dipeptidyl Peptidase-4 Inhibitor.

PubMed

Boulton, David W

2017-01-01

Saxagliptin is an orally active, highly potent, selective and competitive dipeptidyl peptidase (DPP)-4 inhibitor used in the treatment of type 2 diabetes mellitus at doses of 2.5 or 5 mg once daily. DPP-4 is responsible for degrading the intestinally derived hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP). Inhibition of DPP-4 increases intact plasma GLP-1 and GIP concentrations, augmenting glucose-dependent insulin secretion. Both saxagliptin and its major active metabolite, 5-hydroxy saxagliptin, demonstrate high degrees of selectivity for DPP-4 compared with other DPP enzymes. Saxagliptin is orally absorbed and can be administered with or without food. The half-life of plasma DPP-4 inhibition with saxagliptin 5 mg is ~27 h, which supports a once-daily dosing regimen. Saxagliptin is metabolized by cytochrome P450 (CYP) 3A4/5 and is eliminated by a combination of renal and hepatic clearance. No clinically meaningful differences in saxagliptin or 5-hydroxy saxagliptin pharmacokinetics have been detected in patients with hepatic impairment. No clinically meaningful differences in saxagliptin or 5-hydroxy saxagliptin pharmacokinetics have been detected in patients with mild renal impairment, whereas dose reduction is recommended in patients with moderate or severe renal impairment because of greater systemic exposure [the area under the plasma concentration-time curve (AUC)] to saxagliptin total active moieties. Clinically relevant drug-drug interactions have not been detected; however, limiting the dose to 2.5 mg once daily is recommended in the USA when saxagliptin is coadministered with strong CYP inhibitors, because of increased saxagliptin exposure. In summary, saxagliptin has a predictable pharmacokinetic and pharmacodynamic profile.

Protection of the public in situations of prolonged radiation exposure. The application of the Commission's system of radiological protection to controllable radiation exposure due to natural sources and long-lived radioactive residues.

PubMed

1999-01-01

This report provides guidance on the application of the ICRP system of radiological protection to prolonged exposure situations affecting members of the public. It addresses the general application of the Commission's system to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations. Additionally, it provides recommendations on generic reference levels for such interventions. The report also considers some specific situations and discusses a number of issues that have been of concern, namely: natural radiation sources that may give rise to high doses; the restoration and rehabilitation of sites where human activities involving radioactive substances have been carried out; the return to 'normality' following an accident that has released radioactive substances to the environment; and the global marketing of commodities for public consumption that contain radioactive substances. Annexes provide some examples of prolonged exposure situations and discuss the radiological protection quantities, radiation-induced health effects and aspects of the Commission's system of radiological protection relevant to prolonged exposure. Quantitative recommendations for prolonged exposures are provided in the report. They must be interpreted with extreme caution; Chapters 4 and 5 stress the upper bound nature of the following values: Generic reference levels for intervention, in terms of existing total annual doses, are given as < approximately 100 mSv, above which intervention is almost always justifiable (situations for which the annual dose threshold for deterministic effects in relevant organs is exceeded will almost always require intervention), and < approximately 10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary). Intervention exemption levels for commodities, especially building materials, are expressed as an additional annual dose of approximately 1 mSv. The dose limit for exposures of the public from practices is expressed as aggregated (prolonged and transitory) additional annual doses from all relevant practices of 1 mSv. Dose constraints for sources within practices are expressed as an additional annual dose lower than 1 mSv (e.g. of approximately 0.3 mSv), which could be approximately 0.1 mSv for the prolonged exposure component. An exemption level for practices is expressed as an additional annual dose of approximately 0.01 mSv.

The effect of dosing regimens on the antimalarial efficacy of dihydroartemisinin-piperaquine: a pooled analysis of individual patient data.

PubMed

2013-12-01

Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy. A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n = 7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan-Meier survival estimates were 97.7% (95% CI 97.3%-98.1%) at day 42 and 97.2% (95% CI 96.7%-97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3-2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%-96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of piperaquine was found to be a significant predictor for recrudescence, the risk increasing by 13% (95% CI 5.0%-21%) for every 5 mg/kg decrease in dose; p = 0.002. In a multivariable model increasing the target minimum total dose of piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would halve the risk of treatment failure and cure at least 95% of patients; such an increment was not associated with gastrointestinal toxicity in the ten studies in which this could be assessed. DP demonstrates excellent efficacy in a wide range of transmission settings; however, treatment failure is associated with a lower dose of piperaquine, particularly in young children, suggesting potential for further dose optimisation.

Pharmacometrics-based dose selection of levofloxacin as a treatment for postexposure inhalational anthrax in children.

PubMed

Li, Fang; Nandy, Partha; Chien, Shuchean; Noel, Gary J; Tornoe, Christoffer W

2010-01-01

Levofloxacin was recently (May 2008) approved by the U.S. Food and Drug Administration as a treatment for children following inhalational exposure to anthrax. Given that no clinical trials to assess the efficacy of a chosen dose was conducted, the basis for the dose recommendation was based upon pharmacometric analyses. The objective of this paper is to describe the basis of the chosen pediatric dose recommended for the label. Pharmacokinetic (PK) data from 90 pediatric patients receiving 7 mg/kg of body weight levofloxacin and two studies of 47 healthy adults receiving 500 and 750 mg/kg levofloxacin were used for the pharmacometric analyses. Body weight was found to be a significant covariate for levofloxacin clearance and the volume of distribution. Consistently with developmental physiology, clearance also was found to be reduced in pediatric patients under 2 years of age due to immature renal function. Different dosing regimens were simulated to match adult exposure (area under the concentration-time curve from 0 to 24 h at steady state, maximum concentration of drug in serum at steady state, and minimum concentration of drug in serum at steady state) following the approved adult dose of 500 mg once a day. The recommended dose of 8 mg/kg twice a day was found to match the exposure of the dose approved for adults in a manner that permitted confidence that this dose in children would achieve efficacy comparable to that of adults.

Breastfeeding considerations of opioid dependent mothers and infants.

PubMed

Hilton, Tara C

2012-01-01

The American Academy of Pediatrics (AAP) has a long-standing recommendation against breastfeeding if the maternal methadone dose is above 20 mg/day. In 2001, the AAP lifted the dose restriction of maternal methadone allowing methadone-maintained mothers to breastfeed. The allowance of breastfeeding among mothers taking methadone has been met with opposition due to the uncertainty that exists related to methadone exposure of the suckling infant. Methadone-maintained mothers are at higher risk for abuse, concomitant psychiatric disorders, limited access to healthcare, and financial hardship. Breastfeeding rates among methadone-maintained women tend to be low compared to the national average. This manuscript will discuss the implications for healthcare practitioners caring for methadone-maintained mothers and infants and associated risks and benefits of breastfeeding. This population of mothers and infants stands to obtain particular benefits from the various well-known advantages of breastfeeding.

IMRT for head and neck cancer: reducing xerostomia and dysphagia

PubMed Central

Wang, XiaoShen; Eisbruch, Avraham

2016-01-01

Dysphagia and xerostomia are the main sequellae of chemoradiotherapy for head and neck cancer, and the main factors in reducing long-term patient quality of life. IMRT uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of non-involved tissues. The decisions about sparing organs and tissues whose damage causes xerostomia and dysphagia depends on the evidence for dose–response relationships for the organs causing these sequellae. This paper discusses the evidence for the contribution of radiotherapy to xerostomia via damage of the major salivary glands (parotid and submandibular) and minor salivary glands within the oral cavity, and the contribution of radiotherapy-related effect on important swallowing structures causing dysphagia. Recommendations for dose limits to these organs, based on measurements of xerostomia and dysphagia following radiotherapy, are provided here. PMID:27538846

Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

PubMed

Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

2014-01-06

Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

Simplifying anemia management in hemodialysis patients: ESAs administered at longer dosing intervals can enhance opportunities to provide patient-focused care.

PubMed

Schiller, Brigitte; Besarab, Anatole

2011-08-01

To review issues and challenges in caring for hemodialysis patients with anemia of chronic kidney disease, specifically focusing on the effects of longer erythropoiesis-stimulating agent (ESA) dosing intervals on processes of care. PubMed searches were performed limited to the last 10 years to February 2011, focusing on articles in English that were 'clinical trials,' assessed processes of care, measured associations of hemoglobin (Hb) with outcomes, and explored/analyzed extended dosing intervals of ESAs in hemodialysis patients and recommendations for increasing the quality of care of these patients. Some limitations included the fact that a meta-analysis was not conducted; many studies were associative and therefore unable to prove causality; and none of the clinical trials directly compared the impact of more frequent or less frequent ESA dosing strategies on patient care and outcomes. Progress over the past several decades has been substantial; however, unmet needs remain and there is room for improvement in efficiencies of care. Many patients fail to meet Hb targets, and nephrology professionals' time is consumed with preparing, administering, and monitoring therapy. Direct interaction between patients and care providers has been lost as attention has shifted to 'cost-effective' (not necessarily patient-centered) ways to deliver care. Use of ESAs at longer dosage intervals represents one opportunity to improve efficiency of care. Newer ESAs have been developed for less frequent dosing. Once-monthly dosing decreases time spent administering/monitoring therapy and allows nephrology professionals to provide comprehensive renal care, wherein the patient rather than task-oriented processes becomes the primary focus. A fragmented, uncoordinated care-delivery model heightens the urgency to systematically address issues related to delivery of care and improve efficiencies in anemia management as part of the patient-centered approach. ESAs designed for administration at longer intervals may effectively and reliably achieve Hb targets with once-monthly dosing, thereby decreasing time spent administering/monitoring therapy.

Budget impact of polio immunization strategy for India: introduction of one dose of inactivated poliomyelitis vaccine and reductions in supplemental polio immunization.

PubMed

Khan, M M; Sharma, S; Tripathi, B; Alvarez, F P

2017-01-01

To conduct a budget impact analysis (BIA) of introducing the immunization recommendations of India Expert Advisory Group (IEAG) for the years 2015-2017. The recommendations include introduction of one inactivated poliomyelitis vaccine (IPV) dose in the regular child immunization programme along with reductions in oral polio vaccine (OPV) doses in supplemental programmes. This is a national level analysis of budget impact of new polio immunization recommendations. Since the states of India vary widely in terms of size, vaccine coverage and supplemental vaccine needs, the study estimated the budget impact for each of the states of India separately to derive the national level budget impact. Based on the recommendations of IEAG, the BIA assumes that all children in India will get an IPV dose at 14 weeks of age in addition to the OPV and DPT (or Pentavalent-3) doses. Cost of introducing the IPV dose was estimated by considering vaccine price and vaccine delivery and administration costs. The cost savings associated with the reduction in number of doses of OPV in supplemental immunization were also estimated. The analysis used India-specific or international cost parameters to estimate the budget impact. Introduction of one IPV dose will increase the cost of vaccines in the regular immunization programme from $20 million to $47 million. Since IEAG recommends lower intensity of supplemental OPV vaccination, polio vaccine cost of supplemental programme is expected to decline from $72 million to $53 million. Cost of administering polio vaccines will also decline from $124 million to $105 million mainly due to the significantly lower intensity of supplemental polio vaccination. The net effect of adopting IEAG's recommendations on polio immunization turns out to be cost saving for India, reducing total polio immunization cost by $6 million. Additional savings could be achieved if India adopts the new policy regarding the handling of multi-dose vials after opening. Introduction of three doses of IPV with the existing polio immunization schedule will increase the budget requirement by $102 million but replacing OPV doses with IPV will increase the budget by about $59 million. Discontinuation of supplemental OPV immunization with replacement of OPV by IPV will reduce the Government of India's (GOI) polio immunization budget by $99 million. Although the overall cost of polio programme will decline with the adoption of IEAG's recommendations, state-level costs will vary widely. In states like Kerala, Karnataka, Uttar Pradesh and Andhra Pradesh, cost of polio immunization will increase while in Punjab and Jharkhand the costs will remain more or less constant. Significant cost reductions will happen in states with high intensity of supplemental polio immunizations (Bihar, Haryana and Delhi). The cost of procuring polio vaccines will more than double from $20 million to about $47 million requiring allocation of additional foreign exchanges. In some states (like Bihar), the decline in polio-related employment will be very high requiring reallocation of personnel from polio to other programmes. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

TH-A-BRC-00: New Task Groups for External Beam QA: An Overview

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

NONE

2016-06-15

AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance -more » Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics Survey of possible calibration protocols for calibration of Gamma Stereotactic Radiosurgery (GSR) devices Overview of modern Quality Assurance techniques for GSR AAPM TG-218 Tolerance Levels and Methodologies for IMRT Verification QA - Moyed Miften Patient-specific IMRT QA measurement is a process designed to identify discrepancies between calculated and delivered doses. Error tolerance limits are not well-defined or consistently applied across centers. The AAPM TG-218 report has been prepared to improve the understanding and consistency of this process by providing recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Learning Objectives: Review measurement methods and methodologies for absolute dose verification Provide recommendations on delivery methods, data interpretation, the use of analysis routines and choice of tolerance limits for IMRT QA Sonja Dieterich has a research agreement with Sun Nuclear Inc. Steven Goetsch is a part-time consultant for Elekta.« less

TH-A-BRC-03: AAPM TG218: Measurement Methods and Tolerance Levels for Patient-Specific IMRT Verification QA

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

Miften, M.

2016-06-15

AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance -more » Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics Survey of possible calibration protocols for calibration of Gamma Stereotactic Radiosurgery (GSR) devices Overview of modern Quality Assurance techniques for GSR AAPM TG-218 Tolerance Levels and Methodologies for IMRT Verification QA - Moyed Miften Patient-specific IMRT QA measurement is a process designed to identify discrepancies between calculated and delivered doses. Error tolerance limits are not well-defined or consistently applied across centers. The AAPM TG-218 report has been prepared to improve the understanding and consistency of this process by providing recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Learning Objectives: Review measurement methods and methodologies for absolute dose verification Provide recommendations on delivery methods, data interpretation, the use of analysis routines and choice of tolerance limits for IMRT QA Sonja Dieterich has a research agreement with Sun Nuclear Inc. Steven Goetsch is a part-time consultant for Elekta.« less

TH-A-BRC-02: AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance

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

Goetsch, S.

AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance -more » Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics Survey of possible calibration protocols for calibration of Gamma Stereotactic Radiosurgery (GSR) devices Overview of modern Quality Assurance techniques for GSR AAPM TG-218 Tolerance Levels and Methodologies for IMRT Verification QA - Moyed Miften Patient-specific IMRT QA measurement is a process designed to identify discrepancies between calculated and delivered doses. Error tolerance limits are not well-defined or consistently applied across centers. The AAPM TG-218 report has been prepared to improve the understanding and consistency of this process by providing recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Learning Objectives: Review measurement methods and methodologies for absolute dose verification Provide recommendations on delivery methods, data interpretation, the use of analysis routines and choice of tolerance limits for IMRT QA Sonja Dieterich has a research agreement with Sun Nuclear Inc. Steven Goetsch is a part-time consultant for Elekta.« less

TH-A-BRC-01: AAPM TG-135U1 QA for Robotic Radiosurgery

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

Dieterich, S.

AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance -more » Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics Survey of possible calibration protocols for calibration of Gamma Stereotactic Radiosurgery (GSR) devices Overview of modern Quality Assurance techniques for GSR AAPM TG-218 Tolerance Levels and Methodologies for IMRT Verification QA - Moyed Miften Patient-specific IMRT QA measurement is a process designed to identify discrepancies between calculated and delivered doses. Error tolerance limits are not well-defined or consistently applied across centers. The AAPM TG-218 report has been prepared to improve the understanding and consistency of this process by providing recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Learning Objectives: Review measurement methods and methodologies for absolute dose verification Provide recommendations on delivery methods, data interpretation, the use of analysis routines and choice of tolerance limits for IMRT QA Sonja Dieterich has a research agreement with Sun Nuclear Inc. Steven Goetsch is a part-time consultant for Elekta.« less

Radiological risk from consuming fish and wildlife to Native Americans on the Hanford Site (USA).

PubMed

Delistraty, Damon; Van Verst, Scott; Rochette, Elizabeth A

2010-02-01

Historical operations at the Hanford Site (Washington State, USA) have released a wide array of non-radionuclide and radionuclide contaminants into the environment. As a result of stakeholder concerns, Native American exposure scenarios have been integrated into Hanford risk assessments. Because its contribution to radiological risk to Native Americans is culturally and geographically specific but quantitatively uncertain, a fish and wildlife ingestion pathway was examined in this study. Adult consumption rates were derived from 20 Native American scenarios (based on 12 studies) at Hanford, and tissue concentrations of key radionuclides in fish, game birds, and game mammals were compiled from the Hanford Environmental Information System (HEIS) database for a recent time interval (1995-2007) during the post-operational period. It was assumed that skeletal muscle comprised 90% of intake, while other tissues accounted for the remainder. Acknowledging data gaps, median concentrations of eight radionuclides (i.e., Co-60, Cs-137, Sr-90, Tc-99, U-234, U-238, Pu-238, and Pu-239/240) in skeletal muscle and other tissues were below 0.01 and 1 pCi/g wet wt, respectively. These radionuclide concentrations were not significantly different (Bonferroni P>0.05) on and off the Hanford Site. Despite no observed difference between onsite and offsite tissue concentrations, radiation dose and risk were calculated for the fish and wildlife ingestion pathway using onsite data. With median consumption rates and radionuclide tissue concentrations, skeletal muscle provided 42% of the dose, while other tissues (primarily bone and carcass) accounted for 58%. In terms of biota, fish ingestion was the largest contributor to dose (64%). Among radionuclides, Sr-90 was dominant, accounting for 47% of the dose. At median intake and radionuclide levels, estimated annual dose (0.36 mrem/yr) was below a dose limit of 15 mrem/yr recommended by the United States Environmental Protection Agency (USEPA), as well as below a dose limit of 100 mrem/yr proposed by the International Commission on Radiation Protection (ICRP). Similarly, lifetime cancer risk (1.7E-5), calculated with median inputs, was below risk levels corresponding to these dose limits. However, our dose and risk estimates apply to only one pathway within a multidimensional exposure scenario for Native Americans. On the other hand, radiation dose and risk corresponding to onsite tissue concentrations were not significantly different from those corresponding to offsite (background) concentrations. Recognizing uncertainties in exposure and toxicity assessments, our results may facilitate informed decision making and optimize resource allocation within a risk assessment framework at the Hanford Site. (c) 2009 Elsevier Inc. All rights reserved.

Radiological risk from consuming fish and wildlife to Native Americans on the Hanford Site (USA)

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

Delistraty, Damon, E-mail: DDEL461@ecy.wa.gov; Verst, Scott Van; Rochette, Elizabeth A.

Historical operations at the Hanford Site (Washington State, USA) have released a wide array of non-radionuclide and radionuclide contaminants into the environment. As a result of stakeholder concerns, Native American exposure scenarios have been integrated into Hanford risk assessments. Because its contribution to radiological risk to Native Americans is culturally and geographically specific but quantitatively uncertain, a fish and wildlife ingestion pathway was examined in this study. Adult consumption rates were derived from 20 Native American scenarios (based on 12 studies) at Hanford, and tissue concentrations of key radionuclides in fish, game birds, and game mammals were compiled from themore » Hanford Environmental Information System (HEIS) database for a recent time interval (1995-2007) during the post-operational period. It was assumed that skeletal muscle comprised 90% of intake, while other tissues accounted for the remainder. Acknowledging data gaps, median concentrations of eight radionuclides (i.e., Co-60, Cs-137, Sr-90, Tc-99, U-234, U-238, Pu-238, and Pu-239/240) in skeletal muscle and other tissues were below 0.01 and 1 pCi/g wet wt, respectively. These radionuclide concentrations were not significantly different (Bonferroni P>0.05) on and off the Hanford Site. Despite no observed difference between onsite and offsite tissue concentrations, radiation dose and risk were calculated for the fish and wildlife ingestion pathway using onsite data. With median consumption rates and radionuclide tissue concentrations, skeletal muscle provided 42% of the dose, while other tissues (primarily bone and carcass) accounted for 58%. In terms of biota, fish ingestion was the largest contributor to dose (64%). Among radionuclides, Sr-90 was dominant, accounting for 47% of the dose. At median intake and radionuclide levels, estimated annual dose (0.36 mrem/yr) was below a dose limit of 15 mrem/yr recommended by the United States Environmental Protection Agency (USEPA), as well as below a dose limit of 100 mrem/yr proposed by the International Commission on Radiation Protection (ICRP). Similarly, lifetime cancer risk (1.7E-5), calculated with median inputs, was below risk levels corresponding to these dose limits. However, our dose and risk estimates apply to only one pathway within a multidimensional exposure scenario for Native Americans. On the other hand, radiation dose and risk corresponding to onsite tissue concentrations were not significantly different from those corresponding to offsite (background) concentrations. Recognizing uncertainties in exposure and toxicity assessments, our results may facilitate informed decision making and optimize resource allocation within a risk assessment framework at the Hanford Site.« less

Use of iodine for water disinfection: iodine toxicity and maximum recommended dose.

PubMed Central

Backer, H; Hollowell, J

2000-01-01

Iodine is an effective, simple, and cost-efficient means of water disinfection for people who vacation, travel, or work in areas where municipal water treatment is not reliable. However, there is considerable controversy about the maximum safe iodine dose and duration of use when iodine is ingested in excess of the recommended daily dietary amount. The major health effect of concern with excess iodine ingestion is thyroid disorders, primarily hypothyroidism with or without iodine-induced goiter. A review of the human trials on the safety of iodine ingestion indicates that neither the maximum recommended dietary dose (2 mg/day) nor the maximum recommended duration of use (3 weeks) has a firm basis. Rather than a clear threshold response level or a linear and temporal dose-response relationship between iodine intake and thyroid function, there appears to be marked individual sensitivity, often resulting from unmasking of underlying thyroid disease. The use of iodine for water disinfection requires a risk-benefit decision based on iodine's benefit as a disinfectant and the changes it induces in thyroid physiology. By using appropriate disinfection techniques and monitoring thyroid function, most people can use iodine for water treatment over a prolonged period of time. PMID:10964787

Patient doses from chest radiography in Victoria.

PubMed

Cardillo, I; Boal, T J; Einsiedel, P F

1997-06-01

This survey examines doses from PA chest radiography at radiology practices, private hospitals and public hospitals throughout metropolitan and country Victoria. Data were collected from 111 individual X-ray units at 86 different practices. Entrance skin doses in air were measured for exposure factors used by the centre for a 23 cm thick male chest. A CDRH LucA1 chest phantom was used when making these measurements. About half of the centres used grid technique and half used non-grid technique. There was a factor of greater than 10 difference in the entrance dose delivered between the highest dose centre and the lowest dose centre for non-grid centres; and a factor of about 5 for centres using grids. Factors contributing to the high doses recorded at some centres were identified. Guidance levels for chest radiography based on the third quartile value of the entrance doses from this survey have been recommended and compared with guidance levels recommended in other countries.

Improvement of the clinical use of computed radiography for mobile chest imaging: Image quality and patient dose

NASA Astrophysics Data System (ADS)

Rill, Lynn Neitzey

Chest radiography is technically difficult because of the wide variation of tissue attenuations in the chest and limitations of screen-film systems. Mobile chest radiography, performed bedside on hospital inpatients, presents additional difficulties due to geometrical and equipment limitations inherent to mobile x-ray procedures and the severity of illness in patients. Computed radiography (CR) offers a new approach for mobile chest radiography by utilizing a photostimulable phosphor. Photostimulable phosphors are more efficient in absorbing lower-energy x-rays than standard intensifying screens and overcome some image quality limitations of mobile chest imaging, particularly because of the inherent latitude. This study evaluated changes in imaging parameters for CR to take advantage of differences between CR and screen-film radiography. Two chest phantoms, made of acrylic and aluminum, simulated x-ray attenuation for average-sized and large- sized adult chests. The phantoms contained regions representing the lungs, heart and subdiaphragm. Acrylic and aluminum disks (1.9 cm diameter) were positioned in the chest regions to make signal-to-noise ratio (SNR) measurements for different combinations of imaging parameters. Disk thicknesses (contrast) were determined from disk visibility. Effective dose to the phantom was also measured for technique combinations. The results indicated that using an anti-scatter grid and lowering x- ray tube potential improved the SNR significantly; however, the dose to the phantom also increased. An evaluation was performed to examine the clinical applicability of the observed improvements in SNR. Parameter adjustments that improved phantom SNRs by more than 50% resulted in perceived image quality improvements in the lung region of clinical mobile chest radiographs. Parameters that produced smaller improvements in SNR had no apparent effect on clinical image quality. Based on this study, it is recommended that a 3:1 grid be used for mobile chest radiography with CR in order to improve image quality. Using a higher kVp (+15 kVp) did not have a detrimental effect on image quality and offered a patient dose savings, including effective dose and breast dose. Higher kVp techniques should be considered when using a grid is not possible.

Measurement of the natural radioactivity in building materials used in Ankara and assessment of external doses.

PubMed

Turhan, S; Baykan, U N; Sen, K

2008-03-01

A total of 183 samples of 20 different commonly used structural and covering building materials were collected from housing and other building construction sites and from suppliers in Ankara to measure the natural radioactivity due to the presence of (226)Ra, (232)Th and (40)K. The measurements were carried out using gamma-ray spectrometry with two HPGe detectors. The specific activities of the different building materials studied varied from 0.5 +/- 0.1 to 144.9 +/- 4.9 Bq kg(-1), 0.6 +/- 0.2 to 169.9 +/- 6.6 Bq kg(-1) and 2.0 +/- 0.1 to 1792.3 +/- 60.8 Bq kg(-1) for (226)Ra, (232)Th and (40)K, respectively. The results show that the lowest mean values of the specific activity of (226)Ra, (232)Th and (40)K are 0.8 +/- 0.5, 0.9 +/- 0.4 and 4.1 +/- 1.4 Bq kg(-1), respectively, measured in travertine tile while the highest mean values of the specific activity of the same radionuclides are 78.5 +/- 18.1 (ceramic wall tile), 77.4 +/- 53.0 (granite tile) and 923.4 +/- 161.0 (white brick), respectively. The radium equivalent activity (Ra(eq)), the gamma-index, the indoor absorbed dose rate and the corresponding annual effective dose were evaluated to assess the potential radiological hazard associated with these building materials. The mean values of the gamma-index and the estimated annual effective dose due to external gamma radiation inside the room for structural building materials ranged from 0.15 to 0.89 and 0.2 to 1.1 mSv, respectively. Applying criteria recently recommended for building materials in the literature, four materials meet the exemption annual dose criterion of 0.3 mSv, five materials meet the annual dose limit of 1 mSv and only one material slightly exceeds this limit. The mean values of the gamma-index for all building materials were lower than the upper limit of 1.

Use of anticonvulsants as prophylaxis for seizures in patients on clozapine.

PubMed

Caetano, Dorgival

2014-02-01

The aim of this study is to conduct a critical review of the literature regarding the use of anticonvulsants in the prophylaxis of clozapine-induced seizures, to examine the relationship of the latter with clozapine daily dose, serum concentration and other factors than dosage that effect clozapine blood concentration, and to make recommendations for the management of clozapine-induced seizures. A systematic review of English-language MEDLINE articles was undertaken. Clozapine-induced seizures may occur at any dose; the risk increases with dose and goes up to 4% at ≥ 600 mg/day. Some authors have advocated that patients on that dose regimen have anticonvulsant added as a primary prophylactic measure. The author discusses the pitfalls of this recommendation and highlights that seizures are better predicted from serum concentration (1300 ng/ml) rather than dose alone, and that serum concentration is strongly influenced by sex, age, smoking habit, drug-drug interactions and variations in the 1A2, 2D6 and 3A4 genotypes. Anticonvulsants are not recommended as a primary prophylaxis for clozapine-induced seizures. When deemed necessary as secondary prophylaxis, the clinician's choice should consider drug-drug interactions that may increase/decrease clozapine serum concentration and lead to more side effects, including neutropenia/agranulocytosis and seizures, or compromise therapeutic response. Recommendations for primary and secondary prophylaxis of clozapine related-seizures are provided.

Imidacloprid application changes microbial dynamics and enzymes in rice soil.

PubMed

Mahapatra, Bibhab; Adak, Totan; Patil, Naveen K B; Pandi G, Guru P; Gowda, G Basana; Jambhulkar, N N; Yadav, Manoj Kumar; Panneerselvam, P; Kumar, Upendra; Munda, Sushmita; Jena, Mayabini

2017-10-01

Extensive use of imidacloprid in rice ecosystem may alter dynamics of microorganisms and can change soil biochemical properties. The objective of this study was to assess the effect of imidacloprid on growth and activities of microbes in tropical rice soil ecosystem. Four treatments, namely, recommended dose (at 25g a.i. ha -1 , RD), double the recommended dose (at 50g a.i. ha -1 , 2RD), five times the recommended dose (at 125g a.i. ha -1 , 5RD) & ten times the recommended dose (at 250g a.i. ha -1 , 10RD) along with control were imposed under controlled condition. Dissipation half lives of imidacloprid in soil were 19.25, 20.38, 21.65 and 33.00 days for RD, 2RD, 5RD and 10RD, respectively. In general bacteria, actinomycetes, fungi and phosphate solubilising bacteria population were disturbed due to imidacloprid application. Changes in diversity indices within bacterial community confirmed that imidacloprid application significantly affected distribution of bacteria. Total soil microbial biomass carbon content was reduced on imidacloprid application. Except dehydrogenase and alkaline phosphatase activities, all other soil enzymes namely, β-glycosidase, fluorescien diacetate hydrolase, acid phosphatase and urease responded negatively to imidacloprid application. The extent of negative effect of imidacloprid depends on dose and exposure time. This study concludes imidacloprid application had transient negative effects on soil microbes. Copyright © 2017 Elsevier Inc. All rights reserved.

Feasibility study of veterinary antibiotic consumption in Germany--comparison of ADDs and UDDs by animal production type, antimicrobial class and indication.

PubMed

Merle, Roswitha; Robanus, Matthias; Hegger-Gravenhorst, Christine; Mollenhauer, Yvonne; Hajek, Peter; Käsbohrer, Annemarie; Honscha, Walther; Kreienbrock, Lothar

2014-01-08

Within a feasibility study the use of antibiotics in pigs and cattle was determined in 24 veterinary practices in Lower Saxony and on 66 farms in North Rhine-Westphalia in Germany. Focus was laid on the comparison of the Used Daily Doses (UDD) (dose per animal and day prescribed by the veterinarians) with the Defined Animal Daily Doses (ADD) (dose per animal and day calculated by means of recommended dosages and estimated live weights). For piglets and calves most of the UDD (50% and 46% of nUDD, respectively) were above the ADD (i.e. UDD/ADD-ratio above 1.25). Regarding sows, fattening pigs, dairy and beef cattle, most of the UDDs (49% to 65% of nUDD) were lower than the respective ADD (i.e. UDD/ADD-ratio below 0.8). In pigs, the UDDs of beta-lactams, fluoroquinolones and cephalosporins, and in cattle, those of macrolides and beta-lactams were often below the ADDs. Tetracyclines were frequently used above the recommended dose.Enteric diseases were more often treated below the recommended dose than respiratory diseases, possibly due to overestimation of the live weight (diarrhea in young animals, respiratory diseases in elder animals) and consequently overestimation of the recommended dose. Comparisons between UDD and ADD can be used to observe differences between antimicrobials and trends in the usage of antibiotics. But individual treatment comparisons of UDD and ADD must be interpreted carefully, because they may be due to lower live weights than estimated. Correlating such data with data on the occurrence of resistant bacteria in future may help to improve resistance prevention and control.

Feasibility study of veterinary antibiotic consumption in Germany - comparison of ADDs and UDDs by animal production type, antimicrobial class and indication

PubMed Central

2014-01-01

Background Within a feasibility study the use of antibiotics in pigs and cattle was determined in 24 veterinary practices in Lower Saxony and on 66 farms in North Rhine-Westphalia in Germany. Focus was laid on the comparison of the Used Daily Doses (UDD) (dose per animal and day prescribed by the veterinarians) with the Defined Animal Daily Doses (ADD) (dose per animal and day calculated by means of recommended dosages and estimated live weights). Results For piglets and calves most of the UDD (50% and 46% of nUDD, respectively) were above the ADD (i.e. UDD/ADD-ratio above 1.25). Regarding sows, fattening pigs, dairy and beef cattle, most of the UDDs (49% to 65% of nUDD) were lower than the respective ADD (i.e. UDD/ADD-ratio below 0.8). In pigs, the UDDs of beta-lactams, fluoroquinolones and cephalosporins, and in cattle, those of macrolides and beta-lactams were often below the ADDs. Tetracyclines were frequently used above the recommended dose. Enteric diseases were more often treated below the recommended dose than respiratory diseases, possibly due to overestimation of the live weight (diarrhea in young animals, respiratory diseases in elder animals) and consequently overestimation of the recommended dose. Conclusion Comparisons between UDD and ADD can be used to observe differences between antimicrobials and trends in the usage of antibiotics. But individual treatment comparisons of UDD and ADD must be interpreted carefully, because they may be due to lower live weights than estimated. Correlating such data with data on the occurrence of resistant bacteria in future may help to improve resistance prevention and control. PMID:24401194

Development, validation and application of a sensitive analytical method for residue determination and dissipation of imidacloprid in sugarcane under tropical field condition.

PubMed

Ramasubramanian, T; Paramasivam, M; Nirmala, R

2016-06-01

A simple and sensitive analytical method has been developed and validated for the determination of trace amounts of imidacloprid in/on sugarcane sett, stalk and leaf. The method optimized in the present study requires less volume of organic solvent and time. Hence, this method is suitable for high-throughput analyses involving large number of samples. The limit of detection (LOD) and limit of quantification (LOQ) of the method were 0.003 and 0.01 mg/kg, respectively. The recovery and relative standard deviation were more than 93 % and less than 4 %, respectively. Thus, it is obvious that the analytical method standardized in this study is more precise and accurate enough to determine the residues of imidacloprid in sugarcane sett, stalk and leaf. The dissipation and translocation of imidacloprid residues from treated cane setts to leaf and stalk were studied by adopting this method. In sugarcane setts, the residues of imidacloprid persisted up to 120 days with half-life of 15.4 days at its recommended dose (70 g a.i./ha). The residues of imidacloprid were found to be translocated from setts to stalk and leaf. The imidacloprid residues were detected up to 105 days in both leaf and stalk. Dipping of sugarcane setts in imidacloprid at its recommended dose may result in better protection of cane setts and established crop because of higher initial deposit (>100 mg/kg) and longer persistence (>120 days).

The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis.

PubMed Central

Blomberg, B.; Spinaci, S.; Fourie, B.; Laing, R.

2001-01-01

There is considerable exigency to take all necessary steps to cure tuberculosis cases and prevent further emergence of drug-resistant tuberculosis. The most important of these steps is to ensure that the treatment, particularly of sputum smear-positive cases, is adequate and that patients adhere to their treatment by supervised, direct observation of drug-taking according to the standardized regimens. Use of fixed-dose combinations (FDCs) of tablets against tuberculosis is now being recommended by WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) as an additional step to ensuring proper treatment. FDCs simplify the prescription of drugs and the management of drug supply, and may also limit the risk of drug-resistant tuberculosis arising as a result of inappropriate drug selection and monotherapy. Only FDCs of proven quality and proven rifampicin bioavailability should be purchased and used. In most situations, blood levels of the drugs are inadequate because of poor drug quality rather than poor absorption. This is true irrespective of the human immunodeficiency virus (HIV) infection status of the tuberculosis patients (other than those with overt acquired immunodeficiency syndrome, with CD4 counts < 200 cells/mm3). Currently, WHO, IUATLD and their partners are developing strategies for ensuring that only quality FDCs are used in tuberculosis programmes. A simplified and effective protocol for assessment of rifampicin bioavailability has been developed, and laboratories are being recruited to form a supranational network for quality assurance of FDCs. Standardization of FDC drug formulations has been proposed, which limits rifampicin-containing preparations to nine (including a four-drug FDC and three paediatric FDCs). PMID:11217670

Recommendations for the referral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada?

PubMed Central

Patel, S.; Kostaras, X.; Parliament, M.; Olivotto, I.A.; Nordal, R.; Aronyk, K.; Hagen, N.

2014-01-01

Background Compared with photon therapy, proton-beam therapy (pbt) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access pbt, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from pbt and suggests an out-of-country referral process. Methods The medline, embase, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after pbt. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. Results Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (rt). In uncontrolled and retrospective studies, local control rates with pbt appear similar to, or in some cases higher than, photon rt. Randomized trials comparing equivalent doses of pbt and photon rt are not available. Summary Referral for pbt is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases. PMID:25302033

Developmental Pharmacokinetic Changes of Lamivudine in Infants and Children

PubMed Central

Tremoulet, Adriana H.; Nikanjam, Mina; Cressey, Tim R.; Chokephaibulkit, Kulkanya; McKinney, Ross; Mirochnick, Mark; Capparelli, Edmund V.

2012-01-01

Lamivudine is a nucleoside reverse transcriptase inhibitor widely used in infants and children in combination antiretroviral therapy to treat human immunodeficiency virus (HIV) infection. Developmental changes in lamivudine pharmacokinetic disposition were assessed by combining data from 7 studies of lamivudine (Pediatric AIDS Clinical Trials Group 300, 353, 356, 358, 386, 1056, and 1069) representing subjects across the pediatric age continuum. A population pharmacokinetic model was developed to identify factors that influence lamivudine disposition. Age and Thai race were independent predictors of apparent clearance (CL/F), whereas the use of a fixed drug combination formulation (GPO-VIR) was an independent predictor of bioavailability, with CL/F more than doubling from birth to adolescence. Serum creatinine was not associated with CL/F. Monte Carlo simulations were used to compare the lamivudine exposure achieved with World Health Organization (WHO) weight band and Food and Drug Administration (FDA) label dosing recommendations. WHO dosing yielded higher exposure during the first few months of life, but this difference was less pronounced between 6 months and 14 years of age. Overall, both FDA and WHO dosing provided similar AUC values to those previously reported in HIV-infected adults. Lamivudine WHO weight band dosing results in therapeutic exposure in infants and children and may improve drug dosing in resource-limited countries. PMID:22180560

Community-acquired pneumonia requiring hospitalization: rational decision making and interpretation of guidelines.

PubMed

Postma, Douwe F; van Werkhoven, Cornelis H; Oosterheert, Jan Jelrik

2017-05-01

This review focuses on the evidence base for guideline recommendations on the diagnosis, the optimal choice, timing and duration of empirical antibiotic therapy, and the use of microbiological tests for patients hospitalized with community-acquired pneumonia (CAP): issues for which guidelines are frequently used as a quick reference. Furthermore, we will discuss possibilities for future research in these topics. Many national and international guideline recommendations, even on critical elements of CAP management, are based on low-to-moderate quality evidence. The diagnosis and management of CAP has hardly changed for decades. The recommendation to cover atypical pathogens in all hospitalized CAP patients is based on observational studies only and is challenged by two recent trials. The following years, improved diagnostic testing, radiologically by low-dose Computed Tomography or ultrasound and/or microbiologically by point-of-care multiplex PCR, has the potential to largely influence the choice and start of antibiotic therapy in hospitalized CAP patients. Rapid microbiological testing will hopefully improve antibiotic de-escalation or early pathogen-directed therapy, both potent ways of reducing broad-spectrum antibiotic use. Current guideline recommendations on the timing and duration of antibiotic therapy are based on limited evidence, but will be hard to improve.

Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

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

Herchenhorn, Daniel, E-mail: herchenhorn@hotmail.co; Dias, Fernando L.; Viegas, Celia M.P.

Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuingmore » during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.« less

Risk assessment and monitoring of dinotefuran and its metabolites for Chinese consumption of apples.

PubMed

Yu, Weiwei; Huang, Min; Chen, Jiaojiao; Wu, Sizhuo; Zheng, Kunming; Zeng, Song; Zhang, Kankan; Hu, Deyu

2017-09-26

Residues of dinotefuran and its metabolites, 1-methyl-3-(tetrahydro-3-furylmethyl)urea (UF) and 1-methyl-3-(tetrahydro-3-furylmethyl)guanidine (DN), in apple were investigated using a "QuEChERS" (quick, easy, cheap, effective, rugged, safe) pretreatment and liquid chromatography-tandem mass spectrometry. Limits of detection (LODs) and quantification (LOQs) of dinotefuran, UF, and DN in apples were 0.011-0.960 and 0.037-3.200 μg/kg, respectively. The average recoveries of dinotefuran, UF, and DN in apple ranged from 70.0 to 83.6% with relative standard deviations less than 13%. A formulation of 20% water-dispersible dinotefuran granules was sprayed at 1-1.5-fold the recommended dose 3-4 times on apple trees. Total terminal residues of dinotefuran in apple were less than 2 mg/kg, which is the maximum residue limit (MRL) set by Japan. When following the recommended application guidelines, dinotefuran is unlikely to present significant health concerns to the Chinese population because the risk quotient (RQ) is less than 100%. This work could provide guidance for the safe use of dinotefuran and serve as a reference for the establishment of a maximum residue limit of dinotefuran in apple in China.

A dose-ranging study of the pharmacokinetics and pharmacodynamics of the selective apoptotic antineoplastic drug (SAAND), OSI-461, in patients with advanced cancer, in the fasted and fed state

PubMed Central

O’Bryant, C. L.; Lieu, C. H.; Leong, S.; Boinpally, R.; Basche, M.; Gore, L.; Leonardi, K.; Schultz, M. K.; Hariharan, S.; Chow, L.; Diab, S.; Gibbs, A.; Eckhardt, S. G.

2010-01-01

Purpose To evaluate the safety, pharmacokinetics and determine the recommended dose of the selective apoptotic antineoplastic drug, OSI-461 administered on a twice-daily regimen to patients with advanced solid malignancies. Methods In this phase I trial, 33 patients were treated with OSI-461 doses ranging from 400 to 1,200 mg given twice daily in 4-week cycles. Pharmacokinetic studies were performed to characterize the plasma disposition of OSI-461 and the effect of food intake on OSI-461 absorption. Secondary biomarker studies were performed to assess the biologic activity of OSI-461 including the measurement of pGSK-3β, a PKG substrate, and pharmacogenetic studies to identify polymorphisms of CYP3A that influence drug metabolism and of ABCG2, involved in drug resistance. Results Thirty-three patients were treated with 86 courses of OSI-461. The dose-limiting toxicities were grade 3 abdominal pain, found in one patient at the 1,000 mg BID fed dose level and all patients at the 1,200 mg BID fed dose level. There was also one episode each of grade 3 fatigue and grade 3 constipation at the 1,000 and 1,200 mg BID fed dose levels, respectively. Other common toxicities included mild to moderate fatigue, nausea, anorexia and mild elevation in bilirubin. Pharmacokinetic studies of OSI-461 revealed approximately a twofold increase in AUC0–24 when OSI-461 was administered with food. An increase in pGSK-3β post-dose was seen in the majority of patients and was greater at higher dose levels. No patients exhibited CYP3A4 polymorphisms, while 100% of patients were found to have the CYP3A5*3/CYP3A5*3 polymorphism. Two known polymorphisms of the ABCG2 gene, G34 → A34 and C421 → A421, occurred at frequencies of 11.76 and 29%, respectively. Conclusions Toxicity and pharmacodynamic data show that the recommended oral dose of OSI-461 is 800 mg twice daily administered with food. The drug appears to be well-tolerated, and overall bioavailability appears to be markedly increased when the drug is administered with food. These results support further disease-directed evaluations of OSI-461 at a dose of 800 mg BID in combination with other chemotherapeutic agents. PMID:18509645

YouTube Video Educational Package Increased Acceptance of Antibiotic Clinical Decision Support System Recommendations

PubMed Central

Heng, Shi Thong; Tan, Michelle; Young, Barnaby; Lye, David; Ng, Tat Ming

2017-01-01

Abstract Background Antibiotic clinical decision support systems (CDSS) were implemented to provide stewardship at the point of ordering of broad-spectrum antibiotics (piperacillin-tazobactam and carbapenems). We postulated that a YouTube based educational video package (EP) with quizzes can help to improve CDSS acceptance. Methods A before-after study was conducted in general wards at Tan Tock Seng Hospital from April 2016 to March 2017. Baseline data were collected for 6 months before EP was implemented and during the next 6 months with EP dissemination to all doctors. Acceptance of CDSS recommendations between both phases were compared. Independent factors associated with acceptance of specific CDSS recommendations were identified by logistic regression. Results Patients recruited before and after EP was 1642 and 1313 respectively. Overall CDSS acceptance rate was similar before and after EP. There was improved acceptance for recommendations for dose optimizaton, antibiotic optimization and set duration (Figures 1 and 2). Independent factors of CDSS acceptance for dose optimizaton, antibiotic optimization and set duration are shown in Table 1. EP implementation was independently associated with acceptance of recommendations to set duration and optimize antibiotics. Conclusion EP was independently associated with increased CDSS acceptance on antibiotic duration and antibiotic optimization. Although acceptance of dose optimization was improved, EP was not associated independently with acceptance of the recommendations. Figure 2 Acceptance of CDSS recommendations by classifications of recommendations Table 1 3 multivariate models of acceptance of CDSS recommendations on antibiotic optimization, dose optimization and duration setting Set duration Antibiotic optimization Dose optimization Factor Odds ratio [95% CI] Lung infection 2.71[2.13–3.45] 2.08[1.71–2.52] 2.79[2.19-3.55] Unknown sepsis source 1.73[1.27–2.35] – 1.44[1.05-1.96] Piperacillin-tazobactam use 3.02[2.17–4.19] – – Temperature during initiation of antibiotics 0.86[0.79–0.94] – – The presence of oxygen supplementation during initiation of antibiotics – 0.76[0.64–0.91] 0.76[0.64–0.91] EP implementation 1.38[1.18–1.62] 1.21[1.02–1.43] - Disclosures All authors: No reported disclosures.

Andecaliximab/GS-5745 alone and combined with mFOLFOX6 in advanced gastric and gastroesophageal junction adenocarcinoma: Results from a phase 1 study.

PubMed

Shah, Manish A; Starodub, Alexander N; Sharma, Sunil; Berlin, Jordan; Patel, Manish R; Wainberg, Zev A; Chaves, Jorge; Gordon, Michael S; Windsor, Kevin; Brachmann, Carrie Baker; Huang, Xi; Vosganian, Greg; Maltzman, Julia D; Smith, Victoria; Silverman, Jeffrey A; Lenz, Heinz-Josef; Bendell, Johanna C

2018-04-24

Matrix metalloproteinase-9 (MMP9) is implicated in pro-tumorigenic processes. Andecaliximab (GS-5745, a monoclonal antibody targeting MMP9) was evaluated as monotherapy and in combination with mFOLFOX6. Three dosages of andecaliximab monotherapy (200, 600, and 1800 mg IV every 2 weeks [q2w]) were investigated in patients with advanced solid tumors (n=13 in a 3+3 design). After determining a recommended dose, patients with advanced HER2-negative gastric/gastroesophageal junction (GEJ) adenocarcinoma (n=40) received 800 mg andecaliximab + mFOLFOX6 q2w. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed. Andecaliximab monotherapy demonstrated no dose-limiting toxicity (DLT) in any cohort, displaying target-mediated drug disposition at the lowest dose (200 mg) and linear pharmacokinetics at higher doses. Based on target engagement, recommended doses for further study are 800 mg q2w or 1200 mg q3w. Maximal andecaliximab target binding, defined as undetectable andecaliximab-free MMP9 in plasma, was observed in the gastric/GEJ adenocarcinoma cohort. We observed no unusual toxicity, although there were 4 deaths on study not attributed to andecaliximab treatment. In first-line patients (n=36), median progression free survival (PFS) was 9.9 months (95% CI 5-13.9 months) and the overall response rate (ORR) was 50%. Among all patients (n=40), median PFS was 7.8 (90% CI, 5.5-13.9) months and ORR was 48%, with a median duration of response of 8.4 months. Andecaliximab monotherapy achieved target engagement without DLT. Andecaliximab + mFOLFOX6 showed encouraging clinical activity without additional toxicity in patients with HER2-negative gastric/GEJ adenocarcinoma. A phase 3 study evaluating mFOLFOX6 +/- andecaliximab in this setting is ongoing. Copyright ©2018, American Association for Cancer Research.

Phase 1/2 Study of the CD56-Targeting Antibody-Drug Conjugate Lorvotuzumab Mertansine (IMGN901) in Combination With Carboplatin/Etoposide in Small-Cell Lung Cancer Patients With Extensive-Stage Disease.

PubMed

Socinski, Mark A; Kaye, Frederic J; Spigel, David R; Kudrik, Fred J; Ponce, Santiago; Ellis, Peter M; Majem, Margarita; Lorigan, Paul; Gandhi, Leena; Gutierrez, Martin E; Nepert, Dale; Corral, Jesus; Ares, Luis Paz

2017-01-01

This trial assessed the safety and efficacy of LM in combination with carboplatin/etoposide therapy compared to carboplatin/etoposide treatment alone in patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). A run-in phase 1 stage was used to determine the recommended phase 2 dose and characterize the dose-limiting toxicities of LM in combination with carboplatin/etoposide followed by LM alone in patients with CD56-positive solid tumors. In phase 2, chemotherapy-naive ED-SCLC patients were randomized 2:1 to carboplatin AUC (area under the plasma concentration vs. time curve) of 5 day 1 + etoposide 100 mg/m 2 days 1 to 3 plus LM (arm 1) or alone (arm 2). In the phase 1 study (n = 33), a dose of LM at 112 mg/m 2 with carboplatin/etoposide was identified as the recommended phase 2 dose. However, because of an increased incidence of peripheral neuropathy events during early phase 2, this dose was reduced to 90 mg/m 2 . In phase 2, a total of 94 and 47 evaluable patients were assigned to arms 1 and 2, respectively. No difference in median progression-free survival was observed between arms 1 and 2 (6.2 vs. 6.7 months). The most common treatment-emergent adverse event leading to discontinuation was peripheral neuropathy (29%). A total of 21 patients had a treatment-emergent adverse event leading to death (18 in arm 1 and 3 in arm 2); for 10 individuals, this was an infection (pneumonia or sepsis) deemed to be related to the study drug. The combination of LM plus carboplatin/etoposide did not improve efficacy over standard carboplatin/etoposide doublet therapy in ED-SCLC patients and showed increased toxicity, including a higher incidence of serious infections with fatal outcomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

Fritz, Brad G.; Dirkes, Roger L.; Napier, Bruce A.

The Hanford Reach National Monument (HRNM) was created by presidential proclamation in 2000. It is located along the Columbia River in south central Washington and consists of five distinct units. The McGee Ranch-Riverlands and the North Slope units are addressed in this report. North Slope refers to two of the HRNM units: the Saddle Mountain Unit and the Wahluke Slope Unit. The Saddle Mountain and Wahluke Slope Units are located north of the Columbia River, while the McGee Ranch-Riverlands Unit is located south of the Columbia River and north and west of Washington State Highway 24. To fulfill internal U.S.more » Department of Energy (DOE) requirements prior to any radiological clearance of land, the DOE must evaluate the potential for residual radioactive contamination on this land and determine compliance with the requirements of DOE Order 5400.5. Authorized limits for residual radioactive contamination were developed based on the DOE annual exposure limit to the public (100 mrem) using future potential land-use scenarios. The DOE Office of Environmental Management approved these authorized limits on March 1, 2004. Historical soil monitoring conducted on and around the HRNM indicated soil concentrations of radionuclides were well below the authorized limits (Fritz et al. 2003). However, the historical sampling was done at a limited number of sampling locations. Therefore, additional soil sampling was conducted to determine if the concentrations of radionuclides in soil on the McGee Ranch-Riverlands and North Slope units were below the authorized limits. Sixty-seven soil samples were collected from the McGee Ranch-Riverlands and North Slope units. A software package (Visual Sample Plan) was used to plan the collection to assure an adequate number of samples were collected. The number of samples necessary to decide with a high level of confidence (99%) that the soil concentrations of radionuclides on the North Slope and McGee Ranch-Riverlands units did not exceed the authorized limits was determined to be 27. Additional soil samples were collected from areas suspected to have a potential for accumulation of radionuclides. This included samples collected from the riparian zone along the Columbia River, Savage Island, and other locations across the North Slope and McGee Ranch-Riverlands units. The 67 soil samples collected from the McGee Ranch-Riverlands and North Slope units all had concentrations of radionuclides far below the authorized limits established by the DOE. Statistical analysis of the results concluded that the Authorized Limits were not exceeded when total uncertainty was considered. The calculated upper confidence limit for each radionuclide measured in this study (which represents the value at which 99% of the measurements reside below with a 99% confidence level) was lower than the Authorized Limit for each radionuclide. The maximum observed soil concentrations for the radionuclides included in the authorized limits would result in a potential annual dose of 0.23 mrem assuming the most probable use scenario, a recreational visitor. This potential dose is well below the DOE 100-mrem/year dose limit for members of the public. Furthermore, the results of the biota dose assessment screen, which used the RESRAD biota code, indicated that the sum of fractions is less than one. This assumed soil concentrations equal to the maximum concentrations of radionuclides measured on the McGee Ranch-Riverlands and North Slope units’ in this study. Since the sum of fractions was less than 1, dose to terrestrial biota will not exceed the recommended biota dose limit for the soil concentrations measured in this study.« less

Radiation doses for pediatric nuclear medicine studies: comparing the North American consensus guidelines and the pediatric dosage card of the European Association of Nuclear Medicine.

PubMed

Grant, Frederick D; Gelfand, Michael J; Drubach, Laura A; Treves, S Ted; Fahey, Frederic H

2015-04-01

Estimated radiation dose is important for assessing and communicating the risks and benefits of pediatric nuclear medicine studies. Radiation dose depends on the radiopharmaceutical, the administered activity, and patient factors such as age and size. Most radiation dose estimates for pediatric nuclear medicine have not been based on administered activities of radiopharmaceuticals recommended by established practice guidelines. The dosage card of the European Association of Nuclear Medicine (EANM) and the North American consensus guidelines each provide recommendations of administered activities of radiopharmaceuticals in children, but there are substantial differences between these two guidelines. For 12 commonly performed pediatric nuclear medicine studies, two established pediatric radiopharmaceutical administration guidelines were used to calculate updated radiation dose estimates and to compare the radiation exposure resulting from the recommendations of each of the guidelines. Estimated radiation doses were calculated for 12 common procedures in pediatric nuclear medicine using administered activities recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North American consensus guidelines for radiopharmaceutical administered activities in pediatrics. Based on standard models and nominal age-based weights, radiation dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult. The resulting effective doses were compared, with differences greater than 20% considered significant. Following either the EANM dosage card or the 2010 North American guidelines, the highest effective doses occur with radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases, following the North American consensus guidelines would result in a substantially higher radiation dose. The guidelines of the EANM dosage card would lead to a substantially higher radiation dose in 39% of all cases, and in 62% of cases in which patients were age 5 years or younger. For 12 commonly performed pediatric nuclear medicine studies, updated radiation dose estimates can guide efforts to reduce radiation exposure and provide current information for discussing radiation exposure and risk with referring physicians, patients and families. There can be substantial differences in radiation exposure for the same procedure, depending upon which of these two guidelines is followed. This discordance identifies opportunities for harmonization of the guidelines, which may lead to further reduction in nuclear medicine radiation doses in children.

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

Prescriptions for chronic high-dose cyclooxygenase-2 inhibitors are often inappropriate and potentially dangerous.

PubMed

Roumie, Christianne L; Arbogast, Patrick G; Mitchel, Edward F; Griffin, Marie R

2005-10-01

To describe the use of coxibs outside of licensed indications and recommended dosing ranges including rofecoxib 50 mg, valdecoxib 20 to 40 mg, and celecoxib 400 mg. Cross-sectional study of coxib utilization in 2002 and 2003 and retrospective cohort analysis of new users. Patients with known age and sex enrolled in Tennessee's Medicaid program. The prevalence of coxib use by dose and duration, and the proportion of persons initially prescribed a high-dose coxib and indications for such use. The estimated daily prevalence of nonaspirin prescription nonsteroidal anti-inflammatory drugs (NSAIDs) was 8.7% in 2002 to 2003 (45.7% coxibs). NSAID use peaked at age 65 to 74 with a prevalence of 19.8% (56.3% coxibs). Doses above the recommended daily dose for osteoarthritis accounted for 33.2% (95% confidence intervals [CIs] 32.4%, 33.9%) of celecoxib use, 14.9% (95% CI 14.4%, 15.5%) of rofecoxib use, and 52.2% (95% CI 50.6%, 53.8%) of valdecoxib use. Most of these prescriptions were for a month's supply. For new coxib users, 13.5% were given a month's supply for the highest dose category, and 28% refilled their prescriptions within 7 days of the end of the original prescription. Of these new chronic high-dose users, 17.2% had ischemic heart disease and 7.1% had heart failure. A substantial portion of coxib prescriptions were for a month's supply at doses above those recommended for most chronic indications. New users were also prescribed high doses despite evidence for cardiovascular comorbidity. These prescribing patterns at doses outside licensed indications are both inappropriate and potentially dangerous.

Prescriptions for Chronic High-Dose Cyclooxygenase-2 Inhibitors are Often Inappropriate and Potentially Dangerous

PubMed Central

Roumie, Christianne L; Arbogast, Patrick G; Mitchel, Edward F; Griffin, Marie R

2005-01-01

Objective To describe the use of coxibs outside of licensed indications and recommended dosing ranges including rofecoxib 50 mg, valdecoxib 20 to 40 mg, and celecoxib 400 mg. Design Cross-sectional study of coxib utilization in 2002 and 2003 and retrospective cohort analysis of new users. Participants Patients with known age and sex enrolled in Tennessee's Medicaid program. Measurements The prevalence of coxib use by dose and duration, and the proportion of persons initially prescribed a high-dose coxib and indications for such use. Results The estimated daily prevalence of nonaspirin prescription nonsteroidal anti-inflammatory drugs (NSAIDs) was 8.7% in 2002 to 2003 (45.7% coxibs). NSAID use peaked at age 65 to 74 with a prevalence of 19.8% (56.3% coxibs). Doses above the recommended daily dose for osteoarthritis accounted for 33.2% (95% confidence intervals [CIs] 32.4%, 33.9%) of celecoxib use, 14.9% (95% CI 14.4%, 15.5%) of rofecoxib use, and 52.2% (95% CI 50.6%, 53.8%) of valdecoxib use. Most of these prescriptions were for a month's supply. For new coxib users, 13.5% were given a month's supply for the highest dose category, and 28% refilled their prescriptions within 7 days of the end of the original prescription. Of these new chronic high-dose users, 17.2% had ischemic heart disease and 7.1% had heart failure. Conclusions A substantial portion of coxib prescriptions were for a month's supply at doses above those recommended for most chronic indications. New users were also prescribed high doses despite evidence for cardiovascular comorbidity. These prescribing patterns at doses outside licensed indications are both inappropriate and potentially dangerous. PMID:16191131

A phase I and pharmacokinetic study of the quinoxaline antitumour Agent R(+)XK469 in patients with advanced solid tumours

PubMed Central

Undevia, Samir D.; Innocenti, Federico; Ramirez, Jacqueline; House, Larry; Desai, Apurva A.; Skoog, Linda A.; Singh, Deepti A.; Karrison, Theodore; Kindler, Hedy L.; Ratain, Mark J.

2009-01-01

Purpose To investigate the safety and pharmacokinetics of R(+)XK469, a quinoxaline analogue, in patients with advanced refractory solid tumours. Preclinical studies suggested that efficacy was independent of schedule but that toxicity was decreased by dividing the dose. Methods R(+)XK469 was initially administered as a 30 min intravenous infusion on days 1–5 of a 21-d cycle. Based on the demonstration of a long half-life, the dosing schedule was subsequently amended to infusion on days 1, 3 and 5 of a 21-d cycle. An alternate single-dose schedule of once every 21 d was also explored. Blood samples were collected for pharmaco-kinetic studies. Results Dose-limiting toxicity (DLT) was neutropaenia. There was significant interindividual variability in clearance as evidenced by a coefficient of variation of 46%. A flat-dosing scheme (not based on body surface area) was justified by the absence of correlation between clearance and body surface area. A partial response was observed in a patient with nasopharyngeal carcinoma. Conclusions The recommended phase II doses are 850–1100 mg/d on days 1, 3 and 5 of a 21-d cycle and 2500 mg on day 1 of a 21-d cycle. The observed interpatient pharmacokinetic variability should prompt investigation into the presence of genetic polymorphism in relevant metabolizing enzymes. PMID:18650079

A radiological assessment of nuclear power and propulsion operations near Space Station Freedom

NASA Technical Reports Server (NTRS)

Bolch, Wesley E.; Thomas, J. Kelly; Peddicord, K. Lee; Nelson, Paul; Marshall, David T.; Busche, Donna M.

1990-01-01

Scenarios were identified which involve the use of nuclear power systems in the vicinity of Space Station Freedom (SSF) and their radiological impact on the SSF crew was quantified. Several of the developed scenarios relate to the use of SSF as an evolutionary transportation node for lunar and Mars missions. In particular, radiation doses delivered to SSF crew were calculated for both the launch and subsequent return of a Nuclear Electric Propulsion (NEP) cargo vehicle and a Nuclear Thermal Rocket (NTR) personnel vehicle to low earth orbit. The use of nuclear power on co-orbiting platforms and the storage and handling issues associated with radioisotope power systems were also explored as they relate to SSF. A central philosophy in these analyses was the utilization of a radiation dose budget, defined as the difference between recommended dose limits from all radiation sources and estimated doses received by crew members from natural space radiations. Consequently, for each scenario examined, the dose budget concept was used to identify and quantify constraints on operational parameters such as launch separation distances, returned vehicle parking distances, and reactor shutdown times prior to vehicle approach. The results indicate that realistic scenarios do not exist which would preclude the use of nuclear power sources in the vicinity of SSF. The radiation dose to the SSF crew can be maintained at safe levels solely by implementing proper and reasonable operating procedures.

Atmospheric radiation modeling of galactic cosmic rays using LRO/CRaTER and the EMMREM model with comparisons to balloon and airline based measurements

NASA Astrophysics Data System (ADS)

Joyce, C. J.; Schwadron, N. A.; Townsend, L. W.; deWet, W. C.; Wilson, J. K.; Spence, H. E.; Tobiska, W. K.; Shelton-Mur, K.; Yarborough, A.; Harvey, J.; Herbst, A.; Koske-Phillips, A.; Molina, F.; Omondi, S.; Reid, C.; Reid, D.; Shultz, J.; Stephenson, B.; McDevitt, M.; Phillips, T.

2016-09-01

We provide an analysis of the galactic cosmic ray radiation environment of Earth's atmosphere using measurements from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) aboard the Lunar Reconnaissance Orbiter (LRO) together with the Badhwar-O'Neil model and dose lookup tables generated by the Earth-Moon-Mars Radiation Environment Module (EMMREM). This study demonstrates an updated atmospheric radiation model that uses new dose tables to improve the accuracy of the modeled dose rates. Additionally, a method for computing geomagnetic cutoffs is incorporated into the model in order to account for location-dependent effects of the magnetosphere. Newly available measurements of atmospheric dose rates from instruments aboard commercial aircraft and high-altitude balloons enable us to evaluate the accuracy of the model in computing atmospheric dose rates. When compared to the available observations, the model seems to be reasonably accurate in modeling atmospheric radiation levels, overestimating airline dose rates by an average of 20%, which falls within the uncertainty limit recommended by the International Commission on Radiation Units and Measurements (ICRU). Additionally, measurements made aboard high-altitude balloons during simultaneous launches from New Hampshire and California provide an additional comparison to the model. We also find that the newly incorporated geomagnetic cutoff method enables the model to represent radiation variability as a function of location with sufficient accuracy.

Estimation of the indoor radon and the annual effective dose from granite samples

NASA Astrophysics Data System (ADS)

Sola, P.; Srinuttrakul, W.; Kewsuwan, P.

2015-05-01

Inhalation of radon and thoron daughters increases the risk of lung cancer. The main sources of indoor radon are building materials. The aim of this research is to estimate the indoor radon and the annual effective dose from the building materials. Eighteen granite samples bought from the markets in Thailand were measured using an ionization chamber (ATMOS 12 DPX) for the radon concentration in air. Radon exhalation rates were calculated from the radon concentration in chamber. The indoor radon from the granite samples ranged from 10.04 to 55.32 Bq·m-2·h-1 with an average value of 20.30 Bq·m-2·h-1 and the annual effective dose ranged from 0.25 to 1.39 mSv·y-1 with an average value of 0.48 mSv·y-1. The results showed that the annual effective doses of three granite samples were higher than the annual exposure limit for the general public (1 mSv·y-1) recommended by the International Commission on Radiological Protection (ICRP). In addition, the relationship between the colours and radon exhalation rates of granite samples was also explained.

A Pilot Safety Study of Lenalidomide and Radiotherapy for Patients With Newly Diagnosed Glioblastoma Multiforme

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

Drappatz, Jan; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Wong, Eric T.

2009-01-01

Purpose: To define the maximum tolerated dose (MTD) of lenalidomide, an analogue of thalidomide with enhanced immunomodulatory and antiangiogenic properties and a more favorable toxicity profile, in patients with newly diagnosed glioblastoma multiforme (GBM) when given concurrently with radiotherapy. Patients and Methods: Patients with newly diagnosed GBM received radiotherapy concurrently with lenalidomide given for 3 weeks followed by a 1-week rest period and continued lenalidomide until tumor progression or unacceptable toxicity. Dose escalation occurred in groups of 6. Determination of the MTD was based on toxicities during the first 12 weeks of therapy. The primary endpoint was toxicity. Results: Twenty-threemore » patients were enrolled, of whom 20 were treated and evaluable for both toxicity and tumor response and 2 were evaluable for toxicity only. Common toxicities included venous thromboembolic disease, fatigue, and nausea. Dose-limiting toxicities were eosinophilic pneumonitis and transaminase elevations. The MTD for lenalidomide was determined to be 15 mg/m{sup 2}/d. Conclusion: The recommended dose for lenalidomide with radiotherapy is 15 mg/m{sup 2}/d for 3 weeks followed by a 1-week rest period. Venous thromboembolic complications occurred in 4 patients, and prophylactic anticoagulation should be considered.« less

Flight attendant radiation dose from solar particle events.

PubMed

Anderson, Jeri L; Mertens, Christopher J; Grajewski, Barbara; Luo, Lian; Tseng, Chih-Yu; Cassinelli, Rick T

2014-08-01

Research has suggested that work as a flight attendant may be related to increased risk for reproductive health effects. Air cabin exposures that may influence reproductive health include radiation dose from galactic cosmic radiation and solar particle events. This paper describes the assessment of radiation dose accrued during solar particle events as part of a reproductive health study of flight attendants. Solar storm data were obtained from the National Oceanic and Atmospheric Administration Space Weather Prediction Center list of solar proton events affecting the Earth environment to ascertain storms relevant to the two study periods (1992-1996 and 1999-2001). Radiation dose from exposure to solar energetic particles was estimated using the NAIRAS model in conjunction with galactic cosmic radiation dose calculated using the CARI-6P computer program. Seven solar particle events were determined to have potential for significant radiation exposure, two in the first study period and five in the second study period, and over-lapped with 24,807 flight segments. Absorbed (and effective) flight segment doses averaged 6.5 μGy (18 μSv) and 3.1 μGy (8.3 μSv) for the first and second study periods, respectively. Maximum doses were as high as 440 μGy (1.2 mSv) and 20 flight segments had doses greater than 190 μGy (0.5 mSv). During solar particle events, a pregnant flight attendant could potentially exceed the equivalent dose limit to the conceptus of 0.5 mSv in a month recommended by the National Council on Radiation Protection and Measurements.

Duration of protection against hepatitis A for the current two-dose vaccine compared to a three-dose vaccine schedule in children

PubMed Central

Raczniak, Gregory A.; Thomas, Timothy K.; Bulkow, Lisa R.; Negus, Susan E.; Zanis, Carolyn L.; Bruce, Michael G.; Spradling, Philip R.; Teshale, Eyasu H.; McMahon, Brian J.

2015-01-01

Background Hepatitis A is mostly a self-limiting disease but causes substantial economic burden. Consequently, United States Advisory Committee for Immunization Practices recommends inactivated hepatitis A vaccination for all children beginning at age 1 year and for high risk adults. The hepatitis A vaccine is highly effective but the duration of protection is unknown. Methods We examined the proportion of children with protective hepatitis A antibody levels (anti-HAV ≥20 mIU/mL) as well as the geometric mean concentration (GMC) of anti-HAV in a cross sectional convenience sample of individuals aged 12–24 years, who had been vaccinated with a two-dose schedule in childhood, with the initial dose at least 5 years ago. We compared a subset of data from persons vaccinated with two-doses (720 EL.U.) at age 3–6 years with a demographically similar prospective cohort that received a three-dose (360 EL.U.) schedule and have been followed for 17 years. Results No significant differences were observed when comparing GMC between the two cohorts at 10 (P = 0.467), 12 (P = 0.496), and 14 (P = 0.175) years post-immunization. For the three-dose cohort, protective antibody levels remain for 17 years and have leveled-off over the past 7 years. Conclusion The two- and three-dose schedules provide similar protection >14 years after vaccination, indicating a booster dose is not needed at this time. Plateauing anti-HAV GMC levels suggest protective antibody levels may persist long-term. PMID:23470239

A review of the efficacy and safety of oral antidiabetic drugs

PubMed Central

Stein, Stephanie Aleskow; Lamos, Elizabeth Mary; Davis, Stephen N

2014-01-01

Introduction Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes. Areas covered The efficacy and safety of metformin, SUs, TZDs, dipeptidyl peptidase-IV (DPP-4) inhibitors, meglitinide analogs, α-glucosidase inhibitors (AGIs), bile-acid sequestrants (BAS) and bromocriptine will be reviewed. Expert opinion Several new oral agents have been approved for type 2 diabetes management in recent years. It is important to understand the efficacy and safety of these medications in addition to the older agents to best maximize oral drug therapy for diabetes. Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin. They are a recommended alternative when metformin use is limited by gastrointestinal (GI) side effects or when SU treatment results in significant hypoglycemia or weight gain. Meglitinide analogs are limited by their frequent dosing, expense and hypoglycemia (repaglinide > nateglinide), while AGIs are also limited by their dosing schedule and GI side-effect profile. BAS and bromocriptine have the lowest efficacy with regard to HbA1c reduction, also are plagued by GI adverse reactions, but have a low risk of hypoglycemia. PMID:23241069

[LDL cholesterol lowering therapy: no target value but personalised treatment].

PubMed

Simoons, Maarten L; Deckers, Jaap W

2015-01-01

We previously recommended that LDL cholesterol lowering therapy be based on the risk for (recurrent) coronary events, rather than on arbitrary targets for serum LDL cholesterol concentration. We also recommended refraining from therapy with ezetimibe until its efficacy in preventing cardiovascular events had been documented. At the American Heart Association scientific sessions 2014 the results of the IMPROVE-IT study were reported. In this large, randomised trial, a modest benefit of the combination of simvastatin plus ezetimibe over simvastatin alone was reported after 7 years of treatment. The efficacy of such combination therapy was similar to the efficacy of high-dose statin therapy, while the combination therapy is much more expensive. Comparing the efficacy and costs of different preventive therapies, we recommend first prescribing aspirin and a moderate dose of statin, secondly an ACE inhibitor. A high-dose statin should be considered in high-risk patients. The combination of simvastatin and ezetimibe should be prescribed only in high-risk patients (e.g. diabetics after myocardial infarction) who do not tolerate high-dose statins.

[Vaccination schedule of the Spanish Association of Pediatrics: recommendations 2005].

PubMed

2005-02-01

The Advisory Committee on Vaccines of the Spanish Association of Pediatrics provides information and comments on the new developments in vaccines that have taken place in 2004 and recommends a few modifications to the Immunization Schedule for 2005. Concerning the meningococcal C vaccine, no change is made to the possibility of administering two doses for the first vaccination with one of the available formulations. The existence of immunization failure in children who have received a first vaccination with three vaccine doses before the age of 12 months is discussed, and the health authorities will probably include a booster dose in the second year of life throughout 2005. The recommendations of the European Medicines Evaluation Agency (EMEA) on hexavalent vaccines continue to be valid and consequently the use of these vaccines should not be stopped. This year the need for adolescents to receive a booster dose of the pertussis vaccine, with administration of an acellular, low antigenic load preparation together with the adult diphtheria and tetanus vaccine is stressed.

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

PubMed

Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

2012-04-01

Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

Comparison of Levetiracetam Dosing Regimens in End-Stage Renal Disease Patients Undergoing Intermittent Hemodialysis.

PubMed

Shiue, Harn J; Taylor, Maria; Sands, Kara A

2017-10-01

Levetiracetam (LEV) is primarily renally eliminated. In end-stage renal disease (ESRD) patients on hemodialysis (HD), pharmacokinetic studies recommend daily dosing with 50% supplemental doses after 4-hour HD sessions. However, poor medication adherence after HD could result in fluctuating plasma drug levels. To compare two LEV dosing regimens, daily versus twice-daily (BID), in ESRD patients undergoing HD. Consecutive ESRD patients (April 2013 to May 2014) receiving maintenance inpatient HD and prescribed LEV prior to admission to our academic tertiary hospital were prospectively analyzed. Demographics, initial lab values, adverse reactions, seizures, and LEV regimens were recorded. LEV levels were obtained pre-HD and post-HD along with levels after receiving post-HD doses. Recovery of plasma levels after HD was assessed by comparison of levels predialysis versus postdialysis and post-HD doses. We identified 22 patients who met inclusion criteria; 14 BID and 8 daily dosing. Mean predialysis, postdialysis, and post-HD dose plasma levels were higher in patients receiving LEV BID compared with daily (43.1 ± 6.3, 19.4 ± 5.2, 34.9 ± 4.3 vs 21.1 ± 3.9, 6.9 ± 1.5, 11.9 ± 1.7 µg/mL; P < 0.05). BID post-HD levels were 41.9 ± 4.6% of predialysis levels versus 36.9 ± 7.3% with daily dosing ( P = 0.275). Post-HD dose levels were 81.4±4.3% of predialysis on LEV BID versus 65.7 ± 8.8% on LEV daily ( P = 0.045). No seizures were reported during hospital admission in either group. Compared to LEV daily, BID dosing achieved significantly higher levels and a better recovery to predialysis levels. Although limited by small numbers, a similar relationship between postdialysis levels was not detected.

A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor

PubMed Central

Bendell, Johanna C; Javle, Milind; Bekaii-Saab, Tanios S; Finn, Richard S; Wainberg, Zev A; Laheru, Daniel A; Weekes, Colin D; Tan, Benjamin R; Khan, Gazala N; Zalupski, Mark M; Infante, Jeffrey R; Jones, Suzanne; Papadopoulos, Kyriakos P; Tolcher, Anthony W; Chavira, Renae E; Christy-Bittel, Janna L; Barrett, Emma; Patnaik, Amita

2017-01-01

Background: Binimetinib (MEK162; ARRY-438162) is a potent and selective oral MEK 1/2 inhibitor. This phase 1 study determined the maximum tolerated dose (MTD), safety, pharmacokinetic and pharmacodynamic profiles, and preliminary anti-tumour activity of binimetinib in patients with advanced solid tumours, with expansion cohorts of patients with biliary cancer or KRAS- or BRAF-mutant colorectal cancer. Methods: Binimetinib was administered twice daily. Expansion cohorts were enroled after MTD determination following a 3+3 dose-escalation design. Pharmacokinetic properties were determined from plasma samples. Tumour samples were assessed for mutations in RAS, RAF, and other relevant genes. Pharmacodynamic properties were evaluated in serum and skin punch biopsy samples. Results: Ninety-three patients received binimetinib (dose-escalation phase, 19; expansion, 74). The MTD was 60 mg twice daily, with dose-limiting adverse events (AEs) of dermatitis acneiform and chorioretinopathy. The dose for expansion patients was subsequently decreased to 45 mg twice daily because of the frequency of treatment-related ocular toxicity at the MTD. Common AEs across all dose levels included rash (81%), nausea (56%), vomiting (52%), diarrhoea (51%), peripheral oedema (46%), and fatigue (43%); most were grade 1/2. Dose-proportional increases in binimetinib exposure were observed and target inhibition was demonstrated in serum and skin punch biopsy samples. Three patients with biliary cancer had objective responses (one complete and two partial). Conclusions: Binimetinib demonstrated a manageable safety profile, target inhibition, and dose-proportional exposure. The 45 mg twice daily dose was identified as the recommended phase 2 dose. The three objective responses in biliary cancer patients are encouraging and support further evaluation in this population. PMID:28152546

Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

PubMed

Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

2016-05-01

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Analysis of dose to patient, spouse/caretaker, and staff, from an implanted trackable radioactive fiducial for use in the radiation treatment of prostate cancer

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

Neustadter, David; Barnea, Gideon; Stokar, Saul

Purpose: A fiducial tracking system based on a novel radioactive tracking technology is being developed for real-time target tracking in radiation therapy. In this study, the authors calculate the radiation dose to the patient, the spouse/caretaker, and the medical staff that would result from a 100 {mu}Ci Ir192 radioactive fiducial marker permanently implanted in the prostate of a radiation therapy patient. Methods: Local tissue dose was calculated by Monte Carlo simulation. The patient's whole body effective dose equivalent was calculated by summing the doses to the sensitive organs. Exposure of the spouse/caretaker was calculated from the NRC guidelines. Exposure ofmore » the medical staff was based on estimates of proximity to and time spent with the patient. Results: The local dose is below 40 Gy at 5 mm from the marker and below 10 Gy at 10 mm from the marker. The whole body effective dose equivalent to the patient is 64 mSv. The dose to the spouse/caretaker is 0.25 mSv. The annual exposures of the medical staff are 0.2 mSv for a doctor performing implantations and 0.34 mSv for a radiation therapist positioning patients for therapy. Conclusions: The local dose is not expected to have any clinically significant effect on the surrounding tissue which is irradiated during therapy. The dose to the patient is small in comparison to the whole body dose received from the therapy itself. The exposure of all other people is well below the recommended limits. The authors conclude that there is no radiation exposure related contraindication for use of this technology in the radiation treatment of prostate cancer.« less

Drug dosing in chronic kidney disease.

PubMed

Gabardi, Steven; Abramson, Stuart

2005-05-01

Patients with chronic kidney disease (CKD) are at high risk for adverse drug reactions and drug-drug interactions. Drug dosing in these patients often proves to be a difficult task. Renal dysfunction-induced changes in human pathophysiology regularly results may alter medication pharmacodynamics and handling. Several pharmacokinetic parameters are adversely affected by CKD, secondary to a reduced oral absorption and glomerular filtration; altered tubular secretion; and reabsorption and changes in intestinal, hepatic, and renal metabolism. In general, drug dosing can be accomplished by multiple methods; however, the most common recommendations are often to reduce the dose or expand the dosing interval, or use both methods simultaneously. Some medications need to be avoided all together in CKD either because of lack of efficacy or increased risk of toxicity. Nevertheless, specific recommendations are available for dosing of certain medications and are an important resource, because most are based on clinical or pharmacokinetic trials.

Pharmacokinetic studies in children: recommendations for practice and research.

PubMed

Barker, Charlotte I S; Standing, Joseph F; Kelly, Lauren E; Hanly Faught, Lauren; Needham, Allison C; Rieder, Michael J; de Wildt, Saskia N; Offringa, Martin

2018-04-19

Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in understanding the dose-concentration-effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Characteristics of Apixaban-Treated Patients, Evaluation of the Dose Prescribed, and the Persistence of Treatment: A Cohort Study in Catalonia.

PubMed

Gomez-Lumbreras, Ainhoa; Cortes, Jordi; Giner-Soriano, Maria; Quijada-Manuitt, M Angeles; Morros, Rosa

2018-01-01

Apixaban is a direct oral anticoagulant, which inhibits factor Xa. It has demonstrated clinical efficacy in prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation and a better safety profile compared to warfarin. (1) To describe the characteristics of patients with nonvalvular atrial fibrillation beginning treatment with apixaban, (2) to analyze concomitant prescriptions of medications that could potentially interact with apixaban, (3) to evaluate the level of appropriate usage according to the recommended dosage, and (4) to estimate the level of apixaban persistence among naive and non-naive patients. Cohort study using data from primary care (System for Research in Primary Care database, users of the Institut Català de la Salut; Catalonia, Spain) from August 2013 to December 2015. Mean age for apixaban-treated patients was 71.8 years (standard deviation = 11.1) and 55.6% were male. In all, 3.2% of patients receiving apixaban were taking drugs described as potentially related to either pharmacokinetic or pharmacodynamic interactions. According to the summary of product characteristics, 81.1% of patients with a recommended dose of 2.5 mg twice daily and 51.8% with a recommended dose of 5 mg twice daily actually took this dose. After 1 year of follow-up, 62.6% of the apixaban users showed good adherence. The prescribed dose of apixaban did not fully follow the recommended dose, particularly in patients who were treatment naive. Patients with a prior history of anticoagulant treatment were more likely to remain persistent to treatment with apixaban.

Decorporation Approach after Rat Lung Contamination with Plutonium: Evaluation of the Key Parameters Influencing the Efficacy of a Protracted Chelation Treatment.

PubMed

Grémy, Olivier; Coudert, Sylvie; Renault, Daniel; Miccoli, Laurent

2017-11-01

While the efficacy of a protracted zinc (Zn)- or calcium (Ca)-diethylenetriaminepentaacetic acid (DTPA) treatment in reducing transuranic body burden has already been demonstrated, questions about therapeutic variables remain. In response to this, we designed animal experiments primarily to assess both the effect of fractionation of a given dose and the effect of the frequency of dose fraction, with the same total dose. In our study, rats were contaminated intravenously with plutonium (Pu) then treated several days later with Ca-DTPA given at once or in various split-dose regimens cumulating to the same total dose and spread over several days. Similar efficacies were induced by the injection of the total dose or by splitting the dose in several smaller doses, independent of the number of doses and the dose level per injection. In a second study, rats were pulmonary contaminated, and three weeks later they received a Ca-DTPA dose 11-fold higher than the maximal daily recommended dose, administered either as a single bolus or as numerous multiple injections cumulating to the same dose, based on different injection frequency schedules. Independent of frequency schedule, the various split-dose regimens spread over weeks/months were as efficient as single delivery of the total dose in mobilizing lung plutonium, and had a therapeutic advantage for removal of retained hepatic and bone plutonium burdens. We concluded that cumulative dose level was a therapeutic variable of greater importance than the distribution of split doses for the success of a repeated treatment regimen on retained tissue plutonium. In addition, pulmonary administration of clodronate, which aims at killing alveolar macrophages and subsequently releasing their plutonium content, and which is associated with a continuous Ca-DTPA infusion regimen, suggested that the efficacy of injected Ca-DTPA in decorporating lung deposit is limited, due to its restricted penetration into alveolar macrophages and not because plutonium, as a physicochemical form, is unavailable for chelation.

Real-life GH dosing patterns in children with GHD, TS or born SGA: a report from the NordiNet® International Outcome Study.

PubMed

Blankenstein, Oliver; Snajderova, Marta; Blair, Jo; Pournara, Effie; Pedersen, Birgitte Tønnes; Petit, Isabelle Oliver

2017-08-01

To describe real-life dosing patterns in children with growth hormone deficiency (GHD), born small for gestational age (SGA) or with Turner syndrome (TS) receiving growth hormone (GH) and enrolled in the NordiNet International Outcome Study (IOS; Nbib960128) between 2006 and 2016. This non-interventional, multicentre study included paediatric patients diagnosed with GHD (isolated (IGHD) or multiple pituitary hormone deficiency (MPHD)), born SGA or with TS and treated according to everyday clinical practice from the Czech Republic (IGHD/MPHD/SGA/TS: n  = 425/61/316/119), France ( n  = 1404/188/970/206), Germany ( n  = 2603/351/1387/411) and the UK ( n  = 259/60/87/35). GH dosing was compared descriptively across countries and indications. Proportions of patients by GH dose group (low/medium/high) or GH dose change (decrease/increase/no change) during years 1 and 2 were also evaluated across countries and indications. In the Czech Republic, GH dosing was generally within recommended levels. In France, average GH doses were higher for patients with IGHD, MPHD and SGA than in other countries. GH doses in TS tended to be at the lower end of the recommended label range, especially in Germany and the UK; the majority of patients were in the low-dose group. A significant inverse association between baseline height standard deviation score and GH dose was shown ( P  < 0.05); shorter patients received higher doses. Changes in GH dose, particularly increases, were more common in the second (40%) than in the first year (25%). GH dosing varies considerably across countries and indications. In particular, almost half of girls with TS received GH doses below practice guidelines and label recommendations. © 2017 The authors.

Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): a systematic review.

PubMed

Schloss, Janet M; Colosimo, Maree; Airey, Caroline; Masci, Paul P; Linnane, Anthony W; Vitetta, Luis

2013-12-01

Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Radiation treatment of pharmaceuticals

NASA Astrophysics Data System (ADS)

Dám, A. M.; Gazsó, L. G.; Kaewpila, S.; Maschek, I.

1996-03-01

Product specific doses were calculated for pharmaceuticals to be radiation treated. Radio-pasteurization dose were determined for some heat sensitive pharmaceutical basic materials (pancreaton, neopancreatin, neopancreatin USP, duodenum extract). Using the new recommendation (ISO standards, Method 1) dose calculations were performed and radiation sterilization doses were determined for aprotinine and heparine Na.

WE-AB-201-04: The Recommendations of MPPG #5 and Practical Implementation Strategies

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

Smilowitz, J.

Treatment planning systems (TPS) are a cornerstone of modern radiation therapy. Errors in their commissioning or use can have a devastating impact on many patients. To support safe and high quality care, medical physicists must conduct efficient and proper commissioning, good clinical integration, and ongoing quality assurance (QA) of the TPS. AAPM Task Group 53 and related publications have served as seminal benchmarks for TPS commissioning and QA over the past two decades. Over the same time, continuing innovations have made the TPS even more complex and more central to the clinical process. Medical goals are now expressed in termsmore » of the dose and margins around organs and tissues that are delineated from multiple imaging modalities (CT, MR and PET); and even temporally resolved (i.e., 4D) imaging. This information is passed on to optimization algorithms to establish accelerator movements that are programmed directly for IMRT, VMAT and stereotactic treatments. These advances have made commissioning and QA of the TPS much more challenging. This education session reviews up-to-date experience and guidance on this subject; including the recently published AAPM Medical Physics Practice Guideline (MPPG) #5 “Commissioning and QA of Treatment Planning Dose Calculations: Megavoltage Photon and Electron Beams”. Treatment Planning System Commissioning and QA: Challenges and Opportunities (Greg Salomons) This session will provide some key background and review publications describing prominent incidents relating to TPS commissioning and QA. Traditional approaches have been hardware and feature oriented. They aim to establish a functional configuration and establish specifications for regular testing of features (like dose calculation) to assure stable operation and detect failures. With the advent of more complex systems, more patient-specific testing has also been adopted. A number of actual TPS defects will be presented along with heuristics for identifying similar defects in the future. Finally, the Gamma test has become a popular metric for reporting TPS Commissioning and QA results. It simplifies complex testing into a numerical index, but noisy data and casual application can make it misleading. A brief review of the issues around the use of the Gamma test will be presented. TPS commissioning and QA: A process orientation and application of control charts (Michael Sharpe) A framework for commissioning a treatment planning system will be presented, focusing on preparations, practical aspects of configuration, priorities, specifications, and establishing performance. The complexity of the modern TPS make modular testing of features inadequate, and modern QA tools can provide “too much information” about the performance of techniques like IMRT and VMAT. We have adopted a process orientation and quality tools, like control charts, for ongoing TPS QA and assessment of patient-specific tests. The trending nature of these tools reveals the overall performance of the TPS system, and quantifies the variations that arise from individual plans, discrete calculations, and experimentation based on discrete measurements. Examples demonstrating application of these tools to TPS QA will be presented. TPS commissioning and QA: Incorporating the entire planning process (Sasa Mutic) The TPS and its features do not perform in isolation. Instead, the features and modules are key components in a complex process that begins with CT Simulation and extends to treatment delivery, along with image guidance and verification. Most importantly, the TPS is used by people working in a multi-disciplinary environment. It is very difficult to predict the outcomes of human interactions with software. Therefore, an interdisciplinary approach to training, commissioning and QA will be presented, along with an approach to the physics chart check and end-to-end testing as a tool for TPS QA. The role of standardization and automation in QA will also be discussed. The recommendations of MPPG #5 and practical implementation strategies (Jennifer Smilowitz) The recently published recommendations from Task Group No. 244, Medical Physics Practice Guideline on Commissioning and QA of Treatment Planning Dose Calculations: Megavoltage Photon and Electron Beams will be presented. The recommendations focus on the validation of commissioning data and dose calculations. Tolerance values for non-IMRT beam configurations are summarized based on established criteria and data collected by the IROC. More stringent evaluation criteria for IMRT dose calculations are suggested to test the limitations of the TPS dose algorithms for advanced delivery conditions. The MPPG encourages users to create a suite of validation tests for dose calculation for various conditions for static photon beams, heterogeneities, IMRT/VMAT and electron beams. This test suite is intended to be used for subsequent testing, including TPS software upgrades. In the past, the recommendations of some reports have not been widely implemented due to practical limitations. Implementation strategies, tools and processes developed by multiple centers for efficient and “do-able” MPPG #5 testing will be presented, as well as a discussion on the overall validation experience. Learning Objectives: Identify some of the key documents relevant for TPS commissioning and QA Understand strategies for testing TPS software Gain a practical knowledge of the Gamma test criteria Increase familiarity with the process of commissioning a TPS Learn about the use of Control Charts for TPS QA Review the role of the TPS in the overall planning process Increase awareness of the link between TPS QA and chart checking Gain an increased appreciation for the importance of interdisciplinary communication Understand the new recommendations from MPPG #5 on TPS Dose Algorithm Commissioning and QC/QA Learn practical implementation processes and tools for MPPG #5 validation recommendations.« less

Red blood cells metabolome changes upon treatment with different X-ray irradiation doses.

PubMed

Baroni, Fabio; Marraccini, Chiara; Merolle, Lucia; Piccagli, Vando; Lambertini, Daniele; Iori, Mauro; Fasano, Tommaso; Casali, Emanuela; Spisni, Alberto; Baricchi, Roberto; Pertinhez, Thelma A

2018-06-07

The upholding of red blood cells (RBC) quality and the removal of leukocytes are two essential issues in transfusion therapy. Leukodepletion provides optimum results, nonetheless there are cases where irradiation is recommended for some groups of hematological patients such as the ones with chronic graft-vs-host disease, congenital cellular immunodeficiency, and hematopoietic stem cell transplant recipients. The European guidelines suggest irradiation doses from 25 to 50 Gray (Gγ). We evaluated the effect of different prescribed doses (15 to 50 Gγ) of X-ray irradiation on fresh leukodepleted RBCs bags using a novel protocol that provides a controlled irradiation. Biochemical assays integrated with RBCs metabolome profile, assessed by nuclear magnetic resonance spectroscopy, were performed on RBC units supernatant, during 14 days storage. Metabolome analysis evidenced a direct correlation between concentration increase of three metabolites, glycine, glutamine and creatine, and irradiation dose. Higher doses (35 and 50 Gγ) effect on RBC mean corpuscular volume, hemolysis, and ammonia concentration are considerable after 7 and 14 days of storage. Our data show that irradiation with 50 Gγ should be avoided and we suggest that 35 Gγ should be the upper limit. Moreover, we suggest for leukodepleted RBCs units the irradiation with the prescribed dose of 15 Gγ, value at center of bag, and ranging between 13.35-15 Gγ, measured over the entire bag volume, may guarantee the same benefits of a 25 Gγ dose assuring, in addition, a better quality of RBCs.

Determining the applicability of the Landauer nanoDot as a general public dosimeter in a research imaging facility.

PubMed

Charlton, Michael A; Thoreson, Kelly F; Cerecero, Jennifer A

2012-11-01

The Research Imaging Institute (RII) building at the University of Texas Health Science Center at San Antonio (UTHSCSA) houses two cyclotron particle accelerators, positron emission tomography (PET) machines, and a fluoroscopic unit. As part of the radiation protection program (RPP) and meeting the standard for achieving ALARA (as low as reasonably achievable), it is essential to minimize the ionizing radiation exposure to the general public through the use of controlled areas and area dose monitoring. Currently, thirty-four whole body Luxel+ dosimeters, manufactured by Landauer, are being used in various locations within the RII to monitor dose to the general public. The intent of this research was to determine if the nanoDot, a single point dosimeter, can be used as a general public dosimeter in a diagnostic facility. This was tested by first verifying characteristics of the nanoDot dosimeter including dose linearity, dose rate dependence, angular dependence, and energy dependence. Then, the response of the nanoDot dosimeter to the Luxel+ dosimeter when placed in a continuous, low dose environment was investigated. Finally, the nanoDot was checked for appropriate response in an acute, high dose environment. Based on the results, the current recommendation is that the nanoDot should not replace the Luxel+ dosimeter without further work to determine the energy spectra in the RII building and without considering the limitation of the microStar reader, portable on-site OSL reader, at doses below 0.1 mGy (10 mrad).

MIRD Pamphlet No. 21: A Generalized Schema for Radiopharmaceutical Dosimetry-Standardization of Nomenclature

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

Bolch, W E; Eckerman, Keith F; Sgouros, George

2009-03-01

The internal dosimetry schema of the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine has provided a broad framework for assessment of the absorbed dose to whole organs, tissue subregions, voxelized tissue structures, and individual cellular compartments for use in both diagnostic and therapeutic nuclear medicine. The schema was originally published in 1968, revised in 1976, and republished in didactic form with comprehensive examples as the MIRD primer in 1988 and 1991. The International Commission on Radiological Protection (ICRP) is an organization that also supplies dosimetric models and technical data, for use in providing recommendations formore » limits on ionizing radiation exposure to workers and members of the general public. The ICRP has developed a dosimetry schema similar to that of the MIRD Committee but has used different terminology and symbols for fundamental quantities such as the absorbed fraction, specific absorbed fraction, and various dose coefficients. The MIRD Committee objectives for this pamphlet are 3-fold: to restate its schema for assessment of absorbed dose in a manner consistent with the needs of both the nuclear medicine and the radiation protection communities, with the goal of standardizing nomenclature; to formally adopt the dosimetry quantities equivalent dose and effective dose for use in comparative evaluations of potential risks of radiation-induced stochastic effects to patients after nuclear medicine procedures; and to discuss the need to identify dosimetry quantities based on absorbed dose that address deterministic effects relevant to targeted radionuclide therapy.« less

Technical Note: Dosimetric evaluation of Monte Carlo algorithm in iPlan for stereotactic ablative body radiotherapy (SABR) for lung cancer patients using RTOG 0813 parameters.

PubMed

Pokhrel, Damodar; Badkul, Rajeev; Jiang, Hongyu; Kumar, Pravesh; Wang, Fen

2015-01-08

For stereotactic ablative body radiotherapy (SABR) in lung cancer patients, Radiation Therapy Oncology Group (RTOG) protocols currently require radiation dose to be calculated using tissue heterogeneity corrections. Dosimetric criteria of RTOG 0813 were established based on the results obtained from non-Monte Carlo (MC) algorithms, such as superposition/convolutions. Clinically, MC-based algorithms are now routinely used for lung SABR dose calculations. It is essential to confirm that MC calculations in lung SABR meet RTOG guidelines. This report evaluates iPlan MC plans for SABR in lung cancer patients using dose-volume histogram normalization per current RTOG 0813 compliance criteria. Eighteen Stage I-II non-small cell lung cancer (NSCLC) patients with centrally located tumors, who underwent MC-based lung SABR with heterogeneity correction using X-ray Voxel Monte Carlo (XVMC) algorithm (BrainLAB iPlan version 4.1.2), were analyzed. Total dose of 60 Gy in 5 fractions was delivered to planning target volume (PTV) with at least V100% = 95%. Internal target volumes (ITVs) were delineated on maximum intensity projection (MIP) images of 4D CT scans. PTV (ITV + 5 mm margin) volumes ranged from 10.0 to 99.9 cc (mean = 36.8 ± 20.7 cc). Organs at risk (OARs) were delineated on average images of 4D CT scans. Optimal clinical MC SABR plans were generated using a combination of non-coplanar conformal arcs and beams for the Novalis-TX consisting of high definition multileaf collimators (MLCs) and 6 MV-SRS (1000 MU/min) mode. All plans were evaluated using the RTOG 0813 high and intermediate dose spillage criteria: conformity index (R100%), ratio of 50% isodose volume to the PTV (R50%), maximum dose 2 cm away from PTV in any direction (D2 cm), and percent of normal lung receiving 20 Gy (V20) or more. Other organs-at-risk (OARs) doses were tabulated, including the volume of normal lung receiving 5 Gy (V5), maximum cord dose, dose to < 15 cc of heart, and dose to <5 cc of esophagus. Only six out of 18 patients met all RTOG 0813 compliance criteria. Eight of 18 patients had minor deviations in R100%, four in R50%, and nine in D2 cm. However, only one patient had minor deviation in V20. All other OARs doses, such as maximum cord dose, dose to < 15 cc of heart, and dose to < 5 cc of esophagus, were satisfactory for RTOG criteria, except for one patient, for whom the dose to < 15 cc of heart was higher than RTOG guidelines. The preliminary results for our limited iPlan XVMC dose calculations indicate that the majority (i.e., 2/3) of our patients had minor deviations in the dosimetric guidelines set by RTOG 0813 protocol in one way or another. When using an exclusive highly sophisticated XVMC algorithm, the RTOG 0813 dosimetric compliance criteria such as R100% and D2 cm may need to be revisited. Based on our limited number of patient datasets, in general, about 6% for R100% and 9% for D2 cm corrections could be applied to pass the RTOG 0813 compliance criteria in most of those patients. More patient plans need to be evaluated to make recommendation for R50%. No adjustment is necessary for OAR dose tolerances, including normal lung V20. In order to establish new MC specific dose parameters, further investigation with a large cohort of patients including central, as well as peripheral lung tumors, is anticipated and strongly recommended.

Ultraviolet spectral distribution and erythema-weighted irradiance from indoor tanning devices compared with solar radiation exposures.

PubMed

Sola, Yolanda; Baeza, David; Gómez, Miguel; Lorente, Jerónimo

2016-08-01

Concern regarding the impact of indoor tanning devices on human health has led to different regulations and recommendations, which set limits on erythema-weighted irradiance. Here, we analyze spectral emissions from 52 tanning devices in Spanish facilities and compare them with surface solar irradiance for different solar zenith angles. Whereas most of the devices emitted less UV-B radiation than the midday summer sun, the unweighted UV-A irradiance was 2-6 times higher than solar radiation. Moreover, the spectral distributions of indoor devices were completely different from that of solar radiation, differing in one order of magnitude at some UV-A wavelengths, depending on the lamp characteristics. In 21% of the devices tested, the erythema-weighted irradiance exceeded 0.3Wm(-2): the limit fixed by the European standard and the Spanish regulation. Moreover, 29% of the devices fall within the UV type 4 classification, for which medical advice is required. The high variability in erythema-weighted irradiance results in a wide range of exposure times to reach 1 standard erythemal dose (SED: 100Jm(-2)), with 62% of devices requiring exposures of <10min to reach 1 SED. Nevertheless, the unweighted UV-A dose during this time period would be from 1.4 to 10.3 times more than the solar UV-A dose. Copyright © 2016 Elsevier B.V. All rights reserved.

Natural radioactivity in various water samples and radiation dose estimations in Bolu province, Turkey.

PubMed

Gorur, F Korkmaz; Camgoz, H

2014-10-01

The level of natural radioactivity for Bolu province of north-western Turkey was assessed in this study. There is no information about radioactivity measurement reported in water samples in the Bolu province so far. For this reason, gross α and β activities of 55 different water samples collected from tap, spring, mineral, river and lake waters in Bolu were determined. The mean activity concentrations were 68.11 mBq L(-1), 169.44 mBq L(-1) for gross α and β in tap water. For all samples the gross β activity is always higher than the gross α activity. All value of the gross α were lower than the limit value of 500 mBq L(-1) while two spring and one mineral water samples were found to have gross β activity concentrations of greater than 1000 mBq L(-1). The associated age-dependent dose from all water ingestion in Bolu was estimated. The total dose for adults had an average value exceeds the WHO recommended limit value. The risk levels from the direct ingestion of the natural radionuclides in tap and mineral water in Bolu were determinated. The mean (210)Po and (228)Ra risk the value of tap and mineral waters slightly exceeds what some consider on acceptable risk of 10(-4) or less. Copyright © 2014 Elsevier Ltd. All rights reserved.

Radon Concentration And Dose Assessment In Well Water Samples From Karbala Governorate Of Iraq

NASA Astrophysics Data System (ADS)

Al-Alawy, I. T.; Hasan, A. A.

2018-05-01

There are numerous studies around the world about radon concentrations and their risks to the health of human beings. One of the most important social characteristics is the use of water wells for irrigation, which is a major source of water pollution with radon gas. In the present study, six well water samples have been collected from different locations in Karbala governorate to investigate radon concentration level using CR-39 technique. The maximum value 4.112±2.0Bq/L was in Al-Hurr (Al-Qarih Al-Easariah) region, and the lowest concentration of radon was in Hay Ramadan region which is 2.156±1.4Bq/L, with an average value 2.84±1.65Bq/L. The highest result of annual effective dose (AED) was in Al-Hurr (Al-Qarih Al-Easariah) region which is equal to 15.00±3.9μSv/y, while the minimum was recorded in Hay Ramadan 7.86±2.8μSv/y, with an average value 10.35±3.1μSv/y. The current results have shown that the radon concentrations in well water samples are lower than the recommended limit 11.1Bq/L and the annual effective dose in these samples are lower than the permissible international limit 1mSv/y.

Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.

PubMed

Gosselin, Sophie; Hoegberg, Lotte C G; Hoffman, Robert S; Graudins, Andis; Stork, Christine M; Thomas, Simon H L; Stellpflug, Samuel J; Hayes, Bryan D; Levine, Michael; Morris, Martin; Nesbitt-Miller, Andrea; Turgeon, Alexis F; Bailey, Benoit; Calello, Diane P; Chuang, Ryan; Bania, Theodore C; Mégarbane, Bruno; Bhalla, Ashish; Lavergne, Valéry

2016-12-01

Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning. Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method. For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid ® 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence. Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.

[Immunisation schedule of the Spanish Association of Paediatrics: 2015 recommendations].

PubMed

Moreno-Pérez, D; Álvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

2015-01-01

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on the safety, effectiveness and efficiency of current vaccines, including levels of recommendation. In our opinion, this is the optimal vaccination calendar for all children resident in Spain. Regarding the vaccines included in the official unified immunization schedule, the Committee emphasizes the administration of the first dose of hepatitis B either at birth or at 2 months of life; the recommendation of the first dose of MMR and varicella vaccine at the age of 12 months, with the second dose at the age of 2-3 years; DTaP or Tdap vaccine at the age of 6 years, followed by another Tdap booster dose at 11-12 years old; Tdap strategies for pregnant women and household contacts of the newborn, and immunization against human papillomavirus in girls aged 11-12 years old with a 2 dose scheme (0, 6 months). The Committee reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule, the same as it is being conducted in Western European countries. The recently authorised meningococcal B vaccine, currently blocked in Spain, exhibits the profile of a universal vaccine. The Committe insists on the need of having the vaccine available in communitary pharmacies. It has also proposed the free availability of varicella vaccines. Their efectiveness and safety have been confirmed when they are administred from the second year of life. Vaccination against rotavirus is recommended in all infants. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. Copyright © 2014. Published by Elsevier Espana.

SU-E-T-86: A Systematic Method for GammaKnife SRS Fetal Dose Estimation

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

Geneser, S; Paulsson, A; Sneed, P

Purpose: Estimating fetal dose is critical to the decision-making process when radiation treatment is indicated during pregnancy. Fetal doses less than 5cGy confer no measurable non-cancer developmental risks but can produce a threefold increase in developing childhood cancer. In this study, we estimate fetal dose for a patient receiving Gamma Knife stereotactic radiosurgery (GKSRS) treatment and develop a method to estimate dose directly from plan details. Methods: A patient underwent GKSRS on a Perfexion unit for eight brain metastases (two infratentorial and one brainstem). Dose measurements were performed using a CC13, head phantom, and solid water. Superficial doses to themore » thyroid, sternum, and pelvis were measured using MOSFETs during treatment. Because the fetal dose was too low to accurately measure, we obtained measurements proximally to the isocenter, fitted to an exponential function, and extrapolated dose to the fundus of the uterus, uterine midpoint, and pubic synthesis for both the preliminary and delivered plans. Results: The R-squared fit for the delivered doses was 0.995. The estimated fetal doses for the 72 minute preliminary and 138 minute delivered plans range from 0.0014 to 0.028cGy and 0.07 to 0.38cGy, respectively. MOSFET readings during treatment were just above background for the thyroid and negligible for all inferior positions. The method for estimating fetal dose from plan shot information was within 0.2cGy of the measured values at 14cm cranial to the fetal location. Conclusion: Estimated fetal doses for both the preliminary and delivered plan were well below the 5cGy recommended limit. Due to Pefexion shielding, internal dose is primarily governed by attenuation and drops off exponentially. This is the first work that reports fetal dose for a GK Perfexion unit. Although multiple lesions were treated and the duration of treatment was long, the estimated fetal dose remained very low.« less

WHO position on the use of fractional doses - June 2017, addendum to vaccines and vaccination against yellow fever WHO: Position paper - June 2013.

PubMed

World Health Organization

2017-10-13

This article presents the World Health Organization's (WHO) recommendations on the use of fractional doses of yellow fever vaccines excerpted from the "Yellow fever vaccine: WHO position on the use of fractional doses - June 2017, Addendum to Vaccines and vaccination against yellow fever WHO: Position Paper - June 2013″, published in the Weekly Epidemiological Record [1,2]. This addendum to the 2013 position paper pertains specifically to use of fractional dose YF (fYF) vaccination (fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as usual per manufacturer recommendations) in the context of YF vaccine supply shortages beyond the capacity of the global stockpile. The current WHO position on the use of yellow fever (YF) vaccine is set out in the 2013 WHO position paper on vaccines and vaccination against YF and those recommendations are unchanged. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of Yellow Fever vaccines were discussed by SAGE in October 2016; evidence presented at these meetings can be accessed at: www.who.int/immunization/sage/meetings/2016/October/presentations_background_docs/en/. Copyright © 2017. Published by Elsevier Ltd.

Efficacy of albendazole against nematode parasites isolated from a goat farm in Ethiopia: relationship between dose and efficacy in goats.

PubMed

Eguale, Tadesse; Chaka, Hassen; Gizaw, Daniel

2009-10-01

A suspected case of albendazole resistance in a goat farm of Hawassa University was examined using faecal egg count reduction test (FECRT), controlled anthelmintic efficacy test and egg hatch assay (EHA) to verify the development of resistance and/or the need for higher doses of the drug in goats than in sheep. The experiment was conducted in 12 sheep (2 groups: treatment versus control) and 24 goats (4 groups: 3 treatments versus control, n = 6; per group) following artificial infection with infective larvae of Haemonchus contortus and Oesophagostomum columbianum. The first group of sheep and goats were treated orally with albendazole at the dose rate of 3.8 mg/kg body weight (i.e. manufacturer's recommended dose for sheep) while the second group of sheep and the fourth group of goats were left untreated. The second and the third group of goats were treated with albendazole at 5.7 and 7.6 mg/kg respectively. The FECRT showed an efficacy of albendazole in goats to be 65.5, 81.4 and 84.1% at the dose rate of 3.8, 5.7 and 7.6 mg/kg body weight respectively while in sheep it was 62% at the dose rate of 3.8 mg/kg. Increasing the dose to 1.5 the sheep recommended dose induced minor improvement of efficacy in goats; however the efficacy was almost the same at 1.5 and twice the dose recommended for sheep. Worm counts at day 15 post-treatment revealed that H. contortus has developed resistance to albendazole. EHA results also supported these findings. On the other hand, O. columbianum was 100% susceptible at all dose levels tested.

[Vaccination schedule of the Spanish Association of Pediatrics: recommendations 2004].

PubMed

2004-05-01

The Vaccine Assessment Committee of the Spanish Association of Pediatrics discusses vaccine developments in 2003 and recommends some modifications to the vaccination schedule. The recommendation of substituting the oral polio vaccine for the inactivated polio vaccine, suppressing the fifth dose, is maintained. The introduction of the conjugate pneumococcal vaccine and the varicella vaccine is stressed. Concerning the meningococcal C vaccine, the improvement introduced by being able to immunize with just two doses is discussed. In agreement with the information received from the European Medicines Agency, there appear to be no well-founded reasons to abandon hexavalent preparations.

Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study.

PubMed

Gadgeel, Shirish M; Gandhi, Leena; Riely, Gregory J; Chiappori, Alberto A; West, Howard L; Azada, Michele C; Morcos, Peter N; Lee, Ruey-Min; Garcia, Linta; Yu, Li; Boisserie, Frederic; Di Laurenzio, Laura; Golding, Sophie; Sato, Jotaro; Yokoyama, Shumpei; Tanaka, Tomohiro; Ou, Sai-Hong Ignatius

2014-09-01

Patients with non-small-cell lung cancer (NSCLC) and ALK rearrangements generally have a progression-free survival of 8-11 months while on treatment with the ALK inhibitor crizotinib. However, resistance inevitably develops, with the brain a common site of progression. More potent ALK inhibitors with consistently demonstrable CNS activity and good tolerability are needed urgently. Alectinib is a novel, highly selective, and potent ALK inhibitor that has shown clinical activity in patients with crizotinib-naive ALK-rearranged NSCLC. We did a phase 1/2 study of alectinib to establish the recommended phase 2 dose of the drug and examine its activity in patients resistant or intolerant to crizotinib. We enrolled patients with ALK-rearranged NSCLC who progressed on or were intolerant to crizotinib. We administered various oral doses of alectinib (300-900 mg twice a day) during the dose-escalation portion of the study (phase 1), to ascertain the recommended dose for phase 2. We used Response Evaluation Criteria in Solid Tumors criteria (version 1.1) to investigate the activity of alectinib in all patients with a baseline scan and at least one post-treatment scan (CT or MRI), with central radiological review of individuals with brain metastases. We assessed safety in all patients who received at least one dose of alectinib. Here, we present data for the phase 1 portion of the study, the primary objective of which was to establish the recommended phase 2 dose; phase 2 is ongoing. This trial is registered at ClinicalTrials.gov, number NCT01588028. 47 patients were enrolled. Alectinib was well tolerated, with the most common adverse events being fatigue (14 [30%]; all grade 1-2), myalgia (eight [17%]; all grade 1-2), and peripheral oedema (seven [15%] grade 1-2, one [2%] grade 3). Dose-limiting toxic effects were recorded in two patients in the cohort receiving alectinib 900 mg twice a day; one individual had grade 3 headache and the other had grade 3 neutropenia. The most common grade 3-4 adverse events were increased levels of γ-glutamyl transpeptidase (two [4%]), a reduction in the number of neutrophils (two [4%]), and hypophosphataemia (two [4%]). Three patients reported four grade 4 serious adverse events that were deemed unrelated to alectinib: acute renal failure; pleural effusion and pericardial effusion; and brain metastasis. At data cut-off (median follow-up 126 days [IQR 84-217]), 44 patients could be assessed for activity. Investigator-assessed objective responses were noted in 24 (55%) patients, with a confirmed complete response in one (2%), a confirmed partial response in 14 (32%), and an unconfirmed partial response in nine (20%). 16 (36%) patients had stable disease; the remaining four (9%) had progressive disease. Of 21 patients with CNS metastases at baseline, 11 (52%) had an objective response; six (29%) had a complete response (three unconfirmed) and five (24%) had a partial response (one unconfirmed); eight (38%) patients had stable disease and the remaining two (10%) had progressive disease. Pharmacokinetic data indicated that mean exposure (AUC0-10) after multiple doses of alectinib (300-600 mg twice a day) was dose-dependent. Alectinib was well tolerated, with promising antitumour activity in patients with ALK-rearranged NSCLC resistant to crizotinib, including those with CNS metastases. On the basis of activity, tolerability, and pharmacokinetic data, we chose alectinib 600 mg twice a day as the recommended dose for phase 2. Chugai Pharmaceuticals, F Hoffmann La-Roche. Copyright © 2014 Elsevier Ltd. All rights reserved.

Persistence of azoxystrobin in/on grapes and soil in different grapes growing areas of India.

PubMed

Gajbhiye, Vijay Tularam; Gupta, Suman; Mukherjee, Irani; Singh, Shashi Bala; Singh, Neera; Dureja, Prem; Kumar, Yogesh

2011-01-01

Persistence of azoxystrobin was studied in/on grapes when applied @ 150 g ai ha⁻¹ (recommended dose) and 300 g ai ha⁻¹ (double the recommended dose) in three grapes growing states of India, namely Karnataka, Maharashtra and Tamil Nadu, in the year 2006-2007. A total of five sprays were given at an interval of about 15 days. Grapes and soil samples were collected after 5th spray, extracted and analysed by gas chromatography using electron capture detector. Half life of azoxystrobin on grapes varied from 5.4 to 11.2 days. Residues of azoxystrobin were much below the prescribed MRL (0.5 mg kg⁻¹) after 21 days. The dissipation of azoxystrobin in soil followed first order rate kinetics with an average half life of 8.1 days at the recommended dose of application.

Dose constraints for moderate hypofractionated radiotherapy for prostate cancer: The French genito-urinary group (GETUG) recommendations.

PubMed

Langrand-Escure, J; de Crevoisier, R; Llagostera, C; Créhange, G; Delaroche, G; Lafond, C; Bonin, C; Bideault, F; Sargos, P; Belhomme, S; Pasquier, D; Latorzeff, I; Supiot, S; Hennequin, C

2018-04-01

Considering recent phase III trials results, moderate hypofractionated radiotherapy can be considered as a standard treatment for low and intermediate risk prostate cancer management. This assessment call for a framework allowing homogeneous and reproducible practices in the different centers using this radiotherapy schedule. The French Genito-Urinary Group (GETUG) provides here recommendations for daily practice of moderate hypofractionated radiotherapy for prostate cancer, with indications, dose, fractionation, pre-treatment planning, volume of interest delineation (target volume and organs at risk) and margins, dose constraints and radiotherapy techniques. Copyright © 2018. Published by Elsevier SAS.

Oxygen Therapy in the Delivery Room: What Is the Right Dose?

PubMed

Kapadia, Vishal; Wyckoff, Myra H

2018-06-01

Oxygen is the most commonly used medicine used during neonatal resuscitation in the delivery room. Oxygen therapy in delivery room should be used judiciously to avoid oxygen toxicity while delivering sufficient oxygen to prevent hypoxia. Measurement of appropriate oxygenation relies on pulse oximetry, but adequate ventilation and perfusion are equally important for oxygen delivery. In this article, we review oxygenation while transitioning from fetal to neonatal life, the importance of appropriate oxygen therapy, its measurement in the delivery room, and current recommendations for oxygen therapy and its limitations. Copyright © 2018 Elsevier Inc. All rights reserved.

Variation of annual effective dose due to radon level in indoor air in Marwar region of Rajasthan, India

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

Rani, Asha, E-mail: ashasachdeva78@gmail.com; Mittal, Sudhir, E-mail: sudhirmittal03@gmail.com; Mehra, Rohit

In the present work, indoor radon and thoron measurements have been carried out from different locations of Jodhpur and Nagaur districts of Northern Rajasthan, India using RAD7, a solid state alpha detector. The radon and thoron concentration in indoor air varies from 8.75 to 61.25 Bq m{sup −3} and 32.7 to 147.2 Bq m{sup −3} with the mean value of 32 and 73 Bq m{sup −3} respectively. The observed indoor radon concentration values are well below the action level recommended by International Commission on Radiological Protection (200-300 Bq m{sup −3}) and Environmental Protection Agency (148 Bq m{sup −3}). The surveymore » reveals that the thoron concentration values in the indoor air are well within the International Commission on Radiological Protection (2005). The calculated total annual effective dose due to radon level in indoor air varies from 0.22 to 1.54 mSv y{sup −1} with the mean value of 0.81 mSv y{sup −1} which is less than even the lower limit of action level 3-10 mSv y{sup −1} recommended by International Commission on Radiological Protection (2005)« less

Feasibility of tuberculosis treatment monitoring by video directly observed therapy: a binational pilot study.

PubMed

Garfein, R S; Collins, K; Muñoz, F; Moser, K; Cerecer-Callu, P; Raab, F; Rios, P; Flick, A; Zúñiga, M L; Cuevas-Mota, J; Liang, K; Rangel, G; Burgos, J L; Rodwell, T C; Patrick, K

2015-09-01

Although directly observed therapy (DOT) is recommended worldwide for monitoring anti-tuberculosis treatment, transportation and personnel requirements limit its use. To evaluate the feasibility and acceptability of 'video DOT' (VDOT), which allows patients to record and transmit medication ingestion via videos watched remotely by health care providers to document adherence. We conducted a single-arm trial among tuberculosis (TB) patients in San Diego, California, USA, (n = 43) and Tijuana, Mexico (n = 9) to represent high- and low-resource settings. Pre-/post-treatment interviews assessed participant characteristics and experiences. Adherence was defined as the proportion of observed doses to expected doses. The mean age was 37 years (range 18-86), 50% were male, and 88% were non-Caucasian. The mean duration of VDOT use was 5.5 months (range 1-11). Adherence was similar in San Diego (93%) and Tijuana (96%). Compared to time on in-person DOT, 92% preferred VDOT, 81% thought VDOT was more confidential, 89% never/rarely had problems recording videos, and 100% would recommend VDOT to others. Seven (13%) participants were returned to in-person DOT and six (12%) additional participants had their phones lost, broken or stolen. VDOT was feasible and acceptable, with high adherence in both high- and low-resource settings. Efficacy and cost-effectiveness studies are needed.

ICRP Publication 125: Radiological Protection in Security Screening.

PubMed

Cool, D A; Lazo, E; Tattersall, P; Simeonov, G; Niu, S

2014-07-01

The use of technologies to provide security screening for individuals and objects has been increasing rapidly, in keeping with the significant increase in security concerns worldwide. Within the spectrum of technologies, the use of ionizing radiation to provide backscatter and transmission screening capabilities has also increased. The Commission has previously made a number of statements related to the general topic of deliberate exposures of individuals in non-medical settings. This report provides advice on how the radiological protection principles recommended by the Commission should be applied within the context of security screening. More specifically, the principles of justification, optimisation of protection, and dose limitation for planned exposure situations are directly applicable to the use of ionising radiation in security screening. In addition, several specific topics are considered in this report, including the situation in which individuals may be exposed because they are concealed (‘stowaways’) in a cargo container or conveyance that may be subject to screening. The Commission continues to recommend that careful justification of screening should be considered before decisions are made to employ the technology. If a decision is made that its use is justified, the framework for protection as a planned exposure situation should be employed, including optimization of protection with the use of dose constraints and the appropriate provisions for authorisation and inspection.

Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol.

PubMed

Franken, L G; de Winter, B C M; van Esch, H J; van Zuylen, L; Baar, F P M; Tibboel, D; Mathôt, R A A; van Gelder, T; Koch, B C P

2016-06-01

A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life. This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination. Specific considerations are also given for three commonly prescribed drugs in palliative care: morphine, midazolam and haloperidol). The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines. Until then knowledge of pharmacokinetics and the physiological changes that occur in the final days of life can provide a base for dosing adjustments that will improve the quality of life of terminally ill patients. As the interaction of drugs with the physiology of dying is complex, pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.

Review of Copper Provision in the Parenteral Nutrition of Adults [Formula: see text].

PubMed

Livingstone, Callum

2017-04-01

The essential trace element copper (Cu) is required for a range of physiologic processes, including wound healing and functioning of the immune system. The correct amount of Cu must be provided in parenteral nutrition (PN) if deficiency and toxicity are to be avoided. While provision in line with the standard recommendations should suffice for most patients, Cu requirements may be higher in patients with increased gastrointestinal losses and severe burns and lower in those with cholestasis. The tests of Cu status that are currently available for clinical use are unreliable. Serum Cu concentration is the most commonly ordered test but is insensitive to Cu deficiency and toxicity and is misleadingly increased during the acute phase response. These limitations make it difficult for prescribers to assess Cu status and to decide how much Cu to provide. There is a need for better tests of Cu status to be developed to decrease uncertainty and improve individualization of Cu dosing. More information is needed on Cu requirements in disease and Cu contamination of PN components and other intravenous fluids. New multi-trace element products should be developed that provide Cu doses in line with the 2012 American Society for Parenteral and Enteral Nutrition recommendations. This article discusses the evaluation and treatment of Cu deficiency and toxicity in patients treated with PN.

Exposure to cosmic radiation of British Airways flying crew on ultralonghaul routes.

PubMed

Bagshaw, M; Irvine, D; Davies, D M

1996-07-01

British Airways has carried out radiation monitoring in Concorde for more than 20 years and has used a heuristic model based on data quoted by the National Aeronautics and Space Administration (NASA) to model radiation exposure in all longhaul fleets. From these data it has been calculated that no flight deck crew would exceed the control level of 6 mSv/y currently under consideration by regulatory authorities, which is three tenths of the occupational dose limit of 20 mSv/y recommended by the International Commission on Radiological Protection (ICRP). The model suggested that less than 4% of cabin crew based in Tokyo flying only between London and Japan could reach or exceed the 6 mSv/y level, based on a predicted effective dose rate of 7 microSv/h. To validate this calculation a sampling measurement programme was carried out on nine round trips flown by a Boeing 747-400 between London and Tokyo. The radiation field was measured with dosimeters used for routine personal monitoring (thermoluminescence dosimeters (TLDs) and polyallydiglycol carbonate neutron dosimeters). The limitations of the methodology are acknowledged, but the results indicate that the effective dose rate was 6 microSv/h which is consistent with the predicted effective dose rate of 7 microSv/h. This result, which is in accordance with other reported studies indicates that it is unlikely that any of the cabin crew based in Tokyo exceeded the 6 mSv/y level. In accordance with "as low as reasonably achievable" principles British Airways will continue to monitor flying crew routes and hours flown to ensure compliance.

Single Low Dose Primaquine (0.25 mg/kg) Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects.

PubMed

Bancone, Germana; Chowwiwat, Nongnud; Somsakchaicharoen, Raweewan; Poodpanya, Lalita; Moo, Paw Khu; Gornsawun, Gornpan; Kajeechiwa, Ladda; Thwin, May Myo; Rakthinthong, Santisuk; Nosten, Suphak; Thinraow, Suradet; Nyo, Slight Naw; Ling, Clare L; Wiladphaingern, Jacher; Kiricharoen, Naw Lily; Moore, Kerryn A; White, Nicholas J; Nosten, Francois

2016-01-01

Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75 mg/kg (adult dose 45 mg) but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15-20%) in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25 mg/kg (adult dose 15 mg) to Artemisinin-based Combination Therapies (ACTs) without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant) approximates 15%. The tolerability and safety of primaquine (single dose 0.25 mg base/kg) combined with dihydroartemisinin-piperaquine (DHA-PPQ) given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4.7%) were greater than in G6PD normal subjects (0.3%, -0.8 and -1.7%) but were clinically insignificant. Fractional drops in haemoglobin concentration larger than 25% following single dose primaquine were observed in 1.8% of the population but were asymptomatic. The single low dose (0.25mg/kg) of primaquine is clinically well tolerated and can be used safely without prior G6PD testing in populations with high prevalence of G6PD deficiency. The present evidence supports a broader use of low dose primaquine without G6PD testing for the treatment and elimination of falciparum malaria. ClinicalTrials.gov NCT01872702.

Weight-based dosing in medication use: what should we know?

PubMed Central

Pan, Sheng-dong; Zhu, Ling-ling; Chen, Meng; Xia, Ping; Zhou, Quan

2016-01-01

Background Weight-based dosing strategy is still challenging due to poor awareness and adherence. It is necessary to let clinicians know of the latest developments in this respect and the correct circumstances in which weight-based dosing is of clinical relevance. Methods A literature search was conducted using PubMed. Results Clinical indications, physiological factors, and types of medication may determine the applicability of weight-based dosing. In some cases, the weight effect may be minimal or the proper dosage can only be determined when weight is combined with other factors. Medications within similar therapeutic or structural class (eg, anticoagulants, antitumor necrosis factor medications, P2Y12-receptor antagonists, and anti-epidermal growth factor receptor antibodies) may exhibit differences in requirements on weight-based dosing. In some cases, weight-based dosing is superior to currently recommended fixed-dose regimen in adult patients (eg, hydrocortisone, vancomycin, linezolid, and aprotinin). On the contrary, fixed dosing is noninferior to or even better than currently recommended weight-based regimen in adult patients in some cases (eg, cyclosporine microemulsion, recombinant activated Factor VII, and epoetin α). Ideal body-weight-based dosing may be superior to the currently recommended total body-weight-based regimen (eg, atracurium and rocuronium). For dosing in pediatrics, whether weight-based dosing is better than body surface-area-based dosing is dependent on the particular medication (eg, methotrexate, prednisone, prednisolone, zidovudine, didanosine, growth hormone, and 13-cis-retinoic acid). Age-based dosing strategy is better than weight-based dosing in some cases (eg, intravenous busulfan and dalteparin). Dosing guided by pharmacogenetic testing did not show pharmacoeconomic advantage over weight-adjusted dosing of 6-mercaptopurine. The common viewpoint (ie, pediatric patients should be dosed on the basis of body weight) is not always correct. Effective weight-based dosing interventions include standardization of weight estimation, documentation and dosing determination, dosing chart, dosing protocol, order set, pharmacist participation, technological information, and educational measures. Conclusion Although dosing methods are specified in prescribing information for each drug and there are no principal pros and cons to be elaborated, this review of weight-based dosing strategy will enrich the knowledge of medication administration from the perspectives of safety, efficacy, and pharmacoeconomics, and will also provide research opportunities in clinical practice. Clinicians should be familiar with dosage and administration of the medication to be prescribed as well as the latest developments. PMID:27110105

Eye lens dose in interventional cardiology.

PubMed

Principi, S; Delgado Soler, C; Ginjaume, M; Beltran Vilagrasa, M; Rovira Escutia, J J; Duch, M A

2015-07-01

The ICRP has recently recommended reducing the occupational exposure dose limit for the lens of the eye to 20 mSv y(-1), averaged over a period of 5 y, with no year exceeding 50 mSv, instead of the current 150 mSv y(-1). This reduction will have important implications for interventional cardiology and radiology (IC/IR) personnel. In this work, lens dose received by a staff working in IC is studied in order to determine whether eye lens dose monitoring or/and additional radiological protection measures are required. Eye lens dose exposure was monitored in 10 physicians and 6 nurses. The major IC procedures performed were coronary angiography and percutaneous transluminal coronary angioplasty. The personnel were provided with two thermoluminescent dosemeters (TLDs): one calibrated in terms of Hp(3) located close to the left ear of the operator and a whole-body dosemeter calibrated in terms of Hp(10) and Hp(0.07) positioned on the lead apron. The estimated annual eye lens dose for physicians ranged between 8 and 60 mSv, for a workload of 200 procedures y(-1). Lower doses were collected for nurses, with estimated annual Hp(3) between 2 and 4 mSv y(-1). It was observed that for nurses the Hp(0.07) measurement on the lead apron is a good estimate of eye lens dose. This is not the case for physicians, where the influence of both the position and use of protective devices such as the ceiling shield is very important and produces large differences among doses both at the eyes and on the thorax. For physicians, a good correlation between Hp(3) and dose area product is shown. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.

PubMed

Rangwala, Reshma; Leone, Robert; Chang, Yunyoung C; Fecher, Leslie A; Schuchter, Lynn M; Kramer, Amy; Tan, Kay-See; Heitjan, Daniel F; Rodgers, Glenda; Gallagher, Maryann; Piao, Shengfu; Troxel, Andrea B; Evans, Tracey L; DeMichele, Angela M; Nathanson, Katherine L; O'Dwyer, Peter J; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; Amaravadi, Ravi K

2014-08-01

Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.

Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study.

PubMed

Lulla, Rishi R; Goldman, Stewart; Yamada, Tohru; Beattie, Craig W; Bressler, Linda; Pacini, Michael; Pollack, Ian F; Fisher, Paul Graham; Packer, Roger J; Dunkel, Ira J; Dhall, Girish; Wu, Shengjie; Onar, Arzu; Boyett, James M; Fouladi, Maryam

2016-09-01

p53 is a promising target in human cancer. p28 is a cell-penetrating peptide that preferentially enters cancer cells and binds to both wild-type and mutant p53 protein, inhibiting COP1-mediated ubiquitination and proteasomal degradation. This results in increased levels of p53, which induces cell cycle arrest at G2/M. We conducted a phase I study to determine the maximum-tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) and pharmacokinetics (PKs) of p28 in children. Children aged 3-21 years with recurrent or progressive central nervous system tumors were eligible. Intravenous p28 was administered 3 times weekly for 4 consecutive weeks of a 6-week cycle at 4.16 mg/kg/dose (the adult recommended phase II dose) using a rolling-6 study design. Expression status of p53 was characterized by immunohistochemistry, and serum PK parameters were established on the second dose. Of the 18 eligible patients enrolled in the study, 12 completed the DLT monitoring period and were evaluable for toxicity. p28 was well-tolerated; 7 participants received ≥2 courses, and the most common adverse event attributed to the drug was transient grade 1 infusion-related reaction. PK analysis revealed a profile similar to adults; however, an increased area under the curve was observed in pediatric patients. High p53 expression in tumor cell nuclei was observed in 6 of 12 available tissue samples. There were no objective responses; 2 participants remained stable on the study for >4 cycles. This phase I study demonstrated that p28 is well-tolerated in children with recurrent CNS malignancies at the adult recommended phase II dose. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Role of UV light in photodamage, skin aging, and skin cancer: importance of photoprotection.

PubMed

Gonzaga, Evelyn R

2009-01-01

Solar, and particularly UV, radiation causes molecular and cellular damage with resultant histopathologic and clinical degenerative changes, leading in turn to photosensitivity, photo-aging, and skin cancer. While our bodies have some natural UV defenses, additional protection from the sun is essential, including sun avoidance, physical protection, and sunscreen use. Sun avoidance includes limiting exposure during peak UV times (10am-4pm), avoiding UV-reflective surfaces such as sand, snow and water, and eliminating photosensitizing drugs. Physical protection includes wearing photoprotective clothing such as a broad-brimmed hat and long sleeves and use of UV-blocking films on windows. Sunscreen containing avobenzone, titanium dioxide, zinc oxide or encamsule should be used daily and frequently reapplied. To guard against the UVB spectrum, zinc oxide and titanium dioxide are particularly recommended. Sunscreen is generally under-applied at only 25% of the recommended dose, seriously compromising photoprotection. Dosage guidelines recommend using more than half a teaspoon each on head and neck area and each arm, and more than a teaspoon each on anterior torso, posterior torso, and each leg (approximately 2 mg/cm(2)).

Basis for standards: ICRP activities.

PubMed

Vano, E

2015-07-01

The purpose of this chapter is to describe work achieved recently by the International Commission on Radiological Protection (ICRP) and especially by Committee 3 (Protection in Medicine) and its use for standards. In March 1960, the Board of Governors of the International Atomic Energy Agency approved the Agency's 'Health and Safety Measures', stating that the Agency's 'Basic Safety Standards' (BSS) would be based, to the extent possible, on the recommendations of the ICRP. In a similar way, the Council of the European Union took into account the new recommendations of the ICRP when adopting the new Directive 2013/59/EURATOM that laid down BSS for protection against the dangers arising from exposure to ionising radiation. The new limit for the lens of the eyes for occupational exposures has been incorporated into these international standards and several articles dealing with medical exposures: justification, optimisation, recording patient doses, the use of diagnostic reference levels, training, accidental and unintended exposures, etc. have also been included in agreement with the ICRP recommendations. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of radium-228 determination in water among Australian laboratories.

PubMed

Zawadzki, Atun; Cook, Megan; Cutmore, Brodie; Evans, Fiona; Fierro, Daniela; Gedz, Alicea; Harrison, Jennifer J; Loosz, Tom; Medley, Peter; Mokhber-Shahin, Lida; Mullins, Sarah; Sdraulig, Sandra

2017-11-01

The National Health and Medical Research Council and Natural Resource Management Ministerial Council of Australia developed the current Australian Drinking Water Guidelines which recommend an annual radiation dose value of 1 mSv year -1 . One of the potential major contributors to the radiation dose from drinking water is radium-228, a naturally occurring radionuclide arising from the thorium decay series. Various methods of analysing for radium-228 in water have been established and adapted by analytical radiochemistry laboratories. Seven laboratories in Australia participated in analysing radium-228 spiked water samples with activity concentrations ranging from 6 mBq L -1 to 20 Bq L -1 . The aim of the exercise was to compare and evaluate radium-228 results reported by the participating laboratories, the methods used and the detection limits. This paper presents the outcome of the exercise. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Radiation exposure control from the application of nuclear gauges in the mining industry in Ghana.

PubMed

Faanu, A; Darko, E O; Awudu, A R; Schandorf, C; Emi-Reynolds, G; Yeboah, J; Glover, E T; Kattah, V K

2010-05-01

The use of nuclear gauges for process control and elemental analysis in the mining industry in Ghana, West Africa, is wide spread and on the increase in recent times. The Ghana Radiation Protection Board regulates nuclear gauges through a system of notification and authorization by registration or licensing, inspection, and enforcement. Safety assessments for authorization and enforcement have been established to ensure the safety and security of radiation sources as well as protection of workers and the general public. Appropriate training of mine staff is part of the efforts to develop the necessary awareness about the safety and security of radiation sources. The knowledge and skills acquired will ensure the required protection and safety at the workplaces. Doses received by workers monitored over a period between 1998 and 2007 are well below the annual dose limit of 20 mSv recommended by the International Commission on Radiological Protection.

Amitriptyline for the treatment of fibromyalgia: a comprehensive review.

PubMed

Rico-Villademoros, Fernando; Slim, Mahmoud; Calandre, Elena P

2015-10-01

Fibromyalgia is characterized by chronic generalized pain accompanied by a wide range of clinical manifestations. Most clinical practice guidelines recommend multidisciplinary treatment using a combination of pharmacological and non-pharmacological therapies. The tricyclic antidepressant amitriptyline has been most thoroughly studied in fibromyalgia. Amitriptyline has been evaluated in placebo-controlled studies, and it has served as an active comparator to other therapeutic interventions in the treatment of fibromyalgia. In addition, several systematic reviews and meta-analyses have evaluated its efficacy and safety for the treatment of fibromyalgia. Data from individual studies as well as from systematic reviews indicate that low doses (10-75 mg/day) of amitriptyline are effective for the treatment of fibromyalgia and, despite the limited quality of the data, they do not seem to be associated with relevant tolerability or safety issues. Consistent with some clinical guidelines, we believe amitriptyline in low doses should be considered a first-line drug for the treatment of fibromyalgia.

Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline.

PubMed

Reece, D; Imrie, K; Stevens, A; Smith, C A

2006-10-01

In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate?What is the toxicity associated with the use of bortezomib?Which patients are more or less likely to benefit from treatment with bortezomib? Evidence was selected and reviewed by two members of the Hematology Disease Site Group and by methodologists from the Program in Evidence-based Care (pebc) at Cancer Care Ontario. The practice guideline report was reviewed and approved by the Hematology Disease Site Group, which comprises hematologists, medical and radiation oncologists, and a patient representative. As part of an external review process, the report was disseminated to practitioners throughout Ontario to obtain their feedback. Outcomes of interest were overall survival, quality of life, response rates and duration, and rates of adverse events. A systematic search was conducted of the medline, embase, HealthStar, cinahl, and Cochrane Library databases for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. Those recommendations were appraised by a sample of practitioners in Ontario and modified in response to the feedback received. The systematic review and modified recommendations were approved by a review body w theithin pebc. The literature review found one randomized controlled trial (rct)-the only published rct of bortezomib in relapsed myeloma. A number of phase ii studies were also retrieved, including a randomized phase ii study. No randomized trials were retrieved for lymphoma. The rct found bortezomib to be superior to high-dose dexamethasone for median time to progression and 1-year survival in patients with relapsed myeloma, although grade 3 adverse events were more common in the bortezomib arm. Bortezomib is recommended as the preferred treatment option in patients with myeloma relapsing within 1 year of the conclusion of initial treatment; it may also be a reasonable option in patients relapsing at least 1 year after autologous stem-cell transplantation. This evidence-based series applies to adult patients with myeloma, Waldenström macroglobulinemia, or lymphoma of any type, stage, histology, or performance status. Based on the results of a large well-conducted rct, which represents the only published randomized study in relapsed myeloma, the Hematology Disease Site Group (dsg) offers the following recommendations: For patients with myeloma refractory to or relapsing within 1 year of the conclusion of initial or subsequent treatment or treatments, including autologous stem-cell transplantation, and who are candidates for further chemotherapy, bortezomib is recommended as the preferred treatment option.Bortezomib is also a reasonable option for patients relapsing at least 1 year after autologous stem-cell transplantation. The dsg is aware that thalidomide, alkylating agents, or repeat transplantation may also be options for these patients. However, evaluation of these other options is beyond the scope of this practice guideline.For patients with myeloma relapsing at least 1 year after the conclusion of alkylating agent-based chemotherapy who are candidates for further chemotherapy, further treatment with alkylating agent-based chemotherapy is recommended.Evidence is insufficient to support the use of bortezomib in patients with non-Hodgkin lymphoma or Waldenström macroglobulinemia outside of clinical trials. Limited evidence supports the appropriateness of a specific time-to-relapse period as being indicative of treatment-insensitive disease. The 1-year threshold provided in the foregoing recommendations is based on the opinion of the Hematology dsg. For specific details related to the administration of bortezomib therapy, the dsg suggests that clinicians refer to the protocols used in major trials. Some of those details are provided here for informational purposes. Bortezomib 1.3,g/m(2) is given as a rapid intravenous bolus over 3-5 seconds on days 1, 4, 8, and 11 of a 21-day cycle; a minimum of 72 hours between doses is required to allow for recovery of normal proteasome function. Vital signs should be checked before and after each dose. A complete blood count is recommended before each dose, with blood chemistries (including electrolyte and creatinine levels) monitored at a minimum on days 1 and 8 of each cycle. The dose of bortezomib should be reduced or held immediately upon development of painful neuropathy, as described in the product monograph; dose modification may also be required for peripheral sensory neuropathy without pain or for other toxicities. Most toxicities are reversible if dose modification guidelines are followed. RESPONSE TO TREATMENT: Responses are usually apparent by 6 weeks (2 cycles). For patients achieving complete remission (determined by negative electrophoresis and immunofixation), bortezomib should be given for 2 additional cycles beyond the date of confirmed complete remission. In patients with progressive disease after 2 cycles or stable disease after 4 cycles, dexamethasone added to the bortezomib regimen (20 mg by mouth the day of and the day after each bortezomib dose) may produce an objective response. Bortezomib (with or without dexamethasone) should be continued in patients showing benefit from therapy (excluding those in complete remission) unless disease progression or significant toxicity is observed. Therapy should be discontinued in patients who do not respond to bortezomib alone if disease progression is seen within 2 cycles of the addition of dexamethasone. The Hematology dsg recognizes that thalidomide is an active agent in multiple myeloma patients who have relapsed after autologous stem-cell transplantation or who are refractory to alkylating agent-based chemotherapy. To date, no reported rcts have evaluated thalidomide in this role, and specifically, no trials have compared thalidomide with bortezomib. Given these limitations, the members of the Hematology dsg regard thalidomide or bortezomib as therapy alternatives to dexamethasone.

Methodological Challenges in Describing Medication Dosing Errors in Children

DTIC Science & Technology

2005-01-01

recommendations. As an example, amoxicillin is the most commonly used medication in children. This one drug accounts for approximately 10 percent of...and a team intervention on prevention of serious medication errors. JAMA 1998;280(15):1311–6. 13. Bates DW, Teich JM, Lee J, et al. The impact of...barriers include prescribing medication that is not labeled for use in children, discrepancies in published dosing recommendations for many

Cancer inpatients morphine usage: a new England area survey.

PubMed

Trollor, John

2003-08-01

This is a one year study of the use of morphine in cancer patients in 10 inpatient facilities in the New England Area Health Service in the north-west of New South Wales. The study explored 170 admissions relating to 122 patients, most of whom were cared for by their general practitioners. The use of morphine in these cancer patients was compared with the recommendations made by the expert working group of the European Association of Palliative Care.1 Those items which matched the recommendations included the initial doses for new users of morphine and the subcutaneous route being the preferred parenteral route. The data in this study differed from the recommendations in that only half of the patients received the immediate release morphine when first given oral morphine, only 43% had orders for immediate release oral morphine for breakthrough pain (with a variable frequency) and a significant number of orders for parenteral and immediate release oral morphine for breakthrough pain were outside the recommended doses (100% and 86.2%, respectively). Written orders for immediate release oral and parenteral morphine involved a dose range in significant numbers while only 30% of patients had orders for parenteral morphine for breakthrough pain. There was a low use of fixed interval variable dose (FIVD) morphine charts despite these being available in most facilities.

Overdosing of benzodiazepines/Z-drugs and falls in older adults: Costs for the health system.

PubMed

Díaz-Gutiérrez, María José; Cengotitabengoa, Mónica Martínez; Bermúdez-Ampudia, Cristina; García, Sainza; López, Purificación; Martínez-Cengotitabengoa, Mayte; González-Pinto, Ana

2018-05-08

Benzodiazepines and Z drugs (BZD/Z drugs) are commonly used for the treatment of insomnia and anxiety in older adults for long periods of time. Given the physiological and metabolic characteristics of this group of patients, they are more prone to the adverse effects of these drugs which include falls. The recommendations for use of BZD/Z drugs include the need to adjust the dose and select those with a short half-life, to avoid adverse events, which as well as potentially affecting patient outcome, increase healthcare costs. In this study, we have evaluated the hospital-related costs associated with falls in older adults who use BZD/Z drugs at doses higher than recommended for this age group. We conducted a cross-sectional observational study assessing the BZD/Z drug prescriptions of older adults attending the emergency department after a fall. Cost analysis was performed for cases in which the prescriptions exceeded the maximum recommended dose for this age group. A total of 40.6% of the prescriptions recorded were higher than the defined daily dose in older adults (DDD olderadults ). Of the 57 patients who used BZD/Z drugs at higher-than-recommended doses, 53 experienced trauma and 33 required hospitalisation. The costs associated with emergency department services, tests performed and hospitalisation amounted to €1850/patient. Appropriate dosage of BZD/Z drugs in older adults could reduce both patient suffering and costs for the health system. Copyright © 2017. Published by Elsevier Inc.