Does the choice of mobile C-arms lead to a reduction of the intraoperative radiation dose?

PubMed

Richter, P H; Steinbrener, J; Schicho, A; Gebhard, F

2016-08-01

Mobile C-arm imaging is commonly used in operating rooms worldwide. Especially in orthopaedic surgery, intraoperative C-arms are used on a daily basis. Because of new minimally-invasive surgical procedures a development in intraoperative imaging is required. The purpose of this article is investigate if the choice of mobile C-arms with flat panel detector technology (Siemens Cios Alpha and Ziehm Vision RFD) influences image quality and dose using standard, commercially available test devices. For a total of four clinical application settings, two zoom formats, and all dose levels provided, the transmission dose was measured and representative images were recorded for each test device. The data was scored by four observers to assess low contrast and spatial resolution performance. The results were converted to a relative image quality figure allowing for a direct image quality and dose comparison of the two systems. For one test device, the Cios Alpha system achieved equivalent (within the inter-observer standard error) or better low contrast resolution scores at significantly lower dose levels, while the results of the other test device suggested that both systems achieved similar image quality at the same dose. The Cios Alpha system achieved equivalent or better spatial resolution at significantly lower dose for all application settings except for Cardiac, where a comparable spatial resolution was achieved at the same dose. The correct choice of a mobile C-arm is very important, because it can lead to a reduction of the intraoperative radiation dose without negative effects on image quality. This can be a big advantage to reduce intraoperative radiation not only for the patient but also for the entire OR-team. Copyright © 2016. Published by Elsevier Ltd.

Radiation dose reduction in computed tomography: techniques and future perspective

PubMed Central

Yu, Lifeng; Liu, Xin; Leng, Shuai; Kofler, James M; Ramirez-Giraldo, Juan C; Qu, Mingliang; Christner, Jodie; Fletcher, Joel G; McCollough, Cynthia H

2011-01-01

Despite universal consensus that computed tomography (CT) overwhelmingly benefits patients when used for appropriate indications, concerns have been raised regarding the potential risk of cancer induction from CT due to the exponentially increased use of CT in medicine. Keeping radiation dose as low as reasonably achievable, consistent with the diagnostic task, remains the most important strategy for decreasing this potential risk. This article summarizes the general technical strategies that are commonly used for radiation dose management in CT. Dose-management strategies for pediatric CT, cardiac CT, dual-energy CT, CT perfusion and interventional CT are specifically discussed, and future perspectives on CT dose reduction are presented. PMID:22308169

The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments on Schistosoma mansoni Infections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

PubMed Central

Buza, Joram; Mpolya, Emmanuel A.; Angelo, Teckla; Kinung'hi, Safari M.

2017-01-01

Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p < 0.001). The egg reduction rate was higher on repeated dose (97.54%) compared to single dose (87.27%) (p = 0.0062). Geometric mean egg intensity was lower among those on repeated dose (1.30 epg) compared to single dose (3.18 epg) (p = 0.036) but not at 5 (p > 0.05) and 8 (p > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p < 0.001). There was an increase in the mean haemoglobin levels at 8 months with no difference between the two arms (p > 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered with PACTR201601001416338. PMID:29094048

ALARA at nuclear power plants

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

Baum, J.W.

1990-01-01

Implementation of the As Low As Reasonably Achievable (ALARA) principle at nuclear power plants presents a continuing challenge for health physicists at utility corporate and plant levels, for plant designers, and for regulatory agencies. The relatively large collective doses at some plants are being addressed though a variety of dose reduction techniques. It is planned that this report will include material on historical aspects, management, valuation of dose reduction, quantitative and qualitative aspects of optimization, design, operational considerations, and training. The status of this work is summarized in this report. 30 refs., 1 fig., 6 tabs.

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases

NASA Astrophysics Data System (ADS)

Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Murray, Iain; Divoli, Antigoni; McCready, V. Ralph; Dearnaley, David P.; O'Sullivan, Joe M.; Johnson, Bernadette; Flux, Glenn D.

2017-04-01

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  <  0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer.

PubMed

Kourlaba, Georgia; Dimopoulos, Meletios A; Pectasides, Dimitrios; Skarlos, Dimosthenis V; Gogas, Helen; Pentheroudakis, George; Koutras, Angelos; Fountzilas, George; Maniadakis, Nikos

2015-07-01

The aim of this study was to compare the effectiveness of prophylactic single fixed dose of pegfilgrastim and daily administration of filgrastim on febrile neutropenia (FN), severe neutropenia, treatment delay, and dose reduction in patients with breast cancer receiving dose-dense adjuvant chemotherapy. A retrospective cohort study with 1058 breast cancer patients matched by age and chemotherapy was conducted. The primary endpoints were FN, severe (grade 3, 4) neutropenia, dose reduction (>10 % reduction of the dose planned), and treatment delay (dose given more than 2 days later). Eighteen episodes of FN (3.4%) in the filgrastim group and 23 (4.3%) in the pegfilgrastim group (p = 0.500) were recorded. More than half of the total episodes (27/41) occurred during the first 4 cycles of treatment. Patients who received filgrastim were almost three times more likely to experience a severe neutropenia episode and were significantly more likely to experience a dose reduction (18.5%) compared to those who received pegfilgrastim (10.8%) (p < 0.001). The percentage of patients, who received their planned dose on time, was significantly lower in patients receiving filgrastim (58%) compared to those receiving pegfilgrastim (72.4%, p < 0.001). No significant difference was detected on FN rate between daily administration of filgrastim and single administration of pegfilgrastim. However, patients receiving pegfilgrastim had a significantly lower rate of severe neutropenia, as well as dose reduction and treatment delay, thus, achieving a higher dose density.

Periradicular Infiltration of the Cervical Spine: How New CT Scanner Techniques and Protocol Modifications Contribute to the Achievement of Low-Dose Interventions.

PubMed

Elsholtz, Fabian Henry Jürgen; Kamp, Julia Evi-Katrin; Vahldiek, Janis Lucas; Hamm, Bernd; Niehues, Stefan Markus

2018-06-18

 CT-guided periradicular infiltration of the cervical spine is an effective symptomatic treatment in patients with radiculopathy-associated pain syndromes. This study evaluates the robustness and safety of a low-dose protocol on a CT scanner with iterative reconstruction software.  A total of 183 patients who underwent periradicular infiltration therapy of the cervical spine were included in this study. 82 interventions were performed on a new CT scanner with a new intervention protocol using an iterative reconstruction algorithm. Spot scanning was implemented for planning and a basic low-dose setup of 80 kVp and 5 mAs was established during intermittent fluoroscopy. The comparison group included 101 prior interventions on a scanner without iterative reconstruction. The dose-length product (DLP), number of acquisitions, pain reduction on a numeric analog scale, and protocol changes to achieve a safe intervention were recorded.  The median DLP for the whole intervention was 24.3 mGy*cm in the comparison group and 1.8 mGy*cm in the study group. The median pain reduction was -3 in the study group and -2 in the comparison group. A 5 mAs increase in the tube current-time product was required in 5 patients of the study group.  Implementation of a new scanner and intervention protocol resulted in a 92.6 % dose reduction without a compromise in safety and pain relief. The dose needed here is more than 75 % lower than doses used for similar interventions in published studies. An increase of the tube current-time product was needed in only 6 % of interventions.   · The presented ultra-low-dose protocol allows for a significant dose reduction without compromising outcome.. · The protocol includes spot scanning for planning purposes and a basic setup of 80 kVp and 5 mAs.. · The iterative reconstruction algorithm is activated during fluoroscopy.. · Elsholtz FH, Kamp JE, Vahldiek JL et al. Periradicular Infiltration of the Cervical Spine: How New CT Scanner Techniques and Protocol Modifications Contribute to the Achievement of Low-Dose Interventions. Fortschr Röntgenstr 2018; DOI: 10.1055/a-0632-3930. © Georg Thieme Verlag KG Stuttgart · New York.

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

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

Lee, J; Chung, J

2015-06-15

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designedmore » for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.« less

Ultralow Dose MSCT Imaging in Dental Implantology

PubMed Central

Widmann, Gerlig; Al-Ekrish, Asma'a A.

2018-01-01

Introduction: The Council Directive 2013/59 Euratom has a clear commitment for keeping medical radiation exposure as low as reasonably achievable and demands a regular review and use of diagnostic reference levels. Methods: In dental implantology, the range of effective doses for cone beam computed tomography (CBCT) shows a broad overlap with multislice computed tomography (MSCT). More recently, ultralow dose imaging with new generations of MSCT scanners may impart radiation doses equal to or lower than CBCT. Dose reductions in MSCT have been further facilitated by the introduction of iterative image reconstruction technology (IRT), which provides substantial noise reduction over the current standard of filtered backward projection (FBP). Aim: The aim of this article is to review the available literature on ultralow dose CT imaging and IRTs in dental implantology imaging and to summarize their influence on spatial and contrast resolution, image noise, tissue density measurements, and validity of linear measurements of the jaws. Conclusion: Application of ultralow dose MSCT with IRT technology in dental implantology offers the potential for very large dose reductions compared with standard dose imaging. Yet, evaluation of various diagnostic tasks related to dental implantology is still needed to confirm the results obtained with various IRTs and ultra-low doses so far. PMID:29492174

Benchmarking the minimum Electron Beam (eBeam) dose required for the sterilization of space foods

NASA Astrophysics Data System (ADS)

Bhatia, Sohini S.; Wall, Kayley R.; Kerth, Chris R.; Pillai, Suresh D.

2018-02-01

As manned space missions extend in length, the safety, nutrition, acceptability, and shelf life of space foods are of paramount importance to NASA. Since food and mealtimes play a key role in reducing stress and boredom of prolonged missions, the quality of food in terms of appearance, flavor, texture, and aroma can have significant psychological ramifications on astronaut performance. The FDA, which oversees space foods, currently requires a minimum dose of 44 kGy for irradiated space foods. The underlying hypothesis was that commercial sterility of space foods could be achieved at a significantly lower dose, and this lowered dose would positively affect the shelf life of the product. Electron beam processed beef fajitas were used as an example NASA space food to benchmark the minimum eBeam dose required for sterility. A 15 kGy dose was able to achieve an approximately 10 log reduction in Shiga-toxin-producing Escherichia coli bacteria, and a 5 log reduction in Clostridium sporogenes spores. Furthermore, accelerated shelf life testing (ASLT) to determine sensory and quality characteristics under various conditions was conducted. Using Multidimensional gas-chromatography-olfactometry-mass spectrometry (MDGC-O-MS), numerous volatiles were shown to be dependent on the dose applied to the product. Furthermore, concentrations of off -flavor aroma compounds such as dimethyl sulfide were decreased at the reduced 15 kGy dose. The results suggest that the combination of conventional cooking combined with eBeam processing (15 kGy) can achieve the safety and shelf-life objectives needed for long duration space-foods.

Physical activity and incident type 2 diabetes mellitus: a systematic review and dose-response meta-analysis of prospective cohort studies.

PubMed

Smith, Andrea D; Crippa, Alessio; Woodcock, James; Brage, Søren

2016-12-01

Inverse associations between physical activity (PA) and type 2 diabetes mellitus are well known. However, the shape of the dose-response relationship is still uncertain. This review synthesises results from longitudinal studies in general populations and uses non-linear models of the association between PA and incident type 2 diabetes. A systematic literature search identified 28 prospective studies on leisure-time PA (LTPA) or total PA and risk of type 2 diabetes. PA exposures were converted into metabolic equivalent of task (MET) h/week and marginal MET (MMET) h/week, a measure only considering energy expended above resting metabolic rate. Restricted cubic splines were used to model the exposure-disease relationship. Our results suggest an overall non-linear relationship; using the cubic spline model we found a risk reduction of 26% (95% CI 20%, 31%) for type 2 diabetes among those who achieved 11.25 MET h/week (equivalent to 150 min/week of moderate activity) relative to inactive individuals. Achieving twice this amount of PA was associated with a risk reduction of 36% (95% CI 27%, 46%), with further reductions at higher doses (60 MET h/week, risk reduction of 53%). Results for the MMET h/week dose-response curve were similar for moderate intensity PA, but benefits were greater for higher intensity PA and smaller for lower intensity activity. Higher levels of LTPA were associated with substantially lower incidence of type 2 diabetes in the general population. The relationship between LTPA and type 2 diabetes was curvilinear; the greatest relative benefits are achieved at low levels of activity, but additional benefits can be realised at exposures considerably higher than those prescribed by public health recommendations.

Paediatric x-ray radiation dose reduction and image quality analysis.

PubMed

Martin, L; Ruddlesden, R; Makepeace, C; Robinson, L; Mistry, T; Starritt, H

2013-09-01

Collaboration of multiple staff groups has resulted in significant reduction in the risk of radiation-induced cancer from radiographic x-ray exposure during childhood. In this study at an acute NHS hospital trust, a preliminary audit identified initial exposure factors. These were compared with European and UK guidance, leading to the introduction of new factors that were in compliance with European guidance on x-ray tube potentials. Image quality was assessed using standard anatomical criteria scoring, and visual grading characteristics analysis assessed the impact on image quality of changes in exposure factors. This analysis determined the acceptability of gradual radiation dose reduction below the European and UK guidance levels. Chest and pelvis exposures were optimised, achieving dose reduction for each age group, with 7%-55% decrease in critical organ dose. Clinicians confirmed diagnostic image quality throughout the iterative process. Analysis of images acquired with preliminary and final exposure factors indicated an average visual grading analysis result of 0.5, demonstrating equivalent image quality. The optimisation process and final radiation doses are reported for Carestream computed radiography to aid other hospitals in minimising radiation risks to children.

Achieving routine submillisievert CT scanning: report from the summit on management of radiation dose in CT.

PubMed

McCollough, Cynthia H; Chen, Guang Hong; Kalender, Willi; Leng, Shuai; Samei, Ehsan; Taguchi, Katsuyuki; Wang, Ge; Yu, Lifeng; Pettigrew, Roderic I

2012-08-01

This Special Report presents the consensus of the Summit on Management of Radiation Dose in Computed Tomography (CT) (held in February 2011), which brought together participants from academia, clinical practice, industry, and regulatory and funding agencies to identify the steps required to reduce the effective dose from routine CT examinations to less than 1 mSv. The most promising technologies and methods discussed at the summit include innovations and developments in x-ray sources; detectors; and image reconstruction, noise reduction, and postprocessing algorithms. Access to raw projection data and standard data sets for algorithm validation and optimization is a clear need, as is the need for new, clinically relevant metrics of image quality and diagnostic performance. Current commercially available techniques such as automatic exposure control, optimization of tube potential, beam-shaping filters, and dynamic z-axis collimators are important, and education to successfully implement these methods routinely is critically needed. Other methods that are just becoming widely available, such as iterative reconstruction, noise reduction, and postprocessing algorithms, will also have an important role. Together, these existing techniques can reduce dose by a factor of two to four. Technical advances that show considerable promise for additional dose reduction but are several years or more from commercial availability include compressed sensing, volume of interest and interior tomography techniques, and photon-counting detectors. This report offers a strategic roadmap for the CT user and research and manufacturer communities toward routinely achieving effective doses of less than 1 mSv, which is well below the average annual dose from naturally occurring sources of radiation.

Treatment of carprofen overdose with therapeutic plasma exchange in a dog.

PubMed

Kjaergaard, Astrid B; Davis, Jennifer L; Acierno, Mark J

2018-06-13

To report the use of therapeutic plasma exchange (TPE) in a dog with carprofen toxicosis. A 6-year-old female neutered Bichon Frise weighing 6.9 kg was examined after it had ingested 72 mg/kg carprofen. Mild dehydration without azotemia and with a urine specific gravity of 1.050 was noted at presentation. Treatment consisted of induction of emesis, symptomatic medical therapy, and TPE. The TPE achieved 1.5 plasma volume exchanges over 3 hours. Blood samples and effluent samples were collected every 30 minutes during TPE and additional blood samples were collected 11 and 35 hours after treatment. Carprofen concentrations in these samples were determined by high-pressure liquid chromatography. A 51% reduction in serum carprofen concentration was achieved following TPE. This report describes the successful reduction of plasma carprofen concentration in a dog using TPE. Although recent studies suggest that this particular dog may not have received a toxic dose, a 51% reduction of plasma carprofen concentration was achieved over 180 minutes, and TPE may be beneficial for treatment of dogs that have ingested higher doses. © Veterinary Emergency and Critical Care Society 2018.

Role of high-dose levetiracetam as add-on therapy for intractable epilepsy: case report and brief review of the literature.

PubMed

Mateo-Carrasco, Hector; Serrano-Castro, Pedro Jesús; Molina-Cuadrado, Emilio; Goodwin, Mel; Nguyen, Timothy V; Kotecha, Primal N

2015-08-01

We discuss the case of a 5-year-old long-standing epileptic woman, who received oxcarbazepine 2.1 g/day, and levetiracetam 3 g/day (started in 2005 and up-titrated according to response). In October/2008, due to poor seizure control, patient consent was obtained and levetiracetam up-titrated to 6 g/day, remaining invariable for 72 months; zonisamide was added in July/2009 and up-titrated to 500 mg/day. This combination achieved seizure frequency reduction ≥50 %, however, the patient ultimately necessitated temporal lobectomy for complete remission. Occasional agitation and moderate depression were the main side effects. Three anti-epileptic drugs (including levetiracetam 6 g/day) achieved statistically-significant seizure frequency reduction ≥50 % compared with lower doses, but not seizure freedom. Low-dose risperidone was initiated due to transient dose-dependent agitation, although it did not lead to discontinuation. This report provides insightful information on the use of high-dose levetiracetam in focal refractory epilepsy. The concomitance of anti-epileptics may have contributed to both efficacy and toxicity. Therefore, the risk/benefit ratio must be individually weighed until larger studies are available.

Task-based image quality evaluation of iterative reconstruction methods for low dose CT using computer simulations

NASA Astrophysics Data System (ADS)

Xu, Jingyan; Fuld, Matthew K.; Fung, George S. K.; Tsui, Benjamin M. W.

2015-04-01

Iterative reconstruction (IR) methods for x-ray CT is a promising approach to improve image quality or reduce radiation dose to patients. The goal of this work was to use task based image quality measures and the channelized Hotelling observer (CHO) to evaluate both analytic and IR methods for clinical x-ray CT applications. We performed realistic computer simulations at five radiation dose levels, from a clinical reference low dose D0 to 25% D0. A fixed size and contrast lesion was inserted at different locations into the liver of the XCAT phantom to simulate a weak signal. The simulated data were reconstructed on a commercial CT scanner (SOMATOM Definition Flash; Siemens, Forchheim, Germany) using the vendor-provided analytic (WFBP) and IR (SAFIRE) methods. The reconstructed images were analyzed by CHOs with both rotationally symmetric (RS) and rotationally oriented (RO) channels, and with different numbers of lesion locations (5, 10, and 20) in a signal known exactly (SKE), background known exactly but variable (BKEV) detection task. The area under the receiver operating characteristic curve (AUC) was used as a summary measure to compare the IR and analytic methods; the AUC was also used as the equal performance criterion to derive the potential dose reduction factor of IR. In general, there was a good agreement in the relative AUC values of different reconstruction methods using CHOs with RS and RO channels, although the CHO with RO channels achieved higher AUCs than RS channels. The improvement of IR over analytic methods depends on the dose level. The reference dose level D0 was based on a clinical low dose protocol, lower than the standard dose due to the use of IR methods. At 75% D0, the performance improvement was statistically significant (p < 0.05). The potential dose reduction factor also depended on the detection task. For the SKE/BKEV task involving 10 lesion locations, a dose reduction of at least 25% from D0 was achieved.

SU-C-18C-06: Radiation Dose Reduction in Body Interventional Radiology: Clinical Results Utilizing a New Imaging Acquisition and Processing Platform

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

Kohlbrenner, R; Kolli, KP; Taylor, A

2014-06-01

Purpose: To quantify the patient radiation dose reduction achieved during transarterial chemoembolization (TACE) procedures performed in a body interventional radiology suite equipped with the Philips Allura Clarity imaging acquisition and processing platform, compared to TACE procedures performed in the same suite equipped with the Philips Allura Xper platform. Methods: Total fluoroscopy time, cumulative dose area product, and cumulative air kerma were recorded for the first 25 TACE procedures performed to treat hepatocellular carcinoma (HCC) in a Philips body interventional radiology suite equipped with Philips Allura Clarity. The same data were collected for the prior 85 TACE procedures performed to treatmore » HCC in the same suite equipped with Philips Allura Xper. Mean values from these cohorts were compared using two-tailed t tests. Results: Following installation of the Philips Allura Clarity platform, a 42.8% reduction in mean cumulative dose area product (3033.2 versus 1733.6 mGycm∧2, p < 0.0001) and a 31.2% reduction in mean cumulative air kerma (1445.4 versus 994.2 mGy, p < 0.001) was achieved compared to similar procedures performed in the same suite equipped with the Philips Allura Xper platform. Mean total fluoroscopy time was not significantly different between the two cohorts (1679.3 versus 1791.3 seconds, p = 0.41). Conclusion: This study demonstrates a significant patient radiation dose reduction during TACE procedures performed to treat HCC after a body interventional radiology suite was converted to the Philips Allura Clarity platform from the Philips Allura Xper platform. Future work will focus on evaluation of patient dose reduction in a larger cohort of patients across a broader range of procedures and in specific populations, including obese patients and pediatric patients, and comparison of image quality between the two platforms. Funding for this study was provided by Philips Healthcare, with 5% salary support provided to authors K. Pallav Kolli and Robert G. Gould for time devoted to the study. Data acquisition and analysis was performed by the authors independent of the funding source.« less

Selection of process conditions by risk assessment for apple juice pasteurization by UV-heat treatments at moderate temperatures.

PubMed

Gayán, E; Torres, J A; Alvarez, I; Condón, S

2014-02-01

The effect of bactericidal UV-C treatments (254 nm) on Escherichia coli O157:H7 suspended in apple juice increased synergistically with temperature up to a threshold value. The optimum UV-C treatment temperature was 55 °C, yielding a 58.9% synergistic lethal effect. Under these treatment conditions, the UV-heat (UV-H55 °C) lethal variability achieving 5-log reductions had a logistic distribution (α = 37.92, β = 1.10). Using this distribution, UV-H55 °C doses to achieve the required juice safety goal with 95, 99, and 99.9% confidence were 41.17, 42.97, and 46.00 J/ml, respectively, i.e., doses higher than the 37.58 J/ml estimated by a deterministic procedure. The public health impact of these results is that the larger UV-H55 °C dose required for achieving 5-log reductions with 95, 99, and 99.9% confidence would reduce the probability of hemolytic uremic syndrome in children by 76.3, 88.6, and 96.9%, respectively. This study illustrates the importance of including the effect of data variability when selecting operational parameters for novel and conventional preservation processes to achieve high food safety standards with the desired confidence level.

Population Pharmacokinetics of Enoxaparin in Pediatric Patients.

PubMed

Moffett, Brady S; Lee-Kim, YoungNa; Galati, Marianne; Mahoney, Donald; Shah, Mona D; Teruya, Jun; Yee, Donald

2018-02-01

There are no studies evaluating the pharmacokinetics of enoxaparin in the hospitalized pediatric patient population. To characterize the pharmacokinetics of enoxaparin in pediatric patients. A retrospective review of inpatients 1 to 18 years of age admitted to our institution who received enoxaparin with anti-factor Xa activity level monitoring was performed. Demographic variables, enoxaparin dosing, and anti-factor Xa activity levels were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. Simulation (n = 10 000) was performed to determine the percentage who achieved targeted anti-Xa levels at various doses. A total of 853 patients (male 52.1%, median age = 12.2 years; interquartile range [IQR] = 4.6-15.8 years) received a mean enoxaparin dose of 0.86 ± 0.31 mg/kg/dose. A median of 3 (IQR = 1-5) anti-factor Xa levels were sampled at 4.4 ± 1.3 hours after a dose, with a mean anti-factor Xa level of 0.52 ± 0.23 U/mL. A 1-compartment model best fit the data, and significant covariates included allometrically scaled weight, serum creatinine, and hematocrit on clearance, and platelets on volume of distribution. Simulations were run for patients both without and with reduced kidney function (creatinine clearance of ≤30 mL/min/1.73 m 2 ). A dose of 1 mg/kg/dose every 12 hours had the highest probability (72.3%) of achieving an anti-Xa level within the target range (0.5-1 U/mL), whereas a dose reduction of ~30% achieved the same result in patients with reduced kidney function. Pediatric patients should initially be dosed at 1-mg/kg/dose subcutaneously every 12 hours for treatment of thromboembolism followed by anti-Xa activity monitoring. Dose reductions of ~30% for creatinine clearance ≤30 mL/min/1.73 m 2 are required.

Dose comparison between conventional and quasi-monochromatic systems for diagnostic radiology

NASA Astrophysics Data System (ADS)

Baldelli, P.; Taibi, A.; Tuffanelli, A.; Gambaccini, M.

2004-09-01

Several techniques have been introduced in the last year to reduce the dose to the patient by minimizing the risk of tumour induced by radiation. In this work the radiological potential of dose reduction in quasi-monochromatic spectra produced via mosaic crystal Bragg diffraction has been evaluated, and a comparison with conventional spectra has been performed for four standard examinations: head, chest, abdomen and lumbar sacral spine. We have simulated quasi-monochromatic x-rays with the Shadow code, and conventional spectra with the Spectrum Processor. By means of the PCXMC software, we have simulated four examinations according to parameters established by the European Guidelines, and calculated absorbed dose for principal organs and the effective dose. Simulations of quasi-monochromatic laminar beams have been performed without anti-scatter grid, because of their inherent scatter geometry, and compared with simulations with conventional beams with anti-scatter grids. Results have shown that the dose reduction due to the introduction of quasi-monochromatic x-rays depends on different parameters related to the quality of the beam, the organ composition and the anti-scatter grid. With parameters chosen in this study a significant dose reduction can be achieved for two out of four kinds of examination.

Evidence of dose saving in routine CT practice using iterative reconstruction derived from a national diagnostic reference level survey.

PubMed

Thomas, P; Hayton, A; Beveridge, T; Marks, P; Wallace, A

2015-09-01

To assess the influence and significance of the use of iterative reconstruction (IR) algorithms on patient dose in CT in Australia. We examined survey data submitted to the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) National Diagnostic Reference Level Service (NDRLS) during 2013 and 2014. We compared median survey dose metrics with categorization by scan region and use of IR. The use of IR results in a reduction in volume CT dose index of between 17% and 44% and a reduction in dose-length product of between 14% and 34% depending on the specific scan region. The reduction was highly significant (p < 0.001, Wilcoxon rank-sum test) for all six scan regions included in the NDRLS. Overall, 69% (806/1167) of surveys included in the analysis used IR. The use of IR in CT is achieving dose savings of 20-30% in routine practice in Australia. IR appears to be widely used by participants in the ARPANSA NDRLS with approximately 70% of surveys submitted employing this technique. This study examines the impact of the use of IR on patient dose in CT on a national scale.

Achieving Routine Submillisievert CT Scanning: Report from the Summit on Management of Radiation Dose in CT

PubMed Central

Chen, Guang Hong; Kalender, Willi; Leng, Shuai; Samei, Ehsan; Taguchi, Katsuyuki; Wang, Ge; Yu, Lifeng; Pettigrew, Roderic I.

2012-01-01

This Special Report presents the consensus of the Summit on Management of Radiation Dose in Computed Tomography (CT) (held in February 2011), which brought together participants from academia, clinical practice, industry, and regulatory and funding agencies to identify the steps required to reduce the effective dose from routine CT examinations to less than 1 mSv. The most promising technologies and methods discussed at the summit include innovations and developments in x-ray sources; detectors; and image reconstruction, noise reduction, and postprocessing algorithms. Access to raw projection data and standard data sets for algorithm validation and optimization is a clear need, as is the need for new, clinically relevant metrics of image quality and diagnostic performance. Current commercially available techniques such as automatic exposure control, optimization of tube potential, beam-shaping filters, and dynamic z-axis collimators are important, and education to successfully implement these methods routinely is critically needed. Other methods that are just becoming widely available, such as iterative reconstruction, noise reduction, and postprocessing algorithms, will also have an important role. Together, these existing techniques can reduce dose by a factor of two to four. Technical advances that show considerable promise for additional dose reduction but are several years or more from commercial availability include compressed sensing, volume of interest and interior tomography techniques, and photon-counting detectors. This report offers a strategic roadmap for the CT user and research and manufacturer communities toward routinely achieving effective doses of less than 1 mSv, which is well below the average annual dose from naturally occurring sources of radiation. © RSNA, 2012 PMID:22692035

Dose reduction of up to 89% while maintaining image quality in cardiovascular CT achieved with prospective ECG gating

NASA Astrophysics Data System (ADS)

Londt, John H.; Shreter, Uri; Vass, Melissa; Hsieh, Jiang; Ge, Zhanyu; Adda, Olivier; Dowe, David A.; Sabllayrolles, Jean-Louis

2007-03-01

We present the results of dose and image quality performance evaluation of a novel, prospective ECG-gated Coronary CT Angiography acquisition mode (SnapShot Pulse, LightSpeed VCT-XT scanner, GE Healthcare, Waukesha, WI), and compare it to conventional retrospective ECG gated helical acquisition in clinical and phantom studies. Image quality phantoms were used to measure noise, slice sensitivity profile, in-plane resolution, low contrast detectability and dose, using the two acquisition modes. Clinical image quality and diagnostic confidence were evaluated in a study of 31 patients scanned with the two acquisition modes. Radiation dose reduction in clinical practice was evaluated by tracking 120 consecutive patients scanned with the prospectively gated scan mode. In the phantom measurements, the prospectively gated mode resulted in equivalent or better image quality measures at dose reductions of up to 89% compared to non-ECG modulated conventional helical scans. In the clinical study, image quality was rated excellent by expert radiologist reviewing the cases, with pathology being identical using the two acquisition modes. The average dose to patients in the clinical practice study was 5.6 mSv, representing 50% reduction compared to a similar patient population scanned with the conventional helical mode.

Model-based iterative reconstruction for reduction of radiation dose in abdominopelvic CT: comparison to adaptive statistical iterative reconstruction.

PubMed

Yasaka, Koichiro; Katsura, Masaki; Akahane, Masaaki; Sato, Jiro; Matsuda, Izuru; Ohtomo, Kuni

2013-12-01

To evaluate dose reduction and image quality of abdominopelvic computed tomography (CT) reconstructed with model-based iterative reconstruction (MBIR) compared to adaptive statistical iterative reconstruction (ASIR). In this prospective study, 85 patients underwent referential-, low-, and ultralow-dose unenhanced abdominopelvic CT. Images were reconstructed with ASIR for low-dose (L-ASIR) and ultralow-dose CT (UL-ASIR), and with MBIR for ultralow-dose CT (UL-MBIR). Image noise was measured in the abdominal aorta and iliopsoas muscle. Subjective image analyses and a lesion detection study (adrenal nodules) were conducted by two blinded radiologists. A reference standard was established by a consensus panel of two different radiologists using referential-dose CT reconstructed with filtered back projection. Compared to low-dose CT, there was a 63% decrease in dose-length product with ultralow-dose CT. UL-MBIR had significantly lower image noise than L-ASIR and UL-ASIR (all p<0.01). UL-MBIR was significantly better for subjective image noise and streak artifacts than L-ASIR and UL-ASIR (all p<0.01). There were no significant differences between UL-MBIR and L-ASIR in diagnostic acceptability (p>0.65), or diagnostic performance for adrenal nodules (p>0.87). MBIR significantly improves image noise and streak artifacts compared to ASIR, and can achieve radiation dose reduction without severely compromising image quality.

Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

NASA Astrophysics Data System (ADS)

Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

2014-03-01

We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

Prospective ECG-Triggered Coronary CT Angiography: Clinical Value of Noise-Based Tube Current Reduction Method with Iterative Reconstruction

PubMed Central

Shen, Junlin; Du, Xiangying; Guo, Daode; Cao, Lizhen; Gao, Yan; Yang, Qi; Li, Pengyu; Liu, Jiabin; Li, Kuncheng

2013-01-01

Objectives To evaluate the clinical value of noise-based tube current reduction method with iterative reconstruction for obtaining consistent image quality with dose optimization in prospective electrocardiogram (ECG)-triggered coronary CT angiography (CCTA). Materials and Methods We performed a prospective randomized study evaluating 338 patients undergoing CCTA with prospective ECG-triggering. Patients were randomly assigned to fixed tube current with filtered back projection (Group 1, n = 113), noise-based tube current with filtered back projection (Group 2, n = 109) or with iterative reconstruction (Group 3, n = 116). Tube voltage was fixed at 120 kV. Qualitative image quality was rated on a 5-point scale (1 = impaired, to 5 = excellent, with 3–5 defined as diagnostic). Image noise and signal intensity were measured; signal-to-noise ratio was calculated; radiation dose parameters were recorded. Statistical analyses included one-way analysis of variance, chi-square test, Kruskal-Wallis test and multivariable linear regression. Results Image noise was maintained at the target value of 35HU with small interquartile range for Group 2 (35.00–35.03HU) and Group 3 (34.99–35.02HU), while from 28.73 to 37.87HU for Group 1. All images in the three groups were acceptable for diagnosis. A relative 20% and 51% reduction in effective dose for Group 2 (2.9 mSv) and Group 3 (1.8 mSv) were achieved compared with Group 1 (3.7 mSv). After adjustment for scan characteristics, iterative reconstruction was associated with 26% reduction in effective dose. Conclusion Noise-based tube current reduction method with iterative reconstruction maintains image noise precisely at the desired level and achieves consistent image quality. Meanwhile, effective dose can be reduced by more than 50%. PMID:23741444

Utilizing placebo mechanisms for dose reduction in pharmacotherapy.

PubMed

Doering, Bettina K; Rief, Winfried

2012-03-01

The knowledge and systematic application of the placebo effect remains limited, although its importance to the treatment of various medical conditions has increasingly been recognized. A possible application of the placebo effect to pharmacotherapy is seen in conditioning processes that aim at a placebo-controlled dose reduction of drugs while maintaining the efficacy of the medical treatment. The pairing of a placebo and a pharmacological agent may achieve satisfactory treatment outcomes in combination with a lower dose of medication. This procedure includes classic and instrumental conditioning processes that involve both conscious and non-conscious information processing. Although recent studies have gathered preliminary evidence for the efficacy of placebo-controlled dose reduction (e.g. in psoriasis and attention deficit hyperactivity disorder [ADHD]), they have also illustrated the difficulties that are inherent to this approach. We critically review previous approaches and discuss designs for clinical trials that seem appropriate to the investigation of conditioned placebo effects in pharmacotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

TH-EF-BRB-03: Significant Cord and Esophagus Dose Reduction by 4π Non-Coplanar Spine Stereotactic Body Radiation Therapy and Stereotactic Radiosurgery

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

Yu, V; Tran, A; Nguyen, D

Purpose: To demonstrate significant organ-at-risk (OAR) sparing achievable with 4π non-coplanar radiotherapy on spine SBRT and SRS patients. Methods: Twenty-five stereotactic spine cases previously treated with VMAT (n = 23) or IMRT (n = 2) were included in this study. A computer-aided-design model of a Linac with a 3D-scanned human surface was utilized to determine the feasible beam space throughout the 4π steradian and beam specific source-to-target-distances (STD) required for collision avoidance. 4π radiotherapy plans integrating beam orientation and fluence map optimization were then created using a column-generation algorithm. Twenty optimal beams were selected for each case. To evaluate themore » tradeoff between dosimetric benefit and treatment complexity, 4π plans including only isocentrically deliverable beams were also created. Beam angles of all standard and isocentric 4π plans were imported into Eclipse to recalculate the dose using the same calculation engine as the clinical plans for unbiased comparison. OAR and PTV dose statistics for the clinical, standard-4π, and isocentric-4π plans were compared. Results: Comparing standard-4π to clinical plans, particularly significant average percent reduction in the [mean, maximum] dose of the cord and esophagus of [41%, 21.7%], and [38.7%, 36.4%] was observed, along with global decrease in all other OAR dose statistics. The average cord volume receiving more than 50% prescription dose was substantially decreased by 76%. In addition, improved PTV coverage was demonstrated with a maximum dose reduction of 0.93% and 1.66% increase in homogeneity index (D95/D5). All isocentric-4π plans achieved dosimetric performance equivalent to that of the standard-4π plans with higher delivery complexity. Conclusion: 4π radiotherapy significantly improves stereotactic spine treatment dosimetry. With the substantial OAR dose sparing, PTV dose escalation is considerably safer. Isocentric-4π is sufficient to achieve the dosimetric gain. The successful implementation of 4π using an FDA approved planning system paves the way for a prospective clinical trial. Varian Medical Systems, NIH R43CA183390 and R01CA188300, NSF graduate research fellowship DGE-1144087.« less

SU-G-BRC-02: A Novel Multi-Criteria Optimization Approach to Generate Deliverable Intensity-Modulated Radiation Therapy (IMRT) Treatment Plans

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

Kirlik, G; D’Souza, W; Zhang, H

2016-06-15

Purpose: To present a novel multi-criteria optimization (MCO) solution approach that generates treatment plans with deliverable apertures using column generation. Methods: We demonstrate our method with 10 locally advanced head-and-neck cancer cases retrospectively. In our MCO formulation, we defined an objective function for each structure in the treatment volume. This resulted in 9 objective functions, including 3 distinct objectives for primary target volume, high-risk and low-risk target volumes, 5 objectives for each of the organs-at-risk (OARs) (two parotid glands, spinal cord, brain stem and oral cavity), and one for the non-target non-OAR normal tissue. Conditional value-at-risk (CVaR) constraints were utilizedmore » to ensure at least certain fraction of the target volumes receiving the prescription doses. To directly generate deliverable plans, column generation algorithm was embedded within our MCO approach for aperture shape generation. Final dose distributions for all plans were generated using a Monte Carlo kernel-superposition dose calculation. We compared the MCO plans with the clinical plans, which were created by clinicians. Results: At least 95% target coverage was achieved by both MCO plans and clinical plans. However, the average conformity indices of clinical plans and the MCO plans were 1.95 and 1.35, respectively (31% reduction, p<0.01). Compared to the conventional clinical plan, the proposed MCO method achieved average reductions in left parotid mean dose of 5% (p=0.06), right parotid mean dose of 18% (p<0.01), oral cavity mean dose of 21% (p=0.03), spinal cord maximum dose of 20% (p<0.01), brain stem maximum dose of 61% (p<0.01), and normal tissue maximum dose of 5% (p<0.01), respectively. Conclusion: We demonstrated that the proposed MCO method was able to obtain deliverable IMRT treatment plans while achieving significant improvements in dosimetric plan quality.« less

Dose reduction of risperidone and olanzapine and estimated dopamine D₂ receptor occupancy in stable patients with schizophrenia: findings from an open-label, randomized, controlled study.

PubMed

Takeuchi, Hiroyoshi; Suzuki, Takefumi; Bies, Robert R; Remington, Gary; Watanabe, Koichiro; Mimura, Masaru; Uchida, Hiroyuki

2014-11-01

While acute-phase antipsychotic response has been attributed to 65%-80% dopamine D₂ receptor blockade, the degree of occupancy for relapse prevention in the maintenance treatment of schizophrenia remains unknown. In this secondary study of an open-label, 28-week, randomized, controlled trial conducted between April 2009 and August 2011, clinically stable patients with schizophrenia (DSM-IV) treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50%) or maintenance group (dose kept constant). Plasma antipsychotic concentrations at peak and trough before and after dose reduction were estimated with population pharmacokinetic techniques, using 2 collected plasma samples. Corresponding dopamine D₂ occupancy levels were then estimated using the model we developed. Relapse was defined as worsening in 4 Positive and Negative Syndrome Scale-Positive subscale items: delusion, conceptual disorganization, hallucinatory behavior, and suspiciousness. Plasma antipsychotic concentrations were available for 16 and 15 patients in the reduction and maintenance groups, respectively. Estimated dopamine D₂ occupancy (mean ± SD) decreased following dose reduction from 75.6% ± 4.9% to 66.8% ± 6.4% at peak and 72.3% ± 5.7% to 62.0% ± 6.8% at trough. In the reduction group, 10 patients (62.5%) did not demonstrate continuous D₂ receptor blockade above 65% (ie, < 65% at trough) after dose reduction; furthermore, 7 patients (43.8%) did not achieve a threshold of 65% occupancy even at peak. Nonetheless, only 1 patient met our relapse criteria after dose reduction during the 6 months of the study. The results suggest that the therapeutic threshold regarding dopamine D₂ occupancy may be lower for those who are stable in antipsychotic maintenance versus acute-phase treatment. Positron emission tomography studies are warranted to further test our preliminary findings. UMIN Clinical Trials Registry identifier: UMIN000001834. © Copyright 2014 Physicians Postgraduate Press, Inc.

Pediatric CT: implementation of ASIR for substantial radiation dose reduction while maintaining pre-ASIR image noise.

PubMed

Brady, Samuel L; Moore, Bria M; Yee, Brian S; Kaufman, Robert A

2014-01-01

To determine a comprehensive method for the implementation of adaptive statistical iterative reconstruction (ASIR) for maximal radiation dose reduction in pediatric computed tomography (CT) without changing the magnitude of noise in the reconstructed image or the contrast-to-noise ratio (CNR) in the patient. The institutional review board waived the need to obtain informed consent for this HIPAA-compliant quality analysis. Chest and abdominopelvic CT images obtained before ASIR implementation (183 patient examinations; mean patient age, 8.8 years ± 6.2 [standard deviation]; range, 1 month to 27 years) were analyzed for image noise and CNR. These measurements were used in conjunction with noise models derived from anthropomorphic phantoms to establish new beam current-modulated CT parameters to implement 40% ASIR at 120 and 100 kVp without changing noise texture or magnitude. Image noise was assessed in images obtained after ASIR implementation (492 patient examinations; mean patient age, 7.6 years ± 5.4; range, 2 months to 28 years) the same way it was assessed in the pre-ASIR analysis. Dose reduction was determined by comparing size-specific dose estimates in the pre- and post-ASIR patient cohorts. Data were analyzed with paired t tests. With 40% ASIR implementation, the average relative dose reduction for chest CT was 39% (2.7/4.4 mGy), with a maximum reduction of 72% (5.3/18.8 mGy). The average relative dose reduction for abdominopelvic CT was 29% (4.8/6.8 mGy), with a maximum reduction of 64% (7.6/20.9 mGy). Beam current modulation was unnecessary for patients weighing 40 kg or less. The difference between 0% and 40% ASIR noise magnitude was less than 1 HU, with statistically nonsignificant increases in patient CNR at 100 kVp of 8% (15.3/14.2; P = .41) for chest CT and 13% (7.8/6.8; P = .40) for abdominopelvic CT. Radiation dose reduction at pediatric CT was achieved when 40% ASIR was implemented as a dose reduction tool only; no net change to the magnitude of noise in the reconstructed image or the patient CNR occurred. © RSNA, 2013.

Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies

PubMed Central

Gomes, Melba; Ribeiro, Isabela; Warsame, Marian; Karunajeewa, Harin; Petzold, Max

2008-01-01

Background Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria. Methods Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of Plasmodium falciparum parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success. Results Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether. Conclusion Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy. PMID:18373841

Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd.

PubMed

Hughes, Timothy P; Munhoz, Eduardo; Aurelio Salvino, Marco; Ong, Tee Chuan; Elhaddad, Alaa; Shortt, Jake; Quach, Hang; Pavlovsky, Carolina; Louw, Vernon J; Shih, Lee-Yung; Turkina, Anna G; Meillon, Luis; Jin, Yu; Acharya, Sandip; Dalal, Darshan; Lipton, Jeffrey H

2017-10-01

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188). © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate.

PubMed

Bonekamp, David; Wolf, M B; Roethke, M C; Pahernik, S; Hadaschik, B A; Hatiboglu, G; Kuru, T H; Popeneciu, I V; Chin, J L; Billia, M; Relle, J; Hafron, J; Nandalur, K R; Staruch, R M; Burtnyk, M; Hohenfellner, M; Schlemmer, H-P

2018-06-25

To quantitatively assess 12-month prostate volume (PV) reduction based on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non-perfused volume (NPV), and to compare measurements with predictions of acute and delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology review of the Phase I clinical trial of MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer. Treatment day MRI and 12-month follow-up MRI and biopsy were available for central radiology review in 29 of 30 patients from the published institutional review board-approved, prospective, multi-centre, single-arm Phase I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in 12-month biopsy cores. Reduction of viable PV was compared to predictions based on the fraction of the prostate covered by the MR-t derived acute thermal ablation volume (ATAV, 55°C isotherm), delayed thermal ablation volume (DTAV, 240 cumulative equivalent minutes at 43°C thermal dose isocontour) and treatment-day NPV. We also report linear and volumetric comparisons between metrics. After TULSA, the median 12-month reduction in viable PV was 88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53% volume reduction, and underestimated ATAV and DTAV by 36% and 51%. Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV (240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue reduction at 12 months. Immediate post-treatment NPV underestimates tissue ablation. • MRI-guided transurethral ultrasound ablation (TULSA) achieved an 88% reduction of viable prostate tissue volume at 12 months, in excellent agreement with expectation from thermal dose calculations. • Non-perfused volume on immediate post-treatment contrast-enhanced MRI represents only 64% of the acute thermal ablation volume (ATAV), and reports only 60% (53% instead of 88% achieved) of the reduction in viable prostate tissue volume at 12 months. • MR-thermometry-based predictions of 12-month prostate volume reduction based on 240 cumulative equivalent minute thermal dose volume are in excellent agreement with reduction in viable prostate tissue volume measured on pre- and 12-month post-treatment T2w-MRI.

A novel applicator design for intracavitary brachytherapy of the nasopharynx: Simulated reconstruction, image-guided adaptive brachytherapy planning, and dosimetry.

PubMed

Bacorro, Warren R; Agas, Ryan Anthony F; Cabrera, Stellar Marie R; Bojador, Maureen R; Sogono, Paolo G; Mejia, Michael Benedict A; Sy Ortin, Teresa T

2018-05-11

In nasopharyngeal cancer, brachytherapy is given as boost in primary treatment or as salvage for recurrent or persistent disease. The Rotterdam nasopharyngeal applicator (RNA) allows for suboptimal reduction of soft palate radiation dose, based on image-guided brachytherapy plans. Building on the RNA, we propose a novel design, the Benavides nasopharyngeal applicator (BNA). The virtual BNA was reconstructed on two cases (one T1, one T2) previously treated with intracavitary brachytherapy using the RNA. Dose was prescribed to the high-risk clinical target volumes (CTVs) and optimization was such that high-risk CTV D90 ≥ 100% of prescribed dose (PD), intermediate-risk-CTV D90 ≥ 75% PD, and soft palate D2cc ≤ 120% PD. The optimized RNA and BNA image-guided brachytherapy plans were compared in terms of CTV coverage and organs-at-risk sparing. Optimization objectives were more easily met with the BNA. For the T1 case, all three planning objectives were easily achieved in both the RNA and BNA, but with 18-19% lower soft palate doses with the BNA. For the T2 case, the CTV planning objectives were achieved in both the RNA and BNA, but the soft palate constraint was only achieved with the BNA, with 38-41% lower soft palate doses. Compared to the RNA, the BNA permits easier optimization and improves therapeutic ratio by a significant reduction of soft palate doses, based on simulation using a proposed system for CTV/organs-at-risk delineation, prescription, and optimization for image-guided adaptive brachytherapy. Clinical piloting using a prototype is necessary to evaluate its feasibility and utility. Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

A study on the dependence of exposure dose reduction and image evaluation on the distance from the dental periapical X-ray machine

NASA Astrophysics Data System (ADS)

Joo, Kyu-Ji; Shin, Jae-Woo; Dong, Kyung-Rae; Lim, Chang-Seon; Chung, Woon-Kwan; Kim, Young-Jae

2013-11-01

Reducing the exposure dose from a periapical X-ray machine is an important aim in dental radiography. Although the radiation exposure dose is generally low, any radiation exposure is harmful to the human body. Therefore, this study developed a method that reduces the exposure dose significantly compared to that encountered in a normal procedure, but still produces an image with a similar resolution. The correlation between the image resolution and the exposure dose of the proposed method was examined with increasing distance between the dosimeter and the X-ray tube. The results were compared with those obtained from the existing radiography method. When periapical radiography was performed once according to the recommendations of the International Commission on Radiological Protection (ICRP), the measured skin surface dose was low at 7 mGy or below. In contrast, the skin surface dose measured using the proposed method was only 1.57 mGy, showing a five-fold reduction. These results suggest that further decreases in dose might be achieved using the proposed method.

Emerging Techniques for Dose Optimization in Abdominal CT

PubMed Central

Platt, Joel F.; Goodsitt, Mitchell M.; Al-Hawary, Mahmoud M.; Maturen, Katherine E.; Wasnik, Ashish P.; Pandya, Amit

2014-01-01

Recent advances in computed tomographic (CT) scanning technique such as automated tube current modulation (ATCM), optimized x-ray tube voltage, and better use of iterative image reconstruction have allowed maintenance of good CT image quality with reduced radiation dose. ATCM varies the tube current during scanning to account for differences in patient attenuation, ensuring a more homogeneous image quality, although selection of the appropriate image quality parameter is essential for achieving optimal dose reduction. Reducing the x-ray tube voltage is best suited for evaluating iodinated structures, since the effective energy of the x-ray beam will be closer to the k-edge of iodine, resulting in a higher attenuation for the iodine. The optimal kilovoltage for a CT study should be chosen on the basis of imaging task and patient habitus. The aim of iterative image reconstruction is to identify factors that contribute to noise on CT images with use of statistical models of noise (statistical iterative reconstruction) and selective removal of noise to improve image quality. The degree of noise suppression achieved with statistical iterative reconstruction can be customized to minimize the effect of altered image quality on CT images. Unlike with statistical iterative reconstruction, model-based iterative reconstruction algorithms model both the statistical noise and the physical acquisition process, allowing CT to be performed with further reduction in radiation dose without an increase in image noise or loss of spatial resolution. Understanding these recently developed scanning techniques is essential for optimization of imaging protocols designed to achieve the desired image quality with a reduced dose. © RSNA, 2014 PMID:24428277

Weight Loss and Variation of Levothyroxine Requirements in Hypothyroid Obese Patients After Bariatric Surgery.

PubMed

Fierabracci, Paola; Martinelli, Silvia; Tamberi, Anna; Piaggi, Paolo; Basolo, Alessio; Pelosini, Caterina; Ricco, Ilaria; Magno, Silvia; Querci, Giorgia; Ceccarini, Giovanni; Scartabelli, Giovanna; Salvetti, Guido; Vitti, Paolo; Santini, Ferruccio

2016-04-01

Obesity and hypothyroidism are both common disorders within the general population. Obese hypothyroid subjects require higher doses of levothyroxine (LT4) compared with normal weight individuals. Previous studies on the effects of bariatric surgery on LT4 dose requirements in hypothyroid subjects have provided conflicting results. The aim of this study was to evaluate the LT4 requirements in a group of obese subjects with acquired hypothyroidism, before and after weight loss achieved by bariatric surgery. Ninety-three obese hypothyroid subjects (mean age = 48 ± 9 years; mean body mass index = 45.9 ± 5.6 kg/m(2)), were evaluated before and 28 ± 8 months after bariatric surgery. Changes in the LT4 dose, anthropometric measures, and hormone values were evaluated. In 20 patients, data of body composition, assessed by dual energy X-ray absorptiometry, were also analyzed. On average, after weight loss, a significant reduction of the total dose of LT4 was documented (from 130.6 ± 48.5 to 116.2 ± 38.6 μg/day; p < 0.001). The LT4 dose had to be reduced in 47 patients, was unchanged in 34, and had to be increased in 12 patients affected by autoimmune thyroiditis. Reduction of the LT4 dose was proportional to reduction of the lean body mass. The weight loss achieved with modern surgical bariatric procedures is associated with a reduction of LT4 requirements in most hypothyroid subjects, which appears to be related to a decrease of the lean body mass. Occasionally, a concurrent decline of residual thyroid function, as it occurs in autoimmune thyroiditis, can counteract this phenomenon and eventually produce an increase of LT4 needs. It is believed that during the weight loss phase that follows bariatric surgery, there is no need for preventive adjustments of the LT4 dose, but serum thyroid hormones and thyrotropin should be periodically monitored in order to detect possible variations of LT4 requirements and to allow proper corrections of the therapy.

Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy.

PubMed

Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G

2013-12-01

Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06mg/kg) under an FR 3 schedule during daily 23h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose-response relationships were very well described by the exponential demand function (r(2) values>0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. Copyright © 2013 Elsevier Inc. All rights reserved.

Coverage, efficacy or dosing interval: which factor predominantly influences the impact of routine childhood vaccination for the prevention of varicella? A model-based study for Italy.

PubMed

Holl, Katsiaryna; Sauboin, Christophe; Amodio, Emanuele; Bonanni, Paolo; Gabutti, Giovanni

2016-10-21

Varicella is a highly infectious disease with a significant public health and economic burden, which can be prevented with childhood routine varicella vaccination. Vaccination strategies differ by country. Some factors are known to play an important role (number of doses, coverage, dosing interval, efficacy and catch-up programmes), however, their relative impact on the reduction of varicella in the population remains unclear. This paper aims to help policy makers prioritise the critical factors to achieve the most successful vaccination programme with the available budget. Scenarios assessed the impact of different vaccination strategies on reduction of varicella disease in the population. A dynamic transmission model was used and adapted to fit Italian demographics and population mixing patterns. Inputs included coverage, number of doses, dosing intervals, first-dose efficacy and availability of catch-up programmes, based on strategies currently used or likely to be used in different countries. The time horizon was 30 years. Both one- and two-dose routine varicella vaccination strategies prevented a comparable number of varicella cases with complications, but two-doses provided broader protection due to prevention of a higher number of milder varicella cases. A catch-up programme in susceptible adolescents aged 10-14 years old reduced varicella cases by 27-43 % in older children, which are often more severe than in younger children. Coverage, for all strategies, sustained at high levels achieved the largest reduction in varicella. In general, a 20 % increase in coverage resulted in a further 27-31 % reduction in varicella cases. When high coverage is reached, the impact of dosing interval and first-dose vaccine efficacy had a relatively lower impact on disease prevention in the population. Compared to the long (11 years) dosing interval, the short (5 months) and medium (5 years) interval schedules reduced varicella cases by a further 5-13 % and 2-5 %, respectively. Similarly, a 10 % increase in first-dose efficacy (from 65 to 75 % efficacy) prevented 2-5 % more varicella cases, suggesting it is the least influential factor when considering routine varicella vaccination. Vaccination strategies can be implemented differently in each country depending on their needs, infrastructure and healthcare budget. However, ensuring high coverage remains the critical success factor for significant prevention of varicella when introducing varicella vaccination in the national immunisation programme.

Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations

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

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Bussière, Marc R.; Chapman, Paul H.

2016-07-01

Purpose: To optimally exploit fractionation effects in the context of radiosurgery treatments of large cerebral arteriovenous malformations (AVMs). In current practice, fractionated treatments divide the dose evenly into several fractions, which generally leads to low obliteration rates. In this work, we investigate the potential benefit of delivering distinct dose distributions in different fractions. Methods and Materials: Five patients with large cerebral AVMs were reviewed and replanned for intensity modulated arc therapy delivered with conventional photon beams. Treatment plans allowing for different dose distributions in all fractions were obtained by performing treatment plan optimization based on the cumulative biologically effective dosemore » delivered at the end of treatment. Results: We show that distinct treatment plans can be designed for different fractions, such that high single-fraction doses are delivered to complementary parts of the AVM. All plans create a similar dose bath in the surrounding normal brain and thereby exploit the fractionation effect. This partial hypofractionation in the AVM along with fractionation in normal brain achieves a net improvement of the therapeutic ratio. We show that a biological dose reduction of approximately 10% in the healthy brain can be achieved compared with reference treatment schedules that deliver the same dose distribution in all fractions. Conclusions: Boosting complementary parts of the target volume in different fractions may provide a therapeutic advantage in fractionated radiosurgery treatments of large cerebral AVMs. The strategy allows for a mean dose reduction in normal brain that may be valuable for a patient population with an otherwise normal life expectancy.« less

Visual grading characteristics and ordinal regression analysis during optimisation of CT head examinations.

PubMed

Zarb, Francis; McEntee, Mark F; Rainford, Louise

2015-06-01

To evaluate visual grading characteristics (VGC) and ordinal regression analysis during head CT optimisation as a potential alternative to visual grading assessment (VGA), traditionally employed to score anatomical visualisation. Patient images (n = 66) were obtained using current and optimised imaging protocols from two CT suites: a 16-slice scanner at the national Maltese centre for trauma and a 64-slice scanner in a private centre. Local resident radiologists (n = 6) performed VGA followed by VGC and ordinal regression analysis. VGC alone indicated that optimised protocols had similar image quality as current protocols. Ordinal logistic regression analysis provided an in-depth evaluation, criterion by criterion allowing the selective implementation of the protocols. The local radiology review panel supported the implementation of optimised protocols for brain CT examinations (including trauma) in one centre, achieving radiation dose reductions ranging from 24 % to 36 %. In the second centre a 29 % reduction in radiation dose was achieved for follow-up cases. The combined use of VGC and ordinal logistic regression analysis led to clinical decisions being taken on the implementation of the optimised protocols. This improved method of image quality analysis provided the evidence to support imaging protocol optimisation, resulting in significant radiation dose savings. • There is need for scientifically based image quality evaluation during CT optimisation. • VGC and ordinal regression analysis in combination led to better informed clinical decisions. • VGC and ordinal regression analysis led to dose reductions without compromising diagnostic efficacy.

Surface dose measurements from air gaps under a bolus by using a MOSFET dosimeter in clinical oblique photon beams

NASA Astrophysics Data System (ADS)

Chung, Jin-Beom; Kim, Jae-Sung; Kim, In-Ah; Lee, Jeong-Woo

2012-10-01

This study is intended to investigate the effects of surface dose from air gaps under the bolus in clinically used oblique photon beams by using a Markus parallel-plate chamber and a metal-oxide semiconductor field-effect transistor (MOSFET) dosimeter. To evaluate the performances of the two detectors, the percentage surface doses of the MOSFET dosimeters in without an air gap under the bolus material were measured and compared with those of the Markus parallel-plate chamber. MOSFET dosimeters at the surface provided results mostly in good agreement with the parallelplate chamber. The MOSFET dosimeters seemed suitable for surface dose measurements having excellent accuracy for clinical used photon beams. The relative surface doses were measured with air gaps (2, 5, 10 mm) and without an air gap under 3 different bolus setups: (1) unbolused (no bolus), (2) 5-mm bolus, and (3) 10-mm bolus. The reductions in the surface dose substantially increased with small field size, thick bolus, and large air gap. The absolute difference in the reductions of the surface dose between the MOSFET dosimeter and the Markus parallel-plate chamber was less than 1.1%. Results at oblique angles of incidence showed larger reductions in surface dose with increasing angle of incidence. The largest reduction in surface dose was recorded for a 6 × 6 cm2 field at a 60° angle of incidence with an 10-mm air gap under a 10-mm bolus. When a 10-mm bolus was used, a reduction in the surface dose with an air gap of up to 10.5% could be achieved by varying the field size and the incident angle. Therefore, air gaps under the bolus should be avoided in radiotherapy treatment, especially for photon beam with highly oblique angles of incidence.

Inhaled corticosteroids in ventilated preterm neonates: a non-randomized dose-ranging study.

PubMed

Raghuram, Kamini; Dunn, Michael; Jangaard, Krista; Reilly, Maureen; Asztalos, Elizabeth; Kelly, Edmond; Vincer, Michael; Shah, Vibhuti

2018-05-07

Inhaled corticosteroids (ICS) offer targeted treatment for bronchopulmonary dysplasia (BPD) with minimal systemic effects compared to systemic steroids. However, dosing of ICS in the management of infants at high-risk of developing BPD is not well established. The objective of this study was to determine an effective dose of ICS for the treatment of ventilator-dependent infants to facilitate extubation or reduce fractional inspired oxygen concentration. Forty-one infants born at < 32 weeks gestational age (GA) or < 1250 g who were ventilator-dependent at 10-28 days postnatal age were included. A non-randomized dose-ranging trial was performed using aerosolized inhaled beclomethasone with hydrofluoralkane propellant (HFA-BDP). Four dosing groups (200, 400, 600 and 800 μg twice daily for 1 week) with 11, 11, 10 and 9 infants in each group, respectively, were studied. The primary outcome was therapeutic efficacy (successful extubation or reduction in FiO 2 of > 75% from baseline) in ≥60% of infants in the group. Oxygen requirements, complications and long-term neurodevelopmental outcomes were also assessed. The median age at enrollment was 22 (10-28) postnatal days. The primary outcome, therapeutic efficacy as defined above, was not achieved in any group. However, there was a significant reduction in post-treatment FiO 2 at a dose of 800 μg bid. No obvious trends were seen in long-term neurodevelopmental outcomes. Therapeutic efficacy was not achieved with all studied doses of ICS. A significant reduction in oxygen requirements was noted in ventilator-dependent preterm infants at 10-28 days of age when given 800 μg of HFA-BDP bid. Larger randomized trials of ICS are required to determine efficacy for the management of infants at high-risk for development of BPD. This clinical trial was registered retrospectively on clinicaltrials.gov. The registration number is NCT03503994 .

Comparison of Knowledge-based Iterative Model Reconstruction and Hybrid Reconstruction Techniques for Liver CT Evaluation of Hypervascular Hepatocellular Carcinoma.

PubMed

Park, Hyun Jeong; Lee, Jeong Min; Park, Sung Bin; Lee, Jong Beum; Jeong, Yoong Ki; Yoon, Jeong Hee

The purpose of this work was to evaluate the image quality, lesion conspicuity, and dose reduction provided by knowledge-based iterative model reconstruction (IMR) in computed tomography (CT) of the liver compared with hybrid iterative reconstruction (IR) and filtered back projection (FBP) in patients with hepatocellular carcinoma (HCC). Fifty-six patients with 61 HCCs who underwent multiphasic reduced-dose CT (RDCT; n = 33) or standard-dose CT (SDCT; n = 28) were retrospectively evaluated. Reconstructed images with FBP, hybrid IR (iDose), IMR were evaluated for image quality using CT attenuation and image noise. Objective and subjective image quality of RDCT and SDCT sets were independently assessed by 2 observers in a blinded manner. Image quality and lesion conspicuity were better with IMR for both RDCT and SDCT than either FBP or IR (P < 0.001). Contrast-to-noise ratio of HCCs in IMR-RDCT was significantly higher on delayed phase (DP) (P < 0.001), and comparable on arterial phase, than with IR-SDCT (P = 0.501). Iterative model reconstruction RDCT was significantly superior to FBP-SDCT (P < 0.001). Compared with IR-SDCT, IMR-RDCT was comparable in image sharpness and tumor conspicuity on arterial phase, and superior in image quality, noise, and lesion conspicuity on DP. With the use of IMR, a 27% reduction of effective dose was achieved with RDCT (12.7 ± 0.6 mSv) compared with SDCT (17.4 ± 1.1 mSv) without loss of image quality (P < 0.001). Iterative model reconstruction provides better image quality and tumor conspicuity than FBP and IR with considerable noise reduction. In addition, more than comparable results were achieved with IMR-RDCT to IR-SDCT for the evaluation of HCCs.

Pediatric cT: Implementation of ASIR for Substantial Radiation Dose Reduction While Maintaining Pre-ASIR Image Noise1

PubMed Central

Brady, Samuel L.; Moore, Bria M.; Yee, Brian S.; Kaufman, Robert A.

2015-01-01

Purpose To determine a comprehensive method for the implementation of adaptive statistical iterative reconstruction (ASIR) for maximal radiation dose reduction in pediatric computed tomography (CT) without changing the magnitude of noise in the reconstructed image or the contrast-to-noise ratio (CNR) in the patient. Materials and Methods The institutional review board waived the need to obtain informed consent for this HIPAA-compliant quality analysis. Chest and abdominopelvic CT images obtained before ASIR implementation (183 patient examinations; mean patient age, 8.8 years ± 6.2 [standard deviation]; range, 1 month to 27 years) were analyzed for image noise and CNR. These measurements were used in conjunction with noise models derived from anthropomorphic phantoms to establish new beam current–modulated CT parameters to implement 40% ASIR at 120 and 100 kVp without changing noise texture or magnitude. Image noise was assessed in images obtained after ASIR implementation (492 patient examinations; mean patient age, 7.6 years ± 5.4; range, 2 months to 28 years) the same way it was assessed in the pre-ASIR analysis. Dose reduction was determined by comparing size-specific dose estimates in the pre- and post-ASIR patient cohorts. Data were analyzed with paired t tests. Results With 40% ASIR implementation, the average relative dose reduction for chest CT was 39% (2.7/4.4 mGy), with a maximum reduction of 72% (5.3/18.8 mGy). The average relative dose reduction for abdominopelvic CT was 29% (4.8/6.8 mGy), with a maximum reduction of 64% (7.6/20.9 mGy). Beam current modulation was unnecessary for patients weighing 40 kg or less. The difference between 0% and 40% ASIR noise magnitude was less than 1 HU, with statistically nonsignificant increases in patient CNR at 100 kVp of 8% (15.3/14.2; P = .41) for chest CT and 13% (7.8/6.8; P = .40) for abdominopelvic CT. Conclusion Radiation dose reduction at pediatric CT was achieved when 40% ASIR was implemented as a dose reduction tool only; no net change to the magnitude of noise in the reconstructed image or the patient CNR occurred. PMID:23901128

Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout

PubMed Central

Perez-Ruiz, F; Alonso-Ruiz, A; Calabozo, M; Herrero-Beites, A; Garcia-Erauskin, G; Ruiz-Lucea, E

1998-01-01

OBJECTIVES—To study the efficacy of allopurinol and benzbromarone to reduce serum urate concentrations in patients with primary chronic gout.
METHODS—Prospective, parallel, open study of 86 consecutive male patients with primary chronic gout. Forty nine patients (26 normal excretors and 23 under excretors) were given allopurinol 300 mg/day and 37 under excretors benzbromarone 100 mg/day. After achieving steady plasma urate concentrations with such doses, treatment was then adjusted to obtain optimal plasmatic urate concentrations (under 6 mg/dl).
RESULTS—Patients receiving allopurinol 300 mg/day showed a mean reduction of plasmatic urate of 2.75 mg/dl (from 8.60 to 5.85 mg/dl) and 3.34 mg/dl (from 9.10 to 5.76 mg/dl) in normal excretors and under excretors respectively. Patients receiving benzbromarone 100 mg/day achieved a reduction of plasmatic urate of 5.04 mg/dl (from 8.58 to 3.54 mg/dl). Fifty three per cent of patients receiving allopurinol and 100% receiving benzbromarone achieved optimal plasma urate concentrations at such doses. The patients with poor results with allopurinol 300 mg/day achieved a proper plasma urate concentration with allopurinol 450 to 600 mg/day, the mean final dose being 372 mg/day. Renal fuction improved and no case of renal lithiasis was observed among benzbromarone treated patients, whose mean final dose was 76 mg/day.
CONCLUSION—Benzbromarone is very effective to control plasma urate concentrations at doses ranging from 50 to 100 mg/day. Uricosuric treatment is a suitable approach to the treatment of patients with gout who show underexcretion of urate.

 Keywords: gout; gout suppressants; allopurinol; benzbromarone PMID:9849314

Sex differences in nicotine self-administration in rats during progressive unit dose reduction: Implications for nicotine regulation policy

PubMed Central

Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G.

2013-01-01

Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06 mg/kg) under an FR 3 schedule during daily 23 h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025 mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose–response relationships were very well described by the exponential demand function (r2 values > 0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. PMID:24201048

Gamma Radiation Reduced Toxicity of Azoxystrobin Tested on Artemia franciscana.

PubMed

Dvorak, P; Zdarsky, M; Benova, K; Falis, M; Tomko, M

2016-06-01

Fungicide azoxystrobin toxicity was monitored by means of a 96-h biotest with Artemia franciscana nauplius stages after exposure to solutions with concentrations of 0.2, 0.4, 0.6 and 0.8 mg L(-1) irradiated with (60)Co gamma radiation with doses of 1, 2.5, 5 and 10 kGy. The effects of ionization radiation on azoxystrobin toxicity were mainly manifested by a statistically significant reduction of lethality after 72- and 96-h exposure. A maximum reduction of lethality of 72 % was achieved using doses of 1-5 kGy for an azoxystrobin initial concentration of 0.4 mg L(-1) and after 72 h of exposure. At a 96-h exposure, a difference of lethal effects reached up to 70 % for a dose of 10 kGy. The observed effect of gamma ionizing radiation on azoxystrobin toxicity suggest that this approach can be applied as an alternative for a reduction of azoxystrobin residua in food.

Effect of ketoconazole on cyclosporine dose in healthy dogs.

PubMed

Dahlinger, J; Gregory, C; Bea, J

1998-01-01

To determine the degree to which the dose of oral cyclosporine (CyA), in healthy dogs, can be decreased by concurrent oral administration of ketoconazole. Dogs in this study were observed for physical or biochemical side effects that might have been caused by the administration of CyA and ketoconazole. Prospective research study. Five healthy, intact female Beagle dogs. CyA was administered orally twice daily to achieve stable whole blood trough levels of 400 to 600 ng/mL. Ketoconazole was added at a low therapeutic dose (average dose: 13.6 mg/kg/d) then at a subtherapeutic dose (average dose: 4.7 mg/kg/d). CyA whole blood trough levels were monitored every 3 to 4 days and maintained at 400 to 600 ng/mL by adjusting CyA doses accordingly. Physical examination, CBC, biochemical profile, and urinalysis were performed at 2-week intervals throughout the study period. The initial mean dose of CyA required to achieve target blood levels was 14.5 mg/ kg/d. With concurrent ketoconazole (low therapeutic dose, average dose: 13.6 mg/kg/d) and CyA administration, the CyA dose declined to 3.4 mg/kg/day (range: 1.2 to 5.2 mg/kg/d), representing a 75% reduction in CyA dose and monetary savings of 57.8%. At a subtherapeutic dose of ketoconazole (average dose: 4.7 mg/kg/d), combination therapy resulted in a CyA dose of 10.1 mg/kg/day (4.9 to 10.6 mg/kg/d), representing a 38% reduction in CyA dose and monetary savings of 23.8%. Weight loss and transient hypoalbuminemia of unknown clinical significance were observed. Other physical and biochemical evaluations were unremarkable over the 12-week study period. The oral administration of ketoconazole can be used to reduce substantially the oral CyA dose needed to maintain selected blood levels in healthy dogs. The oral administration of ketoconazole can result in substantial cost savings to owners of dogs receiving CyA after renal allograft transplantation or for the treatment of autoimmune disease.

Primary water chemistry improvement for radiation exposure reduction at Japanese PWR Plants

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

Nishizawa, Eiichi

1995-03-01

Radiation exposure during the refueling outages at Japanese Pressurized Water Reactor (PWR) Plants has been gradually decreased through continuous efforts keeping the radiation dose rates at relatively low level. The improvement of primary water chemistry in respect to reduction of the radiation sources appears as one of the most important contributions to the achieved results and can be classified by the plant operation conditions as follows

Medical management with diazepam for electrical status epilepticus during slow wave sleep in children.

PubMed

Francois, Densley; Roberts, Jessica; Hess, Stephany; Probst, Luke; Eksioglu, Yaman

2014-03-01

Oral diazepam, administered in varying doses, is among the few proposed treatment options for electrical status epilepticus during slow wave sleep in children. We sought to retrospectively evaluate the long-term efficacy of high-dose oral diazepam in reducing electrographic and clinical evidence of electrical status epilepticus during slow wave sleep in children. Additionally, we surveyed caregivers to assess safety and behavioral outcomes related to ongoing therapy. We collected demographic and clinical data on children treated for electrical status epilepticus during slow wave sleep between October 2010 and March 2013. We sought to identify the number of patients who achieved at least a 50% reduction in spike wave index on electroencephalograph after receiving high-dose oral diazepam. We also administered a questionnaire to caregivers to assess for behavioral problems and side effects. We identified 42 evaluable patients who received high-dose diazepam (range 0.23-2.02 mg/kg per day) to treat electrical status epilepticus during slow wave sleep. Twenty-six patients had spike reduction data and 18/26 (69.2%) children achieved a greater than 50% reduction in spike wave count from an average of 15.54 to 5.05 (P = 0.001). We received 28 responses to the questionnaire. Some patients experienced new onset of difficulties with problem-solving and speech and writing development. Sleep disturbances (50%) and irritability (57.1%) were the most frequent side effects reported. There did not appear to be a dose-related effect with electroencephalograph changes, behavioral effects, or side effects. High-dose oral diazepam significantly reduces the spike wave count on electroencephalograph in children with electrical status epilepticus during slow wave sleep. Although this therapy improves electroencephalograph-related findings, it can be associated with concerning neurological and behavioral side effects in some individuals, so further study is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

Application of fluence field modulation to proton computed tomography for proton therapy imaging.

PubMed

Dedes, G; De Angelis, L; Rit, S; Hansen, D; Belka, C; Bashkirov, V; Johnson, R P; Coutrakon, G; Schubert, K E; Schulte, R W; Parodi, K; Landry, G

2017-07-12

This simulation study presents the application of fluence field modulated computed tomography, initially developed for x-ray CT, to proton computed tomography (pCT). By using pencil beam (PB) scanning, fluence modulated pCT (FMpCT) may achieve variable image quality in a pCT image and imaging dose reduction. Three virtual phantoms, a uniform cylinder and two patients, were studied using Monte Carlo simulations of an ideal list-mode pCT scanner. Regions of interest (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy (mean) and noise (standard deviation) of the reconstructed proton relative stopping power compared to reference values. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Pseudo FMpCT scans were created from broad beam experimental data acquired with a list-mode pCT prototype. FMpCT noise in ROIs was equivalent to FF images and accuracy better than  -1.3%(-0.7%) by using 1% of FF for the cylinder (patients). Integral imaging dose reduction of 37% and 56% was achieved for the two patients for that level of modulation. Corresponding DVHs from proton dose calculation on FMpCT images agreed to those from reference images and 96% of BEV profiles had RD below 2 mm, compared to only 1% for uniform 1% of FF. Gamma pass rates (2%, 2 mm) were 98% for FMpCT while for uniform 1% of FF they were as low as 59%. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI, down to 30% modulation. We have shown, using both virtual and experimental pCT scans, that FMpCT is potentially feasible and may allow a means of imaging dose reduction for a pCT scanner operating in PB scanning mode. This may be of particular importance to proton therapy given the low integral dose found outside the target.

Evaluation of the use of automatic exposure control and automatic tube potential selection in low-dose cerebrospinal fluid shunt head CT.

PubMed

Wallace, Adam N; Vyhmeister, Ross; Bagade, Swapnil; Chatterjee, Arindam; Hicks, Brandon; Ramirez-Giraldo, Juan Carlos; McKinstry, Robert C

2015-06-01

Cerebrospinal fluid shunts are primarily used for the treatment of hydrocephalus. Shunt complications may necessitate multiple non-contrast head CT scans resulting in potentially high levels of radiation dose starting at an early age. A new head CT protocol using automatic exposure control and automated tube potential selection has been implemented at our institution to reduce radiation exposure. The purpose of this study was to evaluate the reduction in radiation dose achieved by this protocol compared with a protocol with fixed parameters. A retrospective sample of 60 non-contrast head CT scans assessing for cerebrospinal fluid shunt malfunction was identified, 30 of which were performed with each protocol. The radiation doses of the two protocols were compared using the volume CT dose index and dose length product. The diagnostic acceptability and quality of each scan were evaluated by three independent readers. The new protocol lowered the average volume CT dose index from 15.2 to 9.2 mGy representing a 39 % reduction (P < 0.01; 95 % CI 35-44 %) and lowered the dose length product from 259.5 to 151.2 mGy/cm representing a 42 % reduction (P < 0.01; 95 % CI 34-50 %). The new protocol produced diagnostically acceptable scans with comparable image quality to the fixed parameter protocol. A pediatric shunt non-contrast head CT protocol using automatic exposure control and automated tube potential selection reduced patient radiation dose compared with a fixed parameter protocol while producing diagnostic images of comparable quality.

Facilitating the implementation of pharmacokinetic-guided dosing of prophylaxis in haemophilia care by discrete choice experiment.

PubMed

Lock, J; de Bekker-Grob, E W; Urhan, G; Peters, M; Meijer, K; Brons, P; van der Meer, F J M; Driessens, M H E; Collins, P W; Fijnvandraat, K; Leebeek, F W G; Cnossen, M H

2016-01-01

Patients', parents' and providers' preferences with regard to medical innovations may have a major impact on their implementation. To evaluate barriers and facilitators for individualized pharmacokinetic (PK)-guided dosing of prophylaxis in haemophilia patients, parents of young patients, and treating professionals by discrete choice experiment (DCE) questionnaire. The study population consisted of patients with haemophilia currently or previously on prophylactic treatment with factor concentrate (n = 114), parents of patients aged 12-18 years (n = 19) and haemophilia professionals (n = 91). DCE data analysis was performed, taking preference heterogeneity into account. Overall, patients and parents, and especially professionals were inclined to opt for PK-guided dosing of prophylaxis. In addition, if bleeding was consequently reduced, more frequent infusions were acceptable. However, daily dosing remained an important barrier for all involved. 'Reduction of costs for society' was a facilitator for implementation in all groups. To achieve implementation of individualized PK-guided dosing of prophylaxis in haemophilia, reduction of bleeding risk and reduction of costs for society should be actively discussed as they are motivating for implementation; daily dosing is still reported to be a barrier for all groups. The knowledge of these preferences will enlarge support for this innovation, and aid in the drafting of implementable guidelines and information brochures for patients, parents and professionals. © 2015 John Wiley & Sons Ltd.

Peracetic acid (PAA) disinfection of primary, secondary and tertiary treated municipal wastewaters.

PubMed

Koivunen, J; Heinonen-Tanski, H

2005-11-01

The efficiency of peracetic acid (PAA) disinfection against enteric bacteria and viruses in municipal wastewaters was studied in pilot-scale. Disinfection pilot-plant was fed with the primary or secondary effluent of Kuopio municipal wastewater treatment plant or tertiary effluent from the pilot-scale dissolved air flotation (DAF) unit. Disinfectant doses ranged from 2 to 7 mg/l PAA in the secondary and tertiary effluents, and from 5 to 15 mg/l PAA in the primary effluents. Disinfection contact times were 4-27 min. Disinfection of secondary and tertiary effluents with 2-7 mg/l PAA and 27 min contact time achieved around 3 log reductions of total coliforms (TC) and enterococci (EC). PAA disinfection also significantly improved the hygienic quality of the primary effluents: 10-15 mg/l PAA achieved 3-4 log reductions of TC and EC, 5 mg/l PAA resulting in below 2 log reductions. F-RNA coliphages were more resistant against the PAA disinfection and around 1 log reductions of these enteric viruses were typically achieved in the disinfection treatments of the primary, secondary and tertiary effluents. Most of the microbial reductions occurred during the first 4-18 min of contact time, depending on the PAA dose and microorganism. The PAA disinfection efficiency remained relatively constant in the secondary and tertiary effluents, despite of small changes of wastewater quality (COD, SS, turbidity, 253.7 nm transmittance) or temperature. The disinfection efficiency clearly decreased in the primary effluents with substantially higher microbial, organic matter and suspended solids concentrations. The results demonstrated that PAA could be a good alternative disinfection method for elimination of enteric microbes from different wastewaters.

Olmesartan/amlodipine: a review of its use in the management of hypertension

PubMed Central

Kreutz, R

2011-01-01

Combination therapy is an effective strategy to increase antihypertensive efficacy in those patients with poor blood pressure (BP) control. In order to achieve BP targets, at least 75% of patients may require combination therapy, and European guidelines advocate this approach, particularly in those patients with a high cardiovascular risk. Evidence from large, randomized controlled trials, and the European hypertension treatment guidelines is supportive of the use of an angiotensin receptor blocker (ARB) with a calcium channel blocker (CCB). Fixed-dose combination formulations of olmesartan medoxomil, an ARB, and the CCB amlodipine are approved in several European countries for patients with essential hypertension. The olmesartan/amlodipine combination has demonstrated greater efficacy than its component monotherapies in reducing BP in patients with mild-to-severe hypertension. Significantly greater reductions in seated diastolic BP were observed between baseline and after eight weeks of treatment with olmesartan/amlodipine, compared with equivalent doses of olmesartan or amolodipine monotherapy (P < 0.001), in the factorial Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial. About 85% of the maximal BP reductions after the 8-week treatment period were already observed after two weeks. Uptitration as necessary, with or without hydrochlorothiazide, allowed the majority of patients to achieve BP control in a 44-week open-label extension treatment period to the COACH trial. The use of olmesartan/amlodipine allowed up to 54% of patients, with previously inadequate responses to amlodipine or olmesartan monotherapy, to achieve their BP goals. Data from post-registration studies using tight BP control and forced titration regimens have further demonstrated the high efficacy of olmesartan/amlodipine in achieving BP goal rates. Moreover, consistent reductions in BP were observed over the 24-hour dosing interval using ambulatory measurements. Olmesartan/amlodipine was generally well tolerated over the short- and long-term, with a lower frequency of peripheral edema with olmesartan/amlodipine 40/10 mg than with amlodipine 10 mg monotherapy. PMID:21490944

Does dose matter in reducing gestational weight gain in exercise interventions? A systematic review of literature.

PubMed

McDonald, Samantha M; Liu, Jihong; Wilcox, Sara; Lau, Erica Y; Archer, Edward

2016-04-01

The purpose of this review was to examine the relationship between exercise dose and reductions in weight gain during pregnancy in exercise interventions. Systematic literature review. Four electronic research databases (PubMed, Web of Science, CINAHL, and Academic Search Premiere) were used to identify exercise interventions conducted with pregnant women. Eligible articles must have satisfied the following criteria: inclusion of a control condition, exercise as a major intervention component, weight gain measured and reported for each experimental condition, description of exercise dose (frequency, intensity and duration), and utilized an adequate number of control conditions to assess independent effects of exercise on weight gain. The literature search identified 4837 articles. Of these, 174 abstracts were screened and 21 intervention studies (18 exercise-only, 3 exercise/diet) were eligible for review. Only 38% of the interventions achieved statistically significant reductions in gestational weight gain. Successful interventions possessed higher adherence and lower attrition rates and were predominantly conducted among normal weight populations. No clear patterns or consistencies of exercise dose and reductions in weight gain were evident. An exercise dose associated with reductions in weight gain was unquantifiable among these interventions. Adherence and retention rates were strong contributors to the success of exercise interventions on gestational weight gain. It is strongly suggested that future researchers investigate methods to increase adherence and compliance, especially among overweight and obese women, and utilize objective measurement tools to accurately evaluate exercise dose performed by the participants and the impact on body composition and weight gain. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Radiation Dose Reduction by Indication-Directed Focused z-Direction Coverage for Neck CT.

PubMed

Parikh, A K; Shah, C C

2016-06-01

The American College of Radiology-American Society of Neuroradiology-Society for Pediatric Radiology Practice Parameter for a neck CT suggests that coverage should be from the sella to the aortic arch. It also recommends using CT scans judiciously to achieve the clinical objective. Our purpose was to analyze the potential dose reduction by decreasing the scan length of a neck CT and to assess for any clinically relevant information that might be missed from this modified approach. This retrospective study included 126 children who underwent a neck CT between August 1, 2013, and September 30, 2014. Alteration of the scan length for the modified CT was suggested on the topographic image on the basis of the indication of the study, with the reader blinded to the images and the report. The CT dose index volume of the original scan was multiplied by the new scan length to calculate the dose-length product of the modified study. The effective dose was calculated for the original and modified studies by using age-based conversion factors from the American Association of Physicists in Medicine Report No. 96. Decreasing the scan length resulted in an average estimated dose reduction of 47%. The average reduction in scan length was 10.4 cm, decreasing the overall coverage by 48%. The change in scan length did not result in any missed findings that altered management. Of the 27 abscesses in this study, none extended to the mediastinum. All of the lesions in question were completely covered. Decreasing the scan length of a neck CT according to the indication provides a significant savings in radiation dose, while not altering diagnostic ability or management. © 2016 by American Journal of Neuroradiology.

Progress in global measles control and mortality reduction, 2000-2007.

PubMed

2008-12-05

Despite the availability of a safe and effective vaccine since 1963, measles has been a major killer of children in developing countries (causing an estimated 750,000 deaths as recently as 2000), primarily because of underutilization of the vaccine. At the World Health Assembly in 2008, all World Health Organization (WHO) member states reaffirmed their commitment to achieving a 90% reduction in measles mortality by 2010 compared with 2000, a goal that was established in 2005 as part of the Global Immunization Vision and Strategy (2). This WHO-UNICEF comprehensive strategy for measles mortality reduction (1) focuses on 47 priority countries. The strategy's components include 1) achieving and maintaining high coverage (>90%) with the routinely scheduled first dose of measles-containing vaccine (MCV1) among children aged 1 year; 2) ensuring that all children receive a second opportunity for measles immunization (either through a second routine dose or through periodic supplementary immunization activities [SIAs]); 3) implementing effective laboratory-supported disease surveillance; and 4) providing appropriate clinical management for measles cases. This report updates previously published reports and describes immunization and surveillance activities implemented during 2007. Increased routine measles vaccine coverage and SIAs implemented during 2000--2007 resulted in a 74% decrease in the estimated number of measles deaths globally. An estimated 197,000 deaths from measles occurred in 2007; of these, 136,000 (69%) occurred in the WHO South-East Asian Region. Achievement of the 2010 goal will require full implementation of measles mortality reduction strategies, especially in the WHO South-East Asian Region.

Effect of transfusional iron intake on response to chelation therapy in beta-thalassemia major.

PubMed

Cohen, Alan R; Glimm, Ekkehard; Porter, John B

2008-01-15

The success of chelation therapy in controlling iron overload in patients with thalassemia major is highly variable and may partly depend on the rate of transfusional iron loading. Using data from the 1-year phase III study of deferasirox, including volumes of transfused red blood cells and changes in liver iron concentration (LIC) in 541 patients, the effect of iron loading on achieving neutral or negative iron balance was assessed in patients receiving different doses of deferasirox and the comparator deferoxamine. After dose adjustment, reductions in LIC after 1 year of deferasirox or deferoxamine therapy correlated with transfusional iron intake. At a deferasirox dose of 20 mg/kg per day, neutral or negative iron balance was achieved in 46% and 75% of patients with the highest and lowest transfusional iron intake, respectively; 30 mg/kg per day produced successful control of iron stores in 96% of patients with a low rate of transfusional iron intake. Splenectomized patients had lower transfusional iron intake and greater reductions in iron stores than patients with intact spleens. Transfusional iron intake should be monitored on an ongoing basis in thalassemia major patients, and the rate of transfusional iron loading should be considered when choosing the appropriate dose of an iron-chelating agent. This study is registered at http://clinicaltrials.gov as NCT00061750.

[Thiazide diuretics in the treatment of hypertensive patients].

PubMed

Rasmussen, Knud

2015-05-11

This Cochrane review had the objectives to determine the dose-related decrease in blood pressure due to thiazide diuretics compared with placebo control in the treatment of hypertensive patients. Hydrochlorothiazide has a dose-related blood pressure-lowering effect over the dose range 6.25, 12.5, 25 and 50 mg/day of 4/2, 6/3, 8/3 and 11/5 mmHg, respectively. This exceeds the mean 3 mmHg reduction achieved by angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers as shown in other Cochrane reviews, which have compared these antihypertensive drugs with placebo having used similar inclusion/exclusion criteria.

Radiation dose reduction to the breast in thoracic CT: Comparison of bismuth shielding, organ-based tube current modulation, and use of a globally decreased tube current

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

Wang Jia; Duan Xinhui; Christner, Jodie A.

2011-11-15

Purpose: The purpose of this work was to evaluate dose performance and image quality in thoracic CT using three techniques to reduce dose to the breast: bismuth shielding, organ-based tube current modulation (TCM) and global tube current reduction. Methods: Semi-anthropomorphic thorax phantoms of four different sizes (15, 30, 35, and 40 cm lateral width) were used for dose measurement and image quality assessment. Four scans were performed on each phantom using 100 or 120 kV with a clinical CT scanner: (1) reference scan; (2) scan with bismuth breast shield of an appropriate thickness; (3) scan with organ-based TCM; and (4)more » scan with a global reduction in tube current chosen to match the dose reduction from bismuth shielding. Dose to the breast was measured with an ion chamber on the surface of the phantom. Image quality was evaluated by measuring the mean and standard deviation of CT numbers within the lung and heart regions. Results: Compared to the reference scan, dose to the breast region was decreased by about 21% for the 15-cm phantom with a pediatric (2-ply) shield and by about 37% for the 30, 35, and 40-cm phantoms with adult (4-ply) shields. Organ-based TCM decreased the dose by 12% for the 15-cm phantom, and 34-39% for the 30, 35, and 40-cm phantoms. Global lowering of the tube current reduced breast dose by 23% for the 15-cm phantom and 39% for the 30, 35, and 40-cm phantoms. In phantoms of all four sizes, image noise was increased in both the lung and heart regions with bismuth shielding. No significant increase in noise was observed with organ-based TCM. Decreasing tube current globally led to similar noise increases as bismuth shielding. Streak and beam hardening artifacts, and a resulting artifactual increase in CT numbers, were observed for scans with bismuth shields, but not for organ-based TCM or global tube current reduction. Conclusions: Organ-based TCM produces dose reduction to the breast similar to that achieved with bismuth shielding for both pediatric and adult phantoms. However, organ-based TCM does not affect image noise or CT number accuracy, both of which are adversely affected by bismuth shielding. Alternatively, globally decreasing the tube current can produce the same dose reduction to the breast as bismuth shielding, with a similar noise increase, yet without the streak artifacts and CT number errors caused by the bismuth shields. Moreover, globally decreasing the tube current reduces the dose to all tissues scanned, not simply to the breast.« less

Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis Study

PubMed Central

Sirich, Tammy L.; Fong, Kara D.; Plummer, Natalie S.; Shafi, Tariq; Hwang, Seungyoung; Banerjee, Tanushree; Zhu, Yunnuo; Powe, Neil R.; Hai, Xin; Hostetter, Thomas H.

2016-01-01

The Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose treatment used lowered plasma levels of small uremic solutes other than urea. Measurements made ≥3 months after randomization in 1281 patients in the HEMO Study showed a range in the effect of high-dose treatment compared with that of standard treatment: from no reduction in the level of p-cresol sulfate or asymmetric dimethylarginine to significant reductions in the levels of trimethylamine oxide (−9%; 95% confidence interval [95% CI], −2% to −15%), indoxyl sulfate (−11%; 95% CI, −6% to −15%), and methylguanidine (−22%; 95% CI, −18% to −27%). Levels of three other small solutes also decreased slightly; the level of urea decreased 9%. All-cause mortality did not significantly relate to the level of any of the solutes measured. Modeling indicated that the intermittency of treatment along with the presence of nondialytic clearance and/or increased solute production accounted for the limited reduction in solute levels with the higher Kt/Vurea. In conclusion, failure to achieve greater reductions in solute levels may explain the failure of high Kt/Vurea treatment to improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted for very little of this variation. These results further suggest that an index only on the basis of urea does not provide a sufficient measure of dialysis adequacy. PMID:27026365

Crohn Disease: FDG PET/CT Before and After Initial Dose of Anti-Tumor Necrosis Factor Therapy to Predict Long-term Response.

PubMed

Epelboym, Yan; Shyn, Paul B; Chick, Jeffrey Forris Beecham; Hamilton, Matthew J; OʼConnor, Stacy D; Silverman, Stuart G; Kim, Chun K

2017-11-01

Clinical assessments of Crohn disease activity are limited in their capacity to assess treatment response to biologic therapy. The purpose of this study was to determine if changes in FDG activity between baseline PET and repeat PET performed prior to the second dose of induction anti-tumor necrosis factor (TNF) therapy correlate with clinical response. In this prospective, institutional review board-approved, Health Insurance Portability and Accountability Act-compliant pilot study of 8 adult patients with active Crohn disease, FDG activity before and 2 weeks after initiation of anti-TNF therapy was assessed using low-dose PET/CT. FDG activity was measured in the most inflamed bowel loop using an SUVratio (SUVmax/liver SUVmean). Changes in SUVratio were compared with a blinded gastroenterologist assessment of clinical response and steroid-free remission, as well as C-reactive protein (CRP), during a 12-month follow-up period. Of 8 patients, 7 showed FDG activity decline at 2 weeks, 5 of whom achieved a clinical response and steroid-free remission at 8, 26, and 52 weeks. The remaining 2 patients with FDG activity decline did not achieve a clinical response or steroid-free remission at these time points, but there were reductions in CRP. The 1 patient without FDG activity decline was a clinical nonresponder, had no reduction in CRP, and did not achieve steroid-free remission. A change in FDG activity at FDG PET/CT performed prior to the second induction dose of anti-TNF therapy has the potential to predict clinical response and steroid-free remission in patients with Crohn disease.

Innovative IPV from attenuated Sabin poliovirus or newly designed alternative seed strains.

PubMed

Hamidi, Ahd; Bakker, Wilfried A M

2012-11-01

This article gives an overview of the patent literature related to innovative inactivated polio vaccine (i-IPV) based on using Sabin poliovirus strains and newly developed alternative recombinant poliovirus strains. This innovative approach for IPV manufacturing is considered to attribute to the requirement for affordable IPV in the post-polio-eradication era, which is on the horizon. Although IPV is a well-established vaccine, the number of patent applications in this field was seen to have significantly increased in the past decade. Currently, regular IPV appears to be too expensive for universal use. Future affordability may be achieved by using alternative cell lines, alternative virus seed strains, improved and optimized processes, dose sparing, or the use of adjuvants. A relatively short-term option to achieve cost-price reduction is to work on regular IPV, using wild-type poliovirus strains, or on Sabin-IPV, based on using attenuated poliovirus strains. This price reduction can be achieved by introducing efficiency in processing. There are also multiple opportunities to work on dose sparing, for example, by using adjuvants or fractional doses. Renewed interest in this field was clearly reflected in the number and diversity of patent applications. In a later stage, several innovative approaches may become even more attractive, for example the use of recombinant virus strains or even a totally synthetic vaccine. Currently, such work is mainly carried out by research institutes and universities and therefore clinical data are not available.

High dose simvastatin exhibits enhanced lipid lowering effects relative to simvastatin/ezetimibe combination therapy

USDA-ARS?s Scientific Manuscript database

Technical Abstract: Background: Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reduce in LDL-C. Methods and Results: Thirty-nine patients were treated with either 80mg simvasta...

Radiation Dose Reduction in CT Fluoroscopy-Guided Cervical Transforaminal Epidural Steroid Injection by Modifying Scout and Planning Steps

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

Paik, Nam Chull, E-mail: pncspine@gmail.com

Background and PurposeIn CT fluoroscopy (CTF)-guided cervical transforaminal epidural steroid injection (TFESI), the majority of radiation dose is contributed by the planning CT scan rather than the CTF procedure itself. We replaced the planning helical CT with a spot CTF and accordingly changed the patient posture during scout and planning scans. The aim of this study was to test whether radiation dose reduction would be achieved by this protocol modification while still maintaining technical performance.MethodsOverall, 338 consecutive procedures before (control group: n = 163) and after (study group: n = 175) instituting the above-mentioned protocol modification were analyzed retrospectively, comparing patient characteristics (age, sex,more » neck diameter, and level injected) and technical performance [technical success rate, dose-length product (DLP), inadvertent contrast flow incidence, number of CTF acquisitions, and procedural time] between the two groups.ResultsAll injections were technically successful at every level from C3–C4 to C7–T1 without serious complications in both groups. The median DLP of the study group (7.92 mGy·cm) was significantly reduced compared to that of the control group (39.05 mGy·cm, P < 0.001). There were no significant differences between the two groups regarding the incidence of inadvertent contrast flow (20.6 vs. 17.2 %, P = 0.426), number of CTF acquisitions (median 5 vs. 4, P = 0.123), and the procedural time (median 6.62 vs. 6.90 min, P = 0.100).ConclusionsWhen conducting CTF-guided cervical TFESIs, a significant radiation dose reduction (median 79.7 % in DLP) can be achieved by modifying scout and planning steps, without compromising the technical performance.« less

Successful withdrawal from high-dose benzodiazepine in a young patient through electronic monitoring of polypharmacy: a case report in an ambulatory setting.

PubMed

Loscertales, Hèctor R; Wentzky, Valerie; Dürsteler, Kenneth; Strasser, Johannes; Hersberger, Kurt E; Arnet, Isabelle

2017-05-01

Dependence on high-dose benzodiazepines (BZDs) is well known and discontinuation attempts are generally unsuccessful. A well established protocol for high-dose BZD withdrawal management is lacking. We present the case of withdrawal from high-dose lorazepam (>20 mg daily) in an unemployed 35-year-old male outpatient through agonist substitution with long-acting clonazepam and electronic monitoring over 28 weeks. All medicines were repacked into weekly 7 × 4 cavity multidose punch cards with an electronic monitoring system. The prescribed daily dosages of BZDs were translated into an optimal number of daily tablets, divided into up to four units of use. Withdrawal was achieved by individual leftover of a small quantity of BZDs that was placed in a separate compartment. Feedback with visualization of intake over the past week was given during weekly psychosocial sessions. Stepwise reduction was obtained by reducing the mg content of the cavities proportionally to the leftovers, keeping the number of cavities in order to maintain regular intake behavior, and to determine the dosage decrease. At week 28, the primary objectives were achieved, that is, lorazepam reduction to 5 mg daily and cannabis abstinence. Therapy was continued using multidrug punch cards without electronic monitoring to maintain the management system. At week 48, a smaller size weekly pill organizer with detachable daily containers was dispensed. At week 68, the patient's therapy was constant with 1.5 mg clonazepam + 5 mg lorazepam daily for anxiety symptoms and the last steps of withdrawal were started. Several key factors led to successful withdrawal from high-dose BZD in this outpatient, such as the use of weekly punch cards coupled with electronic monitoring, the patient's empowerment over the withdrawal process, and the collaboration of several healthcare professionals. The major implication for clinical care is reduction by following the leftovers, and not a diktat from the healthcare professionals.

Validation of CT dose-reduction simulation

PubMed Central

Massoumzadeh, Parinaz; Don, Steven; Hildebolt, Charles F.; Bae, Kyongtae T.; Whiting, Bruce R.

2009-01-01

The objective of this research was to develop and validate a custom computed tomography dose-reduction simulation technique for producing images that have an appearance consistent with the same scan performed at a lower mAs (with fixed kVp, rotation time, and collimation). Synthetic noise is added to projection (sinogram) data, incorporating a stochastic noise model that includes energy-integrating detectors, tube-current modulation, bowtie beam filtering, and electronic system noise. Experimental methods were developed to determine the parameters required for each component of the noise model. As a validation, the outputs of the simulations were compared to measurements with cadavers in the image domain and with phantoms in both the sinogram and image domain, using an unbiased root-mean-square relative error metric to quantify agreement in noise processes. Four-alternative forced-choice (4AFC) observer studies were conducted to confirm the realistic appearance of simulated noise, and the effects of various system model components on visual noise were studied. The “just noticeable difference (JND)” in noise levels was analyzed to determine the sensitivity of observers to changes in noise level. Individual detector measurements were shown to be normally distributed (p>0.54), justifying the use of a Gaussian random noise generator for simulations. Phantom tests showed the ability to match original and simulated noise variance in the sinogram domain to within 5.6%±1.6% (standard deviation), which was then propagated into the image domain with errors less than 4.1%±1.6%. Cadaver measurements indicated that image noise was matched to within 2.6%±2.0%. More importantly, the 4AFC observer studies indicated that the simulated images were realistic, i.e., no detectable difference between simulated and original images (p=0.86) was observed. JND studies indicated that observers’ sensitivity to change in noise levels corresponded to a 25% difference in dose, which is far larger than the noise accuracy achieved by simulation. In summary, the dose-reduction simulation tool demonstrated excellent accuracy in providing realistic images. The methodology promises to be a useful tool for researchers and radiologists to explore dose reduction protocols in an effort to produce diagnostic images with radiation dose “as low as reasonably achievable.” PMID:19235386

Mold and aflatoxin reduction by gamma radiation of packed hot peppers and their evolution during storage.

PubMed

Iqbal, Qumer; Amjad, Muhammad; Asi, Muhammad Rafique; Ariño, Agustin

2012-08-01

The effect of gamma radiation on moisture content, total mold counts, Aspergillus counts, and aflatoxins of three hot pepper hybrids (Sky Red, Maha, and Wonder King) was investigated. Whole dried peppers packed in polyethylene bags were gamma irradiated at 0 (control), 2, 4, and 6 kGy and stored at 25°C for 90 days. Gamma radiation proved to be effective in reducing total mold and Aspergillus counts in a dose-dependent relationship. Total mold counts in irradiated peppers immediately after treatments were significantly lowered compared with those in nonirradiated samples, achieving 90 and 99% reduction at 2- and 4-kGy doses, respectively. Aspergillus counts were significantly reduced, by 93 and 97%, immediately after irradiation at doses of 2 and 4 kGy, respectively. A radiation dose of 6 kGy completely eliminated the population of total molds and Aspergillus fungi. The evolution of total molds in control and irradiated samples indicated no further fungal proliferation during 3 months of storage at 25°C. Aflatoxin levels were slightly affected by radiation doses of 2 and 4 kGy and showed a nonsignificant reduction of 6% at the highest radiation dose of 6 kGy. The distinct effectiveness of gamma radiation in molds and aflatoxins can be explained by the target theory of food irradiation, which states that the likelihood of a microorganism or a molecule being inactivated by gamma rays increases as its size increases.

Reducing operator radiation exposure during cardiac resynchronization therapy.

PubMed

Brambilla, Marco; Occhetta, Eraldo; Ronconi, Martina; Plebani, Laura; Carriero, Alessandro; Marino, Paolo

2010-12-01

To quantify the reduction in equivalent dose at operator's hand that can be achieved by placement of a radiation-absorbing drape (RADPAD) during long-lasting cardiac resynchronization therapy (CRT) procedures. This is a prospective observational study that included 22 consecutive patients with drug-refractory heart failure who underwent implantation of a CRT device. The cases were randomly assigned to Group A (11 cases), performed without RADPAD, and to Group B (11 cases), performed using RADPAD. Dose equivalent at the examiner's hand was measured as H(p)(0.07) and as a time-adjusted H(p)(0.07) rate (mGy/min) with a direct reading dosimeter. The mean fluoroscopy time was 20.8 ± 7.7 min and the mean dose area product (DAP) was 118.6 ± 45.3 Gy cm(2). No significant differences were found between body mass index, fluoroscopy time, and DAP between patients examined with or without RADPAD. The correlation between the fluoroscopy time and the DAP was high (R(2) = 0.94, P < 0.001). Mean dose and dose rate measurement without the RADPAD at the finger and hand were H(p)(0.07) = 1.27 ± 0.47 mGy per procedure and H(p)(0.07) rate = 0.057 ± 0.011 mGy/min, respectively. The dosage was reduced with the RADPAD to H(p)(0.07) = 0.48 ± 0.20 (P < 0.05) and to H(p)(0.07) rate = 0.026 ± 0.008 (P < 0.001), respectively. A mean reduction of 54% in the equivalent dose rate to the operator's hand can be achieved with the use of RADPAD. The use of the RADPAD in CRT devices implantation will make unlikely the necessity of limiting the yearly number of implants for high volume operators.

Effective radiation dose of ProMax 3D cone-beam computerized tomography scanner with different dental protocols.

PubMed

Qu, Xing-min; Li, Gang; Ludlow, John B; Zhang, Zu-yan; Ma, Xu-chen

2010-12-01

The aim of this study was to compare effective doses resulting from different scan protocols for cone-beam computerized tomography (CBCT) using International Commission on Radiological Protection (ICRP) 1990 and 2007 calculations of dose. Average tissue-absorbed dose, equivalent dose, and effective dose for a ProMax 3D CBCT with different dental protocols were calculated using thermoluminescent dosimeter chips in a human equivalent phantom. Effective doses were derived using ICRP 1990 and the superseding 2007 recommendations. Effective doses (ICRP 2007) for default patient sizes from small to large ranged from 102 to 298 μSv. The coefficient of determination (R(2)) between tube current and effective dose (ICRP 2007) was 0.90. When scanning with lower resolution settings, the effective doses were reduced significantly (P < .05). ProMax 3D can provide a wide range of radiation dose levels. Reduction in radiation dose can be achieved when using lower settings of exposure parameters. Copyright © 2010 Mosby, Inc. All rights reserved.

A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

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

Yao Rui; Bernard, Damian; Turian, Julius

2012-04-15

Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lungmore » dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.« less

Pharmacodynamic assessment of the activity of high-dose (750 mg) levofloxacin, ciprofloxacin, and gatifloxacin against clinical strains of Pseudomonas aeruginosa.

PubMed

Garrison, Mark W

2006-01-01

The objective of this study was to comparatively evaluate specific bacterial killing ability of high-dose (750 mg) levofloxacin, ciprofloxacin, and gatifloxacin against 2 clinical isolates of Pseudomonas aeruginosa (PA-21 and PA-2105). An in vitro pharmacodynamic modeling apparatus was used to expose the P. aeruginosa isolates to total peak concentrations and elimination characteristics associated with each quinolone. All experiments were conducted over 24 h, and a subsequent dose of ciprofloxacin was given at 12 h to emulate twice-daily dosing. Respective 3-log reductions in PA-24 occurred after 0.6, 1.0, and 2.6 h for levofloxacin, ciprofloxacin, and gatifloxacin; regrowth was seen with all 3 agents, but was greatest with gatifloxacin. PA-2105 had 2- to 4-fold higher minimal inhibitory concentrations (MICs) than PA-24. Gatifloxacin failed to achieve a 3-log reduction. Levofloxacin and ciprofloxacin took roughly 3.5 h to decrease initial inoculum by 3 logs, but regrowth of PA-2105 followed. Simulated doses of levofloxacin and ciprofloxacin showed comparable activity against each study isolate; less activity was observed with gatifloxacin. Levofloxacin versus PA-24 was the only regimen that approached the desired AUC/MIC(0-24) ratio of greater than 100-125 and achieved the targeted peak/MIC ratio of > or =8. Although quinolones are typically used in combination with other antibiotics for P. aeruginosa, differences in activity favor the use of levofloxacin or ciprofloxacin for the study isolates. Use of gatifloxacin may contribute to the increased rate of quinolone-resistant P. aeruginosa.

The diagnostic performance of reduced-dose CT for suspected appendicitis in paediatric and adult patients: A systematic review and diagnostic meta-analysis.

PubMed

Yoon, Hee Mang; Suh, Chong Hyun; Cho, Young Ah; Kim, Jeong Rye; Lee, Jin Seong; Jung, Ah Young; Kim, Jung Heon; Lee, Jeong-Yong; Kim, So Yeon

2018-06-01

To evaluate the diagnostic performance of reduced-dose CT for suspected appendicitis. A systematic search of the MEDLINE and EMBASE databases was carried out through to 10 January 2017. Studies evaluating the diagnostic performance of reduced-dose CT for suspected appendicitis in paediatric and adult patients were selected. Pooled summary estimates of sensitivity and specificity were calculated using hierarchical logistic regression modelling. Meta-regression was performed. Fourteen original articles with a total of 3,262 patients were included. For all studies using reduced-dose CT, the summary sensitivity was 96 % (95 % CI 93-98) with a summary specificity of 94 % (95 % CI 92-95). For the 11 studies providing a head-to-head comparison between reduced-dose CT and standard-dose CT, reduced-dose CT demonstrated a comparable summary sensitivity of 96 % (95 % CI 91-98) and specificity of 94 % (95 % CI 93-96) without any significant differences (p=.41). In meta-regression, there were no significant factors affecting the heterogeneity. The median effective radiation dose of the reduced-dose CT was 1.8 mSv (1.46-4.16 mSv), which was a 78 % reduction in effective radiation dose compared to the standard-dose CT. Reduced-dose CT shows excellent diagnostic performance for suspected appendicitis. • Reduced-dose CT shows excellent diagnostic performance for evaluating suspected appendicitis. • Reduced-dose CT has a comparable diagnostic performance to standard-dose CT. • Median effective radiation dose of reduced-dose CT was 1.8 mSv (1.46-4.16). • Reduced-dose CT achieved a 78 % dose reduction compared to standard-dose CT.

An agent-based model for control strategies of Echinococcus granulosus.

PubMed

Huang, Liang; Huang, Yan; Wang, Qian; Xiao, Ning; Yi, Deyou; Yu, Wenjie; Qiu, Dongchuan

2011-06-30

Cystic echinococcosis is a widespread zoonosis, caused by Echinococcus granulosus. The definitive hosts are carnivores and the intermediate hosts are grazing animals. Because humans are often accidentally infected with the cystic stage of the parasite, a control program is being developed for Western China. Western Sichuan Province in China is a highly endemic area. In this study, we built an agent-based model (ABM) to simulate and assess possible control strategies. These included dog dosing, control of livestock slaughter, health education, vaccination of intermediate hosts, vaccination of definitive hosts, slow-released praziquantel injections for dogs, removing unproductive old livestock, dog population reduction. These strategies were examined singly and in various combinations. The results show that vaccination based control strategies and also combined control strategies (dog dosing, slaughter control, removing old livestock, dog population reduction) can achieve a higher efficiency and be more feasible. Although monthly dog dosing achieved the highest efficiency, it required a high frequency and reliability, which were not feasible or sustainable. The model also indicated that transmission would recover soon after the chosen control strategy was stopped, indicating the need to move from a successful attack phase to a sustainable consolidation phase. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Effect of x-ray tube parameters and iodine concentration on image quality and radiation dose in cerebral pediatric and adult CT angiography: a phantom study.

PubMed

Papadakis, Antonios E; Perisinakis, Kostas; Raissaki, Maria; Damilakis, John

2013-04-01

The aim of the present phantom study was to investigate the effect of x-ray tube parameters and iodine concentration on image quality and radiation dose in cerebral computed tomographic (CT) angiographic examinations of pediatric and adult individuals. Four physical anthropomorphic phantoms that represent the average individual as neonate, 1-year-old, 5-year-old, and 10-year-old children and the RANDO phantom that simulates the average adult individual were used. Cylindrical vessels were bored along the brain-equivalent plugs of each physical phantom. To simulate the brain vasculature, vessels of 0.6, 1, 2, and 3 mm in diameter were created. These vessels were filled with contrast medium (CM) solutions at different iodine concentrations, that is, 5.6, 4.2, 2.7, and 1.4 mg I/mL. The phantom heads were scanned at 120, 100, and 80 kV. The applied quality reference tube current-time product values ranged from a minimum of 45 to a maximum of 680. The CT acquisitions were performed on a 16-slice CT scanner using the automatic exposure control system. Image quality was evaluated on the basis of image noise and contrast-to-noise ratio (CNR) between the contrast-enhanced iodinated vessels and the unenhanced regions of interest. Dose reduction was calculated as the percentage difference of the CT dose index value at the quality reference tube current-time product and the CT dose index at the mean modulated tube current-time product. Image noise that was measured using the preset tube current-time product settings varied significantly among the different phantoms (P < 0.0001). Hounsfield unit number of iodinated vessels was linearly related to CM concentration (r² = 0.907) and vessel diameter (r² = 0.918). The Hounsfield unit number of iodinated vessels followed a decreasing trend from the neonate phantom to the adult phantom at all kilovoltage settings. For the same image noise level, a CNR improvement of up to 69% and a dose reduction of up to 61% may be achieved when CT acquisition is performed at 80 kV compared with 120 kV. For the same CNR, a reduction by 25% of the administered CM concentration may be achieved when CT acquisition is performed at 80 kV compared with 120 kV. In cerebral CT angiographic studies, appropriate adjustment of the preset tube current-time product settings is required to achieve the same image noise level among participants of different age. Cerebral CT angiography at 80 kV significantly improves CNR and significantly reduces radiation dose. Moreover, at 80 kV, a considerable reduction of the administered amount of the CM may be reached, thus reducing potential risks for contrast-induced nephropathy.

Combined effects of coagulation and adsorption on ultrafiltration membrane fouling control and subsequent disinfection in drinking water treatment.

PubMed

Xing, Jiajian; Liang, Heng; Cheng, Xiaoxiang; Yang, Haiyan; Xu, Daliang; Gan, Zhendong; Luo, Xinsheng; Zhu, Xuewu; Li, Guibai

2018-06-02

This study investigated the combined effects of coagulation and powdered activated carbon (PAC) adsorption on ultrafiltration (UF) membrane fouling control and subsequent disinfection efficiency through filtration performance, dissolved organic carbon (DOC) removal, fluorescence excitation-emission matrix (EEM) spectroscopy, and disinfectant curve. The fouling behavior of UF membrane was comprehensively analyzed especially in terms of pollutant removal and fouling reversibility to understand the mechanism of fouling accumulation and disinfectant dose reduction. Pre-coagulation with or without adsorption both achieved remarkable effect of fouling mitigation and disinfection dose reduction. The two pretreatments were effective in total fouling control and pre-coagulation combined with PAC adsorption even decreased hydraulically irreversible fouling notably. Besides, pre-coagulation decreased residual disinfectant decline due to the removal of hydrophobic components of natural organic matters (NOM). Pre-coagulation combined with adsorption had a synergistic effect on further disinfectant decline rate reduction and decreased total disinfectant consumption due to additional removal of hydrophilic NOM by PAC adsorption. The disinfectant demand was further reduced after membrane. These results show that membrane fouling and disinfectant dose can be reduced in UF coupled with pretreatment, which could lead to the avoidance of excessive operation cost disinfectant dose for drinking water supply.

Clinical experience in treating hypertension with fixed-dose combination therapy: angiotensin II receptor blocker losartan plus hydrochlorothiazide.

PubMed

Abe, Masanori; Okada, Kazuyoshi; Matsumoto, Koichi

2009-10-01

The goal of antihypertensive treatment is to reduce cardiovascular and cerebrovascular events associated with high blood pressure. A combination therapy with different antihypertensive agents is more successful than monotherapy in most hypertensive patients, with the added advantage of a better safety profile. Therefore, treatment of hypertensive patients with fixed-dose combination therapy consisting of the angiotensin II receptor blocker losartan along with hydrochlorothiazide (HCTZ) has several potential benefits over monotherapy with each individual component. It provides more effective blood pressure control, a reduction in the likelihood of adverse effects and facilitation of patient compliance due to a simple once-daily regimen. One of the advantages of the combination of losartan with HCTZ is the potential reduction in HCTZ-induced metabolic disorders; in particular, this combination can have attractive benefits for patients of hyperuricemia. Losartan plus HCTZ fixed-dose combination therapy is frequently recommended for the treatment of hypertension and lowers blood pressure in mild-to-moderate and even severe hypertensive patients to a level comparable with other classes of antihypertensive agents in combination with HCTZ. Fixed-dose combination therapy with losartan plus HCTZ is a logical choice as antihypertensive therapy for patients in whom combination therapy is necessary to achieve additional blood pressure reduction.

Statistical model based iterative reconstruction in clinical CT systems. Part III. Task-based kV/mAs optimization for radiation dose reduction

PubMed Central

Li, Ke; Gomez-Cardona, Daniel; Hsieh, Jiang; Lubner, Meghan G.; Pickhardt, Perry J.; Chen, Guang-Hong

2015-01-01

Purpose: For a given imaging task and patient size, the optimal selection of x-ray tube potential (kV) and tube current-rotation time product (mAs) is pivotal in achieving the maximal radiation dose reduction while maintaining the needed diagnostic performance. Although contrast-to-noise (CNR)-based strategies can be used to optimize kV/mAs for computed tomography (CT) imaging systems employing the linear filtered backprojection (FBP) reconstruction method, a more general framework needs to be developed for systems using the nonlinear statistical model-based iterative reconstruction (MBIR) method. The purpose of this paper is to present such a unified framework for the optimization of kV/mAs selection for both FBP- and MBIR-based CT systems. Methods: The optimal selection of kV and mAs was formulated as a constrained optimization problem to minimize the objective function, Dose(kV,mAs), under the constraint that the achievable detectability index d′(kV,mAs) is not lower than the prescribed value of d℞′ for a given imaging task. Since it is difficult to analytically model the dependence of d′ on kV and mAs for the highly nonlinear MBIR method, this constrained optimization problem is solved with comprehensive measurements of Dose(kV,mAs) and d′(kV,mAs) at a variety of kV–mAs combinations, after which the overlay of the dose contours and d′ contours is used to graphically determine the optimal kV–mAs combination to achieve the lowest dose while maintaining the needed detectability for the given imaging task. As an example, d′ for a 17 mm hypoattenuating liver lesion detection task was experimentally measured with an anthropomorphic abdominal phantom at four tube potentials (80, 100, 120, and 140 kV) and fifteen mA levels (25 and 50–700) with a sampling interval of 50 mA at a fixed rotation time of 0.5 s, which corresponded to a dose (CTDIvol) range of [0.6, 70] mGy. Using the proposed method, the optimal kV and mA that minimized dose for the prescribed detectability level of d℞′=16 were determined. As another example, the optimal kV and mA for an 8 mm hyperattenuating liver lesion detection task were also measured using the developed framework. Both an in vivo animal and human subject study were used as demonstrations of how the developed framework can be applied to the clinical work flow. Results: For the first task, the optimal kV and mAs were measured to be 100 and 500, respectively, for FBP, which corresponded to a dose level of 24 mGy. In comparison, the optimal kV and mAs for MBIR were 80 and 150, respectively, which corresponded to a dose level of 4 mGy. The topographies of the iso-d′ map and the iso-CNR map were the same for FBP; thus, the use of d′- and CNR-based optimization methods generated the same results for FBP. However, the topographies of the iso-d′ and iso-CNR map were significantly different in MBIR; the CNR-based method overestimated the performance of MBIR, predicting an overly aggressive dose reduction factor. For the second task, the developed framework generated the following optimization results: for FBP, kV = 140, mA = 350, dose = 37.5 mGy; for MBIR, kV = 120, mA = 250, dose = 18.8 mGy. Again, the CNR-based method overestimated the performance of MBIR. Results of the preliminary in vivo studies were consistent with those of the phantom experiments. Conclusions: A unified and task-driven kV/mAs optimization framework has been developed in this work. The framework is applicable to both linear and nonlinear CT systems such as those using the MBIR method. As expected, the developed framework can be reduced to the conventional CNR-based kV/mAs optimization frameworks if the system is linear. For MBIR-based nonlinear CT systems, however, the developed task-based kV/mAs optimization framework is needed to achieve the maximal dose reduction while maintaining the desired diagnostic performance. PMID:26328971

Reviewing long-term antidepressants can reduce drug burden: a prospective observational cohort study

PubMed Central

Johnson, Chris F; Macdonald, Hector J; Atkinson, Pauline; Buchanan, Alasdair I; Downes, Noreen; Dougall, Nadine

2012-01-01

Background Antidepressant prescribing continues to rise. Contributing factors are increased long-term prescribing and possibly the use of higher selective serotonin re-uptake inhibitor (SSRI) doses. Aim To review general practice patients prescribed the same antidepressant long-term (≥2 years) and evaluate prescribing and management pre and post-review. Design and setting Prospective observational cohort study using routine data from 78 urban general practices, Scotland. Method All patients prescribed antidepressants (excluding amitriptyline) for ≥2 years were identified from records November 2009 to March 2010. GPs selected patients for face-to-face review of clinical condition and medication, December 2009 to September 2010. Pre- and post-review data were collected; average antidepressant doses and changes in prescribed daily doses were calculated. Onward referral to support services was recorded. Results 8.6% (33 312/388 656) of all registered patients were prescribed an antidepressant, 47.1% (15 689) were defined as long-term users and 2849 (18.2%) were reviewed. 811 (28.5%) patients reviewed had a change in antidepressant therapy: 7.0% stopped, 12.8% reduced dose, 5.3% increased dose, and 3.4% changed antidepressant, resulting in 9.5% (95% CI = 9.1% to 9.8% P<0.001) reduction in prescribed daily dose and 8.1% reduction in prescribing costs. 6.3% were referred onwards, half to NHS Mental Health Services. Pre-review SSRI doses were 10–30% higher than previously reported. Conclusion Almost half of all people prescribed antidepressants were long-term users. Appropriate reductions in prescribing can be achieved by reviewing patients. Higher SSRI doses may be contributing to current antidepressant growth. PMID:23211181

Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer Treated with I-131.

PubMed

Khan, Shahbaz Ahmad; Khan, Muhammad Saqib; Arif, Muhammad; Durr-e-Sabih; Rahim, Muhammad Kashif; Ahmad, Israr

2015-07-01

To determine the patterns of dose rate reduction in single and multiple radioiodine (I-131) therapies in cases of well differentiated thyroid cancer patients. Analytical series. Department of Nuclear Medicine and Radiation Physics, Multan Institute of Nuclear Medicine and Radiotherapy (MINAR), Multan, Pakistan, from December 2006 to December 2013. Ninety three patients (167 therapies) with well differentiated thyroid cancer treated with different doses of I-131 as an in-patient were inducted. Fifty four patients were given only single I-131 therapy dose ranging from 70 mCi (2590 MBq) to 150 mCi (5550 MBq). Thirty nine patients were treated with multiple I-131 radioisotope therapy doses ranging from 80 mCi (2960 MBq) to 250 mCi (9250 MBq). T-test was applied on the sample data showed statistically significant difference between the two groups with p-value (p < 0.01) less than 0.05 taken as significant. There were 68 females and 25 males with an age range of 15 to 80 years. Mean age of the patients were 36 years. Among the 93 cases of first time Radio Active Iodine (RAI) therapy, 59 cases (63%) were discharged after 48 hours. Among 39 patients who received RAI therapy second time or more, most were discharged earlier after achieving acceptable discharge dose rate i.e 25 µSv/hour; 2 out of 39 (5%) were discharged after 48 hours. In 58% patients, given single I-131 therapy dose, majority of these were discharged after 48 hours without any major complications. For well differentiated thyroid cancer patients, rapid dose rate reduction is seen in patients receiving second or subsequent radioiodine (RAI) therapy, as compared to first time receiving RAI therapy.

Ochrobactrum anthropi used to control ammonium for nitrate removal by starch-stabilized nanoscale zero valent iron.

PubMed

Zhou, Jun; Sun, Qianyu; Chen, Dan; Wang, Hongyu; Yang, Kai

2017-10-01

In this study, the hydrogenotrophic denitrifying bacterium Ochrobactrum anthropi was added in to the process of nitrate removal by starch-stabilized nanoscale zero valent iron (nZVI) to minimize undesirable ammonium. The ammonium control performance and cooperative mechanism of this combined process were investigated, and batch experiments were conducted to discuss the effects of starch-stabilized nZVI dose, biomass, and pH on nitrate reduction and ammonium control of this system. The combined system achieved satisfactory performance because the anaerobic iron corrosion process generates H 2 , which is used as an electron donor for the autohydrogenotrophic bacterium Ochrobactrum anthropi to achieve the autohydrogenotrophic denitrification process converting nitrate to N 2 . When starch-stabilized nZVI dose was increased from 0.5 to 2.0 g/L, nitrate reduction rate gradually increased, and ammonium yield also increased from 9.40 to 60.51 mg/L. Nitrate removal rate gradually decreased and ammonium yield decreased from 14.93 to 2.61 mg/L with initial OD 600 increasing from 0.015 to 0.080. The abiotic Fe 0 reduction process played a key role in nitrate removal in an acidic environment and generated large amounts of ammonium. Meanwhile, the nitrate removal rate decreased and ammonium yield also reduced in an alkaline environment.

Model-based iterative reconstruction in low-dose CT colonography-feasibility study in 65 patients for symptomatic investigation.

PubMed

Vardhanabhuti, Varut; James, Julia; Nensey, Rehaan; Hyde, Christopher; Roobottom, Carl

2015-05-01

To compare image quality on computed tomographic colonography (CTC) acquired at standard dose (STD) and low dose (LD) using filtered-back projection, adaptive statistical iterative reconstruction, and model-based iterative reconstruction (MBIR) techniques. A total of 65 symptomatic patients were prospectively enrolled for the study and underwent STD and LD CTC with filtered-back projection, adaptive statistical iterative reconstruction, and MBIR to allow direct per-patient comparison. Objective image noise, subjective image analyses, and polyp detection were assessed. Objective image noise analysis demonstrates significant noise reduction using MBIR technique (P < .05) despite being acquired at lower doses. Subjective image analyses were superior for LD MBIR in all parameters except visibility of extracolonic lesions (two-dimensional) and visibility of colonic wall (three-dimensional) where there were no significant differences. There was no significant difference in polyp detection rates (P > .05). Doses: LD (dose-length product, 257.7), STD (dose-length product, 483.6). LD MBIR CTC objectively shows improved image noise using parameters in our study. Subjectively, image quality is maintained. Polyp detection shows no significant difference but because of small numbers needs further validation. Average dose reduction of 47% can be achieved. This study confirms feasibility of using MBIR in this context of CTC in symptomatic population. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

Characterization of adaptive statistical iterative reconstruction algorithm for dose reduction in CT: A pediatric oncology perspective

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

Brady, S. L.; Yee, B. S.; Kaufman, R. A.

Purpose: This study demonstrates a means of implementing an adaptive statistical iterative reconstruction (ASiR Trade-Mark-Sign ) technique for dose reduction in computed tomography (CT) while maintaining similar noise levels in the reconstructed image. The effects of image quality and noise texture were assessed at all implementation levels of ASiR Trade-Mark-Sign . Empirically derived dose reduction limits were established for ASiR Trade-Mark-Sign for imaging of the trunk for a pediatric oncology population ranging from 1 yr old through adolescence/adulthood. Methods: Image quality was assessed using metrics established by the American College of Radiology (ACR) CT accreditation program. Each image quality metricmore » was tested using the ACR CT phantom with 0%-100% ASiR Trade-Mark-Sign blended with filtered back projection (FBP) reconstructed images. Additionally, the noise power spectrum (NPS) was calculated for three common reconstruction filters of the trunk. The empirically derived limitations on ASiR Trade-Mark-Sign implementation for dose reduction were assessed using (1, 5, 10) yr old and adolescent/adult anthropomorphic phantoms. To assess dose reduction limits, the phantoms were scanned in increments of increased noise index (decrementing mA using automatic tube current modulation) balanced with ASiR Trade-Mark-Sign reconstruction to maintain noise equivalence of the 0% ASiR Trade-Mark-Sign image. Results: The ASiR Trade-Mark-Sign algorithm did not produce any unfavorable effects on image quality as assessed by ACR criteria. Conversely, low-contrast resolution was found to improve due to the reduction of noise in the reconstructed images. NPS calculations demonstrated that images with lower frequency noise had lower noise variance and coarser graininess at progressively higher percentages of ASiR Trade-Mark-Sign reconstruction; and in spite of the similar magnitudes of noise, the image reconstructed with 50% or more ASiR Trade-Mark-Sign presented a more smoothed appearance than the pre-ASiR Trade-Mark-Sign 100% FBP image. Finally, relative to non-ASiR Trade-Mark-Sign images with 100% of standard dose across the pediatric phantom age spectrum, similar noise levels were obtained in the images at a dose reduction of 48% with 40% ASIR Trade-Mark-Sign and a dose reduction of 82% with 100% ASIR Trade-Mark-Sign . Conclusions: The authors' work was conducted to identify the dose reduction limits of ASiR Trade-Mark-Sign for a pediatric oncology population using automatic tube current modulation. Improvements in noise levels from ASiR Trade-Mark-Sign reconstruction were adapted to provide lower radiation exposure (i.e., lower mA) instead of improved image quality. We have demonstrated for the image quality standards required at our institution, a maximum dose reduction of 82% can be achieved using 100% ASiR Trade-Mark-Sign ; however, to negate changes in the appearance of reconstructed images using ASiR Trade-Mark-Sign with a medium to low frequency noise preserving reconstruction filter (i.e., standard), 40% ASiR Trade-Mark-Sign was implemented in our clinic for 42%-48% dose reduction at all pediatric ages without a visually perceptible change in image quality or image noise.« less

SU-E-I-57: Evaluation and Optimization of Effective-Dose Using Different Beam-Hardening Filters in Clinical Pediatric Shunt CT Protocol

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

Gill, K; Aldoohan, S; Collier, J

Purpose: Study image optimization and radiation dose reduction in pediatric shunt CT scanning protocol through the use of different beam-hardening filters Methods: A 64-slice CT scanner at OU Childrens Hospital has been used to evaluate CT image contrast-to-noise ratio (CNR) and measure effective-doses based on the concept of CT dose index (CTDIvol) using the pediatric head shunt scanning protocol. The routine axial pediatric head shunt scanning protocol that has been optimized for the intrinsic x-ray tube filter has been used to evaluate CNR by acquiring images using the ACR approved CT-phantom and radiation dose CTphantom, which was used to measuremore » CTDIvol. These results were set as reference points to study and evaluate the effects of adding different filtering materials (i.e. Tungsten, Tantalum, Titanium, Nickel and Copper filters) to the existing filter on image quality and radiation dose. To ensure optimal image quality, the scanner routine air calibration was run for each added filter. The image CNR was evaluated for different kVps and wide range of mAs values using above mentioned beam-hardening filters. These scanning protocols were run under axial as well as under helical techniques. The CTDIvol and the effective-dose were measured and calculated for all scanning protocols and added filtration, including the intrinsic x-ray tube filter. Results: Beam-hardening filter shapes energy spectrum, which reduces the dose by 27%. No noticeable changes in image low contrast detectability Conclusion: Effective-dose is very much dependent on the CTDIVol, which is further very much dependent on beam-hardening filters. Substantial reduction in effective-dose is realized using beam-hardening filters as compare to the intrinsic filter. This phantom study showed that significant radiation dose reduction could be achieved in CT pediatric shunt scanning protocols without compromising in diagnostic value of image quality.« less

In vitro neurotoxic effects of 1 GeV/n iron particles assessed in retinal explants.

PubMed

Vazquez, M E; Kirk, E

2000-01-01

The heavy ion component of the cosmic radiation remains problematic to the assessment of risk in manned space flight. The biological effectiveness of HZE particles has yet to be established, particularly with regard to nervous tissue. Using heavy ions accelerated at the AGS of Brookhaven National Laboratory, we study the neurotoxic effects of iron particles. We exposed retinal explants, taken from chick embryos, to determine the dose response relationships for neurite outgrowth. Morphometric techniques were used to evaluate the in vitro effects of 1 GeV/a iron particles (LET 148 keV/micrometer). Iron particles produced a dose-dependent reduction of neurite outgrowth with a maximal effect achieved with a dose of 100 cGy. Doses as low as 10-50 cGy were able to induce reductions of the neurite outgrowth as compared to the control group. Neurite generation is a more sensitive parameter than neurite elongation, suggesting different mechanism of radiation damage in our model. These results showed that low doses/fluences of iron particles could impair the retinal ganglion cells' capacity to generate neurites indicating the highly neurotoxic capability of this heavy charged particle.

Effective radiation dose and eye lens dose in dental cone beam CT: effect of field of view and angle of rotation.

PubMed

Pauwels, R; Zhang, G; Theodorakou, C; Walker, A; Bosmans, H; Jacobs, R; Bogaerts, R; Horner, K

2014-10-01

To quantify the effect of field of view (FOV) and angle of rotation on radiation dose in dental cone beam CT (CBCT) and to define a preliminary volume-dose model. Organ and effective doses were estimated using 148 thermoluminescent dosemeters placed in an anthropomorphic phantom. Dose measurements were undertaken on a 3D Accuitomo 170 dental CBCT unit (J. Morita, Kyoto, Japan) using six FOVs as well as full-rotation (360°) and half-rotation (180°) protocols. For the 360° rotation protocols, effective dose ranged between 54 µSv (4 × 4 cm, upper canine) and 303 µSv (17 × 12 cm, maxillofacial). An empirical relationship between FOV dimension and effective dose was derived. The use of a 180° rotation resulted in an average dose reduction of 45% compared with a 360° rotation. Eye lens doses ranged between 95 and 6861 µGy. Significant dose reduction can be achieved by reducing the FOV size, particularly the FOV height, of CBCT examinations to the actual region of interest. In some cases, a 180° rotation can be preferred, as it has the added value of reducing the scan time. Eye lens doses should be reduced by decreasing the height of the FOV rather than using inferior FOV positioning, as the latter would increase the effective dose considerably. The effect of the FOV and rotation angle on the effective dose in dental CBCT was quantified. The dominant effect of FOV height was demonstrated. A preliminary model has been proposed, which could be used to predict effective dose as a function of FOV size and position.

Contura Multi-Lumen Balloon breast brachytherapy catheter: comparative dosimetric findings of a phase 4 trial.

PubMed

Arthur, Douglas W; Vicini, Frank A; Todor, Dorin A; Julian, Thomas B; Cuttino, Laurie W; Mukhopadhyay, Nitai D

2013-06-01

Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥ 95% of the prescribed dose (PD) covering ≥ 95% of the target volume (TV); maximum skin dose ≤ 125% of the PD; maximum rib dose ≤ 145% of the PD; and V150 ≤50 cc and V200 ≤ 10 cc. Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P ≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals. Copyright © 2013 Elsevier Inc. All rights reserved.

Contura Multi-Lumen Balloon Breast Brachytherapy Catheter: Comparative Dosimetric Findings of a Phase 4 Trial

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

Arthur, Douglas W., E-mail: darthur@mcvh-vcu.edu; Vicini, Frank A.; Todor, Dorin A.

2013-06-01

Purpose: Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. Methods and Materials: Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥95% of the prescribed dose (PD) covering ≥95% of the target volume (TV); maximum skin dose ≤125%more » of the PD; maximum rib dose ≤145% of the PD; and V150 ≤50 cc and V200 ≤10 cc. Results: Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. Conclusions: Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals.« less

Preliminary validation of a new methodology for estimating dose reduction protocols in neonatal chest computed radiographs

NASA Astrophysics Data System (ADS)

Don, Steven; Whiting, Bruce R.; Hildebolt, Charles F.; Sehnert, W. James; Ellinwood, Jacquelyn S.; Töpfer, Karin; Masoumzadeh, Parinaz; Kraus, Richard A.; Kronemer, Keith A.; Herman, Thomas; McAlister, William H.

2006-03-01

The risk of radiation exposure is greatest for pediatric patients and, thus, there is a great incentive to reduce the radiation dose used in diagnostic procedures for children to "as low as reasonably achievable" (ALARA). Testing of low-dose protocols presents a dilemma, as it is unethical to repeatedly expose patients to ionizing radiation in order to determine optimum protocols. To overcome this problem, we have developed a computed-radiography (CR) dose-reduction simulation tool that takes existing images and adds synthetic noise to create realistic images that correspond to images generated with lower doses. The objective of our study was to determine the extent to which simulated, low-dose images corresponded with original (non-simulated) low-dose images. To make this determination, we created pneumothoraces of known volumes in five neonate cadavers and obtained images of the neonates at 10 mR, 1 mR and 0.1 mR (as measured at the cassette plate). The 10-mR exposures were considered "relatively-noise-free" images. We used these 10 mR-images and our simulation tool to create simulated 0.1- and 1-mR images. For the simulated and original images, we identified regions of interest (ROI) of the entire chest, free-in-air region, and liver. We compared the means and standard deviations of the ROI grey-scale values of the simulated and original images with paired t tests. We also had observers rate simulated and original images for image quality and for the presence or absence of pneumothoraces. There was no statistically significant difference in grey-scale-value means nor standard deviations between simulated and original entire chest ROI regions. The observer performance suggests that an exposure >=0.2 mR is required to detect the presence or absence of pneumothoraces. These preliminary results indicate that the use of the simulation tool is promising for achieving ALARA exposures in children.

Treatment modifications in tumour necrosis factor-α (TNF)-based isolated limb perfusion in patients with advanced extremity soft tissue sarcomas.

PubMed

Deroose, Jan P; Grünhagen, Dirk J; de Wilt, Johannes H W; Eggermont, Alexander M M; Verhoef, Cornelis

2015-02-01

Tumour necrosis factor-α (TNF) and melphalan based isolated limb perfusion (TM-ILP) is an attractive treatment option for advanced extremity soft tissue sarcomas (STS). This study reports on a 20-year single centre experience and discusses the evolution and changes in methodology since the introduction of TNF in ILP. We performed 306 TM-ILPs in 275 patients with extremity STS. All patients were candidates for amputation or mutilating surgery in order to achieve local control. Clinical response evaluation consisted of clinical examination and magnetic resonance imaging. To evaluate the importance of TNF-dose, treatment results of two periods (1991-2003 high dose (3-4 mg) TNF; 2003-2012 reduced dose (1-2mg) TNF) were compared. During the study period, more femoral perfusions were done instead of iliac perfusions. Reduction of TNF dose and reduction of total ILP time did not lead to different clinical response rates (70% and 69% for periods 1 and 2 respectively) or different local recurrence rates, but was associated with less local toxicity (23% and 14% for periods 1 and 2 respectively). Hospital stay was significantly reduced during the study period. There was an improved pathological response in the high dose TNF group without consequences for clinical outcome. TM-ILP remains a very effective treatment modality for limb threatening extremity STS. Moreover, reduction of dose and the growing experience in ILP led to less local toxicity and shorter hospital stay. Copyright © 2014 Elsevier Ltd. All rights reserved.

Does dose matter in reducing gestational weight gain in exercise interventions? A systematic review of literature

PubMed Central

McDonald, Samantha M.; Liu, Jihong; Wilcox, Sara; Lau, Erica Y.; Archer, Edward

2015-01-01

Objective This purpose of this review was to examine the relationship between exercise dose and reductions in weight gain during pregnancy in exercise interventions. Design and Methods Four electronic research databases (PubMed, Web of Science, CINAHL, and Academic Search Premiere) were used to identify exercise interventions conducted with pregnant women. Eligible articles must have satisfied the following criteria: inclusion of a control condition, exercise as a major intervention component, weight gain measured and reported for each experimental condition, description of exercise dose (frequency, intensity and duration), and utilized an adequate number of control conditions to assess independent effects of exercise on weight gain. Results The literature search identified 4837 articles, of these, 174 abstracts were screened and 21 intervention studies (18 exercise-only, 3 exercise/diet) were eligible for review. Only 38% of the interventions achieved statistically significant reductions in weight gain during pregnancy. Successful interventions possessed higher adherence and lower attrition rates and were predominantly conducted among normal weight populations. No clear patterns or consistencies of exercise dose and weight gain were evident. Conclusions Adherence and retention rates were strong contributors to the success of exercise interventions on weight gain during pregnancy. However, an exercise dose associated with reductions in weight gain was unquantifiable among these interventions. It is strongly suggested that future researchers investigate methods to increase adherence and compliance, especially among overweight and obese women, and utilize objective measurement tools to accurately evaluate exercise dose performed by the participants and the impact on both body composition and weight gain. PMID:25846125

Dosimetric Considerations in Respiratory-Gated Deep Inspiration Breath-Hold for Left Breast Irradiation.

PubMed

Walston, Steve; Quick, Allison M; Kuhn, Karla; Rong, Yi

2017-02-01

To present our clinical workflow of incorporating AlignRT for left breast deep inspiration breath-hold treatments and the dosimetric considerations with the deep inspiration breath-hold protocol. Patients with stage I to III left-sided breast cancer who underwent lumpectomy or mastectomy were considered candidates for deep inspiration breath-hold technique for their external beam radiation therapy. Treatment plans were created on both free-breathing and deep inspiration breath-hold computed tomography for each patient to determine whether deep inspiration breath-hold was beneficial based on dosimetric comparison. The AlignRT system was used for patient setup and monitoring. Dosimetric measurements and their correlation with chest wall excursion and increase in left lung volume were studied for free-breathing and deep inspiration breath-hold plans. Deep inspiration breath-hold plans had significantly increased chest wall excursion when compared with free breathing. This change in geometry resulted in reduced mean and maximum heart dose but did not impact lung V 20 or mean dose. The correlation between chest wall excursion and absolute reduction in heart or lung dose was found to be nonsignificant, but correlation between left lung volume and heart dose showed a linear association. It was also identified that higher levels of chest wall excursion may paradoxically increase heart or lung dose. Reduction in heart dose can be achieved for many left-sided breast and chest wall patients using deep inspiration breath-hold. Chest wall excursion as well as left lung volume did not correlate with reduction in heart dose, and it remains to be determined what metric will provide the most optimal and reliable dosimetric advantage.

Optimization of the scan protocols for CT-based material extraction in small animal PET/CT studies

NASA Astrophysics Data System (ADS)

Yang, Ching-Ching; Yu, Jhih-An; Yang, Bang-Hung; Wu, Tung-Hsin

2013-12-01

We investigated the effects of scan protocols on CT-based material extraction to minimize radiation dose while maintaining sufficient image information in small animal studies. The phantom simulation experiments were performed with the high dose (HD), medium dose (MD) and low dose (LD) protocols at 50, 70 and 80 kVp with varying mA s. The reconstructed CT images were segmented based on Hounsfield unit (HU)-physical density (ρ) calibration curves and the dual-energy CT-based (DECT) method. Compared to the (HU;ρ) method performed on CT images acquired with the 80 kVp HD protocol, a 2-fold improvement in segmentation accuracy and a 7.5-fold reduction in radiation dose were observed when the DECT method was performed on CT images acquired with the 50/80 kVp LD protocol, showing the possibility to reduce radiation dose while achieving high segmentation accuracy.

Tertiary treatment using microfiltration and UV disinfection for water reclamation

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

Jolis, D.; Hirano, R.; Pitt, P.

Microfiltration and UV disinfection are two alternative technologies for water reclamation. The results of a pilot study combining these two processes are presented. In addition to producing filtrate turbidites averaging 0.06 nephelometric turbidity units, microfiltration was an effective barrier to pathogens, demonstrating average log reductions of 4.5 for total coliforms and 2.9 for MS2 bacteriophage. Ultraviolet disinfection following microfiltration reliably met the California Wastewater Reclamation Criteria (Title 22) total coliform standard of 2.2 colony-forming units/100 mL at a UV dose of 450 J/m{sup 2}. The MS2 bacteriophage standard, which requires a 5-log reduction, was achieved by microfiltration and a UVmore » dose of 880 J/m{sup 2}. A model of the kinetics of inactivation of MS2 bacteriophage was used in further analysis of disinfection data. The model indicated that considerable backmixing occurred in the pilot UV disinfection unit, and observed UV doses could be reduced with improved hydraulics.« less

Measles control strategies in India: position paper of Indian Academy of Pediatrics.

PubMed

Vashishtha, V M; Choudhury, P; Bansal, C P; Gupta, S G

2013-06-08

Measles continues to be a major cause of childhood morbidity and mortality in India. Recent studies estimate that 80,000 Indian children die each year due to measles and its complications, amounting to 4% of under-5 deaths. Immunization against measles directly contributes to the reduction of under five child mortality and hence to the achievement of Millennium Development Goal 4 (MDG 4). The live attenuated measles vaccines are safe, effective and provide long lasting protection. The key strategies being followed globally for measles mortality reduction are high coverage of measles first dose, sensitive laboratory supported surveillance, appropriate case management, and providing second dose of measles vaccine. Prior to 2010, India was the only country in the world that had not introduced a second dose of measles vaccine in its National immunization program. We herein discuss the current status of measles vaccination along with the rationale and challenges of providing a second opportunity for measles vaccination, and the principles of measles catch-up campaigns.

Performance evaluation of iterative reconstruction algorithms for achieving CT radiation dose reduction — a phantom study

PubMed Central

Dodge, Cristina T.; Tamm, Eric P.; Cody, Dianna D.; Liu, Xinming; Jensen, Corey T.; Wei, Wei; Kundra, Vikas

2016-01-01

The purpose of this study was to characterize image quality and dose performance with GE CT iterative reconstruction techniques, adaptive statistical iterative reconstruction (ASiR), and model‐based iterative reconstruction (MBIR), over a range of typical to low‐dose intervals using the Catphan 600 and the anthropomorphic Kyoto Kagaku abdomen phantoms. The scope of the project was to quantitatively describe the advantages and limitations of these approaches. The Catphan 600 phantom, supplemented with a fat‐equivalent oval ring, was scanned using a GE Discovery HD750 scanner at 120 kVp, 0.8 s rotation time, and pitch factors of 0.516, 0.984, and 1.375. The mA was selected for each pitch factor to achieve CTDIvol values of 24, 18, 12, 6, 3, 2, and 1 mGy. Images were reconstructed at 2.5 mm thickness with filtered back‐projection (FBP); 20%, 40%, and 70% ASiR; and MBIR. The potential for dose reduction and low‐contrast detectability were evaluated from noise and contrast‐to‐noise ratio (CNR) measurements in the CTP 404 module of the Catphan. Hounsfield units (HUs) of several materials were evaluated from the cylinder inserts in the CTP 404 module, and the modulation transfer function (MTF) was calculated from the air insert. The results were confirmed in the anthropomorphic Kyoto Kagaku abdomen phantom at 6, 3, 2, and 1 mGy. MBIR reduced noise levels five‐fold and increased CNR by a factor of five compared to FBP below 6 mGy CTDIvol, resulting in a substantial improvement in image quality. Compared to ASiR and FBP, HU in images reconstructed with MBIR were consistently lower, and this discrepancy was reversed by higher pitch factors in some materials. MBIR improved the conspicuity of the high‐contrast spatial resolution bar pattern, and MTF quantification confirmed the superior spatial resolution performance of MBIR versus FBP and ASiR at higher dose levels. While ASiR and FBP were relatively insensitive to changes in dose and pitch, the spatial resolution for MBIR improved with increasing dose and pitch. Unlike FBP, MBIR and ASiR may have the potential for patient imaging at around 1 mGy CTDIvol. The improved low‐contrast detectability observed with MBIR, especially at low‐dose levels, indicate the potential for considerable dose reduction. PACS number(s): 87.57.Q‐, 87.57,nf, 87.57.C‐, 87.57.cj, 87.57.cf, 87.57.cm, 87.57.uq PMID:27074454

Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

PubMed

Sood, Sumit; Pokhrel, Damodar; McClinton, Christopher; Lominska, Christopher; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2017-01-01

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D 100% ) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI). Published by Elsevier Inc.

Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial.

PubMed

Eekers, Daniëlle B P; Roelofs, Erik; Jelen, Urszula; Kirk, Maura; Granzier, Marlies; Ammazzalorso, Filippo; Ahn, Peter H; Janssens, Geert O R J; Hoebers, Frank J P; Friedmann, Tobias; Solberg, Timothy; Walsh, Sean; Troost, Esther G C; Kaanders, Johannes H A M; Lambin, Philippe

2016-12-01

In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs). Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT). When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D 2 ) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org. In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls.

PubMed

Mendenhall, William M; Amdur, Robert J; Palta, Jatinder R

2006-06-10

The purpose of this article is to review the role of intensity-modulated radiotherapy (IMRT) in the standard management of patients with head and neck cancer through a critical review of the pertinent literature. IMRT may result in a dose distribution that is more conformal than that achieved with three-dimensional conformal radiotherapy (3D CRT), allowing dose reduction to normal structures and thus decreasing toxicity and possibly enhancing locoregional control through dose escalation. Disadvantages associated with IMRT include increased risk of a marginal miss, decreased dose homogeneity, increased total body dose, and increased labor and expense. Outcomes data after IMRT are limited, and follow-up is relatively short. Locoregional control rates appear to be comparable to those achieved with 3D CRT and, depending on the location and extent of the tumor, late toxicity may be lower. Despite limited data on clinical outcomes, IMRT has been widely adopted as a standard technique in routine practice and clinical trials. The use of IMRT involves a learning curve for the practitioner and will continue to evolve, requiring continuing education and monitoring of outcomes from routine practice. Additional standards pertaining to a variety of issues, including target definitions and dose specification, need to be developed. Phase III trials will better define the role of IMRT in coming years.

Decontamination in a Russian settlement.

PubMed

Fogh, C L; Andersson, K G; Barkovsky, A N; Mishine, A S; Ponamarjov, A V; Ramzaev, V P; Roed, J

1999-04-01

Decontamination was carried out in an area with three houses in Novo Bobovichi, Bryansk region, Russia, in the autumn of 1995. It was demonstrated that significant reductions in the dose rate both indoor (DRF = 0.34) and outdoor (DRF = 0.20) can be achieved when a controlled cleaning is undertaken. This paper describes the decontamination work carried out and the results obtained. The roofs of the houses were swept and cleaned by special roof cleaning equipment. The soil around the houses was removed by hand while carefully monitoring the ground for residual contamination. By monitoring the decline in the dose rate during the different stages of the work the dose reducing effect of each action has been measured.

Rationale and design of the NO-PARTY trial: near-zero fluoroscopic exposure during catheter ablation of supraventricular arrhythmias in young patients.

PubMed

Casella, Michela; Dello Russo, Antonio; Pelargonio, Gemma; Bongiorni, Maria Grazia; Del Greco, Maurizio; Piacenti, Marcello; Andreassi, Maria Grazia; Santangeli, Pasquale; Bartoletti, Stefano; Moltrasio, Massimo; Fassini, Gaetano; Marini, Massimiliano; Di Cori, Andrea; Di Biase, Luigi; Fiorentini, Cesare; Zecchi, Paolo; Natale, Andrea; Picano, Eugenio; Tondo, Claudio

2012-10-01

Radiofrequency catheter ablation is the mainstay of therapy for supraventricular tachyarrhythmias. Conventional radiofrequency catheter ablation requires the use of fluoroscopy, thus exposing patients to ionising radiation. The feasibility and safety of non-fluoroscopic radiofrequency catheter ablation has been recently reported in a wide range of supraventricular tachyarrhythmias using the EnSite NavX™ mapping system. The NO-PARTY is a multi-centre, randomised controlled trial designed to test the hypothesis that catheter ablation of supraventricular tachyarrhythmias guided by the EnSite NavX™ mapping system results in a clinically significant reduction in exposure to ionising radiation compared with conventional catheter ablation. The study will randomise 210 patients undergoing catheter ablation of supraventricular tachyarrhythmias to either a conventional ablation technique or one guided by the EnSite NavX™ mapping system. The primary end-point is the reduction of the radiation dose to the patient. Secondary end-points include procedural success, reduction of the radiation dose to the operator, and a cost-effectiveness analysis. In a subgroup of patients, we will also evaluate the radiobiological effectiveness of dose reduction by assessing acute chromosomal DNA damage in peripheral blood lymphocytes. NO-PARTY will determine whether radiofrequency catheter ablation of supraventricular tachyarrhythmias guided by the EnSite NavX™ mapping system is a suitable and cost-effective approach to achieve a clinically significant reduction in ionising radiation exposure for both patient and operator.

High-pitch computed tomography coronary angiography-a new dose-saving algorithm: estimation of radiation exposure.

PubMed

Ketelsen, Dominik; Buchgeister, Markus; Korn, Andreas; Fenchel, Michael; Schmidt, Bernhard; Flohr, Thomas G; Thomas, Christoph; Schabel, Christoph; Tsiflikas, Ilias; Syha, Roland; Claussen, Claus D; Heuschmid, Martin

2012-01-01

Purpose. To estimate effective dose and organ equivalent doses of prospective ECG-triggered high-pitch CTCA. Materials and Methods. For dose measurements, an Alderson-Rando phantom equipped with thermoluminescent dosimeters was used. The effective dose was calculated according to ICRP 103. Exposure was performed on a second-generation dual-source scanner (SOMATOM Definition Flash, Siemens Medical Solutions, Germany). The following scan parameters were used: 320 mAs per rotation, 100 and 120 kV, pitch 3.4 for prospectively ECG-triggered high-pitch CTCA, scan range of 13.5 cm, collimation 64 × 2 × 0.6 mm with z-flying focal spot, gantry rotation time 280 ms, and simulated heart rate of 60 beats per minute. Results. Depending on the applied tube potential, the effective whole-body dose of the cardiac scan ranged from 1.1 mSv to 1.6 mSv and from 1.2 to 1.8 mSv for males and females, respectively. The radiosensitive breast tissue in the range of the primary beam caused an increased female-specific effective dose of 8.6%±0.3% compared to males. Decreasing the tube potential, a significant reduction of the effective dose of 35.8% and 36.0% can be achieved for males and females, respectively (P < 0.001). Conclusion. The radiologist and the CT technician should be aware of this new dose-saving strategy to keep the radiation exposure as low as reasonablly achievable.

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial.

PubMed

Vossler, David G; Wechsler, Robert T; Williams, Paulette; Byrnes, William; Therriault, Sheila

2016-10-01

To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose. Investigators could adjust the LCM dose to 100-800 mg/day and add up to two antiepileptic drugs to optimize tolerability and seizure reduction. Three hundred twenty-two patients received LCM: 210 patients (65.2%) completed and 112 (34.8%) discontinued, most commonly owing to withdrawal of consent (9.3%). Two hundred fifty-eight patients (80.1%) had ≥1 year of and 216 (67.1%) had ≥2 years of LCM exposure, of whom 179/258 (69.4%) achieved LCM monotherapy lasting for any 12-month period, and 126/216 (58.3%) patients exposed for ≥24 months achieved LCM monotherapy for any 24-month period. Total exposure = 525.5 patient-years. The median modal dose was 500 mg/day. Two hundred ninety-two patients (90.7%) achieved LCM monotherapy at some point during the study. Sixty-five of 87 patients who exited and 193/235 who completed SP902 were exposed for ≥12 months, and 43.1% and 78.2%, respectively, achieved LCM monotherapy for ≥12 months. Median LCM monotherapy duration was 587.0 days (2-791 days); 91.0% of patients reported treatment-emergent adverse events, of which the most common were dizziness (27.3%), headache (17.1%), and nausea (14.3%). Compared with the SP902 study baseline, 74.2% of patients had a ≥50% seizure reduction and 5.6% were seizure-free at 24 months. The majority of patients were receiving LCM monotherapy at 0, 12, and 24 months in this OLE. Lacosamide monotherapy (median dose of 500 mg/day) had a safety profile similar to that of adjunctive therapy studies. These results support the use of lacosamide as long-term monotherapy treatment for adults with POS. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses.

PubMed

Harborne, Lyndal R; Sattar, Naveed; Norman, Jane E; Fleming, Richard

2005-08-01

Metformin treatment of women with polycystic ovary syndrome (PCOS) is widespread, as determined by studies with diverse patient populations. No comparative examination of weight changes or metabolite responses to different doses has been reported. The aim of this study was to determine whether different doses of metformin (1500 or 2550 mg/d) would have different effects on body weight, circulating hormones, markers of inflammation, and lipid profiles. The study included prospective cohorts randomized to two doses of metformin. The study was performed at a university teaching hospital with patients from gynecology/endocrinology clinics. The patients studied were obese (body mass index, 30 to <37 kg/m2; n = 42) and morbidly obese (body mass index, > or =37 kg/m2; n = 41) women with PCOS. Patients were randomized to two doses of metformin, and parameters were assessed after 4 and 8 months. The main outcome measures were changes in body mass, circulating hormones, markers of inflammation, and lipid profiles. Intention to treat analyses showed significant weight loss in both dose groups. Only the obese subgroup showed a dose relationship (1.5 and 3.6 kg in 1500- and 2550-mg groups, respectively; P = 0.04). The morbidly obese group showed similar reductions (3.9 and 3.8 kg) in both groups. Suppression of androstenedione was significant with both metformin doses, but there was no clear dose relationship. Generally, beneficial changes in lipid profiles were not related to dose. Weight loss is a feature of protracted metformin therapy in obese women with PCOS, with greater weight reduction potentially achievable with higher doses. Additional studies are required to determine whether other aspects of the disorder may benefit from the higher dose of metformin.

Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease.

PubMed

Lubanda, Jean-Claude; Anijalg, Ene; Bzdúch, Vladimír; Thurberg, Beth L; Bénichou, Bernard; Tylki-Szymanska, Anna

2009-04-01

Fabry disease, a genetic deficiency of alpha-galactosidase A, is characterized by pathogenic cellular accumulation of globotriaosylceramide. During clinical trials, recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme, Genzyme Corporation, Cambridge, MA), infused intravenously at 1.0 mg/kg every 2 weeks for 6 months, cleared or reduced globotriaosylceramide in renal, cardiac, and dermal microvascular endothelia and other cells, with results sustained for up to 5 years in most patients evaluated. This study explored whether a lower dose could maintain globotriaosylceramide clearance achieved with 1.0 mg/kg. Cellular globotriaosylceramide levels were assessed histologically in kidney and skin biopsies from 21 adult Fabry males treated for 6 months at 1.0 mg/kg/2 weeks followed by 18 months at 0.3 mg/kg/2 weeks. In kidney interstitial capillary endothelium, the primary endpoint, globotriaosylceramide clearance was achieved in 100% of patients with 1.0 mg/kg and maintained in 90% with 0.3 mg/kg. In seven other renal cell types and superficial dermal capillary endothelium, globotriaosylceramide reduction or clearance was maintained with 0.3 mg/kg in approximately 70% of patients. A lower dose of agalsidase beta may be sufficient in some, but not all, patients with Fabry disease to maintain the cellular globotriaosylceramide clearance achieved with 1.0 mg/kg/2 weeks. Long-term clinical effects of transitioning to the lower dose have not been evaluated.

Antitrypanosomal Activity of Fexinidazole Metabolites, Potential New Drug Candidates for Chagas Disease

PubMed Central

Nascimento, Alvaro F. S.; Mazzeti, Ana Lia; Marques, Luiz F.; Gonçalves, Karolina R.; Mota, Ludmilla W. R.; Diniz, Lívia de F.; Caldas, Ivo S.; Talvani, André; Shackleford, David M.; Koltun, Maria; Saunders, Jessica; White, Karen L.; Scandale, Ivan; Charman, Susan A.; Chatelain, Eric

2014-01-01

This study was designed to verify the in vivo efficacy of sulfoxide and sulfone fexinidazole metabolites following oral administration in a murine model of Chagas disease. Female Swiss mice infected with the Y strain of Trypanosoma cruzi were treated orally once per day with each metabolite at doses of 10 to 100 mg/kg of body weight for a period of 20 days. Parasitemia was monitored throughout, and cures were detected by parasitological and PCR assays. The results were compared with those achieved with benznidazole treatment at the same doses. Fexinidazole metabolites were effective in reducing the numbers of circulating parasites and protecting mice against death, compared with untreated mice, but without providing cures at daily doses of 10 and 25 mg/kg. Both metabolites were effective in curing mice at 50 mg/kg/day (30% to 40%) and 100 mg/kg/day (100%). In the benznidazole-treated group, parasitological cure was detected only in animals treated with the higher dose of 100 mg/kg/day (80%). Single-dose pharmacokinetic parameters for each metabolite were obtained from a parallel group of uninfected mice and were used to estimate the profiles following repeated doses. Pharmacokinetic data suggested that biological efficacy most likely resides with the sulfone metabolite (or subsequent reactive metabolites formed following reduction of the nitro group) following administration of either the sulfoxide or the sulfone and that prolonged plasma exposure over the 24-h dosing window is required to achieve high cure rates. Fexinidazole metabolites were effective in treating T. cruzi in a mouse model of acute infection, with cure rates superior to those achieved with either fexinidazole itself or benznidazole. PMID:24841257

SU-C-206-07: A Practical Sparse View Ultra-Low Dose CT Acquisition Scheme for PET Attenuation Correction in the Extended Scan Field-Of-View

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

Miao, J; Fan, J; Gopinatha Pillai, A

Purpose: To further reduce CT dose, a practical sparse-view acquisition scheme is proposed to provide the same attenuation estimation as higher dose for PET imaging in the extended scan field-of-view. Methods: CT scans are often used for PET attenuation correction and can be acquired at very low CT radiation dose. Low dose techniques often employ low tube voltage/current accompanied with a smooth filter before backprojection to reduce CT image noise. These techniques can introduce bias in the conversion from HU to attenuation values, especially in the extended CT scan field-of-view (FOV). In this work, we propose an ultra-low dose CTmore » technique for PET attenuation correction based on sparse-view acquisition. That is, instead of an acquisition of full amount of views, only a fraction of views are acquired. We tested this technique on a 64-slice GE CT scanner using multiple phantoms. CT scan FOV truncation completion was performed based on the published water-cylinder extrapolation algorithm. A number of continuous views per rotation: 984 (full), 246, 123, 82 and 62 have been tested, corresponding to a CT dose reduction of none, 4x, 8x, 12x and 16x. We also simulated sparse-view acquisition by skipping views from the fully-acquired view data. Results: FBP reconstruction with Q. AC filter on reduced views in the full extended scan field-of-view possesses similar image quality to the reconstruction on acquired full view data. The results showed a further potential for dose reduction compared to the full acquisition, without sacrificing any significant attenuation support to the PET. Conclusion: With the proposed sparse-view method, one can potential achieve at least 2x more CT dose reduction compared to the current Ultra-Low Dose (ULD) PET/CT protocol. A pre-scan based dose modulation scheme can be combined with the above sparse-view approaches, which can even further reduce the CT scan dose during a PET/CT exam.« less

Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force.

PubMed

Guirguis-Blake, Janelle M; Evans, Corinne V; Senger, Caitlyn A; O'Connor, Elizabeth A; Whitlock, Evelyn P

2016-06-21

Cardiovascular disease (CVD) is the leading cause of death in the United States. To update a systematic review about the benefits of aspirin for the primary prevention of cardiovascular events in adults aged 40 years or older and to evaluate effect modification in subpopulations. MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (January 2008 to January 2015), and Cochrane Database of Systematic Reviews. Two investigators independently reviewed 3396 abstracts and 65 articles according to prespecified criteria. All included trials evaluated aspirin for the primary prevention of cardiovascular events. Two investigators assessed study quality; data were abstracted by 1 reviewer and checked by a second. Two good-quality and 9 fair-quality randomized, controlled trials were identified. In analyses of all doses, aspirin reduced the risk for nonfatal myocardial infarction (MI) (relative risk [RR], 0.78 [95% CI, 0.71 to 0.87]) but not nonfatal stroke; aspirin showed little or no benefit for all-cause or cardiovascular mortality. Benefits began within the first 5 years. Older adults achieved greater relative MI reduction, but no other effect modifications were found in analyzed subpopulations. In trials with aspirin doses of 100 mg or less per day, the reduction in nonfatal MI benefit persisted (absolute risk reduction, 0.15 to 1.43 events per 1000 person-years) and a 14% reduction in nonfatal stroke benefit was noted, but no benefit was found for all-cause mortality (RR, 0.95 [CI, 0.89 to 1.01]) or cardiovascular mortality (RR, 0.97 [CI, 0.85 to 1.10]). Evidence for aspirin in primary prevention is heterogeneous and limited by rare events and few credible subgroup analyses. The beneficial effect of aspirin for the primary prevention of CVD is modest and occurs at doses of 100 mg or less per day. Older adults seem to achieve a greater relative MI benefit. Agency for Healthcare Research and Quality.

Fluoroscopy-guided hydrostatic reduction of intussusception in infancy: role of pharmacological premedication.

PubMed

Esposito, Francesco; Ambrosio, Concetta; De Fronzo, Simona; Panico, Maria Rita; D'Aprano, Marilena; Giugliano, Anna Marcella; Noviello, Domenico; Oresta, Patrizia

2015-06-01

Intussusception is one of the most common causes of paediatric emergency. Fluoroscopy-guided hydrostatic reduction is a common nonoperative management strategy for the treatment of intussusception. The role of pharmacological premedication in increasing the success rate of hydrostatic reduction is still controversial. The purpose of this study was to verify the presence of a possible correlation between pharmacological premedication and the percentage of hydrostatic reduction of intussusception in paediatric patients. This study considered children with a diagnosis of idiopathic intussusception treated at our hospital between January 2007 and June 2013. One group of patients underwent hydrostatic reduction by barium enema without any preliminary therapy. A second group of patients received pharmacological premedication with both a sedative and an anti-oedematous agent before the procedure. A total of 398 patients were treated with barium enema for therapeutic purposes. In the group of patients who received no premedication (n = 254), 165 (65 %) children achieved hydrostatic reduction of the intussusception. Among the patients who received pharmacological premedication prior to barium enema (n = 144), 122 (85 %) children achieved resolution of the intussusception. Our study shows that the use of pharmacological premedication is effective for the reduction of the intussusception, as its limit patient stress, fluoroscopic time and radiation dose.

Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

PubMed Central

Hale, Martin E; Nalamachu, Srinivas R; Khan, Arif; Kutch, Michael

2013-01-01

Purpose To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER) during dose conversion and titration. Patients and methods A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio), and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs) and serious AEs. Results Mean (standard deviation) final daily dose of OROS hydromorphone ER was 37.5 (17.8) mg. Mean (standard error of the mean [SEM]) numeric rating scale scores decreased from 6.6 (0.1) at screening to 4.3 (0.1) at the final titration visit (mean [SEM] change, −2.3 [0.1], representing a 34.8% reduction). Mean (SEM) change in Patient Global Assessment was −0.6 (0.1), and mean change (SEM) in the Roland–Morris Disability Questionnaire was −2.8 (0.3). Patients achieving a stable dose showed greater improvement than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a ≥30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of OROS hydromorphone ER within 2 to 4 weeks. PMID:23658495

Inactivation of antibiotic resistance genes in municipal wastewater by chlorination, ultraviolet, and ozonation disinfection.

PubMed

Zhuang, Yao; Ren, Hongqiang; Geng, Jinju; Zhang, Yingying; Zhang, Yan; Ding, Lili; Xu, Ke

2015-05-01

This study investigated the inactivation of two antibiotic resistance genes (ARGs)-sul1 and tetG, and the integrase gene of class 1 integrons-intI1 by chlorination, ultraviolet (UV), and ozonation disinfection. Inactivation of sul1, tetG, and intI1 underwent increased doses of three disinfectors, and chlorine disinfection achieved more inactivation of ARGs and intI1 genes (chlorine dose of 160 mg/L with contact time of 120 min for 2.98-3.24 log reductions of ARGs) than UV irradiation (UV dose of 12,477 mJ/cm(2) for 2.48-2.74 log reductions of ARGs) and ozonation disinfection (ozonation dose of 177.6 mg/L for 1.68-2.55 log reductions of ARGs). The 16S rDNA was more efficiently removed than ARGs by ozone disinfection. The relative abundance of selected genes (normalized to 16S rDNA) increased during ozonation and with low doses of UV and chlorine disinfection. Inactivation of sul1 and tetG showed strong positive correlations with the inactivation of intI1 genes (for sul1, R (2)  = 0.929 with p < 0.01; for tetG, R (2)  = 0.885 with p < 0.01). Compared to other technologies (ultraviolet disinfection, ozonation disinfection, Fenton oxidation, and coagulation), chlorination is an alternative method to remove ARGs from wastewater effluents. At a chlorine dose of 40 mg/L with 60 min contact time, the selected genes inactivation efficiency could reach 1.65-2.28 log, and the cost was estimated at 0.041 yuan/m(3).

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans.

PubMed

Chaikh, Abdulhamid; Calugaru, Valentin; Bondiau, Pierre-Yves; Thariat, Juliette; Balosso, Jacques

2018-06-07

The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy. 14 pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value. Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < 0.05, using the three NTCP concepts. However, applying the same TD 50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better. treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Since estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD 50/5 , a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient's plan.

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.

Multidetector CT radiation dose optimisation in adults: short- and long-term effects of a clinical audit.

PubMed

Tack, Denis; Jahnen, Andreas; Kohler, Sarah; Harpes, Nico; De Maertelaer, Viviane; Back, Carlo; Gevenois, Pierre Alain

2014-01-01

To report short- and long-term effects of an audit process intended to optimise the radiation dose from multidetector row computed tomography (MDCT). A survey of radiation dose from all eight MDCT departments in the state of Luxembourg performed in 2007 served as baseline, and involved the most frequently imaged regions (head, sinus, cervical spine, thorax, abdomen, and lumbar spine). CT dose index volume (CTDIvol), dose-length product per acquisition (DLP/acq), and DLP per examination (DLP/exa) were recorded, and their mean, median, 25th and 75th percentiles compared. In 2008, an audit conducted in each department helped to optimise doses. In 2009 and 2010, two further surveys evaluated the audit's impact on the dose delivered. Between 2007 and 2009, DLP/exa significantly decreased by 32-69 % for all regions (P < 0.001) except the lumbar spine (5 %, P = 0.455). Between 2009 and 2010, DLP/exa significantly decreased by 13-18 % for sinus, cervical and lumbar spine (P ranging from 0.016 to less than 0.001). Between 2007 and 2010, DLP/exa significantly decreased for all regions (18-75 %, P < 0.001). Collective dose decreased by 30 % and the 75th percentile (diagnostic reference level, DRL) by 20-78 %. The audit process resulted in long-lasting dose reduction, with DRLs reduced by 20-78 %, mean DLP/examination by 18-75 %, and collective dose by 30 %. • External support through clinical audit may optimise default parameters of routine CT. • Reduction of 75th percentiles used as reference diagnostic levels is 18-75 %. • The effect of this audit is sustainable over time. • Dose savings through optimisation can be added to those achievable through CT.

Low tube voltage dual source computed tomography to reduce contrast media doses in adult abdomen examinations: A phantom study

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

Thor, Daniel; Brismar, Torkel B., E-mail: torkel.brismar@gmail.com; Fischer, Michael A.

Purpose: To evaluate the potential of low tube voltage dual source (DS) single energy (SE) and dual energy (DE) computed tomography (CT) to reduce contrast media (CM) dose in adult abdominal examinations of various sizes while maintaining soft tissue and iodine contrast-to-noise ratio (CNR). Methods: Four abdominal phantoms simulating a body mass index of 16 to 35 kg/m{sup 2} with four inserted syringes of 0, 2, 4, and 8 mgI/ml CM were scanned using a 64-slice DS-CT scanner. Six imaging protocols were used; one single source (SS) reference protocol (120 kV, 180 reference mAs), four low kV SE protocols (70more » and 80 kV using both SS and DS), and one DE protocol at 80/140 kV. Potential CM reduction with unchanged CNRs relative to the 120 kV protocol was calculated along with the corresponding increase in radiation dose. Results: The potential contrast media reductions were determined to be approximately 53% for DS 70 kV, 51% for SS 70 kV, 44% for DS 80 kV, 40% for SS 80 kV, and 20% for DE (all differences were significant, P < 0.05). Constant CNR could be achieved by using DS 70 kV for small to medium phantom sizes (16–26 kg/m{sup 2}) and for all sizes (16–35 kg/m{sup 2}) when using DS 80 kV and DE. Corresponding radiation doses increased by 60%–107%, 23%–83%, and 6%–12%, respectively. Conclusions: DS single energy CT can be used to reduce CM dose by 44%–53% with maintained CNR in adult abdominal examinations at the cost of an increased radiation dose. DS dual-energy CT allows reduction of CM dose by 20% at similar radiation dose as compared to a standard 120 kV single source.« less

Clinical development of a novel inactivated poliomyelitis vaccine based on attenuated Sabin poliovirus strains.

PubMed

Verdijk, Pauline; Rots, Nynke Y; Bakker, Wilfried A M

2011-05-01

Following achievement of polio eradication, the routine use of all live-attenuated oral poliovirus vaccines should be discontinued. However, the costs per vaccine dose for the alternative inactivated poliovirus vaccine (IPV) are significantly higher and the current production capacity is not sufficient for worldwide distribution of the vaccine. In order to achieve cost-prize reduction and improve affordability, IPV production processes and dose-sparing strategies should be developed to facilitate local manufacture at a relatively lower cost. The use of attenuated Sabin instead of wild-type polio strains will provide additional safety during vaccine production and permits production in low-cost settings. Sabin-IPV is under development by several manufacturers. This article gives an overview of results from clinical trials with Sabin-IPV and discusses the requirements and challenges in the clinical development of this novel IPV.

Appropriate insulin initiation dosage for insulin-naive type 2 diabetes outpatients receiving insulin monotherapy or in combination with metformin and/or pioglitazone.

PubMed

Liao, Lin; Yang, Ming; Qiu, Lu-Lu; Mou, Ya-Ru; Zhao, Jia-Jun; Dong, Jian-Jun

2010-12-01

Few studies have given suggestions on appropriate initiation insulin dosage when combined with oral antidiabetic drugs (OADs). This research was to investigate appropriate initiation insulin doses for insulin-naive type 2 diabetes patients with different combinations and the relationship between insulin dosage and relevant factors. This was a randomized, open-label, treat to target study. The target was 20% decrease of both fasting plasma glucose (FPG) and 2 hours post-breakfast blood glucose (P2hBG). One hundred and forty-seven insulin-naive Chinese patients recruited were randomly assigned to 3 groups: group A, patients received insulin monotherapy; group B, received insulin plus metformin (0.5 g, tid) and group C, received insulin plus metformin (0.5 g, tid) and pioglitazone (15 mg, qd). Insulin doses were initiated with a dose of 0.3 U×kg(-1)×d(-1) and titrated according to FPG and P2hBG till reached the targets. Both the time of getting 20% reduction of FPG and P2hBG showed significant differences among the three groups. The time was shortest in Group C. The insulin doses needed to achieve glucose reduction of 20% in three treatment groups were (0.40 ± 0.04) U×kg(-1)×d(-1) for Group A, (0.37 ± 0.04) U×kg(-1)×d(-1) for Group B, and (0.35 ± 0.03) U×kg(-1)×d(-1) for Group C, respectively. Multiple linear stepwise regression analysis showed that insulin doses correlated with body weight, FPG, diabetes duration, age and history of sulfonylurea treatment. The standardized regression coefficients were 0.871, 0.322, 0.089, 0.067 and 0.063 (with all P < 0.05). To achieve blood glucose's reduction of 20% within safety context, initial insulin doses were recommended as the following: 0.40 U×kg(-1)×d(-1) for insulin mono-therapy, 0.37 U×kg(-1)×d(-1) for insulin plus metformin treatment, and 0.35 U×kg(-1)×d(-1) for insulin plus metformin and pioglitazone treatment in Chinese type 2 diabetes outpatients. Body weight is found the most closely related factor to the insulin dosage.

Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial.

PubMed

Krayenbuehl, J; Di Martino, M; Guckenberger, M; Andratschke, N

2017-10-02

Whole-brain radiation therapy (WBRT) with hippocampus sparing (HS) has been investigated by the radiation oncology working group (RTOG) 0933 trial for patients with multiple brain metastases. They showed a decrease of adverse neurocognitive effects with HS WBRT compared to WBRT alone. With the development of automated treatment planning system (aTPS) in the last years, a standardization of the plan quality at a high level was achieved. The goal of this study was to evaluate the feasibility of using an aTPS for the treatment of HS WBRT and see if the RTOG 0933 dose constraints could be achieved and improved. Ten consecutive patients treated with HS WBRT were enrolled in this study. 10 × 3 Gy was prescribed according to the RTOG 0933 protocol to 92% of the target volume (whole-brain excluding the hippocampus expanded by 5 mm in 3-dimensions). In contrast to RTOG 0933, the maximum allowed point dose to normal brain was significantly lowered and restricted to 36.5 Gy. All patients were planned with volumetric modulated arc therapy (VMAT) technique using four arcs. Plans were optimized using Auto-Planning (AP) (Philips Radiation Oncology Systems) with one single AP template and optimization. All the constraints from the RTOG 0933 trial were achieved. A significant improvement for the maximal dose to 2% of the brain with a reduction of 4 Gy was achieved (33.5 Gy vs. RTOG 37.5 Gy) and the minimum hippocampus dose was reduced by 10% (8.1 Gy vs. RTOG 9 Gy). A steep dose gradient around the hippocampus was achieved with a mean dose of 27.3 Gy at a distance between 0.5 cm and 1 cm from the hippocampus. The effective working time to optimize a plan was kept below 6'. Automated treatment planning for HS WBRT was able to fulfil all the recommendations from the RTOG 0933 study while significantly improving dose homogeneity and decreasing unnecessary hot spot in the normal brain. With this approach, a standardization of plan quality was achieved and the effective time required for plan optimization was minimized.

Dose tracking and dose auditing in a comprehensive computed tomography dose-reduction program.

PubMed

Duong, Phuong-Anh; Little, Brent P

2014-08-01

Implementation of a comprehensive computed tomography (CT) radiation dose-reduction program is a complex undertaking, requiring an assessment of baseline doses, an understanding of dose-saving techniques, and an ongoing appraisal of results. We describe the role of dose tracking in planning and executing a dose-reduction program and discuss the use of the American College of Radiology CT Dose Index Registry at our institution. We review the basics of dose-related CT scan parameters, the components of the dose report, and the dose-reduction techniques, showing how an understanding of each technique is important in effective auditing of "outlier" doses identified by dose tracking. Copyright © 2014 Elsevier Inc. All rights reserved.

DVH- and NTCP-based dosimetric comparison of different longitudinal margins for VMAT-IMRT of esophageal cancer.

PubMed

Münch, S; Oechsner, M; Combs, S E; Habermehl, D

2017-08-15

To cover the microscopic tumor spread in squamous cell carcinoma of the esophagus (SCC), longitudinal margins of 3-4 cm are used for radiotherapy (RT) protocols. However, smaller margins of 2-3 cm might be reasonable when advanced diagnostic imaging is integrated into target volume delineation. Purpose of this study was to compare the dose distribution and deposition to the organs at risk (OAR) for different longitudinal margins using a DVH- and NTCP-based approach. Ten patients with SCC of the middle or lower third were retrospectively selected. Three planning target volumes (PTV) with longitudinal margins of 4 cm, 3 cm and 2 cm and an axial margin of 1.5 cm to the gross target volume (GTV) were defined for each patient. For each PTV two treatment plans with total doses of 41.4 Gy (neoadjuvant treatment) and 50.4 Gy (definite treatment) were calculated. Dose to the lungs, heart, myelon and liver were then evaluated and compared between different PTVs. When using a longitudinal margin of 3 cm instead of 4 cm, all dose parameters (Dmin, Dmean, Dmedian and V5-V35), except Dmax could be significantly reduced for the lungs. Regarding the heart, a significant reduction was seen for Dmean and V5, but not for Dmin, Dmax, Dmedian and V10-V35. When comparing a longitudinal margin of 4 cm to a longitudinal margin of 2 cm, a significant difference was calculated for Dmin, Dmean, Dmedian and V5-V35 of the lungs and for Dmax, Dmean and V5-V35 of the heart. Nevertheless, no difference was seen for median heart dose. An additional dose reduction for V10 of the heart was achieved for definite treatment plans when using a longitudinal margin of 3 cm. The NTCP-based risk of pneumonitis was significantly reduced by a margin reduction to 2 cm for neoadjuvant and definite treatment plans. Reduction of longitudinal margins from 4 cm to 3 cm can significantly reduce the dose to lungs and Dmean of the heart. Despite clinical benefit and oncologic outcome remain unclear, reduction of the longitudinal margins might provide the opportunity to reduce side effects of chemoradiation (CRT) for SCC in upcoming studies.

Towards Standardization of X-ray Beam Filters in Digital Mammography and Digital Breast Tomosynthesis: Monte Carlo simulations and analytical modelling

PubMed Central

Shrestha, Suman; Vedantham, Srinivasan; Karellas, Andrew

2017-01-01

In digital breast tomosynthesis and digital mammography, the x-ray beam filter material and thickness vary between systems. Replacing K-edge filters with Al was investigated with the intent to reduce exposure duration and to simplify system design. Tungsten target x-ray spectra were simulated with K-edge filters (50μm Rh; 50μm Ag) and Al filters of varying thickness. Monte Carlo simulations were conducted to quantify the x-ray scatter from various filters alone, scatter-to-primary ratio (SPR) with compressed breasts, and to determine the radiation dose to the breast. These data were used to analytically compute the signal-difference-to-noise ratio (SDNR) at unit (1 mGy) mean glandular dose (MGD) for W/Rh and W/Ag spectra. At SDNR matched between K-edge and Al filtered spectra, the reductions in exposure duration and MGD were quantified for three strategies: (i) fixed Al thickness and matched tube potential in kilovolts (kV); (ii) fixed Al thickness and varying the kV to match the half-value layer (HVL) between Al and K-edge filtered spectra; and, (iii) matched kV and varying the Al thickness to match the HVL between Al and K-edge filtered spectra. Monte Carlo simulations indicate that the SPR with and without the breast were not different between Al and K-edge filters. Modelling for fixed Al thickness (700μm) and kV matched to K-edge filtered spectra, identical SDNR was achieved with 37–57% reduction in exposure duration and with 2–20% reduction in MGD, depending on breast thickness. Modelling for fixed Al thickness (700μm) and HVL matched by increasing the kV over [0,4] range, identical SDNR was achieved with 62–65% decrease in exposure duration and with 2–24% reduction in MGD, depending on breast thickness. For kV and HVL matched to K-edge filtered spectra by varying Al filter thickness over [700,880]μm range, identical SDNR was achieved with 23–56% reduction in exposure duration and 2–20% reduction in MGD, depending on breast thickness. These simulations indicate that increased fluence with Al filter of fixed or variable thickness substantially decreases exposure duration while providing for similar image quality with moderate reduction in MGD. PMID:28075335

Activity of AFN-1252, a novel FabI inhibitor, against Staphylococcus aureus in an in vitro pharmacodynamic model simulating human pharmacokinetics

PubMed Central

Tsuji, Brian T; Harigaya, Yoriko; Lesse, Alan J; Forrest, Alan; Ngo, Dung

2013-01-01

AFN-1252, a potent enoyl-ACP reductase (FabI) inhibitor, is under development for the treatment of Staphylococcus aureus infections. The activity of AFN-1252 against two isolates of S. aureus, MSSA 26213 and MRSA S186, was studied in an in vitro pharmacodynamic model simulating AFN-1252 pharmacokinetics in man. Reductions in bacterial viable count over the first 6 hours were generally 1–2 logs and maximal reductions in viable count were generally achieved at fAUC/MIC ratios of 100–200. Maximum reductions in viable count against MSSA 29213 and MRSA S186 were approximately 4 logs, achieved by 450 mg q12h (fAUC/MIC = 1875) dosing at 28 hours. Staphylococcal resistance to AFN-1252 did not develop throughout the 48-hour experiments. As multidrug resistance continues to increase, these studies support the continued investigation of AFN-1252 as a targeted therapeutic for staphylococcal infections. PMID:23433442

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

Podonsky, Glenn S.

The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2012 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protectionmore » of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past 5-year period, the occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site. As an indicator of the overall amount of radiation dose received during the conduct of operations at DOE, the report includes information on collective total effective dose (TED). The TED is comprised of the effective dose (ED) from external sources, which includes neutron and photon radiation, and the internal committed effective dose (CED), which results from the intake of radioactive material into the body. The collective ED from photon exposure decreased by 23% between 2011 and 2012, while the neutron dose increased by 5%. The internal dose components of the collective TED decreased by 7%. Over the past 5-year period, 99.99% of the individuals receiving measurable TED have received doses below the 2 roentgen equivalent in man (rems) (20 millisievert [mSv]) TED administrative control level (ACL), which is well below the DOE regulatory limit of 5 rems (50 mSv) TED annually. The occupational radiation exposure records show that in 2012, DOE facilities continued to comply with DOE dose limits and ACLs and worked to minimize exposure to individuals. The DOE collective TED decreased 17.1% from 2011 to 2012. The collective TED decreased at three of the five sites with the largest collective TED. u Idaho Site – Collective dose reductions were achieved as a result of continuing improvements at the Advanced Mixed Waste Treatment Project (AMWTP) through the planning of drum movements that reduced the number of times a container is handled; placement of waste containers that created highradiation areas in a centralized location; and increased worker awareness of high-dose rate areas. In addition, Idaho had the largest decrease in the total number of workers with measurable TED (1,143 fewer workers). u Hanford Site (Hanford) – An overall reduction of decontamination and decommissioning (D&D) activities at the Plutonium Finishing Plant (PFP) and Transuranic (TRU) retrieval activities resulted in collective dose reductions. u Savannah River Site (SRS) – Reductions were achieved through ALARA initiatives employed site wide. The Solid Waste Management Facility used extended specialty tools, cameras and lead shield walls to facilitate removal of drums. These tools and techniques reduce exposure time through improved efficiency, increase distance from the source of radiation by remote monitoring, shield the workers to lower the dose rate, and reduce the potential for contamination and release of material through repacking of waste. Overall, from 2011 to 2012, there was a 19% decrease in the number of workers with measurable dose. Furthermore, due to a slight decrease in both the DOE workforce (7%) and monitored workers (10%), the ratio of workers with measurable doses to monitored workers decreased to 13%. Another primary indicator of the level of radiation exposure covered in this report is the average measurable dose, which normalizes the collective dose over the population of workers who actually received a measurable dose. The average measurable TED increased by 3% from 2011 to 2012. Additional analyses show that the dose distribution in 2012 was similar to the distribution in 2011. In 2012, 13% of the monitored workers received a measurable TED and the average measurable TED, 0.069 rem, was less than 2% of the DOE limit. From 2011 to 2012, the collective TED and the number of individuals with measurable TED decreased 17.1% and 19%, respectively. These decreases were mainly due to an overall reduction of D&D activities at the PFP and TRU retrieval activities at Hanford; a 78% decrease in the number of targeted waste drums that were processed at the Idaho Site’s Accelerated Retrieval Project (ARP) from 5,566 drums in 2011 to a total of 1,211 drums processed in 2012; and ALARA initiatives employed site wide at SRS. In addition, the decreases were the result of decreased American Recovery and Reinvestment Act (ARRA) activities and continuing D&D, particularly at the DOE sites that comprise the majority of DOE collective dose. Over the past 5 years, the size of the monitored workforce has remained at a fairly stable level (within 12%), while the collective dose has varied up to 37%. No reported doses exceeded the DOE occupational limit of 5 rems TED in 2012 and no reported doses exceeded the DOE ACL of 2 rems TED.« less

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

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

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

Improved spatial resolution and lower-dose pediatric CT imaging: a feasibility study to evaluate narrowing the X-ray photon energy spectrum.

PubMed

Benz, Mark G; Benz, Matthew W; Birnbaum, Steven B; Chason, Eric; Sheldon, Brian W; McGuire, Dale

2014-08-01

This feasibility study has shown that improved spatial resolution and reduced radiation dose can be achieved in pediatric CT by narrowing the X-ray photon energy spectrum. This is done by placing a hafnium filter between the X-ray generator and a pediatric abdominal phantom. A CT system manufactured in 1999 that was in the process of being remanufactured was used as the platform for this study. This system had the advantage of easy access to the X-ray generator for modifications to change the X-ray photon energy spectrum; it also had the disadvantage of not employing the latest post-imaging noise reduction iterative reconstruction technology. Because we observed improvements after changing the X-ray photon energy spectrum, we recommend a future study combining this change with an optimized iterative reconstruction noise reduction technique.

The value of thyroid shielding in intraoral radiography

PubMed Central

Hazenoot, Bart; Sanderink, Gerard C H; Berkhout, W Erwin R

2016-01-01

Objectives: To evaluate the utility of the application of a thyroid shield in intraoral radiography when using rectangular collimation. Methods: Experimental data were obtained by measuring the absorbed dose at the position of the thyroid gland in a RANDO® (The Phantom Laboratory, Salem, NY) male phantom with a dosemeter. Four protocols were tested: round collimation and rectangular collimation, both with and without thyroid shield. Five exposure positions were deployed: upper incisor (Isup), upper canine (Csup), upper premolar (Psup), upper molar (Msup) and posterior bitewing (BW). Exposures were made with 70 kV and 7 mA and were repeated 10 times. The exposure times were as recommended for the exposure positions for the respective collimator type by the manufacturer for digital imaging. The data were statistically analyzed with a three-way ANOVA test. Significance was set at p < 0.01. Results: The ANOVA test revealed that the differences between mean doses of all protocols and geometries were statistically significant, p < 0.001. For the Isup, thyroid dose levels were comparable with both collimators at a level indicating primary beam exposure. Thyroid shield reduced this dose with circa 75%. For the Csup position, round collimation also revealed primary beam exposure, and thyroid shield yield was 70%. In Csup with rectangular collimation, the thyroid dose was reduced with a factor 4 compared with round collimation and thyroid shield yielded an additional 42% dose reduction. The thyroid dose levels for the Csup, Psup, Msup and BW exposures were lower with rectangular collimation without thyroid shield than with round collimation with thyroid shield. With rectangular collimation, the thyroid shield in Psup, Msup and BW reduced the dose 10% or less, where dose levels were already low, implying no clinical significance. Conclusions: For the exposures in the upper anterior region, thyroid shield results in an important dose reduction for the thyroid. For the other exposures, thyroid shield augments little to the reduction achieved by rectangular collimation. The use of thyroid shield is to be advised, when performing upper anterior radiography. PMID:27008105

Effects of lasalocid or monensin on legume or grain (feedlot) bloat.

PubMed

Bartley, E E; Nagaraja, T G; Pressman, E S; Dayton, A D; Katz, M P; Fina, L R

1983-06-01

Doses of .66 to .99 mg monensin/kg body weight reduced legume bloat in cattle about 66% when compared with pretreatment bloat scores. Similar doses of lasalocid reduced legume bloat about 26%. A dose of 44 mg poloxalene/kg body weight (recommended dose for field use) reduced legume bloat 100%. Monensin or lasalocid combined with 25 or 50% of the recommended dose of poloxalene reduced bloat under that of the antibiotics alone, but did not achieve 100% reduction. The antibiotic thiopeptin provided no preventive effect on legume bloat. Lasalocid, monensin or an experimental polyether antibiotic (X-14,547 A) at a dose of 1.32 mg/kg body weight when tested on cattle bloated on high grain diets reduced bloat by 92, 64 and 25%, respectively. Lasalocid at .66 mg/kg effectively prevented bloat from developing when given to animals before the feeding of high grain diets; however, a 1.32-mg dose was required to control bloat in cattle that were already bloating before they were given lasalocid. A dose of 1.32 mg salinomycin was ineffective in controlling grain bloat.

Comparison of different treatment planning optimization methods for vaginal HDR brachytherapy with multichannel applicators: A reduction of the high doses to the vaginal mucosa is possible.

PubMed

Carrara, Mauro; Cusumano, Davide; Giandini, Tommaso; Tenconi, Chiara; Mazzarella, Ester; Grisotto, Simone; Massari, Eleonora; Mazzeo, Davide; Cerrotta, Annamaria; Pappalardi, Brigida; Fallai, Carlo; Pignoli, Emanuele

2017-12-01

A direct planning approach with multi-channel vaginal cylinders (MVCs) used for HDR brachytherapy of vaginal cancers is particularly challenging. Purpose of this study was to compare the dosimetric performances of different forward and inverse methods used for the optimization of MVC-based vaginal treatments for endometrial cancer, with a particular attention to the definition of strategies useful to limit the high doses to the vaginal mucosa. Twelve postoperative vaginal HDR brachytherapy treatments performed with MVCs were considered. Plans were retrospectively optimized with three different methods: Dose Point Optimization followed by Graphical Optimization (DPO + GrO), Inverse Planning Simulated Annealing with two different class solutions as starting conditions (surflPSA and homogIPSA) and Hybrid Inverse Planning Optimization (HIPO). Several dosimetric parameters related to target coverage, hot spot extensions and sparing of organs at risk were analyzed to evaluate the quality of the achieved treatment plans. Dose homogeneity index (DHI), conformal index (COIN) and a further parameter quantifying the proportion of the central catheter loading with respect to the overall loading (i.e., the central catheter loading index: CCLI) were also quantified. The achieved PTV coverage parameters were highly correlated with each other but uncorrelated with the hot spot quantifiers. HomogIPSA and HIPO achieved higher DHIs and CCLIs and lower volumes of high doses than DPO + GrO and surflPSA. Within the investigated optimization methods, HIPO and homoglPSA showed the highest dose homogeneity to the target. In particular, homogIPSA resulted also the most effective in reducing hot spots to the vaginal mucosa. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Occupational dose reduction at Department of Energy contractor facilities: Bibliography of selected readings in radiation protection and ALARA; Volume 5

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

Dionne, B.J.; Sullivan, S.G.; Baum, J.W.

1994-01-01

Promoting the exchange of information related to implementation of the As Low as Reasonably Achievable (ALARA) philosophy is a continuing objective for the Department of Energy (DOE). This report was prepared by the Brookhaven National Laboratory (BNL) ALARA Center for the DOE Office of Health. It contains the fifth in a series of bibliographies on dose reduction at DOE facilities. The BNL ALARA Center was originally established in 1983 under the sponsorship of the Nuclear Regulatory Commission to monitor dose-reduction research and ALARA activities at nuclear power plants. This effort was expanded in 1988 by the DOE`s Office of Environment,more » Safety and Health, to include DOE nuclear facilities. This bibliography contains abstracts relating to various aspects of ALARA program implementation and dose-reduction activities, with a specific focus on DOE facilities. Abstracts included in this bibliography were selected from proceedings of technical meetings, journals, research reports, searches of the DOE Energy, Science and Technology Database (in general, the citation and abstract information is presented as obtained from this database), and reprints of published articles provided by the authors. Facility types and activities covered in the scope of this report include: radioactive waste, uranium enrichment, fuel fabrication, spent fuel storage and reprocessing, facility decommissioning, hot laboratories, tritium production, research, test and production reactors, weapons fabrication and testing, fusion, uranium and plutonium processing, radiography, and accelerators. Information on improved shielding design, decontamination, containments, robotics, source prevention and control, job planning, improved operational and design techniques, as well as on other topics, has been included. In addition, DOE/EH reports not included in previous volumes of the bibliography are in this volume (abstracts 611 to 684). This volume (Volume 5 of the series) contains 217 abstracts.« less

Evaluation of energy in heated water vapor for the application of lung volume reduction in patients with severe emphysema.

PubMed

Henne, Erik; Kesten, Steven; Herth, Felix J F

2013-01-01

A method of achieving endoscopic lung volume reduction for emphysema has been developed that utilizes precise amounts of thermal energy in the form of water vapor to ablate lung tissue. This study evaluates the energy output and implications of the commercial InterVapor system and compares it to the clinical trial system. Two methods of evaluating the energy output of the vapor systems were used, a direct energy measurement and a quantification of resultant thermal profile in a lung model. Direct measurement of total energy and the component attributable to gas (vapor energy) was performed by condensing vapor in a water bath and measuring the temperature and mass changes. Infrared images of a lung model were taken after vapor delivery. The images were quantified to characterize the thermal profile. The total energy and vapor energy of the InterVapor system was measured at various dose levels and compared to the clinical trial system at a dose of 10.0 cal/g. An InterVapor dose of 8.5 cal/g was found to have the most similar vapor energy output with the smallest associated reduction in total energy. This was supported by characterization of the thermal profile in the lung model that demonstrated the profile of InterVapor at 8.5 cal/g to not exceed the profile of the clinical trial system. Considering both total energy and vapor energy is important during the development of clinical vapor applications. For InterVapor, a closer study of both energy types justified a reduced target vapor-dosing range for lung volume reduction. The clinical implication is a potential improvement for benefiting the risk profile. Copyright © 2013 S. Karger AG, Basel.

Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with morning hypertension--a prospective, randomized, open-labeled, parallel-group, multicenter trial.

PubMed

Ueda, Tamenobu; Kai, Hisashi; Imaizumi, Tsutomu

2012-07-01

The treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50 mg losartan and 12.5 mg HCTZ (n=109) or a high-dose therapy with 100 mg losartan (n=107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3±10.1 to 131.5±11.5 mm Hg by combination therapy (P<0.001) and from 151.0±9.3 to 142.5±13.6 mm Hg by high-dose therapy (P<0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (P<0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1 mm Hg (P<0.001), and high-dose therapy decreased evening SBP from 138.9±9.9 to 131.4±13.2 mm Hg (P<0.01). Although both therapies improved target BP achievement rates in the morning and evening (P<0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (P<0.001 and P<0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (P<0.001 and P<0.01, respectively). Combination therapy decreased urine albumin excretion (P<0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (P<0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.

Comparison of gamma and electron beam irradiation in reducing populations of E. coli artificially inoculated on mung bean, clover and fenugreek seeds, and affecting germination and growth of seeds

NASA Astrophysics Data System (ADS)

Fan, Xuetong; Sokorai, Kimberly; Weidauer, André; Gotzmann, Gaby; Rögner, Frank-Holm; Koch, Eckhard

2017-01-01

Sprouts have frequently been implicated in outbreaks of foodborne illnesses, mostly due to contaminated seeds. Intervention technologies to decontaminate seeds without affecting sprout yield are needed. In the present study, we compared gamma rays with electron beam in inactivating E. coli artificially inoculated on three seeds (fenugreek, clover and mung bean) that differed in size and surface morphology. Furthermore, the germination and growth of irradiated seeds were evaluated. Results showed that the D10 values (dose required to achieve 1 log reduction) for E. coli K12 on mung bean, clover, and fenugreek were 1.11, 1.21 and 1.40 kGy, respectively. To achieve a minimum 5-log reduction of E. coli, higher doses were needed on fenugreek than on mung bean or clover. Electron beam treatment at doses up to 12 kGy could not completely inactivate E. coli inoculated on all seeds even though most of the seeds were E. coli-free after 4-12 kGy irradiation. Gamma irradiation at doses up to 6 kGy did not significantly affect the germination rate of clover and fenugreek seeds but reduced the germination rate of mung bean seeds. Doses of 2 kGy gamma irradiation did not influence the growth of seeds while higher doses of gamma irradiation reduced the growth rate. Electron beam treatment at doses up to 12 kGy did not have any significant effect on germination or growth of the seeds. SEM imaging indicated there were differences in surface morphology among the three seeds, and E. coli resided in cracks and openings of seeds, making surface decontamination of seeds with low energy electron beam a challenge due to the low penetration ability. Overall, our results suggested that gamma rays and electron beam had different effects on E. coli inactivation and germination or growth of seeds. Future efforts should focus on optimization of electron bean parameters to increase penetration to inactivate E. coli without causing damage to the seeds.

Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial.

PubMed

Farnier, Michel; Jones, Peter; Severance, Randall; Averna, Maurizio; Steinhagen-Thiessen, Elisabeth; Colhoun, Helen M; Du, Yunling; Hanotin, Corinne; Donahue, Stephen

2016-01-01

To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053). Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL-C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL-C target. Primary endpoint was percent change in calculated LDL-C from baseline to 24 weeks (intent-to-treat). 305 patients were randomized. In the baseline rosuvastatin 10 mg group, significantly greater LDL-C reductions were observed with add-on alirocumab (-50.6%) versus ezetimibe (-14.4%; p < 0.0001) and double-dose rosuvastatin (-16.3%; p < 0.0001). In the baseline rosuvastatin 20 mg group, LDL-C reduction with add-on alirocumab was -36.3% compared with -11.0% with ezetimibe and -15.9% with double-dose rosuvastatin (p = 0.0136 and 0.0453, respectively; pre-specified threshold for significance p < 0.0125). Overall, ∼80% alirocumab patients were maintained on 75 mg Q2W. Of alirocumab-treated patients, 84.9% and 66.7% in the baseline rosuvastatin 10 and 20 mg groups, respectively, achieved risk-based LDL-C targets. Treatment-emergent adverse events occurred in 56.3% of alirocumab patients versus 53.5% ezetimibe and 67.3% double-dose rosuvastatin (pooled data). The addition of alirocumab to rosuvastatin provided incremental LDL-C lowering versus adding ezetimibe or doubling the rosuvastatin dose. Copyright © 2015 Regeneron Pharmaceuticals, Inc. Published by Elsevier Ireland Ltd.. All rights reserved.

Progressive cone beam CT dose control in image-guided radiation therapy

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

Yan Hao; Cervino, Laura; Jiang, Steve B.

2013-06-15

Purpose: Cone beam CT (CBCT) in image-guided radiotherapy (IGRT) offers a tremendous advantage for treatment guidance. The associated imaging dose is a clinical concern. One unique feature of CBCT-based IGRT is that the same patient is repeatedly scanned during a treatment course, and the contents of CBCT images at different fractions are similar. The authors propose a progressive dose control (PDC) scheme to utilize this temporal correlation for imaging dose reduction. Methods: A dynamic CBCT scan protocol, as opposed to the static one in the current clinical practice, is proposed to gradually reduce the imaging dose in each treatment fraction.more » The CBCT image from each fraction is processed by a prior-image based nonlocal means (PINLM) module to enhance its quality. The increasing amount of prior information from previous CBCT images prevents degradation of image quality due to the reduced imaging dose. Two proof-of-principle experiments have been conducted using measured phantom data and Monte Carlo simulated patient data with deformation. Results: In the measured phantom case, utilizing a prior image acquired at 0.4 mAs, PINLM is able to improve the image quality of a CBCT acquired at 0.2 mAs by reducing the noise level from 34.95 to 12.45 HU. In the synthetic patient case, acceptable image quality is maintained at four consecutive fractions with gradually decreasing exposure levels of 0.4, 0.1, 0.07, and 0.05 mAs. When compared with the standard low-dose protocol of 0.4 mAs for each fraction, an overall imaging dose reduction of more than 60% is achieved. Conclusions: PINLM-PDC is able to reduce CBCT imaging dose in IGRT utilizing the temporal correlations among the sequence of CBCT images while maintaining the quality.« less

Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage—a modelling study

NASA Astrophysics Data System (ADS)

Røthe Arnesen, Marius; Paulsen Hellebust, Taran; Malinen, Eirik

2017-03-01

Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra

2016-05-01

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

Potential dosimetric benefits of adaptive tumor tracking over the internal target volume concept for stereotactic body radiation therapy of pancreatic cancer.

PubMed

Karava, Konstantina; Ehrbar, Stefanie; Riesterer, Oliver; Roesch, Johannes; Glatz, Stefan; Klöck, Stephan; Guckenberger, Matthias; Tanadini-Lang, Stephanie

2017-11-09

Radiotherapy for pancreatic cancer has two major challenges: (I) the tumor is adjacent to several critical organs and, (II) the mobility of both, the tumor and its surrounding organs at risk (OARs). A treatment planning study simulating stereotactic body radiation therapy (SBRT) for pancreatic tumors with both the internal target volume (ITV) concept and the tumor tracking approach was performed. The two respiratory motion-management techniques were compared in terms of doses to the target volume and organs at risk. Two volumetric-modulated arc therapy (VMAT) treatment plans (5 × 5 Gy) were created for each of the 12 previously treated pancreatic cancer patients, one using the ITV concept and one the tumor tracking approach. To better evaluate the overall dose delivered to the moving tumor volume, 4D dose calculations were performed on four-dimensional computed tomography (4DCT) scans. The resulting planning target volume (PTV) size for each technique was analyzed. Target and OAR dose parameters were reported and analyzed for both 3D and 4D dose calculation. Tumor motion ranged from 1.3 to 11.2 mm. Tracking led to a reduction of PTV size (max. 39.2%) accompanied with significant better tumor coverage (p<0.05, paired Wilcoxon signed rank test) both in 3D and 4D dose calculations and improved organ at risk sparing. Especially for duodenum, stomach and liver, the mean dose was significantly reduced (p<0.05) with tracking for 3D and 4D dose calculations. By using an adaptive tumor tracking approach for respiratory-induced pancreatic motion management, a significant reduction in PTV size can be achieved, which subsequently facilitates treatment planning, and improves organ dose sparing. The dosimetric benefit of tumor tracking is organ and patient-specific.

Effect of ezetimibe add-on therapy over 52 weeks extension analysis of prospective randomized trial (RESEARCH study) in type 2 diabetes subjects.

PubMed

Sakamoto, Kentaro; Kawamura, Mitsunobu; Watanabe, Takayuki; Ashidate, Keiko; Kohro, Takahide; Tanaka, Akira; Mori, Yasumichi; Tagami, Motoki; Hirano, Tsutomu; Yamazaki, Tsutomu; Shiba, Teruo

2017-06-24

Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited. We investigated the difference in cholesterol lowering effect between ezetimibe (10 mg) add-on statin (EAT) group and double-dose statin (DST) group. Changes of parameters related to atherosclerotic event risks were assessed. The reduction of LDL-C was larger in the EAT group (28.3%) than in the DST group (9.2%) at 52 weeks as well as the primary endpoint of 12 weeks. EAT achieved significant lower levels of TC and apo B, respectively. Both treatments attained significant reduction in sd-LDL-C or hsCRP on this long-term basis. Notably, sd-LDL-C in EAT reduced as low as 36.1 ± 14.9 mg/dl to reach near the threshold (35.0 mg/dl) for atherosclerosis with significantly higher achievement rate (55.6%) than DST treatment. Simultaneously, hsCRP reduction by EAT attained as low value as 0.52 ± 0.43 mg/l. In the present 52-week long-term period, ezetimibe add-on therapy showed a robust advantage in lowering LDL-C and in attaining target LDL-C values compared with the doubling of statin dose. Moreover, it's meaningful that sd-LDL, powerfully atherogenic lipoprotein, exhibited prominent decrease consistently prominently by ezetimibe add-on therapy. DM patients with hypercholesterolemia are at high risk for CAD, and adding ezetimibe onto usual-dose statin treatment in Japan has been suggested as the first-line therapy for those DM patients who failed to attain the target LDL-C value (UMIN000002593).

Predicting film dose to aid in cassette placement for radiation therapy portal verification film images.

PubMed

Keys, Richard A; Marks, James E; Haus, Arthur G

2002-12-01

EC film has improved portal localization images with better contrast and improved distinction of bony structures and air-tissue interfaces. A cassette with slower speed screens was used with EC film to image the treatment portal during the entire course of treatment (verification) instead of taking separate films after treatment. Measurements of film density vs source to film distance (SFD) were made using 15 and 25 cm thick water phantoms with both 6 and 18 MV photons from I to 40 cm past the phantom. A characteristic (H & D) curve was measured in air to compare dose to film density. Results show the reduction in radiation between patient and cassette more closely follows an "inverse cube law" rather than an inverse square law. Formulas to calculate radiation exposure to the film, and the desired SFD were based on patient tumor dose, calculation of the exit dose, and the inverse cube relationship. A table of exposure techniques based on the SFD for a given tumor dose was evaluated and compared to conventional techniques. Although the film has a high contrast, there is enough latitude that excellent films can be achieved using a fixed SFD based simply on the tumor dose and beam energy. Patient diameter has a smaller effect. The benefits of imaging portal films during the entire treatment are more reliability in the accuracy of the portal image, ability to detect patient motion, and reduction in the time it takes to take portal images.

Influence of grid control and object detection on radiation exposure and image quality using mobile C-arms - first results.

PubMed

Gosch, D; Ratzmer, A; Berauer, P; Kahn, T

2007-09-01

The objective of this study was to examine the extent to which the image quality on mobile C-arms can be improved by an innovative exposure rate control system (grid control). In addition, the possible dose reduction in the pulsed fluoroscopy mode using 25 pulses/sec produced by automatic adjustment of the pulse rate through motion detection was to be determined. As opposed to conventional exposure rate control systems, which use a measuring circle in the center of the field of view, grid control is based on a fine mesh of square cells which are overlaid on the entire fluoroscopic image. The system uses only those cells for exposure control that are covered by the object to be visualized. This is intended to ensure optimally exposed images, regardless of the size, shape and position of the object to be visualized. The system also automatically detects any motion of the object. If a pulse rate of 25 pulses/sec is selected and no changes in the image are observed, the pulse rate used for pulsed fluoroscopy is gradually reduced. This may decrease the radiation exposure. The influence of grid control on image quality was examined using an anthropomorphic phantom. The dose reduction achieved with the help of object detection was determined by evaluating the examination data of 146 patients from 5 different countries. The image of the static phantom made with grid control was always optimally exposed, regardless of the position of the object to be visualized. The average dose reduction when using 25 pulses/sec resulting from object detection and automatic down-pulsing was 21 %, and the maximum dose reduction was 60 %. Grid control facilitates C-arm operation, since optimum image exposure can be obtained independently of object positioning. Object detection may lead to a reduction in radiation exposure for the patient and operating staff.

SU-E-T-284: Dose Plan Optimization When Using Hydrogel Prostate-Rectum Spacer: A Single Institution Experience

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

Rajecki, M; Thurber, A; Catalfamo, F

2015-06-15

Purpose: To describe rectal dose reduction achieved and techniques used to take advantage of the increased peri-rectal spacing provided by injected polyethylene-glycol. Methods: Thirty prostate cancer patents were 2:1 randomized during a clinical trial to evaluate the effectiveness of injected poly-ethylene glycol hydrogel (SpaceOAR System) in creating space between the prostate and the anterior rectal wall. All patients received a baseline CT/MR scan and baseline IMRT treatment plan. Patients were randomized to receive hydrogel injection (n=20) or Control (n=10), followed by another CT/MR scan and treatment plan (single arc VMAT, 6 MV photons, 79.2 Gy, 44 fractions). Additional optimization structuresmore » were employed to constrain the dose to the rectum; specifically an avoidance structure to limit V75 <15%, and a control structure to limit the maximum relative dose <105% in the interface region of the anterior rectal wall and the prostate planning target volume. Dose volumetric data was analyzed for rectal volumes receiving 60 through 80 Gy. Results: Rectal dose reduction was observed in all patients who received the hydrogel. Volumetric analysis indicates a median rectal volume and (reduction from baseline plan) following spacer application of 4.9% (8.9%) at V60Gy, 3.8% (8.1%) at V65Gy, 2.5% (7.2%) at V70Gy, 1.6% (5.8%) at V75Gy, and 0.5% (2.5%) at V80Gy. Conclusion: Relative to planning without spacers, rectal dose constraints of 5%, 4%, 3%, 2%, 1% for V60, V65, V70, V75, and V80, should be obtainable when peri-rectal spacers are used. The combined effect of increased peri-rectal space provided by the hydrogel, with strict optimization objectives, resulted in reduced dose to the rectum. To maximize benefit, strict optimization objectives and reduced rectal dose constraints should be employed when creating plans for patients with perirectal spacers. Clinical Trial for SpaceOAR product conducted by Augmenix,Inc. The research site was paid to be a participating site.« less

Metformin as an initial adjunct to low-dose liraglutide enhances the weight-decreasing potential of liraglutide in obese polycystic ovary syndrome: Randomized control study.

PubMed

Jensterle, Mojca; Goricar, Katja; Janez, Andrej

2016-04-01

Liraglutide (LIRA) treatment is associated with the dose-dependent reduction of weight. Higher doses are more effective than lower doses, although higher doses are also more poorly tolerated. Metformin may enhance the weight-lowering potential of LIRA via the stimulatory modulation of incretin in addition to its direct beneficial effects in PCOS. The aim of the present study was to evaluate whether metformin as an adjunct to low-dose LIRA affects body weight with increased efficacy compared with low-dose LIRA alone in obese patients with PCOS. In a 12-week study, 44 obese women with PCOS were randomly offered either combined treatment (COMBO) with 1,000 mg metformin twice a day and 1.2 mg LIRA once a day, or treatment with 1.2 mg LIRA alone. The primary outcome of treatment was an alteration in the levels of obesity. A total of 43 patients [aged 30.3±4.4 years; body mass index (BMI) 37.2±4.5 kg/m 2 ; mean ± standard deviation] completed the study. The subjects treated with COMBO lost on average 6.2±2.4 kg compared with a 3.8±3.5 kg weight loss in the patients treated with LIRA alone (P=0.024). The BMI decreased by 2.2±0.8 kg/m 2 in patients treated with COMBO and by 1.4±1.2 kg/m 2 in patients treated with LIRA alone (P=0.024). A clinically significant ≥5% weight reduction was achieved in 59.1% of patients treated with COMBO and 42.9% of patients treated with LIRA alone. Reductions in glucose levels following oral glucose tolerance testing, as well as in androstenedione levels in the COMBO group were significantly greater compared with those in the LIRA group. The side effects were mild and transient in the two treatment groups. A combination of metformin and low-dose LIRA was more effective than low-dose LIRA alone in reducing body weight in obese patients with PCOS.

Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results.

PubMed

Criner, Gerard J; Pinto-Plata, Victor; Strange, Charlie; Dransfield, Mark; Gotfried, Mark; Leeds, William; McLennan, Geoffrey; Refaely, Yael; Tewari, Sanjiv; Krasna, Mark; Celli, Bartolome

2009-05-01

Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling. Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema. Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life. After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (-6.4 +/- 9.3%; P = 0.002) and HD (-5.5 +/- 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P = 0.021; DeltaFVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life. BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

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

Chuong, Michael D.; Hallemeier, Christopher L.; Jabbour, Salma K.

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with protonmore » beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.« less

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

PubMed

Chuong, Michael D; Hallemeier, Christopher L; Jabbour, Salma K; Yu, Jen; Badiyan, Shahed; Merrell, Kenneth W; Mishra, Mark V; Li, Heng; Verma, Vivek; Lin, Steven H

2016-05-01

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. Copyright © 2016 Elsevier Inc. All rights reserved.

Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.

PubMed

Yang, Danlin; Giragossian, Craig; Castellano, Steven; Lasaro, Marcio; Xiao, Haiguang; Saraf, Himanshu; Hess Kenny, Cynthia; Rybina, Irina; Huang, Zhong-Fu; Ahlberg, Jennifer; Bigwarfe, Tammy; Myzithras, Maria; Waltz, Erica; Roberts, Simon; Kroe-Barrett, Rachel; Singh, Sanjaya

2017-10-01

Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.

Antihypertensive effect of a fixed-dose combination of losartan/hydrochlorothiazide in patients with uncontrolled hypertension: a multicenter study.

PubMed

Hosoya, Tatsuo; Kuriyama, Satoru; Ohno, Iwao; Kawamura, Tetsuya; Ogura, Makoto; Ikeda, Masato; Ishikawa, Masahiro; Hayashi, Fumihiro; Kanai, Tatsuya; Tomonari, Haruo; Soejima, Michimasa; Akaba, Kiyoaki; Tokudome, Goro; Endo, S; Fukui, A; Gomi, H; Hamaguchi, A; Hanaoka, K; Hara, Y; Hara, Y; Hasegawa, T; Hayakawa, H; Hikida, M; Hirano, K; Horiguchi, M; Hosoya, M; Ichida, K; Imai, T; Ishii, T; Ishikawa, H; Kameda, C; Kasai, T; Kobayashi, A; Kobayashi, H; Kurashige, M; Kusama, Y; Maezawa, H; Maezawa, Y; Maruyama, Y; Matsuda, H; Matsuo, N; Matsuo, T; Miura, Y; Miyajima, M; Miyakawa, M; Miyazaki, Y; Mizuguchi, M; Nakao, M; Nokano, H; Ohkido, I; Ohtsuka, Y; Okada, K; Okamoto, H; Okonogi, H; Saikawa, H; Saito, H; Sekiguchi, C; Suetsugu, Y; Sugano, N; Suzuki, T; Suzuki, T; Takahashi, H; Takahashi, Y; Takamizawa, S; Takane, K; Morita, T; Takazoe, K; Tanaka, H; Tanaka, S; Terawaki, H; Toyoshima, R; Tsuboi, N; Udagawa, T; Ueda, H; Ueda, Y; Uetake, M; Unemura, S; Utsunomiya, M; Utsunomiya, Y; Yamada, T; Yamada, Y; Yamaguchi, Y; Yamamoto, H; Yokoo, T; Yokoyama, K; Yonezawa, H; Yoshida, H; Yoshida, M; Yoshizawa, T

2012-04-01

Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

Reducing statistical uncertainties in simulated organ doses of phantoms immersed in water

DOE PAGES

Hiller, Mauritius M.; Veinot, Kenneth G.; Easterly, Clay E.; ...

2016-08-13

In this study, methods are addressed to reduce the computational time to compute organ-dose rate coefficients using Monte Carlo techniques. Several variance reduction techniques are compared including the reciprocity method, importance sampling, weight windows and the use of the ADVANTG software package. For low-energy photons, the runtime was reduced by a factor of 10 5 when using the reciprocity method for kerma computation for immersion of a phantom in contaminated water. This is particularly significant since impractically long simulation times are required to achieve reasonable statistical uncertainties in organ dose for low-energy photons in this source medium and geometry. Althoughmore » the MCNP Monte Carlo code is used in this paper, the reciprocity technique can be used equally well with other Monte Carlo codes.« less

Dose reduction in paediatric MDCT: general principles.

PubMed

Paterson, A; Frush, D P

2007-06-01

The number of multi-detector array computed tomography (MDCT) examinations performed per annum continues to increase in both the adult and paediatric populations. Estimates from 2003 suggested that CT contributed 17% of a radiology department's workload, yet was responsible for up to 75% of the collective population dose from medical radiation. The effective doses for some CT examinations today overlap with those argued to have an increased risk of cancer. This is especially pertinent for paediatric CT, as children are more radiosensitive than adults (and girls more radiosensitive than boys). In addition, children have a longer life ahead of them, in which radiation induced cancers may become manifest. Radiologists must be aware of these facts and practise the ALARA (as low as is reasonably achievable) principle, when it comes to deciding CT protocols and parameters.

Efficient reduction of pathogenic and spoilage microorganisms from apple cider by combining microfiltration with UV treatment.

PubMed

Zhao, Dongjun; Barrientos, Jessie Usaga; Wang, Qing; Markland, Sarah M; Churey, John J; Padilla-Zakour, Olga I; Worobo, Randy W; Kniel, Kalmia E; Moraru, Carmen I

2015-04-01

Thermal pasteurization can achieve the U. S. Food and Drug Administration-required 5-log reduction of pathogenic Escherichia coli O157:H7 and Cryptosporidium parvum in apple juice and cider, but it can also negatively affect the nutritional and organoleptic properties of the treated products. In addition, thermal pasteurization is only marginally effective against the acidophilic, thermophilic, and spore-forming bacteria Alicyclobacillus spp., which is known to cause off-flavors in juice products. In this study, the efficiency of a combined microfiltration (MF) and UV process as a nonthermal treatment for the reduction of pathogenic and nonpathogenic E. coli, C. parvum, and Alicyclobacillus acidoterrestris from apple cider was investigated. MF was used to physically remove suspended solids and microorganisms from apple cider, thus enhancing the effectiveness of UV and allowing a lower UV dose to be used. MF, with ceramic membranes (pore sizes, 0.8 and 1.4 μm), was performed at a temperature of 10 °C and a transmembrane pressure of 155 kPa. The subsequent UV treatment was conducted using at a low UV dose of 1.75 mJ/cm(2). The combined MF and UV achieved more than a 5-log reduction of E. coli, C. parvum, and A. acidoterrestris. MF with the 0.8-μm pore size performed better than the 1.4-μm pore size on removal of E. coli and A. acidoterrestris. The developed nonthermal hurdle treatment has the potential to significantly reduce pathogens, as well as spores, yeasts, molds, and protozoa in apple cider, and thus help juice processors improve the safety and quality of their products.

In vitro combined effect of co-amoxiclav concentrations achievable in serum after a 2000/125 mg oral dose, and polymorphonuclear neutrophils against strains of Streptococcus pneumoniae exhibiting decreased susceptibility to amoxicillin.

PubMed

Amores, Raquel; Alou, Luis; Giménez, María José; Sevillano, David; Gómez-Lus, María Luisa; Aguilar, Lorenzo; Prieto, José

2004-07-01

The in vitro effect that the presence of components of non-specific immunity (serum plus polymorphonuclear neutrophils) has on the bactericidal activity of co-amoxiclav was explored against Streptococcus pneumoniae strains exhibiting an amoxicillin MIC > or =4 mg/L. Eight penicillin-resistant clinical isolates non-susceptible to co-amoxiclav with MICs of 4 (two strains), 8 (four strains) and 16 mg/L (two strains) were used. Values of MBC were identical to MIC values in all cases. Time-kill curves were performed with co-amoxiclav concentrations achievable in serum after a single oral dose administration of the new 2000/125 mg sustained-release formulation. Results were expressed as percentage of reduction of initial inocula after 3 h incubation. Control curves showed growth with no reduction of initial inocula. Against strains with MIC of 4 and 8 mg/L, the results obtained with the antibiotic alone or with the presence of factors of non-specific immunity were similar, with a weak combined effect due to the intrinsic activity of co-amoxiclav (reductions of initial inocula ranging from 70 to 99.16%). Against strains with MIC of 16 mg/L, the addition of PMN in the presence of serum increased the reduction of bacterial load provided by the aminopenicillin, even at sub-inhibitory concentrations (25.8% versus 51.1% at 0.5 x MIC concentration--8/0.5 mg/L). This combined activity against strains with an amoxicillin MIC of 16 mg/L which decreased the bacterial load may be important in preventing bacterial proliferation within the host and the transmission of resistant clones to others.

Treatment efficacy of anti-hypertensive drugs in monotherapy or combination

PubMed Central

Paz, Marco A.; de-La-Sierra, Alejandro; Sáez, Marc; Barceló, María Antonia; Rodríguez, Juan José; Castro, Sonia; Lagarón, Cristina; Garrido, Josep M; Vera, Pilar; Coll-de-Tuero, Gabriel

2016-01-01

Abstract Background: The relative efficacy of antihypertensive drugs/combinations is not well known. Identifying the most effective ones and the patients’ characteristics associated with best performance of the drugs will improve management of hypertensive patients. Objective: To assess the blood pressure (BP) reduction attributed to antihypertensive drugs and identify characteristics associated with BP decrease. Data sources: MEDLINE, Cochrane Central Register of Controlled Trials from inception through July 2012 and selected papers. Study eligibility criteria: Double-blind, randomized clinical trials whose main result was the reduction in BP by antihypertensive treatment, with study population ≥50 or ≥25 if the study was a crossover, follow-up of at least 8 weeks, and available required data. Study appraisal and synthesis methods: Study data were independently extracted by multiple observers and introduced in an electronic database. Inconsistencies were resolved by discussion and referral back to the original articles. Meta-analysis was performed according to PRISMA statement and using a Bayesian framework. Main Outcome(s) and Measure(s): Mean decrease in systolic (SBP) and diastolic blood pressure (DBP) achieved by each drug or combination. Results: Two hundred eight trials including 94,305 patients were identified. In monotherapy, most drugs achieved 10 to 15 mm Hg SBP and 8 to 10 mm Hg DBP decreases. Olmesartan/amlodipine, olmesartan/hydrochlorothiazide, felodipine/metoprolol, and valsartan/hydrochlorothiazide were the combinations leading to the greatest mean SBP reductions (>20 mm Hg). Female sex and body mass index >25 kg/m2 were associated with more pronounced SBP and DBP reductions, whereas Afro-American ethnicity was associated with BP reductions smaller than the median. Results were adjusted by study duration, cardiovascular disease, and diabetes mellitus. Still, the estimation was performed using the mean administered doses, which do not exactly match those of the available drug formats. Limitations: Data corresponded to those obtained in each of the included trials; the analysis of the combinations was limited to the most recent ones; estimations were performed using the mean administered doses. Conclusions and implications: Certain drug combinations achieve BP reductions ranging from 20 to 25/10 to 15 mm Hg. Sex, ethnicity, and obesity are associated with antihypertensive response. This information can contribute to better selection of the antihypertensive drug, depending on the magnitude of pretreatment BP elevation. Guidelines should be revised. PMID:27472680

Intraoral radiology in general dental practices - a comparison of digital and film-based X-ray systems with regard to radiation protection and dose reduction.

PubMed

Anissi, H D; Geibel, M A

2014-08-01

The purpose of this study was to gain insight into the distribution and application of digital intraoral radiographic techniques within general dental practices and to compare these with film-based systems in terms of patient dose reduction. 1100 questionnaires were handed out to general dental practitioners. Data was analyzed with respect to the type of system by using descriptive statistics and nonparametric tests, i.e. Kruskal-Wallis, Mann-Whitney and chi-square test (SPSS 20). 64% of the questioned dentists still use film-based radiology, 23% utilize storage phosphor plate (SPP) systems and 13% use a charge-coupled device (CCD). A strong correlation between the number of dentists working in a practice and the use of digital dental imaging was observed. Almost 3/4 of the film users work with E- or F-speed film. 45% of them refuse to change to a digital system. The use of lead aprons was popular, while only a minority preferred thyroid shields and rectangular collimators. A fourfold reduction of exposure time from D-speed film to CCD systems was observed. Due to detector size and positioning errors, users of CCD systems take significantly more single-tooth radiographs in total. Considering the number of radiographs per patient, there is only a slight tendency towards more X-rays with CCD systems. Up to image generation, digital systems seem to be as or even more difficult to handle than film-based systems, while their handling was favored after radiographic exposure. Despite a slight increase of radiographs taken with CCD systems, there is a significant dosage reduction. Corresponding to the decrease in exposure time, the patient dose for SPP systems is reduced to one half compared to film. The main issues in CCD technology are positioning errors and the size of the X-ray detectors which are difficult to eliminate. The usage of radiation protection measures still needs to be improved. ► Responsible use of digital intraoral radiology results in a significant dose reduction in everyday practice. ► The ALARA principle is only achieved by strict implementation of dose-reducing methods. ► The efforts to use dose-reducing devices must be increased. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT.

PubMed

Murthy, Kk; Shukeili, Ka; Kumar, Ss; Davis, Ca; Chandran, Rr; Namrata, S

2010-01-01

To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma. In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans. The different plans were compared by analyzing the dose coverage of planning target volume using TV(95), D(mean), uniformity index, conformity index and homogeneity index parameters. To assess critical organ sparing, D(mean), D(max), dose to one-third and two-third volumes of the OARs and percentage of volumes receiving more than their tolerance doses were compared. The average dose coverage values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans achieved better target coverage(p<0.001) with higher conformity index value of 0.81±0.07 compared to both the 3D-CRT plans. The doses to the liver and bowel reduced significantly (p<0.001) with IMRT plans compared to other 3D-CRT plans. For all OARs the percentage of volumes receiving more than their tolerance doses were reduced with the IMRT plans. This study showed that a better target coverage and significant dose reduction to OARs could be achieved with the IMRT plans. The IMRT can be preferred with caution for organ motion. The authors are currently studying organ motion in the upper abdomen to use IMRT for patient treatment.

Prospective Intervention of a Novel Levothyroxine Dosing Protocol Based on Body Mass Index after Thyroidectomy.

PubMed

Elfenbein, Dawn M; Schaefer, Sarah; Shumway, Cynthia; Chen, Herbert; Sippel, Rebecca S; Schneider, David F

2016-01-01

Weight-based postoperative levothyroxine (LT4) dosing often fails to appropriately dose overweight and underweight patients. Previously, we created an LT4-dosing algorithm based on BMI. We hypothesize that more patients will achieve euthyroidism at their postoperative visit with the use of the protocol. A prospective evaluation was performed of our previously published BMI-based LT4 dosing. All adults who underwent thyroidectomy for benign disease between January 1, 2011 and December 31, 2013 were included; the new protocol was implemented in October 2012. Serum TSH was measured for all patients 6 to 8 weeks postoperatively, and adjustments were based on TSH. Three hundred and thirty patients were included, with 54% undergoing thyroidectomy after institution of the protocol. The groups were well matched. Before protocol implementation, LT4 was dosed solely by weight and 25% of patients were euthyroid at initial follow-up. After the protocol, 39% of patients were euthyroid (p = 0.01). The percentage of patients who were given too high a dose of LT4 remained the same (46% vs 42%), and there was a significant reduction in the number of patients who were given too little (29% vs 19%; p = 0.05). The effect was most profound in patients with low and normal BMI, and there were slight differences between sexes. Although correct initial dosing of LT4 remains challenging, this dosing protocol that we developed and implemented has improved patient care by increasing the number of patients who achieve euthyroidism at the first postoperative visit. We have made a change to our original protocol to incorporate sex differences into the calculation. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Everolimus with reduced-dose cyclosporine in de novo renal transplant recipients: Philippine experience.

PubMed

Li, J T; Danguilan, R A; Cabanayan-Casasola, C B; Talusan-Tomacruz, Y; Ona, E T

2008-09-01

The objective of this study was to describe the appropriate dose of everolimus to achieve target trough concentrations in standard-risk Filipino kidney transplant recipients. We reviewed all kidney transplant recipients from December 1, 2006 to June 15, 2007 who were given everolimus (1.5 mg/d) in combination with low-dose cyclosporine (5 mg/kg/d) and prednisone but without induction therapy for their immunosuppressive doses, trough levels, as well as hematologic and blood chemistry profiles. Target everolimus trough concentration was 3-8 ng/mL and C2 level was 1000-1400 ng/mL for the first 3 months. Among 148 patients who underwent transplantation during the study period, 26 comprised the study population but only 15 patients completed the 3-month follow-up and are the subject of this report. Their mean age was 33 years, average PRA 2%, and mean HLA mismatches 3. All were from living donors. At 7 days posttransplantation, all patients achieved or exceeded the target everolimus trough and cyclosporine C2 level. At 1 and 3 months posttransplantation the mean everolimus dose was 1.17 and 0.78 mg/d, respectively, whereas the cyclosporine dose was 195 and 148 mg/d, respectively. Three patients showed elevated alanine aminotransferase (ALT) and all patients had hypercholesterolemia after 1 month, which improved with everolimus dose reduction (half required statins). One patient experienced a Banff Grade IA acute rejection episode at 2 months posttransplantation with a serum creatinine value of 2 mg/dL after steroid pulsing. Most standard-risk Filipino kidney transplant recipients required a maintenance everolimus dose of 1 mg/d at 1 month. The cyclosporine dose requirement was also lower. A larger sample size is needed to provide a level of significance compared with other populations.

Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema

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

Binkley, Michael S.; Shrager, Joseph B.; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California

2014-09-01

Purpose: Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema. Methods and Materials: We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABRmore » and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3). Results: 27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, −0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, −3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r{sup 2}=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r{sup 2}=0.47, P<.0001). Conclusions: We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across multiple clinical parameters. These data serve to inform our ongoing prospective trial of stereotactic ablative volume reduction (SAVR) for severe emphysema in poor candidates for LVRS.« less

Implementation of dual-energy technique for virtual monochromatic and linearly mixed CBCTs

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

Li Hao; Giles, William; Ren Lei

Purpose: To implement dual-energy imaging technique for virtual monochromatic (VM) and linearly mixed (LM) cone beam CTs (CBCTs) and to demonstrate their potential applications in metal artifact reduction and contrast enhancement in image-guided radiation therapy (IGRT). Methods: A bench-top CBCT system was used to acquire 80 kVp and 150 kVp projections, with an additional 0.8 mm tin filtration. To implement the VM technique, these projections were first decomposed into acrylic and aluminum basis material projections to synthesize VM projections, which were then used to reconstruct VM CBCTs. The effect of VM CBCT on the metal artifact reduction was evaluated withmore » an in-house titanium-BB phantom. The optimal VM energy to maximize contrast-to-noise ratio (CNR) for iodine contrast and minimize beam hardening in VM CBCT was determined using a water phantom containing two iodine concentrations. The LM technique was implemented by linearly combining the low-energy (80 kVp) and high-energy (150 kVp) CBCTs. The dose partitioning between low-energy and high-energy CBCTs was varied (20%, 40%, 60%, and 80% for low-energy) while keeping total dose approximately equal to single-energy CBCTs, measured using an ion chamber. Noise levels and CNRs for four tissue types were investigated for dual-energy LM CBCTs in comparison with single-energy CBCTs at 80, 100, 125, and 150 kVp. Results: The VM technique showed substantial reduction of metal artifacts at 100 keV with a 40% reduction in the background standard deviation compared to a 125 kVp single-energy scan of equal dose. The VM energy to maximize CNR for both iodine concentrations and minimize beam hardening in the metal-free object was 50 keV and 60 keV, respectively. The difference of average noise levels measured in the phantom background was 1.2% between dual-energy LM CBCTs and equivalent-dose single-energy CBCTs. CNR values in the LM CBCTs of any dose partitioning are better than those of 150 kVp single-energy CBCTs. The average CNR for four tissue types with 80% dose fraction at low-energy showed 9.0% and 4.1% improvement relative to 100 kVp and 125 kVp single-energy CBCTs, respectively. CNRs for low-contrast objects improved as dose partitioning was more heavily weighted toward low-energy (80 kVp) for LM CBCTs. Conclusions: Dual-energy CBCT imaging techniques were implemented to synthesize VM CBCT and LM CBCTs. VM CBCT was effective at achieving metal artifact reduction. Depending on the dose-partitioning scheme, LM CBCT demonstrated the potential to improve CNR for low contrast objects compared to single-energy CBCT acquired with equivalent dose.« less

The effect of head size/shape, miscentering, and bowtie filter on peak patient tissue doses from modern brain perfusion 256-slice CT: How can we minimize the risk for deterministic effects?

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

Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis

Purpose: To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size/shape, head position during the examination and bowtie filter used on peak tissue doses. Methods: The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peakmore » tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size/shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. Results: The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of signal-to-noise ratio mainly to the peripheral region of the phantom. Conclusions: Despite typical peak doses to skin, eye lens, brain, and RBM from the standard low-dose brain perfusion 256-slice CT protocol are well below the corresponding thresholds for the induction of erythema, cataract, cerebrovascular disease, and depression of hematopoiesis, respectively, every effort should be made toward optimization of the procedure and minimization of dose received by these tissues. The current study provides evidence that the use of the narrower bowtie filter available may considerably reduce peak absorbed dose to all above radiosensitive tissues with minimal deterioration in image quality. Considerable reduction in peak eye-lens dose may also be achieved by positioning patient head center a few centimeters above isocenter during the exposure.« less

SU-C-207A-02: Proton Radiography Using Pencil Beam Scanning and a Novel, Low-Cost Range Telescope

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

Dolney, D; Mayers, G; Newcomer, M

Purpose: While the energy of therapeutic proton beams can be adjusted to penetrate to any given depth in water, range uncertainties arise in patients due in part to imprecise knowledge of the stopping power of protons in human tissues [1]. Proton radiography is one approach to reduce the beam range uncertainty [2], thereby allowing for a reduction in treatment margins and dose escalation. Methods: The authors have adapted a novel detector technology based on Micromesh Gaseous Structure (“Micromegas”) for proton therapy beams and have demonstrated fine spatial and time resolution of magnetically scanned proton pencil beams, as well as widemore » dynamic range for dosimetry [3]. The authors have constructed a prototype imaging system comprised of 5 Micromegas layers. Proton radiographs were obtained downstream of solid water assemblies. The position-sensitive monitor chambers in the IBA proton delivery nozzle provide the beam entrance position. Results: Our technique achieves spatial resolution as low as 300 µm and water-equivalent thickness (WET) resolution as good as 0.02% (60 µm out of 31 cm total thickness). The dose delivered to the patient is kept below 2 cGy. The spatial resolution as a function of sample rate and number of delivered protons is found to be near the theoretical Cramer-Rao lower bound. By extrapolating the CR bound, we argue that the imaging dose could be further lowered to 1 mGy, while still achieving submillimeter spatial resolution, by achievable instrumentation and beam delivery modifications. Conclusion: For proton radiography, high spatial and WET resolution can be achieved, with minimal additional dose to patient, by using magnetically scanned proton pencil beams and Micromegas detectors.« less

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

Ahmed, Raef S.; Shen, Sui; Ove, Roger

We wanted to describe a technique for the implementation of intensity-modulated radiotherapy (IMRT) with a real-time position monitor (RPM) respiratory gating system for the treatment of pleural space with intact lung. The technique is illustrated by a case of pediatric osteosarcoma, metastatic to the pleura of the right lung. The patient was simulated in the supine position where a breathing tracer and computed tomography (CT) scans synchronized at end expiration were acquired using the RPM system. The gated CT images were used to define target volumes and critical structures. Right pleural gated IMRT delivered at end expiration was prescribed tomore » a dose of 44 Gy, with 55 Gy delivered to areas of higher risk via simultaneous integrated boost (SIB) technique. IMRT was necessary to avoid exceeding the tolerance of intact lung. Although very good coverage of the target volume was achieved with a shell-shaped dose distribution, dose over the targets was relatively inhomogeneous. Portions of target volumes necessarily intruded into the right lung, the liver, and right kidney, limiting the degree of normal tissue sparing that could be achieved. The radiation doses to critical structures were acceptable and well tolerated. With intact lung, delivering a relatively high dose to the pleura with acceptable doses to surrounding normal tissues using respiratory gated pleural IMRT is feasible. Treatment delivery during a limited part of the respiratory cycle allows for reduced CT target volume motion errors, with reduction in the portion of the planning margin that accounts for respiratory motion, and subsequent increase in the therapeutic ratio.« less

Radiation dose reduction in parasinus CT by spectral shaping.

PubMed

May, Matthias S; Brand, Michael; Lell, Michael M; Sedlmair, Martin; Allmendinger, Thomas; Uder, Michael; Wuest, Wolfgang

2017-02-01

Spectral shaping aims to narrow the X-ray spectrum of clinical CT. The aim of this study was to determine the image quality and the extent of radiation dose reduction that can be achieved by tin prefiltration for parasinus CT. All scans were performed with a third generation dual-source CT scanner. A study protocol was designed using 100 kV tube voltage with tin prefiltration (200 mAs) that provides image noise levels comparable to a low-dose reference protocol using 100 kV without spectral shaping (25 mAs). One hundred consecutive patients were prospectively enrolled and randomly assigned to the study or control group. All patients signed written informed consent. The study protocol was approved by the local Institutional Review Board and applies to the HIPAA. Subjective and objective image quality (attenuation values, image noise, and contrast-to-noise ratio (CNR)) were assessed. Radiation exposure was assessed as volumetric CT dose index, and effective dose was estimated. Mann-Whitney U test was performed for radiation exposure and for image noise comparison. All scans were of diagnostic image quality. Image noise in air, in the retrobulbar fat, and in the eye globe was comparable between both groups (all p > 0.05). CNR eye globe/air did not differ significantly between both groups (p = 0.7). Radiation exposure (1.7 vs. 2.1 mGy, p < 0.01) and effective dose (0.055 vs. 0.066 mSv, p < 0.01) were significantly reduced in the study group. Radiation dose can be further reduced by 17% for low-dose parasinus CT by tin prefiltration maintaining diagnostic image quality.

Failed heart rate control with oral metoprolol prior to coronary CT angiography: effect of additional intravenous metoprolol on heart rate, image quality and radiation dose.

PubMed

Jiménez-Juan, Laura; Nguyen, Elsie T; Wintersperger, Bernd J; Moshonov, Hadas; Crean, Andrew M; Deva, Djeven P; Paul, Narinder S; Torres, Felipe S

2013-01-01

The purpose of this study was to evaluate the effect of intravenous (i.v.) metoprolol after a suboptimal heart rate (HR) response to oral metoprolol (75-150 mg) on HR control, image quality (IQ) and radiation dose during coronary CTA using 320-MDCT. Fifty-three consecutive patients who failed to achieve a target HR of < 60 bpm after an oral dose of metoprolol and required supplementary i.v. metoprolol (5-20 mg) prior to coronary CTA were evaluated. Patients with HR < 60 bpm during image acquisition were defined as responders (R) and those with HR ≥ 60 bpm as non-responders (NR). Two observers assessed IQ using a 3-point scale (1-2, diagnostic and 3, non-diagnostic). Effective dose (ED) was estimated using dose-length product and a 0.014 mSV/mGy.cm conversion factor. Baseline characteristics and HR on arrival were similar in the two groups. 58% of patients didn't achieve the target HR after receiving i.v. metoprolol (NR). R had a significantly higher HR reduction after oral (mean HR 63.9 ± 4.5 bpm vs. 69.6 ± 5.6 bpm) (p < 0.005) and i.v. (mean HR 55.4 ± 3.9 bpm vs. 67.4 ± 5.3 bpm) (p < 0.005) doses of metoprolol. Studies from NR showed a significantly higher ED in comparison to R (8.0 ± 2.9 vs. 6.1 ± 2.2 mSv) (p = 0.016) and a significantly higher proportion of non-diagnostic coronary segments (9.2 vs. 2.5%) (p < 0.001). 58% of patients who do not achieve a HR of <60 bpm prior to coronary CTA with oral fail to respond to additional i.v. metoprolol and have studies with higher radiation dose and worse image quality.

Is the use of the cervical vertebrae maturation method justified to determine skeletal age? A comparison of radiation dose of two strategies for skeletal age estimation.

PubMed

Patcas, Raphael; Signorelli, Luca; Peltomäki, Timo; Schätzle, Marc

2013-10-01

The aim of this study was to assess effective doses of a lateral cephalogram radiograph with and without thyroid shield and compare the differences with the radiation dose of a hand-wrist radiograph. Thermoluminescent dosimeters were placed at 19 different sites in the head and neck of a tissue-equivalent human skull (RANDO phantom). Analogue lateral cephalograms with and without thyroid shield (67 kV, 250 mA, 10 mAs) and hand-wrist radiographs (40 kV, 250 mA, 10 mAs) were obtained. The effective doses were calculated using the 2007 International Commission on Radiological Protection recommendations. The effective dose for conventional lateral cephalogram without a thyroid shield was 5.03 microsieverts (µSv). By applying a thyroid shield to the RANDO phantom, a remarkable dose reduction of 1.73 µSv could be achieved. The effective dose of a conventional hand-wrist radiograph was calculated to be 0.16 µSv. Adding the effective dose of the hand-wrist radiograph to the effective dose of the lateral cephalogram with thyroid shield resulted in a cumulative effective dose of 3.46 µSv. Without thyroid shield, the effective dose of a lateral cephalogram was approximately 1.5-fold increased than the cumulative effective dose of a hand-wrist radiograph and a lateral cephalogram with thyroid shield. Thyroid is an organ that is very sensitive to radiation exposure. Its shielding will significantly reduce the effective dose. An additional hand-wrist radiograph, involving no vulnerable tissues, however, causes very little radiation risk. In accordance with the ALARA (As Low As Reasonably Achievable) principle, if an evaluation of skeletal age is indicated, an additional hand-wrist radiograph seems much more justifiable than removing the thyroid shield.

Haemodialysis dose and serum bicarbonate (chapter 7).

PubMed

Tomson, Charlie; Thomas, David; Rao, Raman; van Schalkwyk, Dirk; Ansell, David

2007-08-01

Data from 21 renal units was insufficient to allow analyses of the dose of dialysis in those units. Amongst the remainder, there is evidence of a progressive increase in the proportion of patients meeting the Renal Association audit standard for urea reduction ratio (URR). In the UK as a whole, 81% of prevalent haemodialysis patients met the standard for URR in 2005. Greater achievement of the standard in a given unit is associated with a higher median URR in that unit, although there is some evidence that some units have been able to narrow the distribution of achieved URR values. Achievement of the standard remains, as in previous years' Reports, less common amongst patients recently established on haemodialysis compared with those established on haemodialysis for longer. Correction of acidosis, as measured by serum bicarbonate concentration remains highly variable, although there is continued uncertainty about the interpretation of routine measurements of venous serum bicarbonate concentration in haemodialysis patients. Overall, approximately 64% of UK haemodialysis patients, and 50% of peritoneal dialysis patients met the Renal Association standard for serum bicarbonate in 2005.

Dose reduction in fluoroscopic interventions using a combination of a region of interest (ROI) x-ray attenuator and spatially different, temporally variable temporal filtering

NASA Astrophysics Data System (ADS)

Swetadri Vasan, S. N.; Pope, Liza; Ionita, Ciprian N.; Titus, A. H.; Bednarek, D. R.; Rudin, S.

2013-03-01

A novel dose reduction technique for fluoroscopic interventions involving a combination of a material x-ray region of interest (ROI) attenuator and spatially different, temporally variable ROI temporal recursive filter, was used to guide the catheter to the ROI in three live animal studies, two involving rabbits and one involving a sheep. In the two rabbit studies presented , a catheter was guided to the entrance of the carotid artery. With the added ROI attenuator the image under the high attenuation region is very noisy. By using temporal filtering with a filter weight of 0.6 on previous frames, the noise is reduced. In the sheep study the catheter was guided to the descending aorta of the animal. The sheep offered a relatively higher attenuation to the incident x-rays and thus a higher temporal filter weight of 0.8 on previous frames was used during the procedure to reduce the noise to levels acceptable by the interventionalist. The image sequences from both studies show that significant dose reduction of 5-6 times can be achieved with acceptable image quality outside the ROI by using the above mentioned technique. Even though the temporal filter weighting outside the ROI is higher, the consequent lag does not prevent perception of catheter movement.

Very high-energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS.

PubMed

Schüler, Emil; Eriksson, Kjell; Hynning, Elin; Hancock, Steven L; Hiniker, Susan M; Bazalova-Carter, Magdalena; Wong, Tony; Le, Quynh-Thu; Loo, Billy W; Maxim, Peter G

2017-06-01

The aim of this study was to evaluate the performance of very high-energy electron beams (VHEE) in comparison to clinically derived treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PPBS) technology. We developed a custom optimization script that could be applied automatically across modalities to eliminate operator bias during IMRT optimization. Four clinical cases were selected (prostate cancer, lung cancer, pediatric brain tumor, and head and neck cancer (HNC)). The VHEE beams were calculated in the EGSnrc/DOSXYZnrc Monte Carlo code for 100 and 200 MeV beams. Treatment plans with VHEE, VMAT, and PPBS were optimized in a research version of RayStation using an in-house developed script to minimize operator bias between the different techniques. The in-house developed script generated similar or superior plans to the clinically used plans. In the comparisons between the modalities, the integral dose was lowest for the PPBS-generated plans in all cases. For the prostate case, the 200 MeV VHEE plan showed reduced integral dose and reduced organ at risk (OAR) dose compared to the VMAT plan. For all other cases, both the 100 and the 200 MeV VHEE plans were superior to the VMAT plans, and the VHEE plans showed better conformity and lower spinal cord dose in the pediatric brain case and lower brain stem dose in the HNC case when compared to the PPBS plan. The automated optimization developed in this study generated similar or superior plans as compared to the clinically used plan and represents an unbiased approach to compare treatment plans generated for different modalities. In the present study, we also show that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases, and VHEE plans can even achieve reductions in OAR doses compared to PPBS plans for shallow targets. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses are achieved. On the whole, VHEE was intermediate between photon VMAT and PPBS for OAR sparing. © 2017 American Association of Physicists in Medicine.

Intravenous Lidocaine as an Adjuvant for Pain Associated with Sickle Cell Disease.

PubMed

Nguyen, Natalie L; Kome, Anne M; Lowe, Denise K; Coyne, Patrick; Hawks, Kelly G

2015-01-01

The objectives of this study were to evaluate the efficacy and safety of adjuvant intravenous (IV) lidocaine in adults with sickle cell disease (SCD). This was a retrospective review. Adults with SCD receiving at least one IV lidocaine infusion from 2004 to 2014 were included. Patient demographics, lidocaine treatment parameters, pain scores, pain medications, and adverse effects were recorded. Eleven patients were identified, yielding 15 IV lidocaine trials. Clinical improvement in pain scores from pre-lidocaine challenge to 24 hours post-lidocaine challenge, defined by ≥ 20% reduction in pain scores, was achieved in 53.3% (8 of 15) of IV lidocaine challenges. Of the 8 clinically successful trials, the mean reduction in morphine dose equivalents (MDE) from 24 hours pre-lidocaine challenge to 24 hours post-lidocaine challenge was 32.2%. Additionally, clinically successful trials had a mean initial and a maximum dose of 1 mg/kg/h (range: 0.5-2.7 mg/kg/h) and 1.3 mg/kg/h (range: 0.5-1.9 mg/kg/h), respectively. On average, these patients underwent 3 dose titrations (range: 1-8) and received lidocaine infusions for 4.4 days (range: 2-8 days). Two patients experienced disorientation and dizziness. The authors conclude that adjuvant IV lidocaine provided pain relief and a mean reduction in MDE during sickle cell pain crisis. These results provide preliminary insight into the use of IV lidocaine for treating pain in patients with SCD, although prospective studies are needed to determine efficacy, dosing, and tolerability of IV lidocaine in this patient population.

Investigation into the Manufacture and Properties of Inhalable High-Dose Dry Powders Produced by Comilling API and Lactose with Magnesium Stearate.

PubMed

Lau, Michael; Young, Paul M; Traini, Daniela

2017-08-01

The aim of the study was to understand the impact of different concentrations of the additive material, magnesium stearate (MGST), and the active pharmaceutical ingredient (API), respectively, on the physicochemical properties and aerosol performance of comilled formulations for high-dose delivery. Initially, blends of API/lactose with different concentrations of MGST (1-7.5% w/w) were prepared and comilled by the jet-mill apparatus. The optimal concentration of MGST in comilled formulations was investigated, specifically for agglomerate structure and strength, particle size, uniformity of content, surface coverage, and aerosol performance. Secondly, comilled formulations with different API (1-40% w/w) concentrations were prepared and similarly analyzed. Comilled 5% MGST (w/w) formulation resulted in a significant improvement in in vitro aerosol performance due to the reduction in agglomerate size and strength compared to the formulation comilled without MGST. Higher concentrations of MGST (7.5% w/w) led to reduction in aerosol performance likely due to excessive surface coverage of the micronized particles by MGST, which led to failure in uniformity of content and an increase in agglomerate strength and size. Generally, comilled formulations with higher concentrations of API increased the agglomerate strength and size, which subsequently caused a reduction in aerosol performance. High-dose delivery was achieved at API concentration of >20% (w/w). The study provided a platform for the investigation of aerosol performance and physicochemical properties of other API and additive materials in comilled formulations for the emerging field of high-dose delivery by dry powder inhalation.

Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

PubMed

Vardeny, Orly; Claggett, Brian; Packer, Milton; Zile, Michael R; Rouleau, Jean; Swedberg, Karl; Teerlink, John R; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

2016-10-01

In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001). In PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Leishmanicidal activity of amphotericin B encapsulated in PLGA-DMSA nanoparticles to treat cutaneous leishmaniasis in C57BL/6 mice.

PubMed

de Carvalho, Ricardo Fontoura; Ribeiro, Ieler Ferreira; Miranda-Vilela, Ana Luisa; de Souza Filho, José; Martins, Olímpia Paschoal; Cintra e Silva, Débora de Oliveira; Tedesco, Antônio Cláudio; Lacava, Zulmira Guerrero Marques; Báo, Sônia Nair; Sampaio, Raimunda Nonata Ribeiro

2013-10-01

The major goal of this work was to design a new nanoparticle drug delivery system for desoxycholate amphotericin B (D-AMB), based on controlled particle size, looking for the most successful release of the active agents in order to achieve the best site-specific action of the drug at the therapeutically optimal rate and dose regimen. For this, AMB nanoencapsulated in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles (Nano-D-AMB) has been developed, and its efficacy was evaluated in the treatment of experimental cutaneous leishmaniasis in C57BL/6 mice, to test if our nano-drug delivery system could favor the reduction of the dose frequency required to achieve the same therapeutic level of free D-AMB, and so, an extended dosing interval. Magnetic citrate-coated maghemite nanoparticles were added to this nanosystem (Nano-D-AMB-MG) aiming to increase controlled release of AMB by magnetohyperthermia. Female mice (N=6/group) were infected intradermally in the right footpad with promastigotes of Leishmania amazonensis in the metacyclic phase, receiving the following intraperitoneal treatments: 1% PBS for 10 consecutive days; D-AMB at 2 mg/kg/day for 10 days (totalizing 20 mg/kg/animal); Nano-D-AMB and Nano-D-AMB-MG at 6 mg/kg on the 1st, 4th and 7th days and at 2 mg/kg on the 10th day, also totalizing 20 mg/kg/animal by treatment end. The Nano-D-AMB-MG group was submitted to an AC magnetic field, allowing the induction of magnetohyperthermia. The evaluations were through paw diameter measurements; parasite number and cell viability were investigated by limiting dilution assay. D-AMB-coated PLGA-DMSA nanoparticles showed the same efficacy as free D-AMB to reduce paw diameter; however, the Nano-D-AMB treatment also promoted a significantly greater reduction in parasite number and cell viability compared with free D-AMB. The nano-drug AMB delivery system appeared more effective than free D-AMB therapy to reduce the dose frequency required to achieve the same therapeutic level. It thus favors a longer interval between doses, as expected with development of a new nano drug delivery system, and may be useful in the treatment of many different pathologies, from cancer to neurodegenerative diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

Innovations in Medication Preparation Safety and Wastage Reduction: Use of a Workflow Management System in a Pediatric Hospital.

PubMed

Davis, Stephen Jerome; Hurtado, Josephine; Nguyen, Rosemary; Huynh, Tran; Lindon, Ivan; Hudnall, Cedric; Bork, Sara

2017-01-01

Background: USP <797> regulatory requirements have mandated that pharmacies improve aseptic techniques and cleanliness of the medication preparation areas. In addition, the Institute for Safe Medication Practices (ISMP) recommends that technology and automation be used as much as possible for preparing and verifying compounded sterile products. Objective: To determine the benefits associated with the implementation of the workflow management system, such as reducing medication preparation and delivery errors, reducing quantity and frequency of medication errors, avoiding costs, and enhancing the organization's decision to move toward positive patient identification (PPID). Methods: At Texas Children's Hospital, data were collected and analyzed from January 2014 through August 2014 in the pharmacy areas in which the workflow management system would be implemented. Data were excluded for September 2014 during the workflow management system oral liquid implementation phase. Data were collected and analyzed from October 2014 through June 2015 to determine whether the implementation of the workflow management system reduced the quantity and frequency of reported medication errors. Data collected and analyzed during the study period included the quantity of doses prepared, number of incorrect medication scans, number of doses discontinued from the workflow management system queue, and the number of doses rejected. Data were collected and analyzed to identify patterns of incorrect medication scans, to determine reasons for rejected medication doses, and to determine the reduction in wasted medications. Results: During the 17-month study period, the pharmacy department dispensed 1,506,220 oral liquid and injectable medication doses. From October 2014 through June 2015, the pharmacy department dispensed 826,220 medication doses that were prepared and checked via the workflow management system. Of those 826,220 medication doses, there were 16 reported incorrect volume errors. The error rate after the implementation of the workflow management system averaged 8.4%, which was a 1.6% reduction. After the implementation of the workflow management system, the average number of reported oral liquid medication and injectable medication errors decreased to 0.4 and 0.2 times per week, respectively. Conclusion: The organization was able to achieve its purpose and goal of improving the provision of quality pharmacy care through optimal medication use and safety by reducing medication preparation errors. Error rates decreased and the workflow processes were streamlined, which has led to seamless operations within the pharmacy department. There has been significant cost avoidance and waste reduction and enhanced interdepartmental satisfaction due to the reduction of reported medication errors.

TH-C-18A-06: Combined CT Image Quality and Radiation Dose Monitoring Program Based On Patient Data to Assess Consistency of Clinical Imaging Across Scanner Models

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

Christianson, O; Winslow, J; Samei, E

2014-06-15

Purpose: One of the principal challenges of clinical imaging is to achieve an ideal balance between image quality and radiation dose across multiple CT models. The number of scanners and protocols at large medical centers necessitates an automated quality assurance program to facilitate this objective. Therefore, the goal of this work was to implement an automated CT image quality and radiation dose monitoring program based on actual patient data and to use this program to assess consistency of protocols across CT scanner models. Methods: Patient CT scans are routed to a HIPPA compliant quality assurance server. CTDI, extracted using opticalmore » character recognition, and patient size, measured from the localizers, are used to calculate SSDE. A previously validated noise measurement algorithm determines the noise in uniform areas of the image across the scanned anatomy to generate a global noise level (GNL). Using this program, 2358 abdominopelvic scans acquired on three commercial CT scanners were analyzed. Median SSDE and GNL were compared across scanner models and trends in SSDE and GNL with patient size were used to determine the impact of differing automatic exposure control (AEC) algorithms. Results: There was a significant difference in both SSDE and GNL across scanner models (9–33% and 15–35% for SSDE and GNL, respectively). Adjusting all protocols to achieve the same image noise would reduce patient dose by 27–45% depending on scanner model. Additionally, differences in AEC methodologies across vendors resulted in disparate relationships of SSDE and GNL with patient size. Conclusion: The difference in noise across scanner models indicates that protocols are not optimally matched to achieve consistent image quality. Our results indicated substantial possibility for dose reduction while achieving more consistent image appearance. Finally, the difference in AEC methodologies suggests the need for size-specific CT protocols to minimize variability in image quality across CT vendors.« less

Implementation of ALARA radiation protection on the ISS through polyethylene shielding augmentation of the Service Module Crew Quarters

NASA Technical Reports Server (NTRS)

Shavers, M. R.; Zapp, N.; Barber, R. E.; Wilson, J. W.; Qualls, G.; Toupes, L.; Ramsey, S.; Vinci, V.; Smith, G.; Cucinotta, F. A.

2004-01-01

With 5-7 month long duration missions at 51.6 degrees inclination in Low Earth Orbit, the ionizing radiation levels to which International Space Station (ISS) crewmembers are exposed will be the highest planned occupational exposures in the world. Even with the expectation that regulatory dose limits will not be exceeded during a single tour of duty aboard the ISS, the "as low as reasonably achievable" (ALARA) precept requires that radiological risks be minimized when possible through a dose optimization process. Judicious placement of efficient shielding materials in locations where crewmembers sleep, rest, or work is an important means for implementing ALARA for spaceflight. Polyethylene (CnHn) is a relatively inexpensive, stable, and, with a low atomic number, an effective shielding material that has been certified for use aboard the ISS. Several designs for placement of slabs or walls of polyethylene have been evaluated for radiation exposure reduction in the Crew Quarters (CQ) of the Zvezda (Star) Service Module. Optimization of shield designs relies on accurate characterization of the expected primary and secondary particle environment and modeling of the predicted radiobiological responses of critical organs and tissues. Results of the studies shown herein indicate that 20% or more reduction in equivalent dose to the CQ occupant is achievable. These results suggest that shielding design and risk analysis are necessary measures for reducing long-term radiological risks to ISS inhabitants and for meeting legal ALARA requirements. Verification of shield concepts requires results from specific designs to be compared with onboard dosimetry. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Implementation of ALARA radiation protection on the ISS through polyethylene shielding augmentation of the Service Module crew quarters

NASA Astrophysics Data System (ADS)

Shavers, M.; Zapp, N.; Barber, R.; Wilson, J.; Qualls, G.; Toupes, L.; Ramsey, S.; Vinci, V.; Smith, G.; Cucinotta, F.

With 5 to 7-month long duration missions at 51.6° inclination in Low Earth Orbit, the ionizing radiation levels to which International Space Station (ISS) crewmembers are exposed will be the highest planned occupational exposures in the world. Even with the expectation that regulatory dose limits will not be exceeded during a single tour of duty aboard the ISS, the "as low as reasonably achievable" (ALARA) precept requires that radiological risks be minimized when possible through an dose optimization process. Judicious placement of efficient shielding materials in locations where crewmembers sleep, rest, or work is an important means for implementing ALARA for spaceflight. Polyethylene (Cn Hn ), is a relatively inexpensive, stable, and, with a low atomic number, an effective shielding material that has been certified for use aboard the ISS. Several designs for placement of slabs or walls of polyethylene have been evaluated for radiation exposure reduction in the Crew Quarters (CQ) of the Zvezda (Star) Service Module. Optimization of shield designs relies on accurate characterization of the expected primary and secondary particle environment and modeling of the predicted radiobiological responses of critical organs and tissues. Results of the studies shown herein indicate that 20% or more reduction in dose equivalent to the CQ occupant is achievable. These results suggest that shielding design and risk analysis are necessary measures for reducing long-term radiological risks to ISS inhabitants and for meeting legal ALARA requirements. Verification of shield concepts requires results from specific designs to be compared with onboard dosimetry.

Implementation of ALARA radiation protection on the ISS through polyethylene shielding augmentation of the Service Module Crew Quarters

NASA Astrophysics Data System (ADS)

Shavers, M. R.; Zapp, N.; Barber, R. E.; Wilson, J. W.; Qualls, G.; Toupes, L.; Ramsey, S.; Vinci, V.; Smith, G.; Cucinotta, F. A.

2004-01-01

With 5-7 month long duration missions at 51.6° inclination in Low Earth Orbit, the ionizing radiation levels to which International Space Station (ISS) crewmembers are exposed will be the highest planned occupational exposures in the world. Even with the expectation that regulatory dose limits will not be exceeded during a single tour of duty aboard the ISS, the "as low as reasonably achievable" (ALARA) precept requires that radiological risks be minimized when possible through a dose optimization process. Judicious placement of efficient shielding materials in locations where crewmembers sleep, rest, or work is an important means for implementing ALARA for spaceflight. Polyethylene (C nH n) is a relatively inexpensive, stable, and, with a low atomic number, an effective shielding material that has been certified for use aboard the ISS. Several designs for placement of slabs or walls of polyethylene have been evaluated for radiation exposure reduction in the Crew Quarters (CQ) of the Zvezda (Star) Service Module. Optimization of shield designs relies on accurate characterization of the expected primary and secondary particle environment and modeling of the predicted radiobiological responses of critical organs and tissues. Results of the studies shown herein indicate that 20% or more reduction in equivalent dose to the CQ occupant is achievable. These results suggest that shielding design and risk analysis are necessary measures for reducing long-term radiological risks to ISS inhabitants and for meeting legal ALARA requirements. Verification of shield concepts requires results from specific designs to be compared with onboard dosimetry.

From iron(III) precursor to magnetite and vice versa

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

Gotic, M., E-mail: gotic@irb.hr; Jurkin, T.; Music, S.

2009-10-15

The syntheses of nanosize magnetite particles by wet-chemical oxidation of Fe{sup 2+} have been extensively investigated. In the present investigation the nanosize magnetite particles were synthesised without using the Fe(II) precursor. This was achieved by {gamma}-irradiation of water-in-oil microemulsion containing only the Fe(III) precursor. The corresponding phase transformations were monitored. Microemulsions (pH {approx} 12.5) were {gamma}-irradiated at a relatively high dose rate of {approx}22 kGy/h. Upon 1 h of {gamma}-irradiation the XRD pattern of the precipitate showed goethite and unidentified low-intensity peaks. Upon 6 h of {gamma}-irradiation, reductive conditions were achieved and substoichiometric magnetite ({approx}Fe{sub 2.71}O{sub 4}) particles with insignificantmore » amount of goethite particles found in the precipitate. Hydrated electrons (e{sub aq}{sup -}), organic radicals and hydrogen gas as radiolytic products were responsible for the reductive dissolution of iron oxide in the microemulsion and the reduction Fe{sup 3+} {yields} Fe{sup 2+}. Upon 18 h of {gamma}-irradiation the precipitate exhibited dual behaviour, it was a more oxidised product than the precipitate obtained after 6 h of {gamma}-irradiation, but it contained magnetite particles in a more reduced form ({approx}Fe{sub 2.93}O{sub 4}). It was presumed that the reduction and oxidation processes existed as concurrent competitive processes in the microemulsion. After 18 h of {gamma}-irradiation the pH of the medium shifted from the alkaline to the acidic range. The high dose rate of {approx}22 kGy/h was directly responsible for this shift to the acidic range. At a slightly acidic pH a further reduction of Fe{sup 3+} {yields} Fe{sup 2+} resulted in the formation of more stoichiometric magnetite particles, whereas the oxidation conditions in the acidic medium permitted the oxidation Fe{sup 2+} {yields} Fe{sup 3+}. The Fe{sup 3+} was much less soluble in the acidic medium and it hydrolysed and recrystallised as goethite. The {gamma}-irradiation of the microemulsion for 25 h at a lower dose rate of 16 kGy/h produced pure substoichiometric nanosize magnetite particles of about 25 nm in size and with the stoichiometry of Fe{sub 2.83}O{sub 4}.« less

Influence of radiation dose and reconstruction algorithm in MDCT assessment of airway wall thickness: A phantom study

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

Gomez-Cardona, Daniel; Nagle, Scott K.; Department of Radiology, University of Wisconsin-Madison School of Medicine and Public Health, 600 Highland Avenue, Madison, Wisconsin 53792

Purpose: Wall thickness (WT) is an airway feature of great interest for the assessment of morphological changes in the lung parenchyma. Multidetector computed tomography (MDCT) has recently been used to evaluate airway WT, but the potential risk of radiation-induced carcinogenesis—particularly in younger patients—might limit a wider use of this imaging method in clinical practice. The recent commercial implementation of the statistical model-based iterative reconstruction (MBIR) algorithm, instead of the conventional filtered back projection (FBP) algorithm, has enabled considerable radiation dose reduction in many other clinical applications of MDCT. The purpose of this work was to study the impact of radiationmore » dose and MBIR in the MDCT assessment of airway WT. Methods: An airway phantom was scanned using a clinical MDCT system (Discovery CT750 HD, GE Healthcare) at 4 kV levels and 5 mAs levels. Both FBP and a commercial implementation of MBIR (Veo{sup TM}, GE Healthcare) were used to reconstruct CT images of the airways. For each kV–mAs combination and each reconstruction algorithm, the contrast-to-noise ratio (CNR) of the airways was measured, and the WT of each airway was measured and compared with the nominal value; the relative bias and the angular standard deviation in the measured WT were calculated. For each airway and reconstruction algorithm, the overall performance of WT quantification across all of the 20 kV–mAs combinations was quantified by the sum of squares (SSQs) of the difference between the measured and nominal WT values. Finally, the particular kV–mAs combination and reconstruction algorithm that minimized radiation dose while still achieving a reference WT quantification accuracy level was chosen as the optimal acquisition and reconstruction settings. Results: The wall thicknesses of seven airways of different sizes were analyzed in the study. Compared with FBP, MBIR improved the CNR of the airways, particularly at low radiation dose levels. For FBP, the relative bias and the angular standard deviation of the measured WT increased steeply with decreasing radiation dose. Except for the smallest airway, MBIR enabled significant reduction in both the relative bias and angular standard deviation of the WT, particularly at low radiation dose levels; the SSQ was reduced by 50%–96% by using MBIR. The optimal reconstruction algorithm was found to be MBIR for the seven airways being assessed, and the combined use of MBIR and optimal kV–mAs selection resulted in a radiation dose reduction of 37%–83% compared with a reference scan protocol with a dose level of 1 mGy. Conclusions: The quantification accuracy of airway WT is strongly influenced by radiation dose and reconstruction algorithm. The MBIR algorithm potentially allows the desired WT quantification accuracy to be achieved with reduced radiation dose, which may enable a wider clinical use of MDCT for the assessment of airway WT, particularly for younger patients who may be more sensitive to exposures with ionizing radiation.« less

Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Morrow, David A; Murphy, Sabina A; Kuder, Julia F; Deenadayalu, Naveen; Jarolim, Petr; Betcher, Joshua; Shi, Minggao; Brown, Karen; Patel, Indravadan; Mercuri, Michele; Antman, Elliott M

2015-06-06

New oral anticoagulants for stroke prevention in atrial fibrillation were developed to be given in fixed doses without the need for the routine monitoring that has hindered usage and acceptance of vitamin K antagonists. A concern has emerged, however, that measurement of drug concentration or anticoagulant activity might be needed to prevent excess drug concentrations, which significantly increase bleeding risk. In the ENGAGE AF-TIMI 48 trial, higher-dose and lower-dose edoxaban were compared with warfarin in patients with atrial fibrillation. Each regimen incorporated a 50% dose reduction in patients with clinical features known to increase edoxaban drug exposure. We aim to assess whether adjustment of edoxaban dose in this trial prevented excess drug concentration and the risk of bleeding events. We analysed data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. We correlated edoxaban dose, plasma concentration, and anti-Factor Xa (FXa) activity and compared efficacy and safety outcomes with warfarin stratified by dose reduction status. Patients with atrial fibrillation and at moderate to high risk of stroke were randomly assigned in a 1:1:1 ratio to receive warfarin, dose adjusted to an international normalised ratio of 2·0-3·0, higher-dose edoxaban (60 mg once daily), or lower-dose edoxaban (30 mg once daily). Randomisation was done with use of a central, 24 h, interactive, computerised response system. International normalised ratio was measured using an encrypted point-of-care device. To maintain masking, sham international normalised ratio values were generated for patients assigned to edoxaban. Edoxaban (or placebo-edoxaban in warfarin group) doses were halved at randomisation or during the trial if patients had creatinine clearance 30-50 mL/min, bodyweight 60 kg or less, or concomitant medication with potent P-glycoprotein interaction. Efficacy outcomes included the primary endpoint of all-cause stroke or systemic embolism, ischaemic stroke, and all-cause mortality. Safety outcomes included the primary safety endpoint of major bleeding, fatal bleeding, intracranial haemorrhage, and gastrointestinal bleeding. This trial is registered with ClinicalTrials.gov, number NCT00781391. Between Nov 19, 2008 and Nov 22, 2010, 21 105 patients were recruited. Patients who met clinical criteria for dose reduction at randomisation (n=5356) had higher rates of stroke, bleeding, and death compared with those who did not have a dose reduction (n=15 749). Edoxaban dose ranged from 15 mg to 60 mg, resulting in a two-fold to three fold gradient of mean trough drug exposure (16·0-48·5 ng/mL in 6780 patients with data available) and mean trough anti-FXa activity (0·35-0·85 IU/mL in 2865 patients). Dose reduction decreased mean exposure by 29% (from 48·5 ng/mL [SD 45·8] to 34·6 ng/mL [30·9]) and 35% (from 24·5 ng/mL [22·7] to 16·0 ng/mL [14·5]) and mean anti-FXa activity by 25% (from 0·85 IU/mL [0·76] to 0·64 IU/mL [0·54]) and 20% (from 0·44 IU/mL [0·37] to 0·35 IU/mL [0·28]) in the higher-dose and lower-dose regimens, respectively. Despite the lower anti-FXa activity, dose reduction preserved the efficacy of edoxaban compared with warfarin (stroke or systemic embolic event: higher dose pinteraction=0·85, lower dose pinteraction=0·99) and provided even greater safety (major bleeding: higher dose pinteraction 0·02, lower dose pinteraction=0·002). These findings validate the strategy that tailoring of the dose of edoxaban on the basis of clinical factors alone achieves the dual goal of preventing excess drug concentrations and helps to optimise an individual patient's risk of ischaemic and bleeding events and show that the therapeutic window for edoxaban is narrower for major bleeding than thromboembolism. Daiichi-Sankyo Pharma Development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-coated tablet formulation in non-hematologic malignancies: Phase 1 dose-escalation study

PubMed Central

Falchook, Gerald; Kurzrock, Razelle; Gouw, Launce; Hong, David; McGregor, Kimberly A.; Zhou, Xiaofei; Shi, Hongliang; Fingert, Howard; Sharma, Sunil

2014-01-01

Background This phase 1b study evaluated an enteric-coated tablet (ECT) formulation of the investigational Aurora A kinase inhibitor, alisertib (MLN8237). Methods Patients with advanced, non-hematologic malignancies received oral alisertib ECT for 7 days BID followed by 14 days treatment-free (21-day cycles; 3+3 dose escalation schema). Objectives were to assess safety, pharmacokinetics, and antitumor activity, and to define a recommended phase 2 dose (RP2D) of alisertib. Results 24 patients were treated. Median age was 57 years. Patients received a median of 2 cycles (range 1–12). The RP2D was determined as 50 mg BID for 7 days (21-day cycles). A cycle 1 dose-limiting toxicity of grade 4 febrile neutropenia was observed in 1 of 13 patients at RP2D. The most common drug-related adverse event (AE) was neutropenia (50%). At doses ≥40 mg BID, 7 patients had drug-related AEs that were serious but largely reversible/manageable by dose reduction and supportive care, including 3 with febrile neutropenia. Pharmacokinetic data were available in 24 patients. Following administration of alisertib ECT, the plasma peak concentration of alisertib was achieved at ~3 h; systemic exposure increased with increasing dose over 10–60 mg BID. Mean t½ was ~21 h following multiple dosing. Renal clearance was negligible. Nine patients achieved stable disease (3.98*, 5.59, 1.28*, 2.56, 5.45*, 3.48, 3.15, 8.31, and 6.93* months; *censored). Conclusions Alisertib ECT was generally well tolerated in adults with advanced, non-hematologic malignancies. The RP2D is 50 mg BID for 7 days and is being evaluated in ongoing phase 2 studies. PMID:24879333

Iterative reconstruction for x-ray computed tomography using prior-image induced nonlocal regularization.

PubMed

Zhang, Hua; Huang, Jing; Ma, Jianhua; Bian, Zhaoying; Feng, Qianjin; Lu, Hongbing; Liang, Zhengrong; Chen, Wufan

2014-09-01

Repeated X-ray computed tomography (CT) scans are often required in several specific applications such as perfusion imaging, image-guided biopsy needle, image-guided intervention, and radiotherapy with noticeable benefits. However, the associated cumulative radiation dose significantly increases as comparison with that used in the conventional CT scan, which has raised major concerns in patients. In this study, to realize radiation dose reduction by reducing the X-ray tube current and exposure time (mAs) in repeated CT scans, we propose a prior-image induced nonlocal (PINL) regularization for statistical iterative reconstruction via the penalized weighted least-squares (PWLS) criteria, which we refer to as "PWLS-PINL". Specifically, the PINL regularization utilizes the redundant information in the prior image and the weighted least-squares term considers a data-dependent variance estimation, aiming to improve current low-dose image quality. Subsequently, a modified iterative successive overrelaxation algorithm is adopted to optimize the associative objective function. Experimental results on both phantom and patient data show that the present PWLS-PINL method can achieve promising gains over the other existing methods in terms of the noise reduction, low-contrast object detection, and edge detail preservation.

Iterative Reconstruction for X-Ray Computed Tomography using Prior-Image Induced Nonlocal Regularization

PubMed Central

Ma, Jianhua; Bian, Zhaoying; Feng, Qianjin; Lu, Hongbing; Liang, Zhengrong; Chen, Wufan

2014-01-01

Repeated x-ray computed tomography (CT) scans are often required in several specific applications such as perfusion imaging, image-guided biopsy needle, image-guided intervention, and radiotherapy with noticeable benefits. However, the associated cumulative radiation dose significantly increases as comparison with that used in the conventional CT scan, which has raised major concerns in patients. In this study, to realize radiation dose reduction by reducing the x-ray tube current and exposure time (mAs) in repeated CT scans, we propose a prior-image induced nonlocal (PINL) regularization for statistical iterative reconstruction via the penalized weighted least-squares (PWLS) criteria, which we refer to as “PWLS-PINL”. Specifically, the PINL regularization utilizes the redundant information in the prior image and the weighted least-squares term considers a data-dependent variance estimation, aiming to improve current low-dose image quality. Subsequently, a modified iterative successive over-relaxation algorithm is adopted to optimize the associative objective function. Experimental results on both phantom and patient data show that the present PWLS-PINL method can achieve promising gains over the other existing methods in terms of the noise reduction, low-contrast object detection and edge detail preservation. PMID:24235272

ABT492 and levofloxacin: comparison of their pharmacodynamics and their abilities to prevent the selection of resistant Staphylococcus aureus in an in vitro dynamic model.

PubMed

Firsov, Alexander A; Vostrov, Sergey N; Lubenko, Irene Yu; Arzamastsev, Alexander P; Portnoy, Yury A; Zinner, Stephen H

2004-07-01

To compare the kinetics of killing/regrowth of differentially susceptible clinical isolates of Staphylococcus aureus exposed to ABT492 and levofloxacin and to explore their relative abilities to prevent the selection of resistant mutants. Three clinical isolates of S. aureus--including two ciprofloxacin-susceptible S. aureus, 201 and 480--and a ciprofloxacin-resistant S. aureus 866, were exposed to clinically achievable ratios of area under the curve (AUC) to MIC in a dynamic model that simulated human pharmacokinetics of ABT492 (400 mg) and levofloxacin (500 mg) as a single dose. In addition, S. aureus 201 was exposed to single and multiple doses of ABT492 and levofloxacin (both once daily for 3 days) over wide ranges of 24 h AUC/MIC (AUC24/MIC) including clinically achievable AUC24/MIC ratios. With each isolate, ABT492 at clinically achievable AUC/MICs produced greater anti-staphylococcal effects than levofloxacin. Areas between the control growth and the time--kill curves (ABBC in single dose simulations and the sum of ABBCs determined after the first, second and third dosing in multiple dose simulations--ABBC(1+2+3)) were higher with ABT492 than levofloxacin. Moreover, at comparable AUC/MICs and AUC24/MICs, the maximal reductions in the starting inoculum of ABT492-exposed S. aureus were more pronounced than with levofloxacin. Loss in susceptibility of S. aureus 201 exposed to ABT492 or levofloxacin depended on the simulated AUC24/MIC. Although the maximal increase in MIC (MICfinal) related to its initial value (MICinitial) was seen at a higher AUC24/MIC ratio of ABT492 (120 h) than levofloxacin (50 h), similar AUC24/MICs (240 and 200 h, respectively) were protective against the selection of resistant S. aureus. These threshold values are readily achievable with 400 mg ABT492 (AUC24/MIC 870 h) but not with 500 mg levofloxacin (AUC24/MIC 70 h). Overall, these findings predict greater efficacy of clinically achievable AUC/MIC (or AUC24/MIC) of ABT492 both in terms of the anti-staphylococcal effect and prevention of the selection of resistant mutants.

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

Head CT: Image quality improvement of posterior fossa and radiation dose reduction with ASiR - comparative studies of CT head examinations.

PubMed

Guziński, Maciej; Waszczuk, Łukasz; Sąsiadek, Marek J

2016-10-01

To evaluate head CT protocol developed to improve visibility of the brainstem and cerebellum, lower bone-related artefacts in the posterior fossa and maintain patient radioprotection. A paired comparison of head CT performed without Adaptive Statistical Iterative Reconstruction (ASiR) and a clinically indicated follow-up with 40 % ASiR was acquired in one group of 55 patients. Patients were scanned in the axial mode with different scanner settings for the brain and the posterior fossa. Objective image quality analysis was performed with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality analysis was based on brain structure visibility and evaluation of the artefacts. We achieved 19 % reduction of total DLP and significantly better image quality of posterior fossa structures. SNR for white and grey matter in the cerebellum were 34 % to 36 % higher, respectively, CNR was improved by 142 % and subjective analyses were better for images with ASiR. When imaging parameters are set independently for the brain and the posterior fossa imaging, ASiR has a great potential to improve CT performance: image quality of the brainstem and cerebellum is improved, and radiation dose for the brain as well as total radiation dose are reduced. •With ASiR it is possible to lower radiation dose or improve image quality •Sequentional imaging allows setting scan parameters for brain and posterior-fossa independently •We improved visibility of brainstem structures and decreased radiation dose •Total radiation dose (DLP) was decreased by 19.

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

Yu, Yao; Chen, Josephine; Leary, Celeste I.

Radiation of the low neck can be accomplished using split-field intensity-modulated radiation therapy (sf-IMRT) or extended-field intensity-modulated radiation therapy (ef-IMRT). We evaluated the effect of these treatment choices on target coverage and thyroid and larynx doses. Using data from 14 patients with cancers of the oropharynx, we compared the following 3 strategies for radiating the low neck: (1) extended-field IMRT, (2) traditional split-field IMRT with an initial cord-junction block to 40 Gy, followed by a full-cord block to 50 Gy, and (3) split-field IMRT with a full-cord block to 50 Gy. Patients were planned using each of these 3 techniques.more » To facilitate comparison, extended-field plans were normalized to deliver 50 Gy to 95% of the neck volume. Target coverage was assessed using the dose to 95% of the neck volume (D{sub 95}). Mean thyroid and larynx doses were computed. Extended-field IMRT was used as the reference arm; the mean larynx dose was 25.7 ± 7.4 Gy, and the mean thyroid dose was 28.6 ± 2.4 Gy. Split-field IMRT with 2-step blocking reduced laryngeal dose (mean larynx dose 15.2 ± 5.1 Gy) at the cost of a moderate reduction in target coverage (D{sub 95} 41.4 ± 14 Gy) and much higher thyroid dose (mean thyroid dose 44.7 ± 3.7 Gy). Split-field IMRT with initial full-cord block resulted in greater laryngeal sparing (mean larynx dose 14.2 ± 5.1 Gy) and only a moderately higher thyroid dose (mean thyroid dose 31 ± 8 Gy) but resulted in a significant reduction in target coverage (D{sub 95} 34.4 ± 15 Gy). Extended-field IMRT comprehensively covers the low neck and achieves acceptable thyroid and laryngeal sparing. Split-field IMRT with a full-cord block reduces laryngeal doses to less than 20 Gy and spares the thyroid, at the cost of substantially reduced coverage of the low neck. Traditional 2-step split-field IMRT similarly reduces the laryngeal dose but also reduces low-neck coverage and delivers very high doses to the thyroid.« less

The Effect of Reduced or Withdrawn Etanercept-methotrexate Therapy on Patient-reported Outcomes in Patients with Early Rheumatoid Arthritis.

PubMed

Wiland, Piotr; Dudler, Jean; Veale, Douglas; Tahir, Hasan; Pedersen, Ron; Bukowski, Jack; Vlahos, Bonnie; Williams, Theresa; Gaylord, Stefanie; Kotak, Sameer

2016-07-01

An analysis of a clinical trial to assess the effects of treatment reduction and withdrawal on patient-reported outcomes (PRO) in patients with early, moderate to severe rheumatoid arthritis (RA) who achieved 28-joint Disease Activity Score (DAS28) low disease activity (LDA) or remission with etanercept (ETN) plus methotrexate (MTX) therapy. During treatment induction, patients received open-label ETN 50 mg weekly plus MTX for 52 weeks. In the reduced-treatment phase, patients with DAS28-erythrocyte sedimentation rate (ESR) ≤ 3.2 at Week 39 and DAS28-ESR < 2.6 at Week 52 in the open-label phase were randomized to double-blind treatment with ETN 25 mg plus MTX, MTX, or placebo (PBO) for 39 weeks (weeks 0-39). In the third phase, patients who achieved DAS28 remission (DAS28-ESR < 2.6) or LDA (2.6 ≤ DAS28-ESR ≤ 3.2) at Week 39 in the double-blind phase had all treatment withdrawn and were observed for an additional 26 weeks (weeks 39-65). Of the 306 patients enrolled, 193 were randomized in the double-blind phase and 131 participated in the treatment-withdrawal phase. After reduction or withdrawal of ETN 50 mg/MTX, patients reduced to ETN 25 mg/MTX experienced slight, nonsignificant declines in the majority of PRO measures, whereas switching to PBO or MTX alone caused significant declines. Presenteeism and activity impairment scores were significantly better in the ETN reduced-dose group versus MTX monotherapy and PBO at Week 39 (p ≤ 0.05). In patients with early RA who achieved remission while receiving full-dose ETN/MTX, continuing combination therapy at a lower dose did not cause a significant worsening of PRO response, but switching to MTX alone or PBO did. ClinicalTrials.gov identifier: NCT00913458.

Evaluation of the stepwise collimation method for the reduction of the patient dose in full spine radiography

NASA Astrophysics Data System (ADS)

Lee, Boram; Lee, Sunyoung; Yang, Injeong; Yoon, Myeonggeun

2014-05-01

The purpose of this study is to evaluate the dose reduction when using the stepwise collimation method for scoliosis patients undergoing full spine radiography. A Monte Carlo simulation was carried out to acquire dose vs. volume data for organs at risk (OAR) in the human body. While the effective doses in full spine radiography were reduced by 8, 15, 27 and 44% by using four different sizes of the collimation, the doses to the skin were reduced by 31, 44, 55 and 66%, indicating that the reduction of the dose to the skin is higher than that to organs inside the body. Although the reduction rates were low for the gonad, being 9, 14, 18 and 23%, there was more than a 30% reduction in the dose to the heart, suggesting that the dose reduction depends significantly on the location of the OARs in the human body. The reduction rate of the secondary cancer risk based on the excess absolute risk (EAR) varied from 0.6 to 3.4 per 10,000 persons, depending on the size of the collimation. Our results suggest that the stepwise collimation method in full spine radiography can effectively reduce the patient dose and the radiation-induced secondary cancer risk.

The Impact of Different Levels of Adaptive Iterative Dose Reduction 3D on Image Quality of 320-Row Coronary CT Angiography: A Clinical Trial

PubMed Central

Feger, Sarah; Rief, Matthias; Zimmermann, Elke; Martus, Peter; Schuijf, Joanne Désirée; Blobel, Jörg; Richter, Felicitas; Dewey, Marc

2015-01-01

Purpose The aim of this study was the systematic image quality evaluation of coronary CT angiography (CTA), reconstructed with the 3 different levels of adaptive iterative dose reduction (AIDR 3D) and compared to filtered back projection (FBP) with quantum denoising software (QDS). Methods Standard-dose CTA raw data of 30 patients with mean radiation dose of 3.2 ± 2.6 mSv were reconstructed using AIDR 3D mild, standard, strong and compared to FBP/QDS. Objective image quality comparison (signal, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), contour sharpness) was performed using 21 measurement points per patient, including measurements in each coronary artery from proximal to distal. Results Objective image quality parameters improved with increasing levels of AIDR 3D. Noise was lowest in AIDR 3D strong (p≤0.001 at 20/21 measurement points; compared with FBP/QDS). Signal and contour sharpness analysis showed no significant difference between the reconstruction algorithms for most measurement points. Best coronary SNR and CNR were achieved with AIDR 3D strong. No loss of SNR or CNR in distal segments was seen with AIDR 3D as compared to FBP. Conclusions On standard-dose coronary CTA images, AIDR 3D strong showed higher objective image quality than FBP/QDS without reducing contour sharpness. Trial Registration Clinicaltrials.gov NCT00967876 PMID:25945924

MO-DE-204-00: International Symposium: Patient Dose Reduction in Diagnostic Radiology

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

NONE

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

Dose reduction and image quality optimizations in CT of pediatric and adult patients: phantom studies

NASA Astrophysics Data System (ADS)

Jeon, P.-H.; Lee, C.-L.; Kim, D.-H.; Lee, Y.-J.; Jeon, S.-S.; Kim, H.-J.

2014-03-01

Multi-detector computed tomography (MDCT) can be used to easily and rapidly perform numerous acquisitions, possibly leading to a marked increase in the radiation dose to individual patients. Technical options dedicated to automatically adjusting the acquisition parameters according to the patient's size are of specific interest in pediatric radiology. A constant tube potential reduction can be achieved for adults and children, while maintaining a constant detector energy fluence. To evaluate radiation dose, the weighted CT dose index (CTDIw) was calculated based on the CT dose index (CTDI) measured using an ion chamber, and image noise and image contrast were measured from a scanned image to evaluate image quality. The dose-weighted contrast-to-noise ratio (CNRD) was calculated from the radiation dose, image noise, and image contrast measured from a scanned image. The noise derivative (ND) is a quality index for dose efficiency. X-ray spectra with tube voltages ranging from 80 to 140 kVp were used to compute the average photon energy. Image contrast and the corresponding contrast-to-noise ratio (CNR) were determined for lesions of soft tissue, muscle, bone, and iodine relative to a uniform water background, as the iodine contrast increases at lower energy (i.e., k-edge of iodine is 33 keV closer to the beam energy) using mixed water-iodine contrast normalization (water 0, iodine 25, 100, 200, and 1000 HU, respectively). The proposed values correspond to high quality images and can be reduced if only high-contrast organs are assessed. The potential benefit of lowering the tube voltage is an improved CNRD, resulting in a lower radiation dose and optimization of image quality. Adjusting the tube potential in abdominal CT would be useful in current pediatric radiography, where the choice of X-ray techniques generally takes into account the size of the patient as well as the need to balance the conflicting requirements of diagnostic image quality and radiation dose optimization.

In-Plane Shielding for CT: Effect of Off-Centering, Automatic Exposure Control and Shield-to-Surface Distance

PubMed Central

Dang, Pragya; Singh, Sarabjeet; Saini, Sanjay; Shepard, Jo-Anne O.

2009-01-01

Objective To assess effects of off-centering, automatic exposure control, and padding on attenuation values, noise, and radiation dose when using in-plane bismuth-based shields for CT scanning. Materials and Methods A 30 cm anthropomorphic chest phantom was scanned on a 64-multidetector CT, with the center of the phantom aligned to the gantry isocenter. Scanning was repeated after placing a bismuth breast shield on the anterior surface with no gap and with 1, 2, and 6 cm of padding between the shield and the phantom surface. The "shielded" phantom was also scanned with combined modulation and off-centering of the phantom at 2 cm, 4 cm and 6 cm below the gantry isocenter. CT numbers, noise, and surface radiation dose were measured. The data were analyzed using an analysis of variance. Results The in-plane shield was not associated with any significant increment for the surface dose or CT dose index volume, which was achieved by comparing the radiation dose measured by combined modulation technique to the fixed mAs (p > 0.05). Irrespective of the gap or the surface CT numbers, surface noise increased to a larger extent compared to Hounsfield unit (HU) (0-6 cm, 26-55%) and noise (0-6 cm, 30-40%) in the center. With off-centering, in-plane shielding devices are associated with less dose savings, although dose reduction was still higher than in the absence of shielding (0 cm off-center, 90% dose reduction; 2 cm, 61%) (p < 0.0001). Streak artifacts were noted at 0 cm and 1 cm gaps but not at 2 cm and 6 cm gaps of shielding to the surface distances. Conclusion In-plane shields are associated with greater image noise, artifactually increased attenuation values, and streak artifacts. However, shields reduce radiation dose regardless of the extent of off-centering. Automatic exposure control did not increase radiation dose when using a shield. PMID:19270862

Poster — Thur Eve — 11: Validation of the orthopedic metallic artifact reduction tool for CT simulations at the Ottawa Hospital Cancer Centre

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

Sutherland, J; Foottit, C

Metallic implants in patients can produce image artifacts in kilovoltage CT simulation images which can introduce noise and inaccuracies in CT number, affecting anatomical segmentation and dose distributions. The commercial orthopedic metal artifact reduction algorithm (O-MAR) (Philips Healthcare System) was recently made available on CT simulation scanners at our institution. This study validated the clinical use of O-MAR by investigating its effects on CT number and dose distributions. O-MAR corrected and uncorrected images were acquired with a Philips Brilliance Big Bore CT simulator of a cylindrical solid water phantom that contained various plugs (including metal) of known density. CT numbermore » accuracy was investigated by determining the mean and standard deviation in regions of interest (ROI) within each plug for uncorrected and O-MAR corrected images and comparing with no-metal image values. Dose distributions were calculated using the Monaco treatment planning system. Seven open fields were equally spaced about the phantom around a ROI near the center of the phantom. These were compared to a “correct” dose distribution calculated by overriding electron densities a no-metal phantom image to produce an image containing metal but no artifacts. An overall improvement in CT number and dose distribution accuracy was achieved by applying the O-MAR correction. Mean CT numbers and standard deviations were found to be generally improved. Exceptions included lung equivalent media, which is consistent with vendor specified contraindications. Dose profiles were found to vary by ±4% between uncorrected or O-MAR corrected images with O-MAR producing doses closer to ground truth.« less

Head CT: Image quality improvement with ASIR-V using a reduced radiation dose protocol for children.

PubMed

Kim, Hyun Gi; Lee, Ho-Joon; Lee, Seung-Koo; Kim, Hyun Ji; Kim, Myung-Joon

2017-09-01

To investigate the quality of images reconstructed with adaptive statistical iterative reconstruction V (ASIR-V), using pediatric head CT protocols. A phantom was scanned at decreasing 20% mA intervals using our standard pediatric head CT protocols. Each study was then reconstructed at 10% ASIR-V intervals. After the phantom study, we reduced mA by 10% in the protocol for <3-year-old patients and applied 30% ASIR-V and by 30% in the protocol for 3- to 15-year-old patients and applied 40% ASIR-V. Increasing the percentage of ASIR-V resulted in lower noise and higher contrast-to-noise ratio (CNR) and preserved spatial resolution in the phantom study. Compared to a conventional-protocol, reduced-dose protocol with ASIR-V achieved 12.8% to 34.0% of dose reduction and showed images of lower noise (9.22 vs. 10.73, P = 0.043) and higher CNR in different levels (centrum semiovale, 2.14 vs. 1.52, P = 0.003; basal ganglia, 1.46 vs. 1.07, P = 0.001; and cerebellum, 2.18 vs. 1.33, P < 0.001). Qualitative analysis showed higher gray-white matter differentiation and sharpness and preserved overall diagnostic quality in the images with ASIR-V. Use of ASIR-V allowed a 12.8% to 34.0% dose reduction in each age group with potential to improve image quality. • It is possible to reduce radiation dose and improve image quality with ASIR-V. • We improved noise and CNR and decreased radiation dose. • Sharpness improved with ASIR-V. • Total radiation dose was decreased by 12.8% to 34.0%.

[Comparison of radiation dose reduction of prospective ECG-gated one beat scan using 320 area detector CT coronary angiography and prospective ECG-gated helical scan with high helical pitch (FlashScan) using 64 multidetector-row CT coronary angiography].

PubMed

Matsutani, Hideyuki; Sano, Tomonari; Kondo, Takeshi; Fujimoto, Shinichiro; Sekine, Takako; Arai, Takehiro; Morita, Hitomi; Takase, Shinichi

2010-12-20

A high radiation dose associated with 64 multidetector-row computed tomography (64-MDCT) is a major concern for physicians and patients alike. A new 320 row area detector computed tomography (ADCT) can obtain a view of the entire heart with one rotation (0.35 s) without requiring the helical method. As such, ADCT is expected to reduce the radiation dose. We studied image quality and radiation dose of ADCT compared to that of 64-MDCT in patients with a low heart rate (HR≤60). Three hundred eighty-five consecutive patients underwent 64-MDCT and 379 patients, ADCT. Patients with an arrhythmia were excluded. Prospective ECG-gated helical scan with high HP (FlashScan) in 64 was used for MDCT and prospective ECG-gated conventional one beat scan, for 320-ADCT. Image quality was visually evaluated by an image quality score. Radiation dose was estimated by DLP (mGy･cm) for 64-MDCT and DLP.e (mGy･cm) for 320-ADCT. Radiation dose of 320-ADCT (208±48 mGy･cm) was significantly (P<0.0001) lower than that of 64-MDCT (484±112 mGy･cm), and image quality score of 320-ADCT (3.0±0.2) was significantly (P=0.0011) higher than that of 64-MDCT (2.9±0.4). Scan time of 320-ADCT (1.4±0.1 s) was also significantly (P<0.0001) shorter than that of 64-MDCT (6.8±0.6 s). 320-ADCT can achieve not only a reduction in radiation dose but also a superior image quality and shortening of scan time compared to 64-MDCT.

Global measles mortality, 2000-2008.

PubMed

2009-12-04

The United Nations (UN) Millennium Development Goals include a goal (MDG 4) to achieve a two thirds overall reduction of child deaths by 2015 compared with the 1990 level. Because many unvaccinated children die from measles, routine measles vaccination coverage is used as an indicator of progress toward this goal. In 2008, all UN member states reaffirmed their commitment to achieving a 90% reduction in measles mortality by 2010 compared with 2000, from an estimated 733,000 deaths in 2000 worldwide to <73,300 by 2010. The World Health Organization (WHO) and UNICEF have identified 47 priority countries with the highest burden of measles for an accelerated strategy for measles mortality reduction. The strategy includes 1) achieving and maintaining high coverage (>or=90% nationally and >or=80% in each district) with 2 doses of measles-containing vaccine (MCV) delivered through routine services or supplemental immunization activities (SIAs) , 2) implementing effective laboratory-supported disease surveillance, and 3) providing appropriate clinical management for measles cases. This report updates a previously published report, provides details on activities implemented during 2008, assesses progress toward the 2010 goal, and evaluates the potential effects of decreased financial support. During 2000--2008, global measles mortality declined by 78%, from an estimated 733,000 deaths in 2000 to 164,000 in 2008, but the reduction in measles mortality has been leveling off since 2007. To reach the 2010 goal, India should fully implement the recommended strategies, and financial support for sustaining measles control in the other 46 priority countries should be secured.

Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with three-dimensional conformal radiation therapy in clinically localized prostate cancer

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

Wang-Chesebro, Alice; Xia Ping; Coleman, Joy

2006-11-01

Purpose: The aim of this study was to quantify gains in lymph node coverage and critical structure dose reduction for whole-pelvis (WP) and extended-field (EF) radiotherapy in prostate cancer using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3DCRT) for the first treatment phase of 45 Gy in the concurrent treatment of lymph nodes and prostate. Methods and Materials: From January to August 2005, 35 patients with localized prostate cancer were treated with pelvic IMRT; 7 had nodes defined up to L5-S1 (Group 1), and 28 had nodes defined above L5-S1 (Group 2). Each patient had 2 plans retrospectively generated:more » 1 WP 3DCRT plan using bony landmarks, and 1 EF 3DCRT plan to cover the vascular defined volumes. Dose-volume histograms for the lymph nodes, rectum, bladder, small bowel, and penile bulb were compared by group. Results: For Group 1, WP 3DCRT missed 25% of pelvic nodes with the prescribed dose 45 Gy and missed 18% with the 95% prescribed dose 42.75 Gy, whereas WP IMRT achieved V{sub 45Gy} = 98% and V{sub 42.75Gy} = 100%. Compared with WP 3DCRT, IMRT reduced bladder V{sub 45Gy} by 78%, rectum V{sub 45Gy} by 48%, and small bowel V{sub 45Gy} by 232 cm{sup 3}. EF 3DCRT achieved 95% coverage of nodes for all patients at high cost to critical structures. For Group 2, IMRT decreased bladder V{sub 45Gy} by 90%, rectum V{sub 45Gy} by 54% and small bowel V{sub 45Gy} by 455 cm{sup 3} compared with EF 3DCRT. Conclusion: In this study WP 3DCRT missed a significant percentage of pelvic nodes. Although EF 3DCRT achieved 95% pelvic nodal coverage, it increased critical structure doses. IMRT improved pelvic nodal coverage while decreasing dose to bladder, rectum, small bowel, and penile bulb. For patients with extended node involvement, IMRT especially decreases small bowel dose.« less

Metronidazole stewardship initiative at Christchurch hospitals-achievable with immediate benefits.

PubMed

Gardiner, Sharon J; Metcalf, Sarah Cl; Chin, Paul Kl; Doogue, Matthew P; Dalton, Simon C; Chambers, Stephen T

2018-04-13

To evaluate an antimicrobial stewardship (AMS) initiative to change hospital prescribing practice for metronidazole. In October 2015, the Canterbury District Health Board (CDHB) AMS committee changed advice for metronidazole to promote two times daily dosing for most indications, prioritisation of the oral route and avoidance of double anaerobic cover. Adoption of the initiative was facilitated via change in prescribing guidelines, education and ongoing pharmacy support. Usage and expenditure on metronidazole for adult inpatients were compared for the five years pre- and two years post-change. Other district health boards (DHBs) were surveyed to determine their dosing recommendation for metronidazole IV. Mean annual metronidazole IV use, as defined daily doses per 1,000 occupied bed days, decreased by 43% post-initiative. Use of non-IV (oral or rectal) formulations increased by 104%. Total savings associated with the initiative were approximately $33,400 in drug costs plus $78,200 per annum in IV giving sets and post-dose flushes. Twelve of 20 (60%) DHBs (including CDHB) endorse twice daily IV dosing. In addition to financial savings, reduction in IV doses has potential benefits, including avoidance of IV catheter-associated complications such as bloodstream infections. Approaches to metronidazole dosing vary across DHBs and could benefit from national coordination.

Intravenous iron administration strategies and anemia management in hemodialysis patients.

PubMed

Michels, Wieneke M; Jaar, Bernard G; Ephraim, Patti L; Liu, Yang; Miskulin, Dana C; Tangri, Navdeep; Crews, Deidra C; Scialla, Julia J; Shafi, Tariq; Sozio, Stephen M; Bandeen-Roche, Karen; Cook, Courtney J; Meyer, Klemens B; Boulware, L Ebony

2017-01-01

The effect of maintenance intravenous (IV) iron administration on subsequent achievement of anemia management goals and mortality among patients recently initiating hemodialysis is unclear. We performed an observational cohort study, in adult incident dialysis patients starting on hemodialysis. We defined IV administration strategies over a 12-week period following a patient's initiation of hemodialysis; all those receiving IV iron at regular intervals were considered maintenance, and all others were considered non-maintenance. We used multivariable models adjusting for demographics, clinical and treatment parameters, iron dose, measures of iron stores and pro-infectious and pro-inflammatory parameters to compare these strategies. The outcomes under study were patients' (i) achievement of hemoglobin (Hb) of 10-12 g/dL, (ii) more than 25% reduction in mean weekly erythropoietin stimulating agent (ESA) dose and (iii) mortality, ascertained over a period of 4 weeks following the iron administration period. Maintenance IV iron was administered to 4511 patients and non-maintenance iron to 8458 patients. Maintenance IV iron administration was not associated with a higher likelihood of achieving an Hb between 10 and 12 g/dL {adjusted odds ratio (OR) 1.01 [95% confidence interval (CI) 0.93-1.09]} compared with non-maintenance, but was associated with a higher odds of achieving a reduced ESA dose of 25% or more [OR 1.33 (95% CI 1.18-1.49)] and lower mortality [hazard ratio (HR) 0.73 (95% CI 0.62-0.86)]. Maintenance IV iron strategies were associated with reduced ESA utilization and improved early survival but not with the achievement of Hb targets. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Evaluation of stabilization techniques for ion implant processing

NASA Astrophysics Data System (ADS)

Ross, Matthew F.; Wong, Selmer S.; Minter, Jason P.; Marlowe, Trey; Narcy, Mark E.; Livesay, William R.

1999-06-01

With the integration of high current ion implant processing into volume CMOS manufacturing, the need for photoresist stabilization to achieve a stable ion implant process is critical. This study compares electron beam stabilization, a non-thermal process, with more traditional thermal stabilization techniques such as hot plate baking and vacuum oven processing. The electron beam processing is carried out in a flood exposure system with no active heating of the wafer. These stabilization techniques are applied to typical ion implant processes that might be found in a CMOS production process flow. The stabilization processes are applied to a 1.1 micrometers thick PFI-38A i-line photoresist film prior to ion implant processing. Post stabilization CD variation is detailed with respect to wall slope and feature integrity. SEM photographs detail the effects of the stabilization technique on photoresist features. The thermal stability of the photoresist is shown for different levels of stabilization and post stabilization thermal cycling. Thermal flow stability of the photoresist is detailed via SEM photographs. A significant improvement in thermal stability is achieved with the electron beam process, such that photoresist features are stable to temperatures in excess of 200 degrees C. Ion implant processing parameters are evaluated and compared for the different stabilization methods. Ion implant system end-station chamber pressure is detailed as a function of ion implant process and stabilization condition. The ion implant process conditions are detailed for varying factors such as ion current, energy, and total dose. A reduction in the ion implant systems end-station chamber pressure is achieved with the electron beam stabilization process over the other techniques considered. This reduction in end-station chamber pressure is shown to provide a reduction in total process time for a given ion implant dose. Improvements in the ion implant process are detailed across several combinations of current and energy.

Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I

PubMed Central

Dickson, Patricia; Peinovich, Maryn; McEntee, Michael; Lester, Thomas; Le, Steven; Krieger, Aimee; Manuel, Hayden; Jabagat, Catherine; Passage, Merry; Kakkis, Emil D.

2008-01-01

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human α-l-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of α-l-iduronidase–specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines. A total of 24 canines with MPS I were either tolerized to iduronidase or left nontolerant. All canines received i.v. recombinant iduronidase at the FDA-approved human dose or a higher dose for 9–44 weeks. Nontolerized canines developed iduronidase-specific antibodies that proportionally reduced in vitro iduronidase uptake. Immune-tolerized canines achieved increased tissue enzyme levels at either dose in most nonreticular tissues and a greater reduction in tissue GAG levels, lysosomal pathology, and urinary GAG excretion. Tolerized MPS I dogs treated with the higher dose received some further benefit in the reduction of GAGs in tissues, urine, and the heart valve. Therefore, immune tolerance to iduronidase improved the efficacy of enzyme replacement therapy with recombinant iduronidase in canine MPS I and could potentially improve outcomes in patients with MPS I and other lysosomal storage diseases. PMID:18654665

Effect of reduced agalsidase Beta dosage in fabry patients: the Australian experience.

PubMed

Ghali, Joanna; Nicholls, Kathy; Denaro, Charles; Sillence, David; Chapman, Ian; Goldblatt, Jack; Thomas, Mark; Fletcher, Janice

2012-01-01

In Australia, enzyme replacement therapy (ERT) for Fabry Disease (FD), both Agalsidase alfa (Replagal, Shire HGT) and beta (Fabrazyme, Genzyme), is funded and monitored through a specific government program. Agalsidase beta supply has been rationed by Genzyme since 2009 due to manufacturing issues. Consequently, the Australian Fabry Disease Advisory Committee has treated patients on Agalsidase beta at 50% of their usual dose from mid-2009, with a further reduction to 30% for some patients from late 2009. To determine the clinical effect of Agalsidase beta dose reduction in the Australian FD patient cohort. A questionnaire assessing FD symptoms was administered to 40 patients on long-term ERT. Clinical data from The Fabry Registry for patients receiving Agalsidase alfa or beta, for at least 2 years prior to the time of enforced Agalsidase beta dose reduction, were reviewed. Disease burden and quality of life (QOL) were graded using the Disease Severity Scoring System, Mainz Severity Score Index, Brief Pain Inventory and Short Form 36 Health Survey at 2 years before dose reduction, at the time of dose reduction and at the most recent clinical review following dose reduction. Disease severity and QOL scores did not change between the ERT groups. Males on Agalsidase beta reported lower energy levels after dose reduction, while no change was reported by females on either product or by males on a stable dose of Agalsidase alfa. This study suggests that energy levels in male patients worsen after dose reduction of Agalsidase beta.

Efficacy of radiation safety glasses in interventional radiology.

PubMed

van Rooijen, Bart D; de Haan, Michiel W; Das, Marco; Arnoldussen, Carsten W K P; de Graaf, R; van Zwam, Wim H; Backes, Walter H; Jeukens, Cécile R L P N

2014-10-01

This study was designed to evaluate the reduction of the eye lens dose when wearing protective eyewear in interventional radiology and to identify conditions that optimize the efficacy of radiation safety glasses. The dose reduction provided by different models of radiation safety glasses was measured on an anthropomorphic phantom head. The influence of the orientation of the phantom head on the dose reduction was studied in detail. The dose reduction in interventional radiological practice was assessed by dose measurements on radiologists wearing either leaded or no glasses or using a ceiling suspended screen. The different models of radiation safety glasses provided a dose reduction in the range of a factor of 7.9-10.0 for frontal exposure of the phantom. The dose reduction was strongly reduced when the head is turned to the side relative to the irradiated volume. The eye closest to the tube was better protected due to side shielding and eyewear curvature. In clinical practice, the mean dose reduction was a factor of 2.1. Using a ceiling suspended lead glass shield resulted in a mean dose reduction of a factor of 5.7. The efficacy of radiation protection glasses depends on the orientation of the operator's head relative to the irradiated volume. Glasses can offer good protection to the eye under clinically relevant conditions. However, the performance in clinical practice in our study was lower than expected. This is likely related to nonoptimized room geometry and training of the staff as well as measurement methodology.

Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

PubMed

Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

2011-05-01

The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

Radiation dose reduction efficiency of buildings after the accident at the Fukushima Daiichi Nuclear Power Station.

PubMed

Monzen, Satoru; Hosoda, Masahiro; Osanai, Minoru; Tokonami, Shinji

2014-01-01

Numerous radionuclides were released from the Fukushima Daiichi Nuclear Power Station (F1-NPS) in Japan following the magnitude 9.0 earthquake and tsunami on March 11, 2011. Local residents have been eager to calculate their individual radiation exposure. Thus, absorbed dose rates in the indoor and outdoor air at evacuation sites in the Fukushima Prefecture were measured using a gamma-ray measuring devices, and individual radiation exposure was calculated by assessing the radiation dose reduction efficiency (defined as the ratio of absorbed dose rate in the indoor air to the absorbed dose rate in the outdoor air) of wood, aluminum, and reinforced concrete buildings. Between March 2011 and July 2011, dose reduction efficiencies of wood, aluminum, and reinforced concrete buildings were 0.55 ± 0.04, 0.15 ± 0.02, and 0.19 ± 0.04, respectively. The reduction efficiency of wood structures was 1.4 times higher than that reported by the International Atomic Energy Agency. The efficiency of reinforced concrete was similar to previously reported values, whereas that of aluminum structures has not been previously reported. Dose reduction efficiency increased in proportion to the distance from F1-NPS at 8 of the 18 evacuation sites. Time variations did not reflect dose reduction efficiencies at evacuation sites although absorbed dose rates in the outdoor air decreased. These data suggest that dose reduction efficiency depends on structure types, levels of contamination, and evacuee behaviors at evacuation sites.

Aripiprazole and Risperidone for Treatment of Methamphetamine-Associated Psychosis in Chinese Patients.

PubMed

Wang, Gang; Zhang, Yao; Zhang, Sheng; Chen, Huijing; Xu, Zaifeng; Schottenfeld, Richard S; Hao, Wei; Chawarski, Marek Cezary

2016-03-01

We evaluated tolerability and efficacy of aripiprazole and risperidone for treatment of methamphetamine (METH) associated psychotic symptoms in China. Patients with acute METH-associated psychotic symptoms (N=42) and with Positive and Negative Syndrome Scale (PANSS) total score between 60 and 120 were randomized to aripiprazole (initial dose 5-10mg per day followed by flexible doses 5-15 mg per day) or risperidone (initial dose 2-4 mg per day followed by flexible doses 4-6 mg per day) from day 3 to 25 of inpatient hospital stay. Outcome measures included PANSS and Clinical Global Impressions-Severity of Illness scale (CGI-S), METH craving Visual Analogue Scale (VAS), Simpson Angus Scale (SAS), Barnes Assessments Akathasia Rating Scale (BARS), and self-reported adverse effects evaluated during treatment. Retention was evaluated using Kaplan-Meier survival analysis and the MIXED models procedure was used to compare the groups on measures of psychotic and extra-pyramidal symptoms. Patients in both aripiprazole and risperidone groups showed statistically significant reductions in psychotic symptomatology from baseline during treatment (p<0.001) with no statistically significant differences between the treatment groups (p=0.73 and p=0.15, respectively). Risperidone-treated patients reported significantly greater METH craving reductions (p<0.001). Overall, 71% of patients completed the entire study, but the aripiprazole group had a significantly lower retention than the risperidone group (p=0.007), primarily due to medication related adverse effects. Aripiprazole-treated patients also had significantly more akathisia (p=0.03) and agitation (p=0.02) than risperidone-treated patients. Patients in both groups who tolerated their medications and completed the entire study achieved comparable reductions of psychotic symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

SU-E-T-396: Dosimetric Accuracy of Proton Therapy for Patients with Metal Implants in CT Scans Using Metal Deletion Technique (MDT) Artifacts Reduction

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

Li, X; Kantor, M; Zhu, X

2014-06-01

Purpose: To evaluate the dosimetric accuracy for proton therapy patients with metal implants in CT using metal deletion technique (MDT) artifacts reduction. Methods: Proton dose accuracies under CT metal artifacts were first evaluated using a water phantom with cylindrical inserts of different materials (titanium and steel). Ranges and dose profiles along different beam angles were calculated using treatment planning system (Eclipse version 8.9) on uncorrected CT, MDT CT, and manually-corrected CT, where true Hounsfield units (water) were assigned to the streak artifacts. In patient studies, the treatment plans were developed on manually-corrected CTs, then recalculated on MDT and uncorrected CTs.more » DVH indices were compared between the dose distributions on all the CTs. Results: For water phantom study with 1/2 inch titanium insert, the proton range differences estimated by MDT CT were with 1% for all beam angles, while the range error can be up to 2.6% for uncorrected CT. For the study with 1 inch stainless steel insert, the maximum range error calculated by MDT CT was 1.09% among all the beam angles compared with maximum range error with 4.7% for uncorrected CT. The dose profiles calculated on MDT CTs for both titanium and steel inserts showed very good agreements with the ones calculated on manually-corrected CTs, while large dose discrepancies calculated using uncorrected CTs were observed in the distal end region of the proton beam. The patient study showed similar dose distribution and DVHs for organs near the metal artifacts recalculated on MDT CT compared with the ones calculated on manually-corrected CT, while the differences between uncorrected and corrected CTs were much pronounced. Conclusion: In proton therapy, large dose error could occur due to metal artifact. The MDT CT can be used for proton dose calculation to achieve similar dose accuracy as the current clinical practice using manual correction.« less

TH-E-BRF-01: Exploiting Tumor Shrinkage in Split-Course Radiotherapy

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

Unkelbach, J; Craft, D; Hong, T

2014-06-15

Purpose: In split-course radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated by radiobiological considerations. However, using modern image-guidance, it also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. In this work, we consider the optimal design of split-course treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. Methods: We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cellmore » repopulation. The design of splitcourse radiotherapy is formulated as a mathematical optimization problem in which the total dose to the liver is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. Results: We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one third of the dose should be delivered in the first stage. The projected benefit of split-course treatments in terms of liver sparing depends on model assumptions. However, the model predicts large liver dose reductions by more than a factor of two for plausible model parameters. Conclusion: The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at split-course radiotherapy for selected disease sites where substantial tumor regression translates into reduced target volumes.« less

Comparative pharmacodynamics of the new fluoroquinolone ABT492 and ciprofloxacin with Escherichia coli and Pseudomonas aeruginosa in an in vitro dynamic model.

PubMed

Zinner, Stephen H; Vostrov, Sergey N; Alferova, Irene V; Lubenko, Irene Yu; Portnoy, Yury A; Firsov, Alexander A

2004-08-01

The killing kinetics of Escherichia coli and Pseudomonas aeruginosa were compared when exposed to ABT492 and ciprofloxacin. E. coli ATCC 25922 and a clinical isolate of P. aeruginosa 4226 were exposed to ABT492 (single dose) and ciprofloxacin (two 12 h doses) at the ratios of area under the curve (AUC) to MIC varying from 60 to 480 h and at clinically achievable AUC/MIC ratios of ABT492 (1,740 and 140 h, respectively) and ciprofloxacin (2,200 and 120 h, respectively) that correspond to a 400 mg dose of ABT492 and two 500 mg doses of ciprofloxacin. In addition, a double dose of ABT492 (800 mg; AUC/MIC 280 h) and two 12 h doses of ABT492 (2 x 400 mg) were used with P. aeruginosa. Maximal reductions in the starting inoculum of E. coli and P. aeruginosa were greater with ABT492 than with ciprofloxacin at a given AUC/MIC ratio (60-480 h), whereas the times to regrowth were shorter with ABT492. A specific AUC/MIC relationship of the antimicrobial effect was inherent in each quinolone-pathogen pair. With both E. coli and P. aeruginosa, AUC/MIC plots of the area between the control growth and the time-kill curves (I(E)) were steeper for ciprofloxacin than ABT492 and they were species-independent. The effect of ABT492 on E. coli at the clinically achievable AUC/MIC ratio (1740h) was more pronounced than the respective AUC/MIC of ciprofloxacin (2,200 h). With P. aeruginosa, a 140 h AUC/MIC of ABT492 (400 mg as a single dose) provided 1.8-fold less effect than a 120 h AUC/MIC of ciprofloxacin (2 x 500 mg). However, two 12 h doses of ABT492 (AUC/MIC 2 x 140 h) but not a double single dose (800 mg) were more efficient than ciprofloxacin. These findings predict comparable efficacies of clinically achievable AUC/MICs of ABT492 and ciprofloxacin against E. coli (q.d. versus b.i.d. quinolone dosing) and P. aeruginosa at b.i.d. but not at q.d. ABT492.

Numerical study and ex vivo assessment of HIFU treatment time reduction through optimization of focal point trajectory

NASA Astrophysics Data System (ADS)

Grisey, A.; Yon, S.; Pechoux, T.; Letort, V.; Lafitte, P.

2017-03-01

Treatment time reduction is a key issue to expand the use of high intensity focused ultrasound (HIFU) surgery, especially for benign pathologies. This study aims at quantitatively assessing the potential reduction of the treatment time arising from moving the focal point during long pulses. In this context, the optimization of the focal point trajectory is crucial to achieve a uniform thermal dose repartition and avoid boiling. At first, a numerical optimization algorithm was used to generate efficient trajectories. Thermal conduction was simulated in 3D with a finite difference code and damages to the tissue were modeled using the thermal dose formula. Given an initial trajectory, the thermal dose field was first computed, then, making use of Pontryagin's maximum principle, the trajectory was iteratively refined. Several initial trajectories were tested. Then, an ex vivo study was conducted in order to validate the efficicency of the resulting optimized strategies. Single pulses were performed at 3MHz on fresh veal liver samples with an Echopulse and the size of each unitary lesion was assessed by cutting each sample along three orthogonal planes and measuring the dimension of the whitened area based on photographs. We propose a promising approach to significantly shorten HIFU treatment time: the numerical optimization algorithm was shown to provide a reliable insight on trajectories that can improve treatment strategies. The model must now be improved in order to take in vivo conditions into account and extensively validated.

Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

PubMed

St Louis, Erik K; Louis, Erik K

2009-06-01

The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

Cholesterol-lowering Action of BNA-based Antisense Oligonucleotides Targeting PCSK9 in Atherogenic Diet-induced Hypercholesterolemic Mice.

PubMed

Yamamoto, Tsuyoshi; Harada-Shiba, Mariko; Nakatani, Moeka; Wada, Shunsuke; Yasuhara, Hidenori; Narukawa, Keisuke; Sasaki, Kiyomi; Shibata, Masa-Aki; Torigoe, Hidetaka; Yamaoka, Tetsuji; Imanishi, Takeshi; Obika, Satoshi

2012-05-15

Recent findings in molecular biology implicate the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in low-density lipoprotein receptor (LDLR) protein regulation. The cholesterol-lowering potential of anti-PCSK9 antisense oligonucleotides (AONs) modified with bridged nucleic acids (BNA-AONs) including 2',4'-BNA (also called as locked nucleic acid (LNA)) and 2',4'-BNA(NC) chemistries were demonstrated both in vitro and in vivo. An in vitro transfection study revealed that all of the BNA-AONs induce dose-dependent reductions in PCSK9 messenger RNA (mRNA) levels concomitantly with increases in LDLR protein levels. BNA-AONs were administered to atherogenic diet-fed C57BL/6J mice twice weekly for 6 weeks; 2',4'-BNA-AON that targeted murine PCSK9 induced a dose-dependent reduction in hepatic PCSK9 mRNA and LDL cholesterol (LDL-C); the 43% reduction of serum LDL-C was achieved at a dose of 20 mg/kg/injection with only moderate increases in toxicological indicators. In addition, the serum high-density lipoprotein cholesterol (HDL-C) levels increased. These results support antisense inhibition of PCSK9 as a potential therapeutic approach. When compared with 2',4'-BNA-AON, 2',4'-BNA(NC)-AON showed an earlier LDL-C-lowering effect and was more tolerable in mice. Our results validate the optimization of 2',4'-BNA(NC)-based anti-PCSK9 antisense molecules to produce a promising therapeutic agent for the treatment of hypercholesterolemia.

Effect of leaded glasses and thyroid shielding on cone beam CT radiation dose in an adult female phantom

PubMed Central

Goren, AD; Prins, RD; Dauer, LT; Quinn, B; Al-Najjar, A; Faber, RD; Patchell, G; Branets, I; Colosi, DC

2013-01-01

Objectives: This study aims to demonstrate the effectiveness of leaded glasses in reducing the lens of eye dose and of lead thyroid collars in reducing the dose to the thyroid gland of an adult female from dental cone beam CT (CBCT). The effect of collimation on the radiation dose in head organs is also examined. Methods: Dose measurements were conducted by placing optically stimulated luminescent dosemeters in an anthropomorphic female phantom. Eye lens dose was measured by placing a dosemeter on the anterior surface of the phantom eye location. All exposures were performed on one commercially available dental CBCT machine, using selected collimation and exposure techniques. Each scan technique was performed without any lead shielding and then repeated with lead shielding in place. To calculate the percent reduction from lead shielding, the dose measured with lead shielding was divided by the dose measured without lead shielding. The percent reduction from collimation was calculated by comparing the dose measured with collimation to the dose measured without collimation. Results: The dose to the internal eye for one of the scans without leaded glasses or thyroid shield was 0.450 cGy and with glasses and thyroid shield was 0.116 cGy (a 74% reduction). The reduction to the lens of the eye was from 0.396 cGy to 0.153 cGy (a 61% reduction). Without glasses or thyroid shield, the thyroid dose was 0.158 cGy; and when both glasses and shield were used, the thyroid dose was reduced to 0.091 cGy (a 42% reduction). Conclusions: Collimation alone reduced the dose to the brain by up to 91%, with a similar reduction in other organs. Based on these data, leaded glasses, thyroid collars and collimation minimize the dose to organs outside the field of view. PMID:23412460

Influence of Al³⁺ addition on the flocculation and sedimentation of activated sludge: comparison of single and multiple dosing patterns.

PubMed

Wen, Yue; Zheng, Wanlin; Yang, Yundi; Cao, Asheng; Zhou, Qi

2015-05-15

In this study, the flocculation and sedimentation performance of activated sludge (AS) with single and multiple dosing of trivalent aluminum (Al(3+)) were studied. The AS samples were cultivated in sequencing batch reactors at 22 °C. The dosages of Al(3+) were 0.00, 0.125, 0.5, 1.0, and 1.5 meq/L for single dosing, and 0.1 meq/L for multiple dosing. Under single dosing conditions, as Al(3+) dosage increased, the zeta potential, total interaction energy, and effluent turbidity decreased, whereas the sludge volume index (SVI) increased, indicating that single Al(3+) dosing could enhance sludge flocculation, but deteriorate sedimentation. By comparison, adding an equal amount of Al(3+) through multiple dosing achieved a similar reduction in turbidity, but the zeta potential was higher, while the loosely bound extracellular polymeric substances (LB-EPS) content and SVI remarkably declined. Although the difference in the flocculation performances between the two dosing patterns was not significant, the underlying mechanisms were quite distinct: the interaction energy played a more important role under single dosing conditions, whereas multiple dosing was more effective in reducing the EPS content. Multiple dosing, which allows sufficient time for sludge restructuring and floc aggregation, could simultaneously optimize sludge flocculation and sedimentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.

PubMed

Oritani, Kenji; Okamoto, Shinichiro; Tauchi, Tetsuzo; Saito, Shigeki; Ohishi, Kohshi; Handa, Hiroshi; Takenaka, Katsuto; Gopalakrishna, Prashanth; Amagasaki, Taro; Ito, Kazuo; Akashi, Koichi

2015-03-01

Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated rapid and durable improvements in splenomegaly and symptoms and a survival benefit in 2 phase 3 trials in patients with myelofibrosis. Ruxolitinib was well tolerated and effectively reduced splenomegaly and symptom burden in Asian patients with myelofibrosis in the Asian multinational, phase 2 Study A2202. We present a subset analysis of Japanese patients (n = 30) in Study A2202. At data cutoff, 22 patients were ongoing; 8 discontinued, mainly due to adverse events (n = 4). At week 24, 33 % of patients achieved ≥35 % reduction from baseline in spleen volume; 56.0 % achieved ≥50 % reduction from baseline in total symptom score, as measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0. The most common adverse events were anemia (63 %), thrombocytopenia (40 %), nasopharyngitis (37 %), decreased platelet counts (30 %), and diarrhea (30 %). Dose reductions or interruptions due to hemoglobin decreases were more frequent in Japanese patients; no loss of efficacy and no discontinuations due to hematologic abnormalities were observed. Ruxolitinib was well tolerated in Japanese patients and provided substantial reductions in splenomegaly and myelofibrosis-related symptoms similar to those observed in the overall Asian population and phase 3 COMFORT studies.

Fetal shielding combined with state of the art CT dose reduction strategies during maternal chest CT.

PubMed

Chatterson, Leslie C; Leswick, David A; Fladeland, Derek A; Hunt, Megan M; Webster, Stephen; Lim, Hyun

2014-07-01

Custom bismuth-antimony shields were previously shown to reduce fetal dose by 53% on an 8DR (detector row) CT scanner without dynamic adaptive section collimation (DASC), automatic tube current modulation (ATCM) or adaptive statistical iterative reconstruction (ASiR). The purpose of this study is to compare the effective maternal and average fetal organ dose reduction both with and without bismuth-antimony shields on a 64DR CT scanner using DASC, ATCM and ASiR during maternal CTPA. A phantom with gravid prosthesis and a bismuth-antimony shield were used. Thermoluminescent dosimeters (TLDs) measured fetal radiation dose. The average fetal organ dose and effective maternal dose were determined using 100 kVp, scanning from the lung apices to the diaphragm utilizing DASC, ATCM and ASiR on a 64DR CT scanner with and without shielding in the first and third trimester. Isolated assessment of DASC was done via comparing a new 8DR scan without DASC to a similar scan on the 64DR with DASC. Average third trimester unshielded fetal dose was reduced from 0.22 mGy ± 0.02 on the 8DR to 0.13 mGy ± 0.03 with the conservative 64DR protocol that included 30% ASiR, DASC and ATCM (42% reduction, P<0.01). Use of a shield further reduced average third trimester fetal dose to 0.04 mGy ± 0.01 (69% reduction, P<0.01). The average fetal organ dose reduction attributable to DASC alone was modest (6% reduction from 0.17 mGy ± 0.02 to 0.16 mGy ± 0.02, P=0.014). First trimester fetal organ dose on the 8DR protocol was 0.07 mGy ± 0.03. This was reduced to 0.05 mGy ± 0.03 on the 64DR protocol without shielding (30% reduction, P=0.009). Shields further reduced this dose to below accurately detectable levels. Effective maternal dose was reduced from 4.0 mSv on the 8DR to 2.5 mSv on the 64DR scanner using the conservative protocol (38% dose reduction). ASiR, ATCM and DASC combined significantly reduce effective maternal and fetal organ dose during CTPA. Shields continue to be an effective means of fetal dose reduction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Factors associated with efficacy of an ibuprofen/pseudoephedrine combination drug in pharmacy customers with common cold symptoms.

PubMed

Klimek, Ludger; Schumacher, Helmut; Schütt, Tanja; Gräter, Heidemarie; Mueck, Tobias; Michel, Martin C

2017-02-01

The aim of this study was to explore factors affecting efficacy of treatment of common cold symptoms with an over-the-counter ibuprofen/pseudoephedrine combination product. Data from an anonymous survey among 1770 pharmacy customers purchasing the combination product for treatment of own common cold symptoms underwent post-hoc descriptive analysis. Scores of symptoms typically responsive to ibuprofen (headache, pharyngeal pain, joint pain and fever), typically responsive to pseudoephedrine (congested nose, congested sinus and runny nose), considered non-specific (sneezing, fatigue, dry cough, cough with expectoration) and comprising all 11 symptoms were analysed. Multiple regression analysis was applied to explore factors associated with greater reduction in symptom intensity or greater probability of experiencing a symptom reduction of at least 50%. After intake of first dose of medication, typically ibuprofen-sensitive, pseudoephedrine-responsive, non-specific and total symptoms were reduced by 60.0%, 46.3%, 45.4% and 52.8%, respectively. A symptom reduction of at least 50% was reported by 73.6%, 55.1%, 50.9% and 61.6% of participants, respectively. A high baseline score was associated with greater reductions in symptom scores but smaller probability of achieving an improvement of at least 50%. Across both multiple regression approaches, two tablets at first dosing were more effective than one and (except for ibuprofen-sensitive symptoms) starting treatment later than day 2 of the cold was generally less effective. Efficacy of an ibuprofen/pseudoephedrine combination in the treatment of common cold symptoms was dose-dependent and greatest when treatment started within the first 2 days after onset of symptoms. © 2016 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

In vitro evaluation of a new iterative reconstruction algorithm for dose reduction in coronary artery calcium scoring

PubMed Central

Allmendinger, Thomas; Kunz, Andreas S; Veyhl-Wichmann, Maike; Ergün, Süleyman; Bley, Thorsten A; Petritsch, Bernhard

2017-01-01

Background Coronary artery calcium (CAC) scoring is a widespread tool for cardiac risk assessment in asymptomatic patients and accompanying possible adverse effects, i.e. radiation exposure, should be as low as reasonably achievable. Purpose To evaluate a new iterative reconstruction (IR) algorithm for dose reduction of in vitro coronary artery calcium scoring at different tube currents. Material and Methods An anthropomorphic calcium scoring phantom was scanned in different configurations simulating slim, average-sized, and large patients. A standard calcium scoring protocol was performed on a third-generation dual-source CT at 120 kVp tube voltage. Reference tube current was 80 mAs as standard and stepwise reduced to 60, 40, 20, and 10 mAs. Images were reconstructed with weighted filtered back projection (wFBP) and a new version of an established IR kernel at different strength levels. Calcifications were quantified calculating Agatston and volume scores. Subjective image quality was visualized with scans of an ex vivo human heart. Results In general, Agatston and volume scores remained relatively stable between 80 and 40 mAs and increased at lower tube currents, particularly in the medium and large phantom. IR reduced this effect, as both Agatston and volume scores decreased with increasing levels of IR compared to wFBP (P < 0.001). Depending on selected parameters, radiation dose could be lowered by up to 86% in the large size phantom when selecting a reference tube current of 10 mAs with resulting Agatston levels close to the reference settings. Conclusion New iterative reconstruction kernels may allow for reduction in tube current for established Agatston scoring protocols and consequently for substantial reduction in radiation exposure. PMID:28607763

Reduction of cardiac and pulmonary complication probabilities after breathing adapted radiotherapy for breast cancer

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

Korreman, Stine S.; Pedersen, Anders N.; Aarup, Lasse Rye

Purpose: Substantial reductions of cardio-pulmonary radiation doses can be achieved using voluntary deep inspiration breath-hold (DIBH) or free breathing inspiration gating (IG) in radiotherapy after conserving surgery for breast cancer. The purpose of this study is to evaluate the radiobiological implications of such dosimetric benefits. Methods and Materials: Patients from previously reported studies were pooled for a total of 33 patients. All patients underwent DIBH and free breathing (FB) scans, and 17 patients underwent an additional IG scan. Tangential conformal treatment plans covering the remaining breast, internal mammary, and periclavicular nodes were optimized for each scan, prescription dose 48 Gy.more » Normal tissue complication probabilities were calculated using the relative seriality model for the heart, and the model proposed by Burman et al. for the lung. Results: Previous computed tomography studies showed that both voluntary DIBH and IG provided reduction of the lung V{sub 5} (relative volume receiving more than 50% of prescription dose) on the order of 30-40%, and a 80-90% reduction of the heart V{sub 5} for left-sided cancers. Corresponding pneumonitis probability of 28.1% (range, 0.7-95.6%) for FB could be reduced to 2.6% (range, 0.1-40.1%) for IG, and 4.3% (range, 0.1-59%) for DIBH. The cardiac mortality probability could be reduced from 4.8% (range, 0.1-23.4%) in FB to 0.5% (range, 0.1-2.6%) for IG and 0.1% (range, 0-3.0%) for DIBH. Conclusions: Remarkable potential is shown for simple voluntary DIBH and free breathing IG to reduce the risk of both cardiac mortality and pneumonitis for the common technique of adjuvant tangential breast irradiation.« less

Australasian trends in intra-aortic balloon counterpulsation weaning: results of a postal survey.

PubMed

Lewis, Peter A; Mullany, Daniel V; Courtney, Mary; Coyer, Fiona

2006-12-01

To generate baseline data describing Australasian intra-aortic balloon counterpulsation (IABP) weaning practice. A five-part questionnaire was mailed in April 2005 to all 192 intensive care units in Australia and New Zealand. 116 ICUs responded (response rate, 60%), and 54 reported using IABP. Most of the 54 were in hospitals which were public government-funded (65%), had between 100 and 500 beds (69%), and treated a minimum of 11 patients annually with IABP (60%). The most common method of withdrawing IABP support was ratio reduction alone (61%). ICUs most likely to undertake ratio weaning were higherend users of IABP (> 20 cases per annum) (P = 0.04). Other weaning practices involved a combination of ratio followed by volume reduction (17%), volume then ratio (11%), and volume only (4%). Approaching statistical significance, ratio reduction weaning less frequently required IABP reinsertion or inotropic increase after balloon removal (P = 0.07). ICUs with documented weaning policies were less likely to require IABP reinsertion or inotropic increase after balloon removal (P = 0.06). Criteria considered important before IABP weaning or removal were: blood pressure (92%); heart rate (76%); pulmonary artery wedge pressure (59%); noradrenaline dose (78%); adrenaline dose (57%); and dobutamine dose (57%). Ninety per cent of ICUs reported increasing inotropes after balloon removal only rarely (1:50 patients) or occasionally (1:10 patients), while 87% of ICUs reported never needing to reinsert the balloon or only rarely. The Australasian approach to IABP weaning is eclectic. While ratio reduction weaning appears the most successful manner of support withdrawal, it may be a consequence of a volume-outcome relationship, with high- end users achieving better results through IABP familiarity.

Impact of Intravenous Lysine Acetylsalicylate Versus Oral Aspirin on Prasugrel-Inhibited Platelets: Results of a Prospective, Randomized, Crossover Study (the ECCLIPSE Trial).

PubMed

Vivas, David; Martín, Agustín; Bernardo, Esther; Ortega-Pozzi, María Aranzazu; Tirado, Gabriela; Fernández, Cristina; Vilacosta, Isidre; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

2015-05-01

Prasugrel and ticagrelor, new P2Y12-adenosine diphosphate receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events compared with clopidogrel in patients with an acute coronary syndrome. However, evidence is lacking about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared with oral aspirin on prasugrel-inhibited platelets. This was a prospective, randomized, single-center, open, 2-period crossover platelet function study conducted in 30 healthy volunteers. Subjects were randomly assigned to receive a loading dose of intravenous LA 450 mg plus oral prasugrel 60 mg or loading dose of aspirin 300 mg plus prasugrel 60 mg orally in a crossover fashion after a 2-week washout period between treatments. Platelet function was evaluated at baseline, 30 minutes, 1 h, 4 h, and 24 h using light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation. The primary end point of the study, inhibition of platelet aggregation after arachidonic acid 1.5 mmol/L at 30 minutes, was significantly higher in subjects treated with LA compared with aspirin: 85.3% versus 44.3%, respectively, P=0.003. This differential effect was observed at 1 hour (P=0.002) and 4 hours (P=0.048), but not at 24 hours. Subjects treated with LA presented less variability and faster and greater inhibition of platelet aggregation with arachidonic acid compared with aspirin. The administration of intravenous LA resulted in a significant reduction of platelet reactivity compared with oral aspirin on prasugrel-inhibited platelets. Loading dose of LA achieves an earlier platelet inhibition and with less variability than aspirin. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02243137. © 2015 American Heart Association, Inc.

Scoping studies of shielding to reduce the shutdown dose rates in the ITER ports

NASA Astrophysics Data System (ADS)

Juárez, R.; Guirao, J.; Pampin, R.; Loughlin, M.; Polunovskiy, E.; Le Tonqueze, Y.; Bertalot, L.; Kolsek, A.; Ogando, F.; Udintsev, V.; Walsh, M.

2018-07-01

The planned in situ maintenance tasks in the ITER port interspace are fundamental to ensure the operation of equipment to control, evaluate and optimize the plasma performance during the entire facility lifetime. They are subject to a limit of shutdown dose rates (SDDR) of 100 µSv h‑1 after 106 s of cooling time, which is nowadays a design driver for the port plugs as well as the application of ALARA. Three conceptual shielding proposals outside the ITER ports are studied in this work to support the achievement of this objective. Considered one by one, they offer reductions ranging from 25% to 50%, which are rather significant. This paper shows that, by combining these shields, the SDDR as low as 57Δ µSv h‑1 can be achieved with a local approach considering only radiation from one port (no cross-talk form neighboring ports). The locally evaluated SDDR are well below the limit which is an essential pre-requisite for achieving 100µSv h‑1 in a global analysis including all contributions. Further studies will have to deal with a realistic port plug design and the cross-talks from neighbour ports.

A high-resolution photon-counting breast CT system with tensor-framelet based iterative image reconstruction for radiation dose reduction

NASA Astrophysics Data System (ADS)

Ding, Huanjun; Gao, Hao; Zhao, Bo; Cho, Hyo-Min; Molloi, Sabee

2014-10-01

Both computer simulations and experimental phantom studies were carried out to investigate the radiation dose reduction with tensor framelet based iterative image reconstruction (TFIR) for a dedicated high-resolution spectral breast computed tomography (CT) based on a silicon strip photon-counting detector. The simulation was performed with a 10 cm-diameter water phantom including three contrast materials (polyethylene, 8 mg ml-1 iodine and B-100 bone-equivalent plastic). In the experimental study, the data were acquired with a 1.3 cm-diameter polymethylmethacrylate (PMMA) phantom containing iodine in three concentrations (8, 16 and 32 mg ml-1) at various radiation doses (1.2, 2.4 and 3.6 mGy) and then CT images were reconstructed using the filtered-back-projection (FBP) technique and the TFIR technique, respectively. The image quality between these two techniques was evaluated by the quantitative analysis on contrast-to-noise ratio (CNR) and spatial resolution that was evaluated using the task-based modulation transfer function (MTF). Both the simulation and experimental results indicated that the task-based MTF obtained from TFIR reconstruction with one-third of the radiation dose was comparable to that from the FBP reconstruction for low contrast target. For high contrast target, the TFIR was substantially superior to the FBP reconstruction in terms of spatial resolution. In addition, TFIR was able to achieve a factor of 1.6-1.8 increase in CNR, depending on the target contrast level. This study demonstrates that the TFIR can reduce the required radiation dose by a factor of two-thirds for a CT image reconstruction compared to the FBP technique. It achieves much better CNR and spatial resolution for high contrast target in addition to retaining similar spatial resolution for low contrast target. This TFIR technique has been implemented with a graphic processing unit system and it takes approximately 10 s to reconstruct a single-slice CT image, which can potentially be used in a future multi-slit multi-slice spiral CT system.

Dose reduction for abdominal and pelvic MDCT after change to graduated weight-based protocol for selecting quality reference tube current, peak kilovoltage, and slice collimation.

PubMed

Herts, Brian R; Baker, Mark E; Obuchowski, Nancy; Primak, Andrew; Schneider, Erika; Rhana, Harpreet; Dong, Frank

2013-06-01

The purpose of this article is to determine the decrease in volume CT dose index (CTDI(vol)) and dose-length product (DLP) achieved by switching from fixed quality reference tube current protocols with automatic tube current modulation to protocols adjusting the quality reference tube current, slice collimation, and peak kilovoltage according to patient weight. All adult patients who underwent CT examinations of the abdomen or abdomen and pelvis during 2010 using weight-based protocols who also underwent a CT examination in 2008 or 2009 using fixed quality reference tube current protocols were identified from the radiology information system. Protocol pages were electronically retrieved, and the CT model, examination date, scan protocol, CTDI(vol), and DLP were extracted from the DICOM header or by optical character recognition. There were 15,779 scans with dose records for 2700 patients. Changes in CTDI(vol) and DLP were compared only between examinations of the same patient and same CT system model for examinations performed in 2008 or 2009 and those performed in 2010. The final analysis consisted of 1117 comparisons in 1057 patients, and 1209 comparisons in 988 patients for CTDI(vol) and DLP, respectively. The change to a weight-based protocol resulted in a statistically significant reduction in CTDI(vol) and DLP on three MDCT system models (p < 0.001). The largest average CTDI(vol) decrease was 13.9%, and the largest average DLP decrease was 16.1% on a 64-MDCT system. Both the CTDI(vol) and DLP decreased the most for patients who weighed less than 250 lb (112.5 kg). Adjusting the CT protocol by selecting parameters according to patient weight is a viable method for reducing CT radiation dose. The largest reductions occurred in the patients weighing less than 250 lb.

A Complier Average Causal Effect Analysis of the Stimulant Reduction Intervention using Dosed Exercise Study.

PubMed

Carmody, Thomas; Greer, Tracy L; Walker, Robrina; Rethorst, Chad D; Trivedi, Madhukar H

2018-06-01

Exercise is a promising treatment for substance use disorders, yet an intention-to-treat analysis of a large, multi-site study found no reduction in stimulant use for exercise versus health education. Exercise adherence was sub-optimal; therefore, secondary post-hoc complier average causal effects (CACE) analysis was conducted to determine the potential effectiveness of adequately dosed exercise. The STimulant use Reduction Intervention using Dosed Exercise study was a randomized controlled trial comparing a 12 kcal/kg/week (KKW) exercise dose versus a health education control conducted at nine residential substance use treatment settings across the U.S. that are affiliated with the National Drug Abuse Treatment Clinical Trials Network. Participants were sedentary but medically approved for exercise, used stimulants within 30 days prior to study entry, and received a DSM-IV stimulant abuse or dependence diagnosis within the past year. A CACE analysis adjusted to include only participants with a minimum threshold of adherence (at least 8.3 KKW) and using a negative-binomial hurdle model focused on 218 participants who were 36.2% female, mean age 39.4 years ( SD =11.1), and averaged 13.0 ( SD =9.2) stimulant use days in the 30 days before residential treatment. The outcome was days of stimulant use as assessed by the self-reported TimeLine Follow Back and urine drug screen results. The CACE-adjusted analysis found a significantly lower probability of relapse to stimulant use in the exercise group versus the health education group (41.0% vs. 55.7%, p <.01) and significantly lower days of stimulant use among those who relapsed (5.0 days vs. 9.9 days, p <.01). The CACE adjustment revealed significant, positive effects for exercise. Further research is warranted to develop strategies for exercise adherence that can ensure achievement of an exercise dose sufficient to produce a significant treatment effect.

Low Dose MDCT with Tube Current Modulation: Role in Detection of Urolithiasis and Patient Effective Dose Reduction

PubMed Central

Kakkar, Chandan; Sripathi, Smiti; Parakh, Anushri; Shrivastav, Rajendra

2016-01-01

Introduction Urolithiasis is one of the major, recurring problem in young individuals and CT being the commonest diagnostic modality used. In order to reduce the radiation dose to the patient who are young and as stone formation is a recurring process; one of the simplest way would be, low dose CT along with tube current modulation. Aim Aim of this study was to compare the sensitivity and specificity of low dose (70mAs) with standard dose (250mAs) protocol in detecting urolithiasis and to define the tube current and mean effective patient dose by these protocols. Materials and Methods A prospective study was conducted in 200 patients over a period of 2 years with acute flank pain presentation. CT was performed in 100 cases with standard dose and another 100 with low dose protocol using tube current modulation. Sensitivity and specificity for calculus detection, percentage reduction of dose and tube current with low dose protocol was calculated. Results Urolithiasis was detected in 138 patients, 67 were examined by high dose and 71 were by low dose protocol. Sensitivity and Specificity of low dose protocol was 97.1% and 96.4% with similar results found in high BMI patients. Tube current modulation resulted in reduction of effective tube current by 12.17%. The mean effective patient dose for standard dose was 10.33 mSv whereas 2.92 mSv for low dose with 51.13–53.8% reduction in low dose protocol. Conclusion The study has reinforced that low-dose CT with tube current modulation is appropriate for diagnosis of urolithiasis with significant reduction in tube current and patient effective dose. PMID:27437322

Low Dose MDCT with Tube Current Modulation: Role in Detection of Urolithiasis and Patient Effective Dose Reduction.

PubMed

Koteshwar, Prakashini; Kakkar, Chandan; Sripathi, Smiti; Parakh, Anushri; Shrivastav, Rajendra

2016-05-01

Urolithiasis is one of the major, recurring problem in young individuals and CT being the commonest diagnostic modality used. In order to reduce the radiation dose to the patient who are young and as stone formation is a recurring process; one of the simplest way would be, low dose CT along with tube current modulation. Aim of this study was to compare the sensitivity and specificity of low dose (70mAs) with standard dose (250mAs) protocol in detecting urolithiasis and to define the tube current and mean effective patient dose by these protocols. A prospective study was conducted in 200 patients over a period of 2 years with acute flank pain presentation. CT was performed in 100 cases with standard dose and another 100 with low dose protocol using tube current modulation. Sensitivity and specificity for calculus detection, percentage reduction of dose and tube current with low dose protocol was calculated. Urolithiasis was detected in 138 patients, 67 were examined by high dose and 71 were by low dose protocol. Sensitivity and Specificity of low dose protocol was 97.1% and 96.4% with similar results found in high BMI patients. Tube current modulation resulted in reduction of effective tube current by 12.17%. The mean effective patient dose for standard dose was 10.33 mSv whereas 2.92 mSv for low dose with 51.13-53.8% reduction in low dose protocol. The study has reinforced that low-dose CT with tube current modulation is appropriate for diagnosis of urolithiasis with significant reduction in tube current and patient effective dose.

Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults.

PubMed

Min, Sherene; Sloan, Louis; DeJesus, Edwin; Hawkins, Trevor; McCurdy, Lewis; Song, Ivy; Stroder, Richard; Chen, Shuguang; Underwood, Mark; Fujiwara, Tamio; Piscitelli, Stephen; Lalezari, Jay

2011-09-10

To evaluate the antiviral activity, safety, pharmacokinetics, and pharmacokinetics/pharmacodynamics of dolutegravir (DTG), a next-generation HIV integrase inhibitor (INI), as short-term monotherapy. A phase IIa, randomized, double-blind, dose-ranging study. In this study, INI-naive, HIV-1-infected adults currently off antiretroviral therapy were randomized to receive DTG (2, 10, or 50 mg) or placebo once daily for 10 days in an eight active and two placebo randomization scheme per DTG dose. Placebo patients were pooled for the purpose of analysis. Thirty-five patients (n = 9 for DTG 2 and 10 mg, n = 10 for DTG 50 mg, and n = 7 for placebo) were enrolled. Baseline characteristics were similar across dose groups. Significant reductions in plasma HIV-1 RNA from baseline to day 11 were observed for all DTG dose groups compared with placebo (P < 0.001), with a mean decrease of 1.51-2.46 log(10) copies/ml. In addition, a well characterized dose-response relationship was observed for viral load decrease. Most patients (seven of 10, 70%) receiving DTG 50 mg achieved plasma HIV-1 RNA less than 50 copies/ml. The pharmacokinetic variability was low (coefficient of variation, range 25-50%). Plasma HIV-1 RNA reduction was best predicted by Cτ using an E(max) model. The most common adverse events were diarrhea, fatigue, and headache; the majority of adverse events were mild or moderate in severity. Dolutegravir demonstrated potent antiviral activity, good short-term tolerability, low pharmacokinetic variability, and a predictable pharmacokinetics/pharmacodynamics relationship, which support once-daily dosing without a pharmacokinetic booster in integrase-naive patients in future studies.

Synergistic interactions between paracetamol and oxcarbazepine in somatic and visceral pain models in rodents.

PubMed

Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

2010-04-01

Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components. The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid-induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis. Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50). The synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain.

Can image enhancement allow radiation dose to be reduced whilst maintaining the perceived diagnostic image quality required for coronary angiography?

PubMed Central

Joshi, Anuja; Gislason-Lee, Amber J; Keeble, Claire; Sivananthan, Uduvil M

2017-01-01

Objective: The aim of this research was to quantify the reduction in radiation dose facilitated by image processing alone for percutaneous coronary intervention (PCI) patient angiograms, without reducing the perceived image quality required to confidently make a diagnosis. Methods: Incremental amounts of image noise were added to five PCI angiograms, simulating the angiogram as having been acquired at corresponding lower dose levels (10–89% dose reduction). 16 observers with relevant experience scored the image quality of these angiograms in 3 states—with no image processing and with 2 different modern image processing algorithms applied. These algorithms are used on state-of-the-art and previous generation cardiac interventional X-ray systems. Ordinal regression allowing for random effects and the delta method were used to quantify the dose reduction possible by the processing algorithms, for equivalent image quality scores. Results: Observers rated the quality of the images processed with the state-of-the-art and previous generation image processing with a 24.9% and 15.6% dose reduction, respectively, as equivalent in quality to the unenhanced images. The dose reduction facilitated by the state-of-the-art image processing relative to previous generation processing was 10.3%. Conclusion: Results demonstrate that statistically significant dose reduction can be facilitated with no loss in perceived image quality using modern image enhancement; the most recent processing algorithm was more effective in preserving image quality at lower doses. Advances in knowledge: Image enhancement was shown to maintain perceived image quality in coronary angiography at a reduced level of radiation dose using computer software to produce synthetic images from real angiograms simulating a reduction in dose. PMID:28124572

Evaluation of various boluses in dose distribution for electron therapy of the chest wall with an inward defect

PubMed Central

Mahdavi, Hoda; Jabbari, Keyvan; Roayaei, Mahnaz

2016-01-01

Delivering radiotherapy to the postmastectomy chest wall can be achieved using matched electron fields. Surgical defects of the chest wall change the dose distribution of electrons. In this study, the improvement of dose homogeneity using simple, nonconformal techniques of thermoplastic bolus application on a defect is evaluated. The proposed phantom design improves the capability of film dosimetry for obtaining dose profiles of a patient's anatomical condition. A modeled electron field of a patient with a postmastectomy inward surgical defect was planned. High energy electrons were delivered to the phantom in various settings, including no bolus, a bolus that filled the inward defect (PB0), a uniform thickness bolus of 5 mm (PB1), and two 5 mm boluses (PB2). A reduction of mean doses at the base of the defect was observed by any bolus application. PB0 increased the dose at central parts of the defect, reduced hot areas at the base of steep edges, and reduced dose to the lung and heart. Thermoplastic boluses that compensate a defect (PB0) increased the homogeneity of dose in a fixed depth from the surface; adversely, PB2 increased the dose heterogeneity. This study shows that it is practical to investigate dose homogeneity profiles inside a target volume for various techniques of electron therapy. PMID:27051169

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

Brady, S; Shulkin, B

Purpose: To develop ultra-low dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultra-low doses (10–35 mAs). CT quantitation: noise, low-contrast resolution, and CT numbers for eleven tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% CTDIvol (0.39/3.64; mGy) radiation dose from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET images were reconstructed withmore » the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUVbw) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation organ dose, as derived from patient exam size specific dose estimate (SSDE), was converted to effective dose using the standard ICRP report 103 method. Effective dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative patient population dose reduction and noise control. Results: CT numbers were constant to within 10% from the non-dose reduced CTAC image down to 90% dose reduction. No change in SUVbw, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols reconstructed with ASiR and down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62%–86% (3.2/8.3−0.9/6.2; mSv). Noise magnitude in dose-reduced patient images increased but was not statistically different from pre dose-reduced patient images. Conclusion: Using ASiR allowed for aggressive reduction in CTAC dose with no change in PET reconstructed images while maintaining sufficient image quality for co-localization of hybrid CT anatomy and PET radioisotope uptake.« less

Dose and risk in diagnostic radiology: How big How little Lecture Number 16

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

Webster, E.W.

1992-01-01

This lecture is divided into two parts: dose and risk. The dose segment is technical and noncontroversial since it deals with straightforward measurements or calculations which do not depend on unproven hypotheses. Some conflicting contributions of low dose epidemiological studies to the appraisal of risk are briefly presented. Attention is focused on the following: dose reduction in radiography; dose reduction in fluoroscopy; limitations of dose reduction; estimated radiation risks for diagnostic radiology examinations; excess breast cancer following X-ray examinations for scoliosis; dose-response relation for human mammary cancer; lung cancer from protracted X-irradiation; leukemia and diagnostic X-ray exposure; and thyroid cancermore » after diagnostic dose of I-131.« less

Dosimetric Evaluation of Metal Artefact Reduction using Metal Artefact Reduction (MAR) Algorithm and Dual-energy Computed Tomography (CT) Method

NASA Astrophysics Data System (ADS)

Laguda, Edcer Jerecho

Purpose: Computed Tomography (CT) is one of the standard diagnostic imaging modalities for the evaluation of a patient's medical condition. In comparison to other imaging modalities such as Magnetic Resonance Imaging (MRI), CT is a fast acquisition imaging device with higher spatial resolution and higher contrast-to-noise ratio (CNR) for bony structures. CT images are presented through a gray scale of independent values in Hounsfield units (HU). High HU-valued materials represent higher density. High density materials, such as metal, tend to erroneously increase the HU values around it due to reconstruction software limitations. This problem of increased HU values due to metal presence is referred to as metal artefacts. Hip prostheses, dental fillings, aneurysm clips, and spinal clips are a few examples of metal objects that are of clinical relevance. These implants create artefacts such as beam hardening and photon starvation that distort CT images and degrade image quality. This is of great significance because the distortions may cause improper evaluation of images and inaccurate dose calculation in the treatment planning system. Different algorithms are being developed to reduce these artefacts for better image quality for both diagnostic and therapeutic purposes. However, very limited information is available about the effect of artefact correction on dose calculation accuracy. This research study evaluates the dosimetric effect of metal artefact reduction algorithms on severe artefacts on CT images. This study uses Gemstone Spectral Imaging (GSI)-based MAR algorithm, projection-based Metal Artefact Reduction (MAR) algorithm, and the Dual-Energy method. Materials and Methods: The Gemstone Spectral Imaging (GSI)-based and SMART Metal Artefact Reduction (MAR) algorithms are metal artefact reduction protocols embedded in two different CT scanner models by General Electric (GE), and the Dual-Energy Imaging Method was developed at Duke University. All three approaches were applied in this research for dosimetric evaluation on CT images with severe metal artefacts. The first part of the research used a water phantom with four iodine syringes. Two sets of plans, multi-arc plans and single-arc plans, using the Volumetric Modulated Arc therapy (VMAT) technique were designed to avoid or minimize influences from high-density objects. The second part of the research used projection-based MAR Algorithm and the Dual-Energy Method. Calculated Doses (Mean, Minimum, and Maximum Doses) to the planning treatment volume (PTV) were compared and homogeneity index (HI) calculated. Results: (1) Without the GSI-based MAR application, a percent error between mean dose and the absolute dose ranging from 3.4-5.7% per fraction was observed. In contrast, the error was decreased to a range of 0.09-2.3% per fraction with the GSI-based MAR algorithm. There was a percent difference ranging from 1.7-4.2% per fraction between with and without using the GSI-based MAR algorithm. (2) A range of 0.1-3.2% difference was observed for the maximum dose values, 1.5-10.4% for minimum dose difference, and 1.4-1.7% difference on the mean doses. Homogeneity indexes (HI) ranging from 0.068-0.065 for dual-energy method and 0.063-0.141 with projection-based MAR algorithm were also calculated. Conclusion: (1) Percent error without using the GSI-based MAR algorithm may deviate as high as 5.7%. This error invalidates the goal of Radiation Therapy to provide a more precise treatment. Thus, GSI-based MAR algorithm was desirable due to its better dose calculation accuracy. (2) Based on direct numerical observation, there was no apparent deviation between the mean doses of different techniques but deviation was evident on the maximum and minimum doses. The HI for the dual-energy method almost achieved the desirable null values. In conclusion, the Dual-Energy method gave better dose calculation accuracy to the planning treatment volume (PTV) for images with metal artefacts than with or without GE MAR Algorithm.

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

Hiller, Mauritius M.; Veinot, Kenneth G.; Easterly, Clay E.

In this study, methods are addressed to reduce the computational time to compute organ-dose rate coefficients using Monte Carlo techniques. Several variance reduction techniques are compared including the reciprocity method, importance sampling, weight windows and the use of the ADVANTG software package. For low-energy photons, the runtime was reduced by a factor of 10 5 when using the reciprocity method for kerma computation for immersion of a phantom in contaminated water. This is particularly significant since impractically long simulation times are required to achieve reasonable statistical uncertainties in organ dose for low-energy photons in this source medium and geometry. Althoughmore » the MCNP Monte Carlo code is used in this paper, the reciprocity technique can be used equally well with other Monte Carlo codes.« less

Bortezomib for antibody mediated rejection treatment: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City.

PubMed

Leyva, Sergio; Marino-Vázquez, Lluvia A; Reyes-Loaeza, Jorge A; Vega, Olynka; Uribe-Uribe, Norma; Alberú, Josefina; Morales-Buenrostro, Luis E

2009-01-01

The use of bortezomib as a treatment modality of AHR improved and stabilized graft function (clinical response) in the majority of patients. Its use in single dose, even combined with rituximab, does not seem to be useful to obtain a sustained clinical response neither to reduce HLAabs level. The use of 4 doses of bortezomib in days 1, 4, 7, and 10 (1.3 mg/m2 BSA each) plus plasmapheresis produced both a good clinical response and a reduction in DSA. Moving forward, it will necessary to define the long-term effectiveness of bortezomib and whether rituximab administration is indispensable to achieve this goal.

Disease activity guided dose reduction and withdrawal of adalimumab or etanercept compared with usual care in rheumatoid arthritis: open label, randomised controlled, non-inferiority trial.

PubMed

van Herwaarden, Noortje; van der Maas, Aatke; Minten, Michiel J M; van den Hoogen, Frank H J; Kievit, Wietske; van Vollenhoven, Ronald F; Bijlsma, Johannes W J; van den Bemt, Bart J F; den Broeder, Alfons A

2015-04-09

To evaluate whether a disease activity guided strategy of dose reduction of two tumour necrosis factor (TNF) inhibitors, adalimumab or etanercept, is non-inferior in maintaining disease control in patients with rheumatoid arthritis compared with usual care. Randomised controlled, open label, non-inferiority strategy trial. Two rheumatology outpatient clinics in the Netherlands, from December 2011 to May 2014. 180 patients with rheumatoid arthritis and low disease activity using adalimumab or etanercept; 121 allocated to the dose reduction strategy, 59 to usual care. Disease activity guided dose reduction (advice to stepwise increase the injection interval every three months, until flare of disease activity or discontinuation) or usual care (no dose reduction advice). Flare was defined as increase in DAS28-CRP (a composite score measuring disease activity) greater than 1.2, or increase greater than 0.6 and current score of at least 3.2. In the case of flare, TNF inhibitor use was restarted or escalated. Difference in proportions of patients with major flare (DAS28-CRP based flare longer than three months) between the two groups at 18 months, compared against a non-inferiority margin of 20%. Secondary outcomes included TNF inhibitor use at study end, functioning, quality of life, radiographic progression, and adverse events. Dose reduction of adalimumab or etanercept was non-inferior to usual care (proportion of patients with major flare at 18 months, 12% v 10%; difference 2%, 95% confidence interval -12% to 12%). In the dose reduction group, TNF inhibitor use could successfully be stopped in 20% (95% confidence interval 13% to 28%), the injection interval successfully increased in 43% (34% to 53%), but no dose reduction was possible in 37% (28% to 46%). Functional status, quality of life, relevant radiographic progression, and adverse events did not differ between the groups, although short lived flares (73% v 27%) and minimal radiographic progression (32% v 15%) were more frequent in dose reduction than usual care. A disease activity guided, dose reduction strategy of adalimumab or etanercept to treat rheumatoid arthritis is non-inferior to usual care with regard to major flaring, while resulting in the successful dose reduction or stopping in two thirds of patients.Trial registration Dutch trial register (www.trialregister.nl), NTR 3216. © van Herwaarden et al 2015.

Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer.

PubMed

Eisbruch, Avraham; Ship, Jonathan A; Dawson, Laura A; Kim, Hyungjin M; Bradford, Carol R; Terrell, Jeffrey E; Chepeha, Douglas B; Teknos, Theodore N; Hogikyan, Norman D; Anzai, Yoshimi; Marsh, Lon H; Ten Haken, Randall K; Wolf, Gregory T

2003-07-01

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is suggested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control.

Ultralow dose computed tomography attenuation correction for pediatric PET CT using adaptive statistical iterative reconstruction

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

Brady, Samuel L., E-mail: samuel.brady@stjude.org; Shulkin, Barry L.

2015-02-15

Purpose: To develop ultralow dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultralow doses (10–35 mA s). CT quantitation: noise, low-contrast resolution, and CT numbers for 11 tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% volume computed tomography dose index (0.39/3.64; mGy) from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET imagesmore » were reconstructed with the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUV{sub bw}) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative dose reduction and noise control. Results: CT numbers were constant to within 10% from the nondose reduced CTAC image for 90% dose reduction. No change in SUV{sub bw}, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols was found down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62% and 86% (3.2/8.3–0.9/6.2). Noise magnitude in dose-reduced patient images increased but was not statistically different from predose-reduced patient images. Conclusions: Using ASiR allowed for aggressive reduction in CT dose with no change in PET reconstructed images while maintaining sufficient image quality for colocalization of hybrid CT anatomy and PET radioisotope uptake.« less

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

Prikhodko, Vitaly Y; Pihl, Josh A; Toops, Todd J

Ethanol is a very effective reductant of nitrogen oxides (NOX) over silver/alumina (Ag/Al2O3) catalysts in lean exhaust environment. With the widespread availability of ethanol/gasoline-blended fuel in the USA, lean gasoline engines equipped with an Ag/Al2O3 catalyst have the potential to deliver higher fuel economy than stoichiometric gasoline engines and to increase biofuel utilization while meeting exhaust emissions regulations. In this work a pre-commercial 2 wt% Ag/Al2O3 catalyst was evaluated on a 2.0-liter BMW lean burn gasoline direct injection engine for the selective catalytic reduction (SCR) of NOX with ethanol/gasoline blends. The ethanol/gasoline blends were delivered via in-pipe injection upstream ofmore » the Ag/Al2O3 catalyst with the engine operating under lean conditions. A number of engine conditions were chosen to provide a range of temperatures and space velocities for the catalyst performance evaluations. High NOX conversions were achieved with ethanol/gasoline blends containing at least 50% ethanol; however, higher C1/N ratio was needed to achieve greater than 90% NOX conversion, which also resulted in significant HC slip. Temperature and HC dosing were important in controlling selectivity to NH3 and N2O. At high temperatures, NH3 and N2O yields increased with increased HC dosing. At low temperatures, NH3 yield was very low, however, N2O levels became significant. The ability to generate NH3 under lean conditions has potential for application of a dual SCR approach (HC SCR + NH3 SCR) to reduce fuel consumption needed for NOX reduction and/or increased NOX conversion, which is discussed in this work.« less

Clinical implementation of a knowledge based planning tool for prostate VMAT.

PubMed

Powis, Richard; Bird, Andrew; Brennan, Matthew; Hinks, Susan; Newman, Hannah; Reed, Katie; Sage, John; Webster, Gareth

2017-05-08

A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as "optimal" and "sub-optimal" by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. Plans identified as "sub-optimal" in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as "optimal" observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data.

Impact of database quality in knowledge-based treatment planning for prostate cancer.

PubMed

Wall, Phillip D H; Carver, Robert L; Fontenot, Jonas D

2018-03-13

This article investigates dose-volume prediction improvements in a common knowledge-based planning (KBP) method using a Pareto plan database compared with using a conventional, clinical plan database. Two plan databases were created using retrospective, anonymized data of 124 volumetric modulated arc therapy (VMAT) prostate cancer patients. The clinical plan database (CPD) contained planning data from each patient's clinically treated VMAT plan, which were manually optimized by various planners. The multicriteria optimization database (MCOD) contained Pareto-optimal plan data from VMAT plans created using a standardized multicriteria optimization protocol. Overlap volume histograms, incorporating fractional organ at risk volumes only within the treatment fields, were computed for each patient and used to match new patient anatomy to similar database patients. For each database patient, CPD and MCOD KBP predictions were generated for D 10 , D 30 , D 50 , D 65 , and D 80 of the bladder and rectum in a leave-one-out manner. Prediction achievability was evaluated through a replanning study on a subset of 31 randomly selected database patients using the best KBP predictions, regardless of plan database origin, as planning goals. MCOD predictions were significantly lower than CPD predictions for all 5 bladder dose-volumes and rectum D 50 (P = .004) and D 65 (P < .001), whereas CPD predictions for rectum D 10 (P = .005) and D 30 (P < .001) were significantly less than MCOD predictions. KBP predictions were statistically achievable in the replans for all predicted dose-volumes, excluding D 10 of bladder (P = .03) and rectum (P = .04). Compared with clinical plans, replans showed significant average reductions in D mean for bladder (7.8 Gy; P < .001) and rectum (9.4 Gy; P < .001), while maintaining statistically similar planning target volume, femoral head, and penile bulb dose. KBP dose-volume predictions derived from Pareto plans were more optimal overall than those resulting from manually optimized clinical plans, which significantly improved KBP-assisted plan quality. This work investigates how the plan quality of knowledge databases affects the performance and achievability of dose-volume predictions from a common knowledge-based planning approach for prostate cancer. Bladder and rectum dose-volume predictions derived from a database of standardized Pareto-optimal plans were compared with those derived from clinical plans manually designed by various planners. Dose-volume predictions from the Pareto plan database were significantly lower overall than those from the clinical plan database, without compromising achievability. Copyright © 2018 Elsevier Inc. All rights reserved.

Does Zika virus infection affect mosquito response to repellents?

PubMed Central

Leal, Walter S.; Barbosa, Rosângela M. R.; Zeng, Fangfang; Faierstein, Gabriel B.; Tan, Kaiming; Paiva, Marcelo H. S.; Guedes, Duschinka R. D.; Crespo, Mônica M.; Ayres, Constância F. J.

2017-01-01

The World Health Organization (WHO) recommends that people travelling to or living in areas with Zika virus (ZIKV) outbreaks or epidemics adopt prophylactic measures to reduce or eliminate mosquito bites, including the use of insect repellents. It is, however, unknown whether repellents are effective against ZIKV-infected mosquitoes, in part because of the ethical concerns related to exposing a human subject’s arm to infected mosquitoes in the standard arm-in-cage assay. We used a previously developed, human subject-free behavioural assay, which mimics a human subject to evaluate the top two recommended insect repellents. Our measurements showed that DEET provided significantly higher protection than picaridin provided against noninfected, host-seeking females of the southern house mosquito, Culex quinquefasciatus, and the yellow fever mosquito, Aedes aegypti. When tested at lower doses, we observed a significant reduction in DEET-elicited protection against ZIKV-infected yellow fever mosquitoes from old and recent laboratory colonies. The reduction in protection is more likely associated with aging than the virus infection and could be compensated by applying a 5x higher dose of DEET. A substantial protection against ZIKV-infected and old noninfected mosquitoes was achieved with 5% DEET, which corresponds approximately to a 30% dose in the conventional arm-in-cage assays. PMID:28205633

Reducing radiation dose to the female breast during CT coronary angiography: A simulation study comparing breast shielding, angular tube current modulation, reduced kV, and partial angle protocols using an unknown-location signal-detectability metric

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

Rupcich, Franco; Gilat Schmidt, Taly; Badal, Andreu

2013-08-15

Purpose: The authors compared the performance of five protocols intended to reduce dose to the breast during computed tomography (CT) coronary angiography scans using a model observer unknown-location signal-detectability metric.Methods: The authors simulated CT images of an anthropomorphic female thorax phantom for a 120 kV reference protocol and five “dose reduction” protocols intended to reduce dose to the breast: 120 kV partial angle (posteriorly centered), 120 kV tube-current modulated (TCM), 120 kV with shielded breasts, 80 kV, and 80 kV partial angle (posteriorly centered). Two image quality tasks were investigated: the detection and localization of 4-mm, 3.25 mg/ml and 1-mm,more » 6.0 mg/ml iodine contrast signals randomly located in the heart region. For each protocol, the authors plotted the signal detectability, as quantified by the area under the exponentially transformed free response characteristic curve estimator (A-caret{sub FE}), as well as noise and contrast-to-noise ratio (CNR) versus breast and lung dose. In addition, the authors quantified each protocol's dose performance as the percent difference in dose relative to the reference protocol achieved while maintaining equivalent A-caret{sub FE}.Results: For the 4-mm signal-size task, the 80 kV full scan and 80 kV partial angle protocols decreased dose to the breast (80.5% and 85.3%, respectively) and lung (80.5% and 76.7%, respectively) with A-caret{sub FE} = 0.96, but also resulted in an approximate three-fold increase in image noise. The 120 kV partial protocol reduced dose to the breast (17.6%) at the expense of increased lung dose (25.3%). The TCM algorithm decreased dose to the breast (6.0%) and lung (10.4%). Breast shielding increased breast dose (67.8%) and lung dose (103.4%). The 80 kV and 80 kV partial protocols demonstrated greater dose reductions for the 4-mm task than for the 1-mm task, and the shielded protocol showed a larger increase in dose for the 4-mm task than for the 1-mm task. In general, the CNR curves indicate a similar relative ranking of protocol performance as the corresponding A-caret{sub FE} curves, however, the CNR metric overestimated the performance of the shielded protocol for both tasks, leading to corresponding underestimates in the relative dose increases compared to those obtained when using the A-caret{sub FE} metric.Conclusions: The 80 kV and 80 kV partial angle protocols demonstrated the greatest reduction to breast and lung dose, however, the subsequent increase in image noise may be deemed clinically unacceptable. Tube output for these protocols can be adjusted to achieve a more desirable noise level with lesser breast dose savings. Breast shielding increased breast and lung dose when maintaining equivalent A-caret{sub FE}. The results demonstrated that comparisons of dose performance depend on both the image quality metric and the specific task, and that CNR may not be a reliable metric of signal detectability.« less

[Clinical evaluation of broncho-vaxom efficiency].

PubMed

Moniuszko, T; Rogalewska, A; Chyrek-Borowska, S

Broncho-vaxom was administered to 40 patients with recurrent respiratory infections, allergic-infectious bronchial asthma and chronic bronchitis. Broncho-vaxom was administered in the dose of one capsule for the first month, and 1 capsule for 10 days in the third, fourth, and fifth month. A favourable clinical effect has been achieved in over 50% of the treated patients manifested by the decrease in the number and severity of respiratory infections and reductions in antibiotics use. These results confirm clinical efficiency of this vaccine.

4D cone-beam computed tomography (CBCT) using a moving blocker for simultaneous radiation dose reduction and scatter correction

NASA Astrophysics Data System (ADS)

Zhao, Cong; Zhong, Yuncheng; Duan, Xinhui; Zhang, You; Huang, Xiaokun; Wang, Jing; Jin, Mingwu

2018-06-01

Four-dimensional (4D) x-ray cone-beam computed tomography (CBCT) is important for a precise radiation therapy for lung cancer. Due to the repeated use and 4D acquisition over a course of radiotherapy, the radiation dose becomes a concern. Meanwhile, the scatter contamination in CBCT deteriorates image quality for treatment tasks. In this work, we propose the use of a moving blocker (MB) during the 4D CBCT acquisition (‘4D MB’) and to combine motion-compensated reconstruction to address these two issues simultaneously. In 4D MB CBCT, the moving blocker reduces the x-ray flux passing through the patient and collects the scatter information in the blocked region at the same time. The scatter signal is estimated from the blocked region for correction. Even though the number of projection views and projection data in each view are not complete for conventional reconstruction, 4D reconstruction with a total-variation (TV) constraint and a motion-compensated temporal constraint can utilize both spatial gradient sparsity and temporal correlations among different phases to overcome the missing data problem. The feasibility simulation studies using the 4D NCAT phantom showed that 4D MB with motion-compensated reconstruction with 1/3 imaging dose reduction could produce satisfactory images and achieve 37% improvement on structural similarity (SSIM) index and 55% improvement on root mean square error (RMSE), compared to 4D reconstruction at the regular imaging dose without scatter correction. For the same 4D MB data, 4D reconstruction outperformed 3D TV reconstruction by 28% on SSIM and 34% on RMSE. A study of synthetic patient data also demonstrated the potential of 4D MB to reduce the radiation dose by 1/3 without compromising the image quality. This work paves the way for more comprehensive studies to investigate the dose reduction limit offered by this novel 4D MB method using physical phantom experiments and real patient data based on clinical relevant metrics.

4D cone-beam computed tomography (CBCT) using a moving blocker for simultaneous radiation dose reduction and scatter correction.

PubMed

Zhao, Cong; Zhong, Yuncheng; Duan, Xinhui; Zhang, You; Huang, Xiaokun; Wang, Jing; Jin, Mingwu

2018-05-03

Four-dimensional (4D) X-ray cone-beam computed tomography (CBCT) is important for a precise radiation therapy for lung cancer. Due to the repeated use and 4D acquisition over a course of radiotherapy, the radiation dose becomes a concern. Meanwhile, the scatter contamination in CBCT deteriorates image quality for treatment tasks. In this work, we propose to use a moving blocker (MB) during the 4D CBCT acquisition ("4D MB") and to combine motion-compensated reconstruction to address these two issues simultaneously. In 4D MB CBCT, the moving blocker reduces the X-ray flux passing through the patient and collects the scatter information in the blocked region at the same time. The scatter signal is estimated from the blocked region for correction. Even though the number of projection views and projection data in each view are not complete for conventional reconstruction, 4D reconstruction with a total-variation (TV) constraint and a motion-compensated temporal constraint can utilize both spatial gradient sparsity and temporal correlations among different phases to overcome the missing data problem. The feasibility simulation studies using the 4D NCAT phantom showed that 4D MB with motion-compensated reconstruction with 1/3 imaging dose reduction could produce satisfactory images and achieve 37% improvement on structural similarity (SSIM) index and 55% improvement on root mean square error (RMSE), compared to 4D reconstruction at the regular imaging dose without scatter correction. For the same 4D MB data, 4D reconstruction outperformed 3D TV reconstruction by 28% on SSIM and 34% on RMSE. A study of synthetic patient data also demonstrated the potential of 4D MB to reduce the radiation dose by 1/3 without compromising the image quality. This work paves the way for more comprehensive studies to investigate the dose reduction limit offered by this novel 4D MB method using physical phantom experiments and real patient data based on clinical relevant metrics. © 2018 Institute of Physics and Engineering in Medicine.

Radiation dose management in thoracic CT: an international survey.

PubMed

Molinari, Francesco; Tack, Denis M; Boiselle, Philip; Ngo, Long; Mueller-Mang, Christina; Litmanovich, Diana; Bankier, Alexander A

2013-01-01

We aimed to examine current practice patterns of international thoracic radiologists regarding radiation dose management in adult thoracic computed tomography (CT) examinations. An electronic questionnaire was sent to 800 members of five thoracic radiology societies in North America, Europe, Asia, and Latin America addressing radiation dose training and education, standard kVp and mAs settings for thoracic CT, dose reduction practices, clinical scenarios, and demographics. Of the 800 radiologists, 146 responded to our survey. Nearly half (66/146, 45% [95% confidence interval, 37%-53%]) had no formal training in dose reduction, with "self-study of the literature" being the most common form of training (54/146, 37% [29%-45%]). One hundred and seventeen (80% [74%-87%]) had automatic exposure control, and 76 (65% [56%-74%]) used it in all patients. Notably, most respondents (89% [84%-94%]) used a 120 to 125 kVp standard setting, whereas none used 140 kVp. The most common average dose-length-product (DLP) value was 150 to 249 mGy.cm (75/146, 51% [43%-59%]), and 59% (51%-67%) delivered less than 250 mGy.cm in a 70 kg patient. There was a tendency towards higher DLP values with multidetector-row CT. Age, gender, and pregnancy were associated more with dose reduction than weight and clinical indication. Efforts for reducing patient radiation dose are highly prevalent among thoracic radiologists. Areas for improvement include reduction of default tube current settings, reduction of anatomical scan coverage, greater use of automatic exposure control, and eventually, reduction of current reference dose values. Our study emphasizes the need for international guidelines to foster greater conformity in dose reduction by thoracic radiologists.

Dose Assessment of Cefquinome by Pharmacokinetic/Pharmacodynamic Modeling in Mouse Model of Staphylococcus aureus Mastitis

PubMed Central

Yu, Yang; Zhou, Yu-Feng; Li, Xiao; Chen, Mei-Ren; Qiao, Gui-Lin; Sun, Jian; Liao, Xiao-Ping; Liu, Ya-Hong

2016-01-01

This work aimed to characterize the mammary gland pharmacokinetics of cefquinome after an intramammary administration and integrate pharmacokinetic/pharmacodynamic model. The pharmacokinetic profiles of cefquinome in gland tissue were measured using high performance liquid chromatograph. Therapeutic regimens covered various dosages ranging from 25 to 800 μg/gland and multiple dosing intervals of 8, 12, and 24 h. The in vivo bacterial killing activity elevated when dosage increased or when dosing intervals were shortened. The best antibacterial effect was demonstrated by a mean 1.5 log10CFU/gland visible count reduction. On the other hand, the results showed that the percentage of time duration of drug concentration exceeding the MIC during a dose interval (%T > MIC) was generally 100% because of the influence of drug distribution caused by the blood-milk barrier. Therefore, pharmacokinetic/pharmacodynamic parameter of the ratio of area under the concentration-time curve over 24 h to the MIC (AUC0-24/MIC) was used to describe the efficacy of cefquinome instead of %T > MIC. When the magnitude of AUC0-24/MIC exceeding 16571.55 h⋅mL/g, considerable activity of about 1.5 log10CFU/g gland bacterial count reduction was observed in vivo. Based on the Monte Carlo simulation, the clinical recommended regimen of three infusions of 75 mg per quarter every 12 h can achieve a 76.67% cure rate in clinical treatment of bovine mastitis caused by Staphylococcus aureus infection. PMID:27774090

Achieving Effective Risk Management Reduction Throughout Decommissioning at the Columbus Closure Project

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

Anderson, K.D.

2006-07-01

Nuclear facility decontamination, dismantlement, and demolition activities provide a myriad of challenges along the path to reaching a safe, effective, and compliant decommissioning. Among the challenges faced during decommissioning, is the constant management and technical effort to eliminate, mitigate, or minimize the potential of risks of radiation exposures and other hazards to the worker, the surrounding community, and the environment. Management strategies to eliminate, mitigate, or minimize risks include incorporating strong safety and As Low As Reasonably Achievable (ALARA) principles into an integrated work planning process. Technical and operational strategies may include utilizing predictive risk analysis tools to establish contaminationmore » limits for demolition and using remote handling equipment to reduce occupational and radiation exposures to workers. ECC and E2 Closure Services, LLC (Closure Services) have effectively utilized these management and technical tools to eliminate, mitigate, and reduce radiation exposures under contract to the U.S. Department of Energy (DOE) for the decontamination and decommissioning Columbus Closure Project (CCP). In particular, Closure Services achieved significant dose reduction during the dismantling, decontamination, and demolition activities for Building JN-1. Management strategies during the interior dismantlement, decontamination, and demolition of the facility demanded an integrated work planning processes that involved project disciplines. Integrated planning processes identified multiple opportunities to incorporate the use of remote handling equipment during the interior dismantling and demolition activities within areas of high radiation. Technical strategies employed predictive risk analysis tools to set upper bounding contamination limits, allowed for the radiological demolition of the building without exceeding administrative dose limits to the worker, general public, and the environment. Adhering to management and technical strategies during the dismantlement, decontamination, and demolition of Building JN-1 enabled Closure Services to achieve strong ALARA performance, maintain absolute compliance under the regulatory requirements and meeting licensing conditions for decommissioning. (authors)« less

Design of spray dried insulin microparticles to bypass deposition in the extrathoracic region and maximize total lung dose.

PubMed

Ung, Keith T; Rao, Nagaraja; Weers, Jeffry G; Huang, Daniel; Chan, Hak-Kim

2016-09-25

Inhaled drugs all too often deliver only a fraction of the emitted dose to the target lung site due to deposition in the extrathoracic region (i.e., mouth and throat), which can lead to increased variation in lung exposure, and in some instances increases in local and systemic side effects. For aerosol medications, improved targeting to the lungs may be achieved by tailoring the micromeritic properties of the particles (e.g., size, density, rugosity) to minimize deposition in the mouth-throat and maximize the total lung dose. This study evaluated a co-solvent spray drying approach to modulate particle morphology and dose delivery characteristics of engineered powder formulations of insulin microparticles. The binary co-solvent system studied included water as the primary solvent mixed with an organic co-solvent, e.g., ethanol. Factors such as the relative rate of evaporation of each component of a binary co-solvent mixture, and insulin solubility in each component were considered in selecting feedstock compositions. A water-ethanol co-solvent mixture with a composition range considered suitable for modulating particle shell formation during drying was selected for experimental investigation. An Alberta Idealized Throat model was used to evaluate the in vitro total lung dose of a series of spray dried insulin formulations engineered with different bulk powder properties and delivered with two prototype inhalers that fluidize and disperse powder using different principles. The in vitro total lung dose of insulin microparticles was improved and favored for powders with low bulk density and small primary particle size, with reduction of deposition in the extrathoracic region. The results demonstrated that a total lung dose >95% of the delivered dose can be achieved with engineered particles, indicating a high degree of lung targeting, almost completely bypassing deposition in the mouth-throat. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptively Tuned Iterative Low Dose CT Image Denoising

PubMed Central

Hashemi, SayedMasoud; Paul, Narinder S.; Beheshti, Soosan; Cobbold, Richard S. C.

2015-01-01

Improving image quality is a critical objective in low dose computed tomography (CT) imaging and is the primary focus of CT image denoising. State-of-the-art CT denoising algorithms are mainly based on iterative minimization of an objective function, in which the performance is controlled by regularization parameters. To achieve the best results, these should be chosen carefully. However, the parameter selection is typically performed in an ad hoc manner, which can cause the algorithms to converge slowly or become trapped in a local minimum. To overcome these issues a noise confidence region evaluation (NCRE) method is used, which evaluates the denoising residuals iteratively and compares their statistics with those produced by additive noise. It then updates the parameters at the end of each iteration to achieve a better match to the noise statistics. By combining NCRE with the fundamentals of block matching and 3D filtering (BM3D) approach, a new iterative CT image denoising method is proposed. It is shown that this new denoising method improves the BM3D performance in terms of both the mean square error and a structural similarity index. Moreover, simulations and patient results show that this method preserves the clinically important details of low dose CT images together with a substantial noise reduction. PMID:26089972

Reducing radiation dose to the female breast during conventional and dedicated breast computed tomography

NASA Astrophysics Data System (ADS)

Rupcich, Franco John

The purpose of this study was to quantify the effectiveness of techniques intended to reduce dose to the breast during CT coronary angiography (CTCA) scans with respect to task-based image quality, and to evaluate the effectiveness of optimal energy weighting in improving contrast-to-noise ratio (CNR), and thus the potential for reducing breast dose, during energy-resolved dedicated breast CT. A database quantifying organ dose for several radiosensitive organs irradiated during CTCA, including the breast, was generated using Monte Carlo simulations. This database facilitates estimation of organ-specific dose deposited during CTCA protocols using arbitrary x-ray spectra or tube-current modulation schemes without the need to run Monte Carlo simulations. The database was used to estimate breast dose for simulated CT images acquired for a reference protocol and five protocols intended to reduce breast dose. For each protocol, the performance of two tasks (detection of signals with unknown locations) was compared over a range of breast dose levels using a task-based, signal-detectability metric: the estimator of the area under the exponential free-response relative operating characteristic curve, AFE. For large-diameter/medium-contrast signals, when maintaining equivalent AFE, the 80 kV partial, 80 kV, 120 kV partial, and 120 kV tube-current modulated protocols reduced breast dose by 85%, 81%, 18%, and 6%, respectively, while the shielded protocol increased breast dose by 68%. Results for the small-diameter/high-contrast signal followed similar trends, but with smaller magnitude of the percent changes in dose. The 80 kV protocols demonstrated the greatest reduction to breast dose, however, the subsequent increase in noise may be clinically unacceptable. Tube output for these protocols can be adjusted to achieve more desirable noise levels with lesser dose reduction. The improvement in CNR of optimally projection-based and image-based weighted images relative to photon-counting was investigated for six different energy bin combinations using a bench-top energy-resolving CT system with a cadmium zinc telluride (CZT) detector. The non-ideal spectral response reduced the CNR for the projection-based weighted images, while image-based weighting improved CNR for five out of the six investigated bin combinations, despite this non-ideal response, indicating potential for image-based weighting to reduce breast dose during dedicated breast CT.

Dose reduction in 64-row whole-body CT in multiple trauma: an optimized CT protocol with iterative image reconstruction on a gemstone-based scintillator.

PubMed

Geyer, Lucas L; Körner, Markus; Harrieder, Andreas; Mueck, Fabian G; Deak, Zsuzsanna; Wirth, Stefan; Linsenmaier, Ulrich

2016-01-01

Evaluation of potential dose savings by implementing adaptive statistical iterative reconstruction (ASiR) on a gemstone-based scintillator in a clinical 64-row whole-body CT (WBCT) protocol after multiple trauma. Dose reports of 152 WBCT scans were analysed for two 64-row multidetector CT scanners (Scanners A and B); the main scanning parameters were kept constant. ASiR and a gemstone-based scintillator were used in Scanner B, and the noise index was adjusted (head: 5.2 vs 6.0; thorax/abdomen: 29.0 vs 46.0). The scan length, CT dose index (CTDI) and dose-length product (DLP) were analysed. The estimated mean effective dose was calculated using normalized conversion factors. Student's t-test was used for statistics. Both the mean CTDI (mGy) (Scanner A: 53.8 ± 2.0, 10.3 ± 2.5, 14.4 ± 3.7; Scanner B: 48.7 ± 2.2, 7.1 ± 2.3, 9.1 ± 3.6; p < 0.001, respectively) and the mean DLP (mGy cm) (Scanner A: 1318.9 ± 167.8, 509.3 ± 134.7, 848.8 ± 254.0; Scanner B: 1190.6 ± 172.6, 354.6 ± 128.3, 561.0 ± 246.7; p < 0.001, respectively) for the head, thorax and abdomen were significantly reduced with Scanner B. There was no relevant difference in scan length. The total mean effective dose (mSv) was significantly decreased with Scanner B (24.4 ± 6.0, 17.2 ± 5.8; p < 0.001). The implementation of ASiR and a gemstone-based scintillator allows for significant dose savings in a clinical WBCT protocol. Recent technical developments can significantly reduce radiation dose of WBCT in multiple trauma. Dose reductions of 10-34% can be achieved.

Cardiac dose-sparing effects of deep-inspiration breath-hold in left breast irradiation : Is IMRT more beneficial than VMAT?

PubMed

Sakka, Mazen; Kunzelmann, Leonie; Metzger, Martin; Grabenbauer, Gerhard G

2017-10-01

Given the reduction in death from breast cancer, as well as improvements in overall survival, adjuvant radiotherapy is considered the standard treatment for breast cancer. However, left-sided breast irradiation was associated with an increased rate of fatal cardiovascular events due to incidental irradiation of the heart. Recently, considerable efforts have been made to minimize cardiac toxicity of left-sided breast irradiation by new treatment methods such as deep-inspiration breath-hold (DIBH) and new radiation techniques, particularly intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). The primary aim of this study was to evaluate the effect of DIBH irradiation on cardiac dose compared with free-breathing (FB) irradiation, while the secondary objective was to compare the advantages of IMRT versus VMAT plans in both the FB and the DIBH position for left-sided breast cancer. In all, 25 consecutive left-sided breast cancer patients underwent CT simulation in the FB and DIBH position. Five patients were excluded with no cardiac displacement following DIBH-CT simulation. The other 20 patients were irradiated in the DIBH position using respiratory gating. Four different treatment plans were generated for each patient, an IMRT and a VMAT plan in the DIBH and in the FB position, respectively. The following parameters were used for plan comparison: dose to the heart, left anterior descending coronary artery (mean dose, maximum dose, D25% and D45%), ipsilateral, contralateral lung (mean dose, D20%, D30%) and contralateral breast (mean dose). The percentage in dose reduction for organs at risk achieved by DIBH for both IMRT and VMAT plans was calculated and compared for each patient by each treatment plan. DIBH irradiation significantly reduced mean dose to the heart and left anterior descending coronary artery (LADCA) using both IMRT (heart -20%; p = 0.0002, LADCA -9%; p = 0.001) and VMAT (heart -23%; p = 0.00003, LADCA -16%; p = 0.01) techniques as compared with FB radiation. There were no significant changes in left lung dose by IMRT; however, with VMAT planning, mean dose to the left lung was reduced by -4% (p = 0.0004). In addition, DIBH significantly increased the mean dose to the contralateral breast with IMRT (+14%, p = 0.002) and significantly reduced the dose to the contralateral breast with VMAT planning (-9%, p = 0.003) compared with the FB position. Additionally, in comparison with VMAT, the IMRT technique reduced mean heart dose both in the FB and the DIBH-position by -30% (p = 0.0004) and -26% (p = 0.002), respectively. Furthermore, IMRT increased the mean dose to the left lung in both the FB and the DIBH position (+5%, p = 0.003, p = 0.006), respectively. There were no significant changes in dose to the right lung and contralateral breast either in the FB or DIBH position between IMRT and VMAT techniques. Left-sided breast irradiation is best performed in the DIBH position, since a considerable dose sparing to the heart and LADCA can be achieved by using either IMRT or VMAT techniques. A significant additional decrease in heart and LADCA dose by IMRT in both FB and DIBH irradiation was seen compared with VMAT.

Generation of the additional fluorescence radiation in the elastomeric shields used in computer tomography (CT).

PubMed

Szajerski, P; Zaborski, M; Bem, H; Baryn, W; Kusiak, E

Two commercially available (EP, Z) and eight new elastomeric composites (M1-M4, G1-G4, of thickness ≈1 mm) containing mixtures of differing proportions of heavy metal additives (Bi, W, Gd and Sb) have been synthesised and examined as protective shields. The intensity of the X-ray fluorescence radiation generated in the typical elastomeric shields for CT, containing Bi and other heavy metal additives influence on the practical shielding properties. A method for assessing the radiation shielding properties of elastomeric composites used in CT examination procedures via X-ray spectrometry has been proposed. To measure the radiation reduction ability of the protective shields, the dose reduction factor (DRF) has been determined. The lead equivalents for the examined composites were within the ranges of 0.046-0.128 and 0.048-0.130 mm for 122.1 and 136.5 keV photons, respectively. The proposed method, unlike to the common approach, includes a dose contribution from the induced X-ray fluorescence radiation of the heavy metal elements in the protective shields. The results clearly indicate that among the examined compositions, the highest values DRF have been achieved with preparations containing Bi+W, Bi+W+Gd and Bi+W+Sb mixtures with gradually decreasing content of heavy metal additives in the following order: Bi, W, Gd and Sb. The respective values of DRF obtained for the investigated composites were 21, 28 and 27 % dose reduction for a 1 mm thick shield and 39 and ~50 % for a 2 mm thick layer (M1-M4).

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia.

PubMed

Ferreira, António Miguel; Marques da Silva, Pedro

2017-06-01

Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and high-density lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatin-ezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction Versus Treatment Switch

PubMed Central

Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; González, Hans Guerrero; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-01-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3–0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m2 (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0–606) mg/g to 216 (0–2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate. PMID:24556354

Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch.

PubMed

Weidemann, Frank; Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; Guerrero González, Hans; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-04-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3-0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m(2) (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0-606) mg/g to 216 (0-2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate.

Relationship between radiation dose reduction and image quality change in photostimulable phosphor luminescence X-ray imaging systems.

PubMed

Sakurai, T; Kawamata, R; Kozai, Y; Kaku, Y; Nakamura, K; Saito, M; Wakao, H; Kashima, I

2010-05-01

The aim of the study was to clarify the change in image quality upon X-ray dose reduction and to re-analyse the possibility of X-ray dose reduction in photostimulable phosphor luminescence (PSPL) X-ray imaging systems. In addition, the study attempted to verify the usefulness of multiobjective frequency processing (MFP) and flexible noise control (FNC) for X-ray dose reduction. Three PSPL X-ray imaging systems were used in this study. Modulation transfer function (MTF), noise equivalent number of quanta (NEQ) and detective quantum efficiency (DQE) were evaluated to compare the basic physical performance of each system. Subjective visual evaluation of diagnostic ability for normal anatomical structures was performed. The NEQ, DQE and diagnostic ability were evaluated at base X-ray dose, and 1/3, 1/10 and 1/20 of the base X-ray dose. The MTF of the systems did not differ significantly. The NEQ and DQE did not necessarily depend on the pixel size of the system. The images from all three systems had a higher diagnostic utility compared with conventional film images at the base and 1/3 X-ray doses. The subjective image quality was better at the base X-ray dose than at 1/3 of the base dose in all systems. The MFP and FNC-processed images had a higher diagnostic utility than the images without MFP and FNC. The use of PSPL imaging systems may allow a reduction in the X-ray dose to one-third of that required for conventional film. It is suggested that MFP and FNC are useful for radiation dose reduction.

Real-time colour pictorial radiation monitoring during coronary angiography: effect on patient peak skin and total dose during coronary angiography.

PubMed

Wilson, Sharon M; Prasan, Ananth M; Virdi, Amy; Lassere, Marissa; Ison, Glenn; Ramsay, David R; Weaver, James C

2016-10-10

The aim of this study was to evaluate whether a real-time (RT) colour pictorial radiation dose monitoring system reduces patient skin and total radiation dose during coronary angiography and intervention. Patient demographics, procedural variables and radiation parameters were recorded before and after institution of the RT skin dose recording system. Peak skin dose as well as traditionally available measures of procedural radiation dose were compared. A total of 1,077 consecutive patients underwent coronary angiography, of whom 460 also had PCI. Institution of the RT skin dose recording system resulted in a 22% reduction in peak skin dose after accounting for confounding variables. Radiation dose reduction was most pronounced in those having PCI but was also seen over a range of subgroups including those with prior coronary artery bypass surgery, high BMI, and with radial arterial access. This was associated with a significant reduction in the number of patients placed at risk of skin damage. Similar reductions in parameters reflective of total radiation dose were also demonstrated after institution of RT radiation monitoring. Institution of an RT skin dose recording reduced patient peak skin and total radiation dose during coronary angiography and intervention. Consideration should be given to widespread adoption of this technology.

A New Proof of Concept in Bacterial Reduction: Antimicrobial Action of Violet-Blue Light (405 nm) in Ex Vivo Stored Plasma

PubMed Central

Maclean, Michelle; Anderson, John G.; MacGregor, Scott J.; White, Tracy

2016-01-01

Bacterial contamination of injectable stored biological fluids such as blood plasma and platelet concentrates preserved in plasma at room temperature is a major health risk. Current pathogen reduction technologies (PRT) rely on the use of chemicals and/or ultraviolet light, which affects product quality and can be associated with adverse events in recipients. 405 nm violet-blue light is antibacterial without the use of photosensitizers and can be applied at levels safe for human exposure, making it of potential interest for decontamination of biological fluids such as plasma. As a pilot study to test whether 405 nm light is capable of inactivating bacteria in biological fluids, rabbit plasma and human plasma were seeded with bacteria and treated with a 405 nm light emitting diode (LED) exposure system (patent pending). Inactivation was achieved in all tested samples, ranging from low volumes to prebagged plasma. 99.9% reduction of low density bacterial populations (≤103 CFU mL−1), selected to represent typical “natural” contamination levels, was achieved using doses of 144 Jcm−2. The penetrability of 405 nm light, permitting decontamination of prebagged plasma, and the nonrequirement for photosensitizing agents provide a new proof of concept in bacterial reduction in biological fluids, especially injectable fluids relevant to transfusion medicine. PMID:27774337

SU-E-T-424: Dosimetric Verification of Modulated Electron Radiation Therapy Delivered Using An Electron Specific Multileaf Collimator for Treatment of Scalp Cases

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

Eldib, A; Al-Azhar University Cairo; Jin, L

2014-06-01

Purpose: Modulated electron radiotherapy (MERT) has the potential to achieve better treatment outcome for shallow tumors such as those of breast and scalp. In a separate study with scalp lesions, MERT was compared to volumetric modulated arc therapy. Our results showed a reduction in the dose reaching the brain with MERT. However dose calculation accuracy and delivery efficiency challenges remain. Thus in the current study we proceed to add more cases to demonstrate MERT beneficial outcome and its delivery accuracy using an electron specific multileaf collimator (eMLC). Methods: We have used the MCBEAM code for treatment head simulation and formore » generating phase space files to be used as radiation source input for our Monte Carlo based treatment planning system (MC TPS). MCPLAN code is used for calculation of patient specific dose deposition coefficient and for final MERT plan dose calculation. An in-house developed optimization code is used for the optimization process. MERT plans were generated for real patients and head and neck phantom. Film was used for dosimetric verification. The film was cut following the contour of the curved phantom surface and then sealed with black masking tape. In the measurement, the sealed film packet was sandwiched between two adjacent slabs of the head and neck phantom. The measured 2D dose distribution was then compared with calculations. Results: The eMLC allows effective treatment of scalps with multi-lesions spreading around the patient head, which was usually difficult to plan or very time consuming with conventional applicators. MERT continues to show better reduction in the brain dose. The dosimetric measurements showed slight discrepancy, which was attributed to the film setup. Conclusion: MERT can improve treatment plan quality for patients with scalp cancers. Our in-house MC TPS is capable of performing treatment planning and accurate dose calculation for MERT using the eMLC.« less

Dosimetric verification of small fields in the lung using lung-equivalent polymer gel and Monte Carlo simulation.

PubMed

Gharehaghaji, Nahideh; Dadgar, Habib Alah

2018-01-01

The main purpose of this study was evaluate a polymer-gel-dosimeter (PGD) for three-dimensional verification of dose distributions in the lung that is called lung-equivalent gel (LEG) and then to compare its result with Monte Carlo (MC) method. In the present study, to achieve a lung density for PGD, gel is beaten until foam is obtained, and then sodium dodecyl sulfate is added as a surfactant to increase the surface tension of the gel. The foam gel was irradiated with 1 cm × 1 cm field size in the 6 MV photon beams of ONCOR SIEMENS LINAC, along the central axis of the gel. The LEG was then scanned on a 1.5 Tesla magnetic resonance imaging scanner after irradiation using a multiple-spin echo sequence. Least-square fitting the pixel values from 32 consecutive images using a single exponential decay function derived the R2 relaxation rates. Moreover, 6 and 18 MV photon beams of ONCOR SIEMENS LINAC are simulated using MCNPX MC Code. The MC model is used to calculate the depth dose water and low-density water resembling the soft tissue and lung, respectively. Percentages of dose reduction in the lung region relative to homogeneous phantom for 6 MV photon beam were 44.6%, 39%, 13%, and 7% for 0.5 cm × 0.5 cm, 1 cm × 1 cm, 2 cm × 2 cm, and 3 cm × 3 cm fields, respectively. For 18 MV photon beam, the results were found to be 82%, 69%, 46%, and 25.8% for the same field sizes, respectively. Preliminary results show good agreement between depth dose measured with the LEG and the depth dose calculated using MCNP code. Our study showed that the dose reduction with small fields in the lung was very high. Thus, inaccurate prediction of absorbed dose inside the lung and also lung/soft-tissue interfaces with small photon beams may lead to critical consequences for treatment outcome.

Treatment and therapeutic monitoring of canine hypothyroidism.

PubMed

Dixon, R M; Reid, S W J; Mooney, C T

2002-08-01

Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone replacement therapy (THRT) and monitored for approximately three months. Good clinical and laboratory control was ultimately achieved in all cases with a mean L-thyroxine (T4) dose of 0.026 mg/kg administered once daily. There was a significant increase and decrease in circulating total T4 and canine thyroid stimulating hormone (cTSH) concentrations, respectively, after starting THRT. After commencing treatment, 11 cases subsequently required an increase and three cases required a decrease in dose to achieve optimal clinical control. Median (semi interquartile range [SIR]) circulating six-hour post-pill total T4 (53.6 [27.91 nmol/litre) and cTSH (0.03 [0] microg/litre) concentrations were significantly increased and decreased, respectively, in treated dogs that did not require a dose change; corresponding values in treated dogs in which an increase in dose was required were 29.3 (12.7) nmol/litre and 0.15 (0.62) microg/litre, respectively. However, circulating cTSH measurement was of limited value in assessing therapeutic control because, although increased values were associated with inadequate therapy, reference range cTSH values were common in inadequately treated dogs. Lethargy and mental demeanour were typically the first clinical signs to improve, with significant bodyweight reduction occurring within two weeks of commencing THRT. Routine clinicopathological monitoring was of value in confirming a general metabolic response to THRT, but was of limited value in accurately monitoring cases or tailoring therapy in individual cases.

A randomized controlled trial of subantimicrobial-dose doxycycline to prevent unscheduled bleeding with continuous oral contraceptive pill use.

PubMed

Kaneshiro, Bliss; Edelman, Alison; Carlson, Nichole E; Nichols, Mark; Forbes, Marci Messerle; Jensen, Jeffrey

2012-04-01

Unscheduled bleeding is the main side effect of continuous oral contraceptive pills (OCPs) and has been correlated with the up-regulation of matrix metalloprotineases (MMPs). The study objective was to determine if prophylactic administration of doxycycline (an MMP inhibitor at low subantimicrobial doses) would prevent unscheduled bleeding during the initiation of a continuous OCP. Subjects using cyclic hormonal contraceptives (combined OCPs, patch or ring) without unscheduled bleeding were switched to continuous OCPs (20 mcg ethinyl estradiol/100 mcg levonorgestrel). They were randomized to receive daily doxycycline [sustained-release subantimicrobial dose (40 mg daily)] or placebo for the first 84 days and then observed for an additional 28 days on the continuous OCP alone. The number of bleeding/spotting days and the time in days it took to achieve amenorrhea were compared using a t test. Sixty-five subjects were randomized. Although the use of doxycycline did not significantly decrease the number of mean bleeding/spotting days in the first 84 days of the study [doxycycline 14.75 (SE 2.30), placebo 17.78 (2.31), p=.36], women who received doxycycline had a significantly earlier onset of amenorrhea [mean last day of bleeding/spotting doxycycline 61.7 (7.7), placebo 85.2 (6.7), p=.03]. The coadministration of subantimicrobial-dose doxycycline during initiation of continuous OCPs results in a significant reduction in the length of time needed to achieve amenorrhea. Copyright © 2012 Elsevier Inc. All rights reserved.

A randomized controlled trial of subantimicrobial-dose doxycycline to prevent unscheduled bleeding with continuous oral contraceptive pill use☆

PubMed Central

Kaneshiro, Bliss; Edelman, Alison; Carlson, Nichole E.; Nichols, Mark; Forbes, Marci Messerle; Jensen, Jeffrey

2016-01-01

Background Unscheduled bleeding is the main side effect of continuous oral contraceptive pills (OCPs) and has been correlated with the up-regulation of matrix metalloprotineases (MMPs). The study objective was to determine if prophylactic administration of doxycycline (an MMP inhibitor at low subantimicrobial doses) would prevent unscheduled bleeding during the initiation of a continuous OCP. Study Design Subjects using cyclic hormonal contraceptives (combined OCPs, patch or ring) without unscheduled bleeding were switched to continuous OCPs (20 mcg ethinyl estradiol/100 mcg levonorgestrel). They were randomized to receive daily doxycycline [sustained-release subantimicrobial dose (40 mg daily)] or placebo for the first 84 days and then observed for an additional 28 days on the continuous OCP alone. The number of bleeding/spotting days and the time in days it took to achieve amenorrhea were compared using a t test. Results Sixty-five subjects were randomized. Although the use of doxycycline did not significantly decrease the number of mean bleeding/spotting days in the first 84 days of the study [doxycycline 14.75 (SE 2.30), placebo 17.78 (2.31), p=.36], women who received doxycycline had a significantly earlier onset of amenorrhea [mean last day of bleeding/spotting doxycycline 61.7 (7.7), placebo 85.2 (6.7), p=.03]. Conclusion The coadministration of subantimicrobial-dose doxycycline during initiation of continuous OCPs results in a significant reduction in the length of time needed to achieve amenorrhea. PMID:22067758

Initial apixaban dosing in patients with atrial fibrillation.

PubMed

Buchholz, Alexander; Ueberham, Laura; Gorczynska, Kaja; Dinov, Borislav; Hilbert, Sebastian; Dagres, Nikolaos; Husser, Daniela; Hindricks, Gerhard; Bollmann, Andreas

2018-05-01

Apixaban is a non-vitamin K oral anticoagulant approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). Current labeling recommends dose reduction based on patient age, weight, and renal function. The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and identify factors associated with inappropriate dose reduction. Patients with AF initiated on apixaban in 2016 were identified in the Heart Center Leipzig database. Records were screened to identify patient characteristics, prescribed apixaban dose, renal function, and further dosing-relevant secondary diagnoses and co-medication. We identified 569 consecutive patients with AF initiated on apixaban. In 301 (52.9%) patients, apixaban was prescribed in standard dose (5 mg b.i.d.) and in 268 (47.1%) in a reduced dose (2.5 mg b.i.d.). Of 268 patients receiving a reduced dose, 163 (60.8%) did not meet labeling criteria for dose reduction. In univariate and multivariate regression analysis, age (OR: 0.736, 95% CI: 0.664-0.816, P < 0.0001), patient weight (OR: 1.120, 95% CI: 1.076-1.166, P < 0.0001), and serum creatinine level (OR: 0.910, 95% CI: 0.881-0.940, P < 0.0001) were independent predictors for apixaban underdosage. In clinical practice, apixaban dosing is frequently inconsistent with labeling. Factors associated with inappropriate dose reduction are age, patient weight, and serum creatinine level, the same factors used as criteria for dose adjustment. However, in underdosed patients, the 3 factors did not meet the criteria for dose reduction. © 2018 Wiley Periodicals, Inc.

Interpretation of the margin of exposure for genotoxic carcinogens - elicitation of expert knowledge about the form of the dose response curve at human relevant exposures.

PubMed

Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi

2013-07-01

The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to "as low as reasonably achievable/practicable" (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the "Margin of Exposure" (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose-response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose-response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose-response relationships at human relevant exposures; the generality of judgments about such dose-response relationships; uncertainties affecting judgments on the nature of such dose-response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts' views on the form of the dose-response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship. Copyright © 2013 Elsevier Ltd. All rights reserved.

Standard and Nonstandard Craniospinal Radiotherapy Using Helical TomoTherapy

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

Parker, William, E-mail: william@medphys.mcgill.c; Brodeur, Marylene; Roberge, David

2010-07-01

Purpose: To show the advantages of planning and delivering craniospinal radiotherapy with helical TomoTherapy (TomoTherapy Inc., Madison, WI) by presenting 4 cases treated at our institution. Methods and Materials: We first present a standard case of craniospinal irradiation in a patient with recurrent myxopapillary ependymoma (MPE) and follow this with 2 cases requiring differential dosing to multiple target volumes. One of these, a patient with recurrent medulloblastoma, required a lower dose to be delivered to the posterior fossa because the patient had been previously irradiated to the full dose, and the other required concurrent boosts to leptomeningeal metastases as partmore » of his treatment for newly diagnosed MPE. The final case presented is a patient with pronounced scoliosis who required spinal irradiation for recurrent MPE. Results: The four cases presented were planned and treated successfully with Helical Tomotherapy. Conclusions: Helical TomoTherapy delivers continuous arc-based intensity-modulated radiotherapy that gives high conformality and excellent dose homogeneity for the target volumes. Increased healthy tissue sparing is achieved at higher doses albeit at the expense of larger volumes of tissue receiving lower doses. Helical TomoTherapy allows for differential dosing of multiple targets, resulting in very elegant dose distributions. Daily megavoltage computed tomography imaging allows for precision of patient positioning, permitting a reduction in planning margins and increased healthy tissue sparing in comparison with standard techniques.« less

Comparison of eye lens dose on neuroimaging protocols between 16- and 64-section multidetector CT: achieving the lowest possible dose.

PubMed

Tan, J S P; Tan, K-L; Lee, J C L; Wan, C-M; Leong, J-L; Chan, L-L

2009-02-01

To our knowledge, there has been no study that compares the radiation dose delivered to the eye lens by 16- and 64-section multidetector CT (MDCT) for standard clinical neuroimaging protocols. Our aim was to assess radiation-dose differences between 16- and 64-section MDCT from the same manufacturer, by using near-identical neuroimaging protocols. Three cadaveric heads were scanned on 16- and 64-section MDCT by using standard neuroimaging CT protocols. Eye lens dose was measured by using thermoluminescent dosimeters (TLD), and each scanning was repeated to reduce random error. The dose-length product, volume CT dose index (CTDI(vol)), and TLD readings for each imaging protocol were averaged and compared between scanners and protocols, by using the paired Student t test. Statistical significance was defined at P < .05. The radiation dose delivered and eye lens doses were lower by 28.1%-45.7% (P < .000) on the 64-section MDCT for near-identical imaging protocols. On the 16-section MDCT, lens dose reduction was greatest (81.1%) on a tilted axial mode, compared with a nontilted helical mode for CT brain scans. Among the protocols studied, CT of the temporal bone delivered the greatest radiation dose to the eye lens. Eye lens radiation doses delivered by the 64-section MDCT are significantly lower, partly due to improvements in automatic tube current modulation technology. However, where applicable, protection of the eyes from the radiation beam by either repositioning the head or tilting the gantry remains the best way to reduce eye lens dose.

Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

PubMed

Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

2002-01-01

The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

Optically stimulated Al2O3:C luminescence dosimeters for teletherapy: Hp(10) performance evaluation.

PubMed

Hashim, S; Musa, Y; Ghoshal, S K; Ahmad, N E; Hashim, I H; Yusop, M; Bradley, D A; Kadir, A B A

2018-05-01

The performance of optically stimulated luminescence dosimeters (OSLDs, Al 2 O 3 :C) was evaluated in terms of the operational quantity of H P (10) in Co-60 external beam teletherapy unit. The reproducibility, signal depletion, and dose linearity of each dosimeter was investigated. For ten repeated readouts, each dosimeter exposed to 50mSv was found to be reproducible below 1.9 ± 3% from the mean value, indicating good reader stability. Meanwhile, an average signal reduction of 0.5% per readout was found. The dose response revealed a good linearity within the dose range of 5-50mSv having nearly perfect regression line with R 2 equals 0.9992. The accuracy of the measured doses were evaluated in terms of operational quantity H P (10), wherein the trumpet curve method was used respecting the 1990 International Commission on Radiological Protection (ICRP) standard. The accuracy of the overall measurements from all dosimeters was discerned to be within the trumpet curve and devoid of outlier. It is established that the achieved OSL Al 2 O 3 :C dosimeters are greatly reliable for equivalent dose assessment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Computed tomography and patient risk: Facts, perceptions and uncertainties

PubMed Central

Power, Stephen P; Moloney, Fiachra; Twomey, Maria; James, Karl; O’Connor, Owen J; Maher, Michael M

2016-01-01

Since its introduction in the 1970s, computed tomography (CT) has revolutionized diagnostic decision-making. One of the major concerns associated with the widespread use of CT is the associated increased radiation exposure incurred by patients. The link between ionizing radiation and the subsequent development of neoplasia has been largely based on extrapolating data from studies of survivors of the atomic bombs dropped in Japan in 1945 and on assessments of the increased relative risk of neoplasia in those occupationally exposed to radiation within the nuclear industry. However, the association between exposure to low-dose radiation from diagnostic imaging examinations and oncogenesis remains unclear. With improved technology, significant advances have already been achieved with regards to radiation dose reduction. There are several dose optimization strategies available that may be readily employed including omitting unnecessary images at the ends of acquired series, minimizing the number of phases acquired, and the use of automated exposure control as opposed to fixed tube current techniques. In addition, new image reconstruction techniques that reduce radiation dose have been developed in recent years with promising results. These techniques use iterative reconstruction algorithms to attain diagnostic quality images with reduced image noise at lower radiation doses. PMID:28070242

Perioperative use of selective alpha-2 agonists and antagonists in small animals

PubMed Central

2004-01-01

Abstract Alpha-2 agonists are the only single class of anesthetic drugs that induce reliable, dose-dependent sedation, analgesia, and muscle relaxation in dogs and cats. Used at low doses, as adjuncts to injectable and inhalational anesthetics, selective alpha-2 agonists dramatically reduce the amount of anesthetic drug required to induce and maintain anesthesia. This reduction in anesthetic requirements is achieved without significant depression of pulmonary function and with limited effects on cardiovascular function. Selective alpha-2 agonists can also be used postoperatively to potentiate the analgesic effects of opioids and other drugs. Given the nearly ideal pharmacodynamic profile and reversibility of alpha-2 agonists, these drugs will play a central role in balanced approaches to anesthesia and the management of perioperative pain in healthy dogs and cats. PMID:15283516

Protective, elective lung irradiation in non-metastatic Ewing's sarcoma.

PubMed

Marinova, L; Hristozova, I; Mihaylova, I; Perenovska, P

2015-07-01

Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy +/- surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Low-dose dual-energy electronic cleansing for fecal-tagging CT Colonography

NASA Astrophysics Data System (ADS)

Cai, Wenli; Zhang, Da; Lee, June-Goo; Yoshida, Hiroyuki

2013-03-01

Dual-energy electronic cleansing (DE-EC) provides a promising means for cleansing the tagged fecal materials in fecaltagging CT colonography (CTC). However, the increased radiation dose due to the double exposures in dual-energy CTC (DE-CTC) scanning is a major limitation for the use of DE-EC in clinical practice. The purpose of this study was to develop and evaluate a low-dose DE-EC scheme in fecal-tagging DE-CTC. In this study, a custom-made anthropomorphic colon phantom, which was filled with simulated tagged materials by non-ionic iodinated contrast agent (Omnipaque iohexol, GE Healthcare), was scanned by a dual-source CT scanner (SOMATON Definition Flash, Siemens Healthcare) at two photon energies: 80 kVp and 140 kVp with nine different tube current settings ranging from 12 to 74 mAs for 140 kVp, and then reconstructed by soft-tissue reconstruction kernel (B30f). The DE-CTC images were subjected to a low-dose DE-EC scheme. First, our image-space DE-CTC denoising filter was applied for reduction of image noise. Then, the noise-reduced images were processed by a virtual lumen tagging method for reduction of partial volume effect and tagging inhomogeneity. The results were compared with the registered CTC images of native phantom without fillings. Preliminary results showed that our low-dose DE-EC scheme achieved the cleansing ratios, defined by the proportion of the cleansed voxels in the tagging mask, between 93.18% (12 mAs) and 96.62% (74 mAs). Also, the soft-tissue preservation ratios, defined by the proportion of the persevered voxels in the soft-tissue mask, were maintained in the range between 94.67% and 96.41%.

Concurrent Etoposide, Steroid, High-dose Ara-C and Platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma, nasal type.

PubMed

Michot, Jean-Marie; Mazeron, Renaud; Danu, Alina; Lazarovici, Julien; Ghez, David; Antosikova, Anna; Willekens, Christophe; Chamseddine, Ali N; Minard, Veronique; Dartigues, Peggy; Bosq, Jacques; Carde, Patrice; Koscielny, Serge; De Botton, Stéphane; Ferme, Christophe; Girinsky, Theodore; Ribrag, Vincent

2015-11-01

Radiation combined with chemotherapy has recently been proposed to treat patients with localised extranodal natural killer (NK)/T lymphoma (ENKTL), nasal type. However, the modalities of the chemoradiotherapy combination and drug choices remain a matter of debate. We conducted a concurrent chemoradiotherapy (CCRT) study with the ESHAP (Etoposide, Steroid, High-dose Ara-C and Platinum) regimen. An induction phase with two upfront courses of CCRT delivering a 40Gy dose of radiation concurrently with two cycles of the ESHAP chemotherapy regimen, followed by a consolidation phase with 2-3 cycles of ESHAP chemotherapy alone. Thirteen patients with localised ENKTL nasal type were enrolled between January 2005 and December 2014. The median age was 62years. Ten and three patients had Ann Arbor stage IE and IIE disease, respectively. They all completed the induction CCRT phase. A median of two consolidation ESHAP cycles were delivered. During consolidation, 8/13 (62%) patients had a reduction in the number of chemotherapy cycles or reduced chemotherapy doses, due to haematologically adverse events. The other five patients (38%) received the full number of ESHAP cycles of chemotherapy scheduled without a dose reduction. All but one patient (92%) experienced grade 3-4 haematological toxicity. The main non-haematological grade 3-4 toxicity was mucositis in 6/13 (46%) patients. All but one patient (92%) achieved a complete remission. Two-year overall survival was 72%. With optimal management of the specific toxicities induced by this treatment modality, CCRT with the ESHAP regimen yielded high efficacy against localised ENKTL, nasal type. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

PubMed

Wilkes, Denise M; Orillosa, Susan J; Hustak, Erik C; Williams, Courtney G; Doulatram, Gulshan R; Solanki, Daneshvari R; Garcia, Eduardo A; Huang, Li-Yen M

2017-06-13

The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Retrospective review of medical records. Private and academic pain clinic practices. Chronic noncancer pain patients. We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (<3 mg/d) of morphine. Furthermore, microdose therapy was feasible, safe, and cost-effective in the outpatient setting. 2017 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.

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.

Estimation of breast dose reduction potential for organ-based tube current modulated CT with wide dose reduction arc

NASA Astrophysics Data System (ADS)

Fu, Wanyi; Sturgeon, Gregory M.; Agasthya, Greeshma; Segars, W. Paul; Kapadia, Anuj J.; Samei, Ehsan

2017-03-01

This study aimed to estimate the organ dose reduction potential for organ-dose-based tube current modulated (ODM) thoracic CT with wide dose reduction arc. Twenty-one computational anthropomorphic phantoms (XCAT, age range: 27- 75 years, weight range: 52.0-105.8 kg) were used to create a virtual patient population with clinical anatomic variations. For each phantom, two breast tissue compositions were simulated: 50/50 and 20/80 (glandular-to-adipose ratio). A validated Monte Carlo program was used to estimate the organ dose for standard tube current modulation (TCM) (SmartmA, GE Healthcare) and ODM (GE Healthcare) for a commercial CT scanner (Revolution, GE Healthcare) with explicitly modeled tube current modulation profile, scanner geometry, bowtie filtration, and source spectrum. Organ dose was determined using a typical clinical thoracic CT protocol. Both organ dose and CTDIvol-to-organ dose conversion coefficients (h factors) were compared between TCM and ODM. ODM significantly reduced all radiosensitive organ doses (p<0.01). The breast dose was reduced by 30+/-2%. For h factors, organs in the anterior region (e.g. thyroid, stomach) exhibited substantial decreases, and the medial, distributed, and posterior region either saw an increase or no significant change. The organ-dose-based tube current modulation significantly reduced organ doses especially for radiosensitive superficial anterior organs such as the breasts.

Correlates of individual differences in compensatory nicotine self-administration in rats following a decrease in nicotine unit dose

PubMed Central

Harris, Andrew C.; Pentel, Paul R.; LeSage, Mark G.

2013-01-01

Rationale The ability of tobacco harm reduction strategies to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon and assessing the feasibility of harm reduction interventions. Objective To use an animal model of human compensatory smoking that involves a decrease in unit dose supporting nicotine self-administration (NSA) to examine potential contributors to individual differences in compensation. Methods Rats were trained for NSA during daily 23 hr sessions at a unit dose of 0.06 mg/kg/inf until responding was stable. The unit dose was then reduced to 0.03 mg/kg/inf for at least 10 sessions. Following reacquisition of NSA at the training dose and extinction, single-dose nicotine pharmacokinetic parameters were determined. Results Decreases in nicotine intake following dose reduction were proportionally less than the decrease in unit dose, indicating partial compensation. Compensatory increases in infusion rates were observed across the course of the 23 hr sessions. The magnitude of compensation differed considerably between rats. Rats exhibiting the highest baseline infusion rates exhibited the lowest levels of compensation. Nicotine pharmacokinetic parameters were not significantly correlated with compensation. Infusion rates immediately returned to pre-reduction levels when baseline conditions were restored. Conclusions These findings provide initial insights into correlates of individual differences in compensation following a reduction in nicotine unit dose. The present assay may be useful for characterizing mechanisms and potential consequences of the marked individual differences in compensatory smoking observed in humans. PMID:19475400

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short‐Acting β‐Agonist Formulations

PubMed Central

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai

2017-01-01

Abstract Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3‐by‐1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration–recommended 3‐by‐1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3‐by‐1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90‐μg test dose and a 720‐μg reference dose (42% cost reduction). Combining a 180‐μg test dose and a 720‐μg reference dose produced an estimated 36% cost reduction. PMID:29281130

Efficacy and Safety of Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, as Add-on to Insulin in Patients With Type 1 Diabetes.

PubMed

Henry, Robert R; Thakkar, Payal; Tong, Cindy; Polidori, David; Alba, Maria

2015-12-01

This study assessed the efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to insulin in adults with type 1 diabetes. This 18-week, double-blind, phase 2 study randomized 351 patients (HbA1c 7.0-9.0% [53-75 mmol/mol]) on multiple daily insulin injections or continuous subcutaneous insulin infusion to canagliflozin 100 or 300 mg or placebo. The primary end point was the proportion of patients achieving at week 18 both HbA1c reduction from baseline of ≥0.4% (≥4.4 mmol/mol) and no increase in body weight. Other end points included changes in HbA1c, body weight, and insulin dose, as well as hypoglycemia incidence. Safety was assessed by adverse event (AE) reports. More patients had both HbA1c reduction ≥0.4% and no increase in body weight with canagliflozin 100 and 300 mg versus placebo at week 18 (36.9%, 41.4%, 14.5%, respectively; P < 0.001). Both canagliflozin doses provided reductions in HbA1c, body weight, and insulin dose versus placebo over 18 weeks. The incidence of hypoglycemia was similar across groups; severe hypoglycemia rates were low (1.7-6.8%). Overall incidence of AEs was 55.6%, 67.5%, and 54.7% with canagliflozin 100 and 300 mg and placebo; discontinuation rates were low (0.9-1.3%). Increased incidence of ketone-related AEs (5.1%, 9.4%, 0%), including the specific AE of diabetic ketoacidosis (DKA) (4.3%, 6.0%, 0%), was seen with canagliflozin 100 and 300 mg versus placebo. Canagliflozin provided reductions in HbA1c, body weight, and insulin dose with no increase in hypoglycemia, but increased rates of ketone-related AEs, including DKA, in adults with type 1 diabetes inadequately controlled with insulin. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial.

PubMed

Wunderink, Lex; Nieboer, Roeline M; Wiersma, Durk; Sytema, Sjoerd; Nienhuis, Fokko J

2013-09-01

Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before. To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial. Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR. One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission. PARTICIPANTS After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment. After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician. Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters. The DR patients experienced twice the recovery rate of the MT patients (40.4% vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates. Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice. isrctn.org Identifier: ISRCTN16228411.

Validation of Fully Automated VMAT Plan Generation for Library-Based Plan-of-the-Day Cervical Cancer Radiotherapy.

PubMed

Sharfo, Abdul Wahab M; Breedveld, Sebastiaan; Voet, Peter W J; Heijkoop, Sabrina T; Mens, Jan-Willem M; Hoogeman, Mischa S; Heijmen, Ben J M

2016-01-01

To develop and validate fully automated generation of VMAT plan-libraries for plan-of-the-day adaptive radiotherapy in locally-advanced cervical cancer. Our framework for fully automated treatment plan generation (Erasmus-iCycle) was adapted to create dual-arc VMAT treatment plan libraries for cervical cancer patients. For each of 34 patients, automatically generated VMAT plans (autoVMAT) were compared to manually generated, clinically delivered 9-beam IMRT plans (CLINICAL), and to dual-arc VMAT plans generated manually by an expert planner (manVMAT). Furthermore, all plans were benchmarked against 20-beam equi-angular IMRT plans (autoIMRT). For all plans, a PTV coverage of 99.5% by at least 95% of the prescribed dose (46 Gy) had the highest planning priority, followed by minimization of V45Gy for small bowel (SB). Other OARs considered were bladder, rectum, and sigmoid. All plans had a highly similar PTV coverage, within the clinical constraints (above). After plan normalizations for exactly equal median PTV doses in corresponding plans, all evaluated OAR parameters in autoVMAT plans were on average lower than in the CLINICAL plans with an average reduction in SB V45Gy of 34.6% (p<0.001). For 41/44 autoVMAT plans, SB V45Gy was lower than for manVMAT (p<0.001, average reduction 30.3%), while SB V15Gy increased by 2.3% (p = 0.011). AutoIMRT reduced SB V45Gy by another 2.7% compared to autoVMAT, while also resulting in a 9.0% reduction in SB V15Gy (p<0.001), but with a prolonged delivery time. Differences between manVMAT and autoVMAT in bladder, rectal and sigmoid doses were ≤ 1%. Improvements in SB dose delivery with autoVMAT instead of manVMAT were higher for empty bladder PTVs compared to full bladder PTVs, due to differences in concavity of the PTVs. Quality of automatically generated VMAT plans was superior to manually generated plans. Automatic VMAT plan generation for cervical cancer has been implemented in our clinical routine. Due to the achieved workload reduction, extension of plan libraries has become feasible.

SU-F-I-46: Optimizing Dose Reduction in Adult Head CT Protocols While Maintaining Image Quality in Postmortem Head Scans

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

Lipnharski, I; Carranza, C; Quails, N

Purpose: To optimize adult head CT protocol by reducing dose to an appropriate level while providing CT images of diagnostic quality. Methods: Five cadavers were scanned from the skull base to the vertex using a routine adult head CT protocol (120 kVp, 270 mA, 0.75 s rotation, 0.5 mm × 32 detectors, 70.8 mGy CTDIvol) followed by seven reduced-dose protocols with varying combinations of reduced tube current, reduced rotation time, and increased detectors with CTDIvol ranging from 38.2 to 65.6 mGy. Organ doses were directly measured with 21 OSL dosimeters placed on the surface and implanted in the head bymore » a neurosurgeon. Two neuroradiologists assessed grey-white matter differentiation, fluid space, ventricular size, midline shift, brain mass, edema, ischemia, and skull fractures on a three point scale: (1) Unacceptable, (2) Borderline Acceptable, and (3) Acceptable. Results: For the standard scan, doses to the skin, lens of the eye, salivary glands, thyroid, and brain were 37.55 mGy, 49.65 mGy, 40.67 mGy, 4.63 mGy, and 27.33 mGy, respectively. Two cadavers had cerebral edema due to changing dynamics of postmortem effects, causing the grey-white matter differentiation to appear less distinct. Two cadavers with preserved grey-white matter received acceptable scores for all image quality features for the protocol with a CTDIvol of 57.3 mGy, allowing organ dose savings ranging from 34% to 45%. One cadaver allowed for greater dose reduction for the protocol with a CTDIvol of 42 mGy. Conclusion: Efforts to optimize scan protocol should consider both dose and clinical image quality. This is made possible with postmortem subjects, whose brains are similar to patients, allowing for an investigation of ideal scan parameters. Radiologists at our institution accepted scan protocols acquired with lower scan parameters, with CTDIvol values closer to the American College of Radiology’s (ACR) Achievable Dose level of 57 mGy.« less

An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid.

PubMed

Zheng, Songyan; Adams, Monica; Mantri, Rao V

2016-03-01

To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers. Copyright © 2016. Published by Elsevier Inc.

Evaluation of forest decontamination using radiometric measurements.

PubMed

Cresswell, Alan J; Kato, Hiroaki; Onda, Yuichi; Nanba, Kenji

2016-11-01

An experiment has been conducted to evaluate the additional dose reduction by clear felling contaminated forestry in Fukushima Prefecture, Japan, and using the timber to cover the areas with wood chips. A portable gamma spectrometry system, comprising a backpack containing a 3 × 3″ NaI(Tl) detector with digital spectrometer and GPS receiver, has been used to map dose rate and radionuclide activity concentrations before, after and at stages during this experiment. The data show the effect of the different stages of the experiment on dose rate at different locations around the site. The spectrometric data have allowed the assessment of the contributions of natural and anthropogenic radionuclides to the dose rate at different parts of the site before and after the experiment. This has clearly demonstrated the value of radiometric methods in evaluating remediation, and the effect of other environmental processes. The value of spectrometric methods which directly measure radionuclide concentrations has also been shown, especially through the identification of the contribution of natural and anthropogenic activity to the measured dose rate. The experiment has shown that clearing trees and applying wood chips can reduce dose rates by 10-15% beyond that achieved by just clearing the forest litter and natural redistribution of radiocaesium. Copyright © 2016 Elsevier Ltd. All rights reserved.

Low-dose vaporized cannabis significantly improves neuropathic pain.

PubMed

Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

Disinfection of an advanced primary effluent with peracetic acid and ultraviolet combined treatment: a continuous-flow pilot plant study.

PubMed

González, Abelardo; Gehr, Ronald; Vaca, Mabel; López, Raymundo

2012-03-01

Disinfection of an advanced primary effluent using a continuous-flow combined peracetic acid/ultraviolet (PAA/UV) radiation system was evaluated. The purpose was to determine whether the maximum microbial content, established under Mexican standards for treated wastewaters meant for reuse--less than 240 most probable number fecal coliforms (FC)/100 mL--could be feasibly accomplished using either disinfectant individually, or the combined PAA/UV system. This meant achieving reduction of up to 5 logs, considering initial concentrations of 6.4 x 10(+6) to 5.8 x 10(+7) colony forming units/100 mL. During the tests performed under these experiments, total coliforms (TC) were counted because FC, at the most, will be equal to TC. Peracetic acid disinfection achieved less than 1.5 logs TC reduction when the C(t) x t product was less than 2.26 mg x minimum (min)/L; 3.8 logs for C(t) x t 4.40 mg x min/L; and 5.9 logs for C(t) x t 24.2 mg x min/L. In continuous-flow UV irradiation tests, at a low-operating flow (21 L/min; conditions which produced an average UV fluence of 13.0 mJ/cm2), the highest TC reduction was close to 2.5 logs. The only condition that produced a disinfection efficiency of approximately 5 logs, when both disinfection agents were used together, was the combined process dosing 30 mg PAA/L at a pilot plant flow of 21 L/min and contact time of 10 minutes to attain an average C(t) x t product of 24.2 mg x min/L and an average UV fluence of 13 mJ/cm2. There was no conclusive evidence of a synergistic effect when both disinfectants were employed in combination as compared to the individual effects achieved when used separately, but this does not take into account the nonlinearity (tailing-off) of the dose-response curve.

Optimisation and establishment of diagnostic reference levels in paediatric plain radiography

NASA Astrophysics Data System (ADS)

Paulo, Graciano do Nascimento Nobre

Purpose: This study aimed to propose Diagnostic Reference Levels (DRLs) in paediatric plain radiography and to optimise the most frequent paediatric plain radiography examinations in Portugal following an analysis and evaluation of current practice. Methods and materials: Anthropometric data (weight, patient height and thickness of the irradiated anatomy) was collected from 9,935 patients referred for a radiography procedure to one of the three dedicated paediatric hospitals in Portugal. National DRLs were calculated for the three most frequent X-ray procedures at the three hospitals: chest AP/PA projection; abdomen AP projection; pelvis AP projection. Exposure factors and patient dose were collected prospectively at the clinical sites. In order to analyse the relationship between exposure factors, the use of technical features and dose, experimental tests were made using two anthropomorphic phantoms: a) CIRSTM ATOM model 705; height: 110cm, weight: 19kg and b) Kyoto kagakuTM model PBU-60; height: 165cm, weight: 50kg. After phantom data collection, an objective image analysis was performed by analysing the variation of the mean value of the standard deviation, measured with OsiriX software (Pixmeo, Switzerland). After proposing new exposure criteria, a Visual Grading Characteristic image quality evaluation was performed blindly by four paediatric radiologists, each with a minimum of 10 years of professional experience, using anatomical criteria scoring. Results: DRLs by patient weight groups have been established for the first time. ESAKP75 DRLs for both patient age and weight groups were also obtained and are described in the thesis. Significant dose reduction was achieved through the implementation of an optimisation programme: an average reduction of 41% and 18% on KAPP75 and ESAKP75, respectively for chest plain radiography; an average reduction of 58% and 53% on KAPP75 and ESAKP75, respectively for abdomen plain radiography; and an average reduction of 47% and 48% on KAPP75 and ESAKP75, respectively for pelvis plain radiography. Conclusion: Portuguese DRLs for plain radiography were obtained for paediatric plain radiography (chest AP/PA, abdomen and pelvis). Experimental phantom tests identified adequate plain radiography exposure criteria, validated by objective and subjective image quality analysis. The new exposure criteria were put into practice in one of the paediatric hospitals, by introducing an optimisation programme. The implementation of the optimisation programme allowed a significant dose reduction to paediatric patients, without compromising image quality. (Abstract shortened by ProQuest.).

Effects of a radiation dose reduction strategy for computed tomography in severely injured trauma patients in the emergency department: an observational study.

PubMed

Kim, Soo Hyun; Jung, Seung Eun; Oh, Sang Hoon; Park, Kyu Nam; Youn, Chun Song

2011-11-03

Severely injured trauma patients are exposed to clinically significant radiation doses from computed tomography (CT) imaging in the emergency department. Moreover, this radiation exposure is associated with an increased risk of cancer. The purpose of this study was to determine some effects of a radiation dose reduction strategy for CT in severely injured trauma patients in the emergency department. We implemented the radiation dose reduction strategy in May 2009. A prospective observational study design was used to collect data from patients who met the inclusion criteria during this one year study (intervention group) from May 2009 to April 2010. The prospective data were compared with data collected retrospectively for one year prior to the implementation of the radiation dose reduction strategy (control group). By comparison of the cumulative effective dose and the number of CT examinations in the two groups, we evaluated effects of a radiation dose reduction strategy. All the patients met the institutional adult trauma team activation criteria. The radiation doses calculated by the CT scanner were converted to effective doses by multiplication by a conversion coefficient. A total of 118 patients were included in this study. Among them, 33 were admitted before May 2009 (control group), and 85 were admitted after May 2009 (intervention group). There were no significant differences between the two groups regarding baseline characteristics, such as injury severity and mortality. Additionally, there was no difference between the two groups in the mean number of total CT examinations per patient (4.8 vs. 4.5, respectively; p = 0.227). However, the mean effective dose of the total CT examinations per patient significantly decreased from 78.71 mSv to 29.50 mSv (p < 0.001). The radiation dose reduction strategy for CT in severely injured trauma patients effectively decreased the cumulative effective dose of the total CT examinations in the emergency department. But not effectively decreased the number of CT examinations.

Physical aspects of total-body irradiation at the Middlesex Hospital (UCL group of hospitals), London 1988-1993: II. In vivo planning and dosimetry.

PubMed

Planskoy, B; Tapper, P D; Bedford, A M; Davis, F M

1996-11-01

Part II of this paper gives the results of applying the TBI methods described in part I, to in vivo patient planning and dosimetry. Patients are planned on nine CT based body slices, five of which pass through the lungs. Planned doses are verified with ten silicon diodes applied bi-laterally to five body sites, at each treatment. LiF TLDs are applied to seven other body sites at the first treatment only. For 84 patients and at least 1016 measurements per body site with the diodes, the mean measured total doses agreed with planned doses within at most 2% except at lung levels, where the mean measured dose was 3% too low. Standard deviations of the measurements about the mean were between 2.4 and 3.1%. For the LiF TLDs, the mean measured doses for all seven body sites were with in +/- 5% of planned doses. A separate assessment of measured entrance and transmitted doses showed that the former agreed well with planned doses, but that the latter tended to be low, especially over the lungs, and that they had a wider dispersion. Possible reasons for this are discussed. These results show measurement uncertainties similar to those for non-TBI treatments of Nilsson et al, Leunens et al and Essers et al. An analysis of the treatment plans showed a mean dose inhomogeneity in the body (75 patients, nine slices) of 19 +/- 6.0% (1 s.d.) and in the lungs (40 patients, five slices) of 9.2 +/- 2.85% (1 s.d.). The conclusions are that, overall, the methods are reasonably satisfactory but that, with an extra effort, even closer agreement between measured and planned doses and a further limited reduction in the body dose inhomogeneity could be obtained. However, if it were thought desirable to make a substantial reduction in the dose inhomogeneity in the body and lungs, this could only be achieved with the available equipment by changing from lateral to anterior-posterior irradiation and any potential advantages of this change would have to be balanced against a likely deterioration in patient comfort and an increase in treatment set-up times.

Measuring radiation dose in computed tomography using elliptic phantom and free-in-air, and evaluating iterative metal artifact reduction algorithm

NASA Astrophysics Data System (ADS)

Morgan, Ashraf

The need for an accurate and reliable way for measuring patient dose in multi-row detector computed tomography (MDCT) has increased significantly. This research was focusing on the possibility of measuring CT dose in air to estimate Computed Tomography Dose Index (CTDI) for routine quality control purposes. New elliptic CTDI phantom that better represent human geometry was manufactured for investigating the effect of the subject shape on measured CTDI. Monte Carlo simulation was utilized in order to determine the dose distribution in comparison to the traditional cylindrical CTDI phantom. This research also investigated the effect of Siemens health care newly developed iMAR (iterative metal artifact reduction) algorithm, arthroplasty phantom was designed and manufactured that purpose. The design of new phantoms was part of the research as they mimic the human geometry more than the existing CTDI phantom. The standard CTDI phantom is a right cylinder that does not adequately represent the geometry of the majority of the patient population. Any dose reduction algorithm that is used during patient scan will not be utilized when scanning the CTDI phantom, so a better-designed phantom will allow the use of dose reduction algorithms when measuring dose, which leads to better dose estimation and/or better understanding of dose delivery. Doses from a standard CTDI phantom and the newly-designed phantoms were compared to doses measured in air. Iterative reconstruction is a promising technique in MDCT dose reduction and artifacts correction. Iterative reconstruction algorithms have been developed to address specific imaging tasks as is the case with Iterative Metal Artifact Reduction or iMAR which was developed by Siemens and is to be in use with the companys future computed tomography platform. The goal of iMAR is to reduce metal artifact when imaging patients with metal implants and recover CT number of tissues adjacent to the implant. This research evaluated iMAR capability of recovering CT numbers and reducing noise. Also, the use of iMAR should allow using lower tube voltage instead of 140 KVp which is used frequently to image patients with shoulder implants. The evaluations of image quality and dose reduction were carried out using an arthroplasty phantom.

Practical Advice on Calculating Confidence Intervals for Radioprotection Effects and Reducing Animal Numbers in Radiation Countermeasure Experiments

PubMed Central

Landes, Reid D.; Lensing, Shelly Y.; Kodell, Ralph L.; Hauer-Jensen, Martin

2014-01-01

The dose of a substance that causes death in P% of a population is called an LDP, where LD stands for lethal dose. In radiation research, a common LDP of interest is the radiation dose that kills 50% of the population by a specified time, i.e., lethal dose 50 or LD50. When comparing LD50 between two populations, relative potency is the parameter of interest. In radiation research, this is commonly known as the dose reduction factor (DRF). Unfortunately, statistical inference on dose reduction factor is seldom reported. We illustrate how to calculate confidence intervals for dose reduction factor, which may then be used for statistical inference. Further, most dose reduction factor experiments use hundreds, rather than tens of animals. Through better dosing strategies and the use of a recently available sample size formula, we also show how animal numbers may be reduced while maintaining high statistical power. The illustrations center on realistic examples comparing LD50 values between a radiation countermeasure group and a radiation-only control. We also provide easy-to-use spreadsheets for sample size calculations and confidence interval calculations, as well as SAS® and R code for the latter. PMID:24164553

SU-E-T-329: Dosimetric Impact of Implementing Metal Artifact Reduction Methods and Metal Energy Deposition Kernels for Photon Dose Calculations

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

Huang, J; Followill, D; Howell, R

2015-06-15

Purpose: To investigate two strategies for reducing dose calculation errors near metal implants: use of CT metal artifact reduction methods and implementation of metal-based energy deposition kernels in the convolution/superposition (C/S) method. Methods: Radiochromic film was used to measure the dose upstream and downstream of titanium and Cerrobend implants. To assess the dosimetric impact of metal artifact reduction methods, dose calculations were performed using baseline, uncorrected images and metal artifact reduction Methods: Philips O-MAR, GE’s monochromatic gemstone spectral imaging (GSI) using dual-energy CT, and GSI imaging with metal artifact reduction software applied (MARs).To assess the impact of metal kernels, titaniummore » and silver kernels were implemented into a commercial collapsed cone C/S algorithm. Results: The CT artifact reduction methods were more successful for titanium than Cerrobend. Interestingly, for beams traversing the metal implant, we found that errors in the dimensions of the metal in the CT images were more important for dose calculation accuracy than reduction of imaging artifacts. The MARs algorithm caused a distortion in the shape of the titanium implant that substantially worsened the calculation accuracy. In comparison to water kernel dose calculations, metal kernels resulted in better modeling of the increased backscatter dose at the upstream interface but decreased accuracy directly downstream of the metal. We also found that the success of metal kernels was dependent on dose grid size, with smaller calculation voxels giving better accuracy. Conclusion: Our study yielded mixed results, with neither the metal artifact reduction methods nor the metal kernels being globally effective at improving dose calculation accuracy. However, some successes were observed. The MARs algorithm decreased errors downstream of Cerrobend by a factor of two, and metal kernels resulted in more accurate backscatter dose upstream of metals. Thus, these two strategies do have the potential to improve accuracy for patients with metal implants in certain scenarios. This work was supported by Public Health Service grants CA 180803 and CA 10953 awarded by the National Cancer Institute, United States of Health and Human Services, and in part by Mobius Medical Systems.« less

No compelling evidence that sibutramine prolongs life in rodents despite providing a dose-dependent reduction in body weight

PubMed Central

Smith, Daniel L.; Robertson, Henry; Desmond, Renee; Nagy, Tim R.; Allison, David B.

2010-01-01

Objective The health and longevity effects of body weight reduction resulting from exercise and caloric restriction in rodents are well known, but less is known about whether similar effects occur with weight reduction from the use of a pharmaceutical agent such as sibutramine, a serotonin-norepinephrine reuptake inhibitor. Results & Conclusion Using data from a two-year toxicology study of sibutramine in CD rats and CD-1 mice, despite a dose-dependent reduction in food intake and body weight in rats compared to controls, and a body weight reduction in mice at the highest dose, there was no compelling evidence for reductions in mortality rate. PMID:21079617

Investigation of ultra low-dose scans in the context of quantum-counting clinical CT

NASA Astrophysics Data System (ADS)

Weidinger, T.; Buzug, T. M.; Flohr, T.; Fung, G. S. K.; Kappler, S.; Stierstorfer, K.; Tsui, B. M. W.

2012-03-01

In clinical computed tomography (CT), images from patient examinations taken with conventional scanners exhibit noise characteristics governed by electronics noise, when scanning strongly attenuating obese patients or with an ultra-low X-ray dose. Unlike CT systems based on energy integrating detectors, a system with a quantum counting detector does not suffer from this drawback. Instead, the noise from the electronics mainly affects the spectral resolution of these detectors. Therefore, it does not contribute to the image noise in spectrally non-resolved CT images. This promises improved image quality due to image noise reduction in scans obtained from clinical CT examinations with lowest X-ray tube currents or obese patients. To quantify the benefits of quantum counting detectors in clinical CT we have carried out an extensive simulation study of the complete scanning and reconstruction process for both kinds of detectors. The simulation chain encompasses modeling of the X-ray source, beam attenuation in the patient, and calculation of the detector response. Moreover, in each case the subsequent image preprocessing and reconstruction is modeled as well. The simulation-based, theoretical evaluation is validated by experiments with a novel prototype quantum counting system and a Siemens Definition Flash scanner with a conventional energy integrating CT detector. We demonstrate and quantify the improvement from image noise reduction achievable with quantum counting techniques in CT examinations with ultra-low X-ray dose and strong attenuation.

Drug delivery.

PubMed

Le Souëf, Peter N

2002-09-16

What we know: In preschool children, small-volume spacers perform better than large-volume spacers. Detergent is the best antistatic agent for spacers, increasing lung delivery two- to threefold, but it must not be rinsed off. A mouthpiece should be used in children aged 2-3 years or older, as lung delivery is two- to threefold higher for oral inhalation than nasal inhalation (ie, by mask). Inhaled drug doses do not generally need to be reduced in infants and young children owing to inefficiencies of delivery in younger patients. Nebulisers are "dinosaurs" and not needed for most children with asthma. What we need to know: What is the best inhalation technique for spacers? How long should children breathe, how many breaths should they take, and at what age should they breath-hold? How should children, parents and doctors be instructed to achieve optimal levels of electrostatic charge reduction for spacers? How much should inhaled steroid dose be reduced when a spacer is used optimally? What dosing instructions should be given for beta(2)-agonists delivered by spacer?

Treatment of Hailey-Hailey Disease With Low-Dose Naltrexone.

PubMed

Albers, Lauren N; Arbiser, Jack L; Feldman, Ron J

2017-10-01

Hailey-Hailey disease is a severe genetic blistering disease of intertriginous skin locations that can lead to poor quality of life and increased morbidities. Multiple therapies are available with inconsistent outcomes and potentially severe adverse effects. To determine whether low-dose naltrexone is an effective treatment for Hailey-Hailey disease. This study was a case series performed at a dermatology outpatient clinic of 3 patients with severe Hailey-Hailey disease recalcitrant to at least 4 therapies. Low-dose naltrexone, 3 mg nightly, titrated to 4.5 mg nightly in 2 patients. Reduction in size of lesions as well as subjective improvement of symptoms. All 3 patients noted significant healing of erosions and plaques starting from the peripheral aspect within 1 to 2 weeks of treatment, and clinical resolution of lesions within 2 months. Discontinuation of low-dose naltrexone resulted in flaring of symptoms, which cleared within 2 to 3 days on rechallenge with low-dose naltrexone. We present herein 3 cases of patients with severe Hailey-Hailey disease treated with low-dose naltrexone who achieved clinical resolution of symptoms. The success of these cases suggests low-dose naltrexone as a novel therapy for Hailey-Hailey disease. The possible mechanism may involve low-dose naltrexone influencing opioid or toll-like receptor signaling to improve calcium mobilization and improve keratinocyte differentiation and wound healing. Future studies are needed to clarify the mechanism and to define the role of low-dose naltrexone for treatment of Hailey-Hailey disease.

Improving IMRT delivery efficiency using intensity limits during inverse planning.

PubMed

Coselmon, Martha M; Moran, Jean M; Radawski, Jeffrey D; Fraass, Benedick A

2005-05-01

Inverse planned intensity modulated radiotherapy (IMRT) fields can be highly modulated due to the large number of degrees of freedom involved in the inverse planning process. Additional modulation typically results in a more optimal plan, although the clinical rewards may be small or offset by additional delivery complexity and/or increased dose from transmission and leakage. Increasing modulation decreases delivery efficiency, and may lead to plans that are more sensitive to geometrical uncertainties. The purpose of this work is to assess the use of maximum intensity limits in inverse IMRT planning as a simple way to increase delivery efficiency without significantly affecting plan quality. Nine clinical cases (three each for brain, prostate, and head/neck) were used to evaluate advantages and disadvantages of limiting maximum intensity to increase delivery efficiency. IMRT plans were generated using in-house protocol-based constraints and objectives for the brain and head/neck, and RTOG 9406 dose volume objectives in the prostate. Each case was optimized at a series of maximum intensity ratios (the product of the maximum intensity and the number of beams divided by the prescribed dose to the target volume), and evaluated in terms of clinical metrics, dose-volume histograms, monitor units (MU) required per fraction (SMLC and DMLC delivery), and intensity map variation (a measure of the beam modulation). In each site tested, it was possible to reduce total monitor units by constraining the maximum allowed intensity without compromising the clinical acceptability of the plan. Monitor unit reductions up to 38% were observed for SMLC delivery, while reductions up to 29% were achieved for DMLC delivery. In general, complicated geometries saw a smaller reduction in monitor units for both delivery types, although DMLC delivery required significantly more monitor units in all cases. Constraining the maximum intensity in an inverse IMRT plan is a simple way to improve delivery efficiency without compromising plan objectives.

Three-day Field Treatment with Ingenol Disoxate (LEO 43204) for Actinic Keratosis

PubMed Central

Tyring, Stephen; Nahm, Walter K.; Østerdal, Marie Louise; Petersen, Astrid H.; Berman, Brian

2017-01-01

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of ingenol disoxate gel using a once-daily, three-day field treatment regimen in patients with actinic keratosis. DESIGN: This was a Phase II, multicenter, open-label trial (clinicaltrials.gov: NCT02305888). SETTING: The study was conducted in 20 trial sites in the United States. PARTICIPANTS: Participants included patients with 5 to 20 clinically typical actinic keratosis lesions on the full face/chest (250cm2), scalp (25–250cm2), or the trunk/extremities (250cm2). MEASUREMENTS: We measured incidence of dose-limiting events based on local skin responses. Percentage reduction in actinic keratosis lesion count from baseline, complete clearance, and partial clearance (≥75%) of actinic keratosis lesions were assessed at Week 8. RESULTS: Nine of 63 (14.3%) patients in the face/chest group reported dose-limiting events; zero of 63 patients in the scalp group reported dose-limiting events; and 11 of 62 (17.7%) patients in the trunk/extremities group reported dose-limiting events. Mean composite local skin response scores peaked at Day 4, then rapidly declined, reaching or approaching baseline levels by Week 4. Less than five percent of patients reported severe adverse events; the most common treatment-related adverse events were application site pain and pruritus. The reduction in actinic keratosis lesion count was 78.9, 76.3, and 69.1 percent for the face/chest, scalp, and trunk/extremities groups, respectively. Complete clearance was achieved in 36.5, 39.7, and 22.6 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. Partial clearance was achieved in 71.4, 65.1, and 50.0 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. CONCLUSION: Ingenol disoxate demonstrated adverse events and local skin reaction profiles similar to results seen in trials evaluating shorter two-day regimens and was effective in patients with actinic keratosis. These data support the use of ingenol disoxate gel for actinic keratosis field treatment. PMID:29399263

Three-day Field Treatment with Ingenol Disoxate (LEO 43204) for Actinic Keratosis: A Phase II Trial.

PubMed

Siegel, Daniel M; Tyring, Stephen; Nahm, Walter K; Østerdal, Marie Louise; Petersen, Astrid H; Berman, Brian

2017-12-01

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of ingenol disoxate gel using a once-daily, three-day field treatment regimen in patients with actinic keratosis. DESIGN: This was a Phase II, multicenter, open-label trial (clinicaltrials.gov: NCT02305888). SETTING: The study was conducted in 20 trial sites in the United States. PARTICIPANTS: Participants included patients with 5 to 20 clinically typical actinic keratosis lesions on the full face/chest (250cm 2 ), scalp (25-250cm 2 ), or the trunk/extremities (250cm 2 ). MEASUREMENTS: We measured incidence of dose-limiting events based on local skin responses. Percentage reduction in actinic keratosis lesion count from baseline, complete clearance, and partial clearance (≥75%) of actinic keratosis lesions were assessed at Week 8. RESULTS: Nine of 63 (14.3%) patients in the face/chest group reported dose-limiting events; zero of 63 patients in the scalp group reported dose-limiting events; and 11 of 62 (17.7%) patients in the trunk/extremities group reported dose-limiting events. Mean composite local skin response scores peaked at Day 4, then rapidly declined, reaching or approaching baseline levels by Week 4. Less than five percent of patients reported severe adverse events; the most common treatment-related adverse events were application site pain and pruritus. The reduction in actinic keratosis lesion count was 78.9, 76.3, and 69.1 percent for the face/chest, scalp, and trunk/extremities groups, respectively. Complete clearance was achieved in 36.5, 39.7, and 22.6 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. Partial clearance was achieved in 71.4, 65.1, and 50.0 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. CONCLUSION: Ingenol disoxate demonstrated adverse events and local skin reaction profiles similar to results seen in trials evaluating shorter two-day regimens and was effective in patients with actinic keratosis. These data support the use of ingenol disoxate gel for actinic keratosis field treatment.

Sinogram-based adaptive iterative reconstruction for sparse view x-ray computed tomography

NASA Astrophysics Data System (ADS)

Trinca, D.; Zhong, Y.; Wang, Y.-Z.; Mamyrbayev, T.; Libin, E.

2016-10-01

With the availability of more powerful computing processors, iterative reconstruction algorithms have recently been successfully implemented as an approach to achieving significant dose reduction in X-ray CT. In this paper, we propose an adaptive iterative reconstruction algorithm for X-ray CT, that is shown to provide results comparable to those obtained by proprietary algorithms, both in terms of reconstruction accuracy and execution time. The proposed algorithm is thus provided for free to the scientific community, for regular use, and for possible further optimization.

Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study.

PubMed

Fernández-Rodríguez, Conrado M; Morillas, Rosa María; Masnou, Helena; Navarro, José María; Bárcena, Rafael; González, José Manuel; Martín-Martín, Leticia; Poyato, Antonio; Miquel-Planas, Mireia; Jorquera, Francisco; Casanovas, Teresa; Salmerón, Javier; Calleja, José Luis; Solà, Ricard; Alonso, Sonia; Planas, Ramón; Romero-Gomez, Manuel

2014-01-01

Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV). To assess the impact of high doses of RBV on SVR in patients with G3 and HVL. Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin β 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin β (B2; n=13). RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%. G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin β were safe and well tolerated (Clin Trials Gov NCT00830609). Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Probabilistic objective functions for margin-less IMRT planning

NASA Astrophysics Data System (ADS)

Bohoslavsky, Román; Witte, Marnix G.; Janssen, Tomas M.; van Herk, Marcel

2013-06-01

We present a method to implement probabilistic treatment planning of intensity-modulated radiation therapy using custom software plugins in a commercial treatment planning system. Our method avoids the definition of safety-margins by directly including the effect of geometrical uncertainties during optimization when objective functions are evaluated. Because the shape of the resulting dose distribution implicitly defines the robustness of the plan, the optimizer has much more flexibility than with a margin-based approach. We expect that this added flexibility helps to automatically strike a better balance between target coverage and dose reduction for surrounding healthy tissue, especially for cases where the planning target volume overlaps organs at risk. Prostate cancer treatment planning was chosen to develop our method, including a novel technique to include rotational uncertainties. Based on population statistics, translations and rotations are simulated independently following a marker-based IGRT correction strategy. The effects of random and systematic errors are incorporated by first blurring and then shifting the dose distribution with respect to the clinical target volume. For simplicity and efficiency, dose-shift invariance and a rigid-body approximation are assumed. Three prostate cases were replanned using our probabilistic objective functions. To compare clinical and probabilistic plans, an evaluation tool was used that explicitly incorporates geometric uncertainties using Monte-Carlo methods. The new plans achieved similar or better dose distributions than the original clinical plans in terms of expected target coverage and rectum wall sparing. Plan optimization times were only about a factor of two higher than in the original clinical system. In conclusion, we have developed a practical planning tool that enables margin-less probability-based treatment planning with acceptable planning times, achieving the first system that is feasible for clinical implementation.

Alefacept is safe and efficacious in the treatment of palmar plantar pustulosis.

PubMed

Guenther, Lyn C

2007-01-01

Alefacept blocks T-cell activation and induces apoptosis of memory T cells. It improves psoriasis vulgaris and may induce prolonged remissions. Experience with alefacept in palmar plantar pustulosis (PPP) is limited. The objective of the study was to observe the effectiveness and safety of alefacept in the treatment of PPP. Alefacept was administered weekly for 16 weeks by intramuscular (IM) injection of 15 mg to 15 patients with moderate to very severe PPP. Patients were followed for an additional 12 weeks. Four weeks after 16 weeks of treatment, there was a 49.6% reduction in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) and a 38.6% and a 64.5% reduction in total and fresh pustules, respectively. Eight weeks after dosing, 53.3% achieved PPPASI 50, 26.7% achieved PPPASI 75, and one patient was clear. The mean percent reduction in total pustules and fresh pustules was 46.1% and 61.2%, respectively; 73% had no pain, 53% had no itching, and 80% had no functional impairment. The palms responded better than the soles. This pilot showed that 16 weeks of once-weekly alefacept 15 mg IM was safe, led to improvement in PPP in all 15 treated patients, and induced a remission in one patient. Larger double-blind studies are warranted.

Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study

PubMed Central

Müller, Daniel J.; Ng, Chee H.; Byron, Keith; Berk, Michael; Singh, Ajeet B.

2017-01-01

Background Pharmacogenetic-based dosing support tools have been developed to personalize antidepressant-prescribing practice. However, the clinical validity of these tools has not been adequately tested, particularly for specific antidepressants. Objective To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of desvenlafaxine needed to achieve symptom remission. Materials and methods A 10-week, open-label, prospective trial of desvenlafaxine among Caucasian adults with major depressive disorder (n=119) was conducted. Dose was clinically adjusted and at the completion of the trial, the clinical dose needed to achieve remission was compared with the predicted dose needed to achieve remission. Results Among remitters (n=95), there was a strong concordance (Kendall’s τ-b=0.84, P=0.0001; Cohen’s κ=0.82, P=0.0001) between the actual and the predicted dose need to achieve symptom remission, showing high sensitivity (≥85%), specificity (≥86%), and accuracy (≥89%) of the tool. Conclusion Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for desvenlafaxine dosing. PMID:27779571

Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study.

PubMed

Bousman, Chad A; Müller, Daniel J; Ng, Chee H; Byron, Keith; Berk, Michael; Singh, Ajeet B

2017-01-01

Pharmacogenetic-based dosing support tools have been developed to personalize antidepressant-prescribing practice. However, the clinical validity of these tools has not been adequately tested, particularly for specific antidepressants. To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of desvenlafaxine needed to achieve symptom remission. A 10-week, open-label, prospective trial of desvenlafaxine among Caucasian adults with major depressive disorder (n=119) was conducted. Dose was clinically adjusted and at the completion of the trial, the clinical dose needed to achieve remission was compared with the predicted dose needed to achieve remission. Among remitters (n=95), there was a strong concordance (Kendall's τ-b=0.84, P=0.0001; Cohen's κ=0.82, P=0.0001) between the actual and the predicted dose need to achieve symptom remission, showing high sensitivity (≥85%), specificity (≥86%), and accuracy (≥89%) of the tool. Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for desvenlafaxine dosing.

Radiotherapy for Early Mediastinal Hodgkin Lymphoma According to the German Hodgkin Study Group (GHSG): The Roles of Intensity-Modulated Radiotherapy and Involved-Node Radiotherapy

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

Koeck, Julia, E-mail: Julia_Koeck@gmx.net; Abo-Madyan, Yasser; Department of Radiation Oncology, Faculty of Medicine, Cairo University, Cairo

2012-05-01

Purpose: Cure rates of early Hodgkin lymphoma (HL) are high, and avoidance of late complications and second malignancies have become increasingly important. This comparative treatment planning study analyzes to what extent target volume reduction to involved-node (IN) and intensity-modulated (IM) radiotherapy (RT), compared with involved-field (IF) and three-dimensional (3D) RT, can reduce doses to organs at risk (OAR). Methods and Materials: Based on 20 computed tomography (CT) datasets of patients with early unfavorable mediastinal HL, we created treatment plans for 3D-RT and IMRT for both the IF and IN according to the guidelines of the German Hodgkin Study Group (GHSG).more » As OAR, we defined heart, lung, breasts, and spinal cord. Dose-volume histograms (DVHs) were evaluated for planning target volumes (PTVs) and OAR. Results: Average IF-PTV and IN-PTV were 1705 cm{sup 3} and 1015 cm{sup 3}, respectively. Mean doses to the PTVs were almost identical for all plans. For IF-PTV/IN-PTV, conformity was better with IMRT and homogeneity was better with 3D-RT. Mean doses to the heart (17.94/9.19 Gy for 3D-RT and 13.76/7.42 Gy for IMRT) and spinal cord (23.93/13.78 Gy for 3D-RT and 19.16/11.55 Gy for IMRT) were reduced by IMRT, whereas mean doses to lung (10.62/8.57 Gy for 3D-RT and 12.77/9.64 Gy for IMRT) and breasts (left 4.37/3.42 Gy for 3D-RT and 6.04/4.59 Gy for IMRT, and right 2.30/1.63 Gy for 3D-RT and 5.37/3.53 Gy for IMRT) were increased. Volume exposed to high doses was smaller for IMRT, whereas volume exposed to low doses was smaller for 3D-RT. Pronounced benefits of IMRT were observed for patients with lymph nodes anterior to the heart. IN-RT achieved substantially better values than IF-RT for almost all OAR parameters, i.e., dose reduction of 20% to 50%, regardless of radiation technique. Conclusions: Reduction of target volume to IN most effectively improves OAR sparing, but is still considered investigational. For the time being, IMRT should be considered for large PTVs especially when the anterior mediastinum is involved.« less

Radiation dose reduction in digital breast tomosynthesis (DBT) by means of deep-learning-based supervised image processing

NASA Astrophysics Data System (ADS)

Liu, Junchi; Zarshenas, Amin; Qadir, Ammar; Wei, Zheng; Yang, Limin; Fajardo, Laurie; Suzuki, Kenji

2018-03-01

To reduce cumulative radiation exposure and lifetime risks for radiation-induced cancer from breast cancer screening, we developed a deep-learning-based supervised image-processing technique called neural network convolution (NNC) for radiation dose reduction in DBT. NNC employed patched-based neural network regression in a convolutional manner to convert lower-dose (LD) to higher-dose (HD) tomosynthesis images. We trained our NNC with quarter-dose (25% of the standard dose: 12 mAs at 32 kVp) raw projection images and corresponding "teaching" higher-dose (HD) images (200% of the standard dose: 99 mAs at 32 kVp) of a breast cadaver phantom acquired with a DBT system (Selenia Dimensions, Hologic, CA). Once trained, NNC no longer requires HD images. It converts new LD images to images that look like HD images; thus the term "virtual" HD (VHD) images. We reconstructed tomosynthesis slices on a research DBT system. To determine a dose reduction rate, we acquired 4 studies of another test phantom at 4 different radiation doses (1.35, 2.7, 4.04, and 5.39 mGy entrance dose). Structural SIMilarity (SSIM) index was used to evaluate the image quality. For testing, we collected half-dose (50% of the standard dose: 32+/-14 mAs at 33+/-5 kVp) and full-dose (standard dose: 68+/-23 mAs at 33+/-5 kvp) images of 10 clinical cases with the DBT system at University of Iowa Hospitals and Clinics. NNC converted half-dose DBT images of 10 clinical cases to VHD DBT images that were equivalent to full dose DBT images. Our cadaver phantom experiment demonstrated 79% dose reduction.

The clinical effect and tolerability of ezetimibe in high-risk patients managed in a specialty cardiovascular risk reduction clinic

PubMed Central

Pearson, Glen J; Francis, Gordon A; Romney, Jacques S; Gilchrist, Dawna M; Opgenorth, Andrea; Gyenes, Gabor T

2006-01-01

INTRODUCTION Ezetimibe (EZ) is a selective cholesterol absorption inhibitor approved for use in Canada. The effect and tolerability of EZ among patients was evaluated in the clinical setting of a specialty cardiovascular risk reduction clinic at the University of Alberta Hospital, Edmonton, Alberta. PATIENTS AND METHODS All patients 18 years of age or older who were prescribed EZ were included, unless they failed to take EZ for a minimum of two weeks, did not have baseline and on-EZ low-density lipoprotein cholesterol (LDL-C) levels, or had concomitant lipid-lowering drugs or dosages changed within one month of starting EZ. RESULTS Eighty-four patients (mean age 57.9 years) were included. By Framingham risk calculation, 71.4% were found to be high-risk patients, 13.1% moderate-risk patients and 15.5% low-risk patients; 66.7% of patients had prior cardiovascular events. On EZ, the mean reductions were: total cholesterol level 1.11 mmol/L (16.5%); LDL-C level 1.01 mmol/L (22.3%); high-density lipoprotein cholesterol level 0.06 mmol/L (4.6%); and ratio of total cholesterol level to high-density lipoprotein cholesterol level 0.68 mmol/L (12.8%); all were statistically significant (P<0.001). Results were similar when stratified by primary (n=28) versus secondary (n=56) prevention. Patients on EZ monotherapy (n=34) had mean LDL-C reductions of 1.03 mmol/L (20.5%) compared with 1.19 mmol/L (30.1%) or 0.95 mmol/L (22.5%), where EZ was added to low-dose or high-dose statins (P<0.01 for all). On EZ, 30 patients (35.7%) achieved previously unattainable target LDL-C levels. Four patients discontinued the drug due to side effects. CONCLUSIONS EZ is safe and effective in high-risk patients treated in the clinical setting of a cardiovascular risk reduction clinic. A mean LDL-C reduction of 1 mmol/L (20% to 30%) in all patient subgroups is consistent with previous clinical trial results. The significant reduction in LDL-C (mean 22.5%) observed in the EZ plus high-dose statin subgroup provides clinical evidence for use of this medication beyond published studies. PMID:16971979

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

PubMed Central

Conover, Christine F.; Beggs, Luke A.; Beck, Darren T.; Otzel, Dana M.; Balaez, Alexander; Combs, Sarah M.; Miller, Julie R.; Ye, Fan; Aguirre, J. Ignacio; Neuville, Kathleen G.; Williams, Alyssa A.; Conrad, Bryan P.; Gregory, Chris M.; Wronski, Thomas J.; Bose, Prodip K.; Borst, Stephen E.

2014-01-01

Abstract Androgen administration protects against musculoskeletal deficits in models of sex-steroid deficiency and injury/disuse. It remains unknown, however, whether testosterone prevents bone loss accompanying spinal cord injury (SCI), a condition that results in a near universal occurrence of osteoporosis. Our primary purpose was to determine whether testosterone-enanthate (TE) attenuates hindlimb bone loss in a rodent moderate/severe contusion SCI model. Forty (n=10/group), 14 week old male Sprague-Dawley rats were randomized to receive: (1) Sham surgery (T9 laminectomy), (2) moderate/severe (250 kdyne) SCI, (3) SCI+Low-dose TE (2.0 mg/week), or (4) SCI+High-dose TE (7.0 mg/week). Twenty-one days post-injury, SCI animals exhibited a 77–85% reduction in hindlimb cancellous bone volume at the distal femur (measured via μCT) and proximal tibia (measured via histomorphometry), characterized by a >70% reduction in trabecular number, 13–27% reduction in trabecular thickness, and increased trabecular separation. A 57% reduction in cancellous volumetric bone mineral density (vBMD) at the distal femur and a 20% reduction in vBMD at the femoral neck were also observed. TE dose dependently prevented hindlimb bone loss after SCI, with high-dose TE fully preserving cancellous bone structural characteristics and vBMD at all skeletal sites examined. Animals receiving SCI also exhibited a 35% reduction in hindlimb weight bearing (triceps surae) muscle mass and a 22% reduction in sublesional non-weight bearing (levator ani/bulbocavernosus [LABC]) muscle mass, and reduced prostate mass. Both TE doses fully preserved LABC mass, while only high-dose TE ameliorated hindlimb muscle losses. TE also dose dependently increased prostate mass. Our findings provide the first evidence indicating that high-dose TE fully prevents hindlimb cancellous bone loss and concomitantly ameliorates muscle loss after SCI, while low-dose TE produces much less profound musculoskeletal benefit. Testosterone-induced prostate enlargement, however, represents a potential barrier to the clinical implementation of high-dose TE as a means of preserving musculoskeletal tissue after SCI. PMID:24378197

MO-PIS-Exhibit Hall-01: Imaging: CT Dose Optimization Technologies I

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

Denison, K; Smith, S

Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The imaging topic this year is CT scanner dose optimization capabilities. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Dose Optimization Capabilities of GE Computed Tomography Scanners Presentation Time: 11:15 – 11:45 AM GE Healthcare is dedicated to the delivery of high quality clinical images through the development of technologies, whichmore » optimize the application of ionizing radiation. In computed tomography, dose management solutions fall into four categories: employs projection data and statistical modeling to decrease noise in the reconstructed image - creating an opportunity for mA reduction in the acquisition of diagnostic images. Veo represents true Model Based Iterative Reconstruction (MBiR). Using high-level algorithms in tandem with advanced computing power, Veo enables lower pixel noise standard deviation and improved spatial resolution within a single image. Advanced Adaptive Image Filters allow for maintenance of spatial resolution while reducing image noise. Examples of adaptive image space filters include Neuro 3-D filters and Cardiac Noise Reduction Filters. AutomA adjusts mA along the z-axis and is the CT equivalent of auto exposure control in conventional x-ray systems. Dynamic Z-axis Tracking offers an additional opportunity for dose reduction in helical acquisitions while SmartTrack Z-axis Tracking serves to ensure beam, collimator and detector alignment during tube rotation. SmartmA provides angular mA modulation. ECG Helical Modulation reduces mA during the systolic phase of the heart cycle. SmartBeam optimization uses bowtie beam-shaping hardware and software to filter off-axis x-rays - minimizing dose and reducing x-ray scatter. The DICOM Radiation Dose Structured Report (RDSR) generates a dose report at the conclusion of every examination. Dose Check preemptively notifies CT operators when scan parameters exceed user-defined dose thresholds. DoseWatch is an information technology application providing vendor-agnostic dose tracking and analysis for CT (and all other diagnostic x-ray modalities) SnapShot Pulse improves coronary CTA dose management. VolumeShuttle uses two acquisitions to increase coverage, decrease dose, and conserve on contrast administration. Color-Coding for Kids applies the Broselow-Luten Pediatric System to facilitate pediatric emergency care and reduce medical errors. FeatherLight achieves dose optimization through pediatric procedure-based protocols. Adventure Series scanners provide a child-friendly imaging environment promoting patient cooperation with resultant reduction in retakes and patient motion. Philips CT Dose Optimization Tools and Advanced Reconstruction Presentation Time: 11:45 ‘ 12:15 PM The first part of the talk will cover “Dose Reduction and Dose Optimization Technologies” present in Philips CT Scanners. The main Technologies to be presented include: DoseRight and tube current modulation (DoseRight, Z-DOM, 3D-DOM, DoseRight Cardiac) Special acquisition modes Beam filtration and beam shapers Eclipse collimator and ClearRay collimator NanoPanel detector DoseRight will cover automatic tube current selection that automatically adjusts the dose for the individual patient. The presentation will explore the modulation techniques currently employed in Philips CT scanners and will include the algorithmic concepts as well as illustrative examples. Modulation and current selection technologies to be covered include the Automatic Current Selection component of DoseRight, ZDOM longitudinal dose modulation, 3D-DOM (combination of longitudinal and rotational dose modulation), Cardiac Dose right (an ECG based dose modulation scheme), and the DoseRight Index (DRI) IQ index. The special acquisition modes covers acquisition techniques such as prospective gating that is designed to reduce exposure to the patient through the Cardiac Step and Shoot scan mode. This mode can substitute the much higher dose retrospective scan modes for certain types of cardiac imaging. The beam filtration and beam shaper portion will discuss the variety of filtration and beam shaping configurations available on Philips scanners. This topic includes the x-ray beam characteristics, tube filtration as well as dose compensator characteristics. The Eclipse collimator, ClearRay collimator and the NanoPanel detector portion will discuss additional technologies specific to wide coverage CT that address some of the unique challenges encountered and techniques employed to optimize image quality and optimize dose utilization. The Eclipse collimator reduces extraneous exposure by actively blocking the radiation tails at either end of helical scans that do not contribute to the image generation. The ClearRay collimator and the NanoPanel detector optimize the quality of the signal that reaches the detectors by addressing the increased scattered radiation present in wide coverage and the NanoPanel detector adds superior electronic noise characteristics valuable when imaging at a low dose level. The second part of the talk will present “Advanced Reconstruction Technologies” currently available on Philips CT Scanners. The talk will cover filtered back projection (FBP), iDose4 and Iterative Model Reconstruction (IMR). Each reconstruction method will include a discussion of the algorithm as well as similarities and differences between the algorithms. Examples illustrating the merits of each algorithm will be presented, and techniques and metrics to characterize the performance of each type of algorithm will be presented. The Filtered Back projection portion will discuss and provide a brief summary of relevant standard image reconstruction techniques in common use, and discuss the common tradeoffs when using the FBP algorithm. The iDose4 portion will present the algorithms used for iDose4 as well the different levels. The meaning of different levels of iDose4 available will be presented and quantified. Guidelines for selection iDose4 parameters based on the imaging need will be explained. The different image quality goals available with iDose4 and specifically how iDose4 enables noise reduction, spatial resolution improvement or both will be explained. The approaches to leveraging the benefits of iDose4 such as improved spatial resolution, decreased noise, and artifact prevention will be described and quantified; and measurements and metrics behind the improvements will be presented. The image quality benefits in specific imaging situations as well as how to best combine the technology with other dose reduction strategies to ensure the best image quality at a given dose level will be presented. Insight into the IMR algorithm as well as contrast to the iDose4 techniques and performance characteristics will be discussed. Metrics and techniques for characterizing this class of algorithm and IQ performance will be presented. The image quality benefits and the dose reduction capabilities of IMR will be explored. Illustrative examples of the noise reduction, spatial resolution improvement, and low contrast detectability improvements of the reconstruction method will be presented: clinical cases and phantom measurements demonstrating the benefits of IMR in the areas of low dose imaging, spatial resolution and low contrast resolution are discussed and the technical details behind the measurements will be presented compared to both iDose4 and traditional filtered back projection (FBP)« less

TU-AB-303-01: A Feasibility Study for Dynamic Adaptive Therapy of Non-Small Cell Lung Cancer

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

Kim, M; Phillips, M

2015-06-15

Purpose: To compare plans for NSCLC optimized using Dynamic Adaptive Therapy (DAT) with conventional IMRT optimization. DAT adapts plans based on changes in the target volume by using dynamic programing techniques to consider expected changes into the optimization process. Information gathered during treatment, e.g. from CBCT, is incorporated into the optimization. Methods and materials: DAT is formulated using stochastic control formalism, which minimizes the total expected number of tumor cells at the end of a treatment course subject to uncertainty inherent in the tumor response and organs-at-risk (OAR) dose constraints. This formulation allows for non-stationary dose distribution as well asmore » non-stationary fractional dose as needed to achieve a series of optimal plans that are conformal to tumor over time. Sixteen phantom cases with various sizes and locations of tumors, and OAR geometries were generated. Each case was planned with DAT and conventional IMRT (60Gy/30fx). Tumor volume change over time was obtained by using, daily MVCT-based, two-level cell population model. Monte Carlo simulations have been performed for each treatment course to account for uncertainty in tumor response. Same OAR dose constraints were applied for both methods. The frequency of plan modification was varied to 1, 2, 5 (weekly), and 29 (daily). The final average tumor dose and OAR doses have been compared to quantify the potential benefit of DAT. Results: The average tumor max, min, mean, and D95 resulted from DAT were 124.0–125.2%, 102.1–114.7%, 113.7–123.4%, and 102.0–115.9% (range dependent on the frequency of plan modification) of those from conventional IMRT. Cord max, esophagus max, lung mean, heart mean, and unspecified tissue D05 resulted from AT were 84–102.4%, 99.8–106.9%, 66.9–85.6%, 58.2–78.8%, and 85.2–94.0% of those from conventional IMRT. Conclusions: Significant tumor dose increase and OAR dose reduction, especially with parallel OAR with mean or dose-volume constraints, can be achieved using DAT.« less

An adaptive algorithm for the detection of microcalcifications in simulated low-dose mammography.

PubMed

Treiber, O; Wanninger, F; Führ, H; Panzer, W; Regulla, D; Winkler, G

2003-02-21

This paper uses the task of microcalcification detection as a benchmark problem to assess the potential for dose reduction in x-ray mammography. We present the results of a newly developed algorithm for detection of microcalcifications as a case study for a typical commercial film-screen system (Kodak Min-R 2000/2190). The first part of the paper deals with the simulation of dose reduction for film-screen mammography based on a physical model of the imaging process. Use of a more sensitive film-screen system is expected to result in additional smoothing of the image. We introduce two different models of that behaviour, called moderate and strong smoothing. We then present an adaptive, model-based microcalcification detection algorithm. Comparing detection results with ground-truth images obtained under the supervision of an expert radiologist allows us to establish the soundness of the detection algorithm. We measure the performance on the dose-reduced images in order to assess the loss of information due to dose reduction. It turns out that the smoothing behaviour has a strong influence on detection rates. For moderate smoothing. a dose reduction by 25% has no serious influence on the detection results. whereas a dose reduction by 50% already entails a marked deterioration of the performance. Strong smoothing generally leads to an unacceptable loss of image quality. The test results emphasize the impact of the more sensitive film-screen system and its characteristics on the problem of assessing the potential for dose reduction in film-screen mammography. The general approach presented in the paper can be adapted to fully digital mammography.

An adaptive algorithm for the detection of microcalcifications in simulated low-dose mammography

NASA Astrophysics Data System (ADS)

Treiber, O.; Wanninger, F.; Führ, H.; Panzer, W.; Regulla, D.; Winkler, G.

2003-02-01

This paper uses the task of microcalcification detection as a benchmark problem to assess the potential for dose reduction in x-ray mammography. We present the results of a newly developed algorithm for detection of microcalcifications as a case study for a typical commercial film-screen system (Kodak Min-R 2000/2190). The first part of the paper deals with the simulation of dose reduction for film-screen mammography based on a physical model of the imaging process. Use of a more sensitive film-screen system is expected to result in additional smoothing of the image. We introduce two different models of that behaviour, called moderate and strong smoothing. We then present an adaptive, model-based microcalcification detection algorithm. Comparing detection results with ground-truth images obtained under the supervision of an expert radiologist allows us to establish the soundness of the detection algorithm. We measure the performance on the dose-reduced images in order to assess the loss of information due to dose reduction. It turns out that the smoothing behaviour has a strong influence on detection rates. For moderate smoothing, a dose reduction by 25% has no serious influence on the detection results, whereas a dose reduction by 50% already entails a marked deterioration of the performance. Strong smoothing generally leads to an unacceptable loss of image quality. The test results emphasize the impact of the more sensitive film-screen system and its characteristics on the problem of assessing the potential for dose reduction in film-screen mammography. The general approach presented in the paper can be adapted to fully digital mammography.

Evaluation of an iterative model-based CT reconstruction algorithm by intra-patient comparison of standard and ultra-low-dose examinations.

PubMed

Noël, Peter B; Engels, Stephan; Köhler, Thomas; Muenzel, Daniela; Franz, Daniela; Rasper, Michael; Rummeny, Ernst J; Dobritz, Martin; Fingerle, Alexander A

2018-01-01

Background The explosive growth of computer tomography (CT) has led to a growing public health concern about patient and population radiation dose. A recently introduced technique for dose reduction, which can be combined with tube-current modulation, over-beam reduction, and organ-specific dose reduction, is iterative reconstruction (IR). Purpose To evaluate the quality, at different radiation dose levels, of three reconstruction algorithms for diagnostics of patients with proven liver metastases under tumor follow-up. Material and Methods A total of 40 thorax-abdomen-pelvis CT examinations acquired from 20 patients in a tumor follow-up were included. All patients were imaged using the standard-dose and a specific low-dose CT protocol. Reconstructed slices were generated by using three different reconstruction algorithms: a classical filtered back projection (FBP); a first-generation iterative noise-reduction algorithm (iDose4); and a next generation model-based IR algorithm (IMR). Results The overall detection of liver lesions tended to be higher with the IMR algorithm than with FBP or iDose4. The IMR dataset at standard dose yielded the highest overall detectability, while the low-dose FBP dataset showed the lowest detectability. For the low-dose protocols, a significantly improved detectability of the liver lesion can be reported compared to FBP or iDose 4 ( P = 0.01). The radiation dose decreased by an approximate factor of 5 between the standard-dose and the low-dose protocol. Conclusion The latest generation of IR algorithms significantly improved the diagnostic image quality and provided virtually noise-free images for ultra-low-dose CT imaging.

Analysis of esophageal-sparing treatment plans for patients with high-grade esophagitis.

PubMed

Niedzielski, Joshua; Bluett, Jaques B; Williamson, Ryan T; Liao, Zhongxing; Gomez, Daniel R; Court, Laurence E

2013-07-08

We retrospectively generated IMRT plans for 14 NSCLC patients who had experienced grade 2 or 3 esophagitis (CTCAE version 3.0). We generated 11-beam and reduced esophagus dose plan types to compare changes in the volume and length of esophagus receiving doses of 50, 55, 60, 65, and 70 Gy. Changes in planning target volume (PTV) dose coverage were also compared. If necessary, plans were renormalized to restore 95% PTV coverage. The critical organ doses examined were mean lung dose, mean heart dose, and volume of spinal cord receiving 50 Gy. The effect of interfractional motion was determined by applying a three-dimensional rigid shift to the dose grid. For the esophagus plan, the mean reduction in esophagus V50, V55, V60, V65, and V70 Gy was 2.8, 4.1, 5.9, 7.3, and 9.5 cm(3), respectively, compared with the clinical plan. The mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 2.0, 3.0, 3.8, 4.0, and 4.6 cm, respectively. The mean heart and lung dose decreased 3.0 Gy and 2.4 Gy, respectively. The mean decreases in 90% and 95% PTV coverage were 1.7 Gy and 2.8 Gy, respectively. The normalized plans' mean reduction of esophagus V50, V55, V60, V65, and V70 Gy were 1.6, 2.0, 2.9, 3.9, and 5.5 cm(3), respectively, compared with the clinical plans. The normalized plans' mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 4.9, 5.2, 5.4, 4.9, and 4.8 cm, respectively. The mean reduction in maximum esophagus dose with simulated interfractional motion was 3.0 Gy and 1.4 Gy for the clinical plan type and the esophagus plan type, respectively. In many cases, the esophagus dose can be greatly reduced while maintaining critical structure dose constraints. PTV coverage can be restored by increasing beam output, while still obtaining a dose reduction to the esophagus and maintaining dose constraints.

Analysis of esophageal‐sparing treatment plans for patients with high‐grade esophagitis

PubMed Central

Bluett, Jaques B.; Williamson, Ryan T.; Liao, Zhongxing; Gomez, Daniel R.; Court, Laurence E.

2013-01-01

We retrospectively generated IMRT plans for 14 NSCLC patients who had experienced grade 2 or 3 esophagitis (CTCAE version 3.0). We generated 11‐beam and reduced esophagus dose plan types to compare changes in the volume and length of esophagus receiving doses of 50, 55, 60, 65, and 70 Gy. Changes in planning target volume (PTV) dose coverage were also compared. If necessary, plans were renormalized to restore 95% PTV coverage. The critical organ doses examined were mean lung dose, mean heart dose, and volume of spinal cord receiving 50 Gy. The effect of interfractional motion was determined by applying a three‐dimensional rigid shift to the dose grid. For the esophagus plan, the mean reduction in esophagus V50, V55, V60, V65, and V70 Gy was 2.8, 4.1, 5.9, 7.3, and 9.5 cm3, respectively, compared with the clinical plan. The mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 2.0, 3.0, 3.8, 4.0, and 4.6 cm, respectively. The mean heart and lung dose decreased 3.0 Gy and 2.4 Gy, respectively. The mean decreases in 90% and 95% PTV coverage were 1.7 Gy and 2.8 Gy, respectively. The normalized plans’ mean reduction of esophagus V50, V55, V60, V65, and V70 Gy were 1.6, 2.0, 2.9, 3.9, and 5.5 cm3, respectively, compared with the clinical plans. The normalized plans’ mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 4.9, 5.2, 5.4, 4.9, and 4.8 cm, respectively. The mean reduction in maximum esophagus dose with simulated interfractional motion was 3.0 Gy and 1.4 Gy for the clinical plan type and the esophagus plan type, respectively. In many cases, the esophagus dose can be greatly reduced while maintaining critical structure dose constraints. PTV coverage can be restored by increasing beam output, while still obtaining a dose reduction to the esophagus and maintaining dose constraints. PACS number: 87.53 Tf PMID:23835390

Efficacy and safety of a 14-day administration of tolvaptan in the treatment of patients with ascites in hepatic oedema.

PubMed

Sakaida, Isao; Yamashita, Satoyoshi; Kobayashi, Tomoo; Komatsu, Masafumi; Sakai, Terufumi; Komorizono, Yasuji; Okada, Mitsuru; Okita, Kiwamu

2013-06-01

To investigate the efficacy and safety of 14 days' orally administered tolvaptan as adjunctive treatment for hepatic oedema in Japanese liver cirrhosis patients with insufficient response to conventional diuretics, with the option to increase dose in those who did not respond initially. This multicentre, single-arm, phase 3 study allocated patients with liver cirrhosis and persistent ascites to 7-day treatment with 7.5 mg/day tolvaptan followed by an additional 7 days' treatment. Responders at day 7 (achieving ≥ 1 kg body-weight reduction) continued on 7.5 mg/day tolvaptan; nonresponders (<1 kg body-weight reduction) received 15 mg/day tolvaptan. Conventional diuretic treatment continued throughout. The primary endpoint was change in body weight from baseline, as a marker of ascites volume. A total of 51 patients received 7.5 mg/day tolvaptan for 7 days, which caused a significant reduction in mean body weight (55% response rate). During the second 7-day treatment period, 30 patients received 7.5 mg/day tolvaptan and 13 patients received tolvaptan 15 mg/day: response rates were 43% and 23%, respectively. Two serious adverse events were observed. Serum sodium was within normal range. Tolvaptan therapy for 14 days (with possible dose increase as necessary), in combination with conventional diuretics, effectively reduced body weight in patients with hepatic oedema.

Method for simulating dose reduction in digital mammography using the Anscombe transformation.

PubMed

Borges, Lucas R; Oliveira, Helder C R de; Nunes, Polyana F; Bakic, Predrag R; Maidment, Andrew D A; Vieira, Marcelo A C

2016-06-01

This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.

Dosimetric Advantages of Midventilation Compared With Internal Target Volume for Radiation Therapy of Pancreatic Cancer

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

Lens, Eelco, E-mail: e.lens@amc.uva.nl; Horst, Astrid van der; Versteijne, Eva

2015-07-01

Purpose: The midventilation (midV) approach can be used to take respiratory-induced pancreatic tumor motion into account during radiation therapy. In this study, the dosimetric consequences for organs at risk and tumor coverage of using a midV approach compared with using an internal target volume (ITV) were investigated. Methods and Materials: For each of the 18 patients, 2 treatment plans (25 × 2.0 Gy) were created, 1 using an ITV and 1 using a midV approach. The midV dose distribution was blurred using the respiratory-induced motion from 4-dimensional computed tomography. The resulting planning target volume (PTV) coverage for this blurred dosemore » distribution was analyzed; PTV coverage was required to be at least V{sub 95%} >98%. In addition, the change in PTV size and the changes in V{sub 10Gy}, V{sub 20Gy}, V{sub 30Gy}, V{sub 40Gy}, D{sub mean} and D{sub 2cc} for the stomach and for the duodenum were analyzed; differences were tested for significance using the Wilcoxon signed-rank test. Results: Using a midV approach resulted in sufficient target coverage. A highly significant PTV size reduction of 13.9% (P<.001) was observed. Also, all dose parameters for the stomach and duodenum, except the D{sub 2cc} of the duodenum, improved significantly (P≤.002). Conclusions: By using the midV approach to account for respiratory-induced tumor motion, a significant PTV reduction and significant dose reductions to the stomach and to the duodenum can be achieved when irradiating pancreatic tumors.« less

Impact of bisphosphonate drug burden in alveolar bone during orthodontic tooth movement in a rat model: a pilot study.

PubMed

Kaipatur, Neelambar R; Wu, Yuchin; Adeeb, Samer; Stevenson, Thomas R; Major, Paul W; Doschak, Michael R

2013-10-01

The aim of this pilot study was to investigate the effect of long-term bisphosphonate drug use (bone burden) on orthodontic tooth movement in a rat model. Sprague Dawley rats were used for orthodontic protraction of the maxillary first molars with nickel-titanium coil springs and temporary anchorage devices as anchorage. Four groups of 5 rats each were included in the study; the first 2 groups were dosed with alendronate or a vehicle during concurrent orthodontic tooth movement. The third and fourth groups were pretreated for 3 months with alendronate or vehicle injections, and bisphosphonate drug treatment was discontinued before orthodontic tooth movement. Tooth movement measurements were obtained at 0, 4, and 8 weeks using high-resolution in-vivo microcomputed tomography, and the tissues were analyzed with histology and dynamic labeling of bone turnover. Appreciable tooth movement was achieved during the 8-week duration of this study with nickel-titanium coil springs and temporary anchorage devices. Both bisphosphonate treatment groups exhibited reduced tooth movement compared with the vehicle-dosed controls with a tendency toward more severe reduction in the bisphosphonate predosed group. Concurrent dosing of the bisphosphonate drug resulted in 56% and 65% reductions in tooth protraction at the 4-week and 8-week times, respectively. The impact of bisphosphonate bone burden in retarding tooth movement was even greater, with 77% and 86% reductions in tooth movement at 4 and 8 weeks, respectively. In this study, we used a robust rat model of orthodontic tooth movement with temporary anchorage devices. It has provided evidence that the bone burden of previous bisphosphonate use will significantly inhibit orthodontic tooth movement. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study.

PubMed

Pivonello, Rosario; Petersenn, Stephan; Newell-Price, John; Findling, James W; Gu, Feng; Maldonado, Mario; Trovato, Andrew; Hughes, Gareth; Salgado, Luiz R; Lacroix, André; Schopohl, Jochen; Biller, Beverly M K

2014-09-01

Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease. Phase III study with double-blind randomization of two pasireotide doses. Patients (n = 162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels ≥1·5× upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900 μg bid). At month 3, patients with UFC ≤2 × ULN and not exceeding the baseline value continued their randomized dose; all others received 300 μg bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200 μg bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control. Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low-density lipoprotein (LDL)-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72·8% of patients. In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased. © 2014 John Wiley & Sons Ltd.

Susceptibility of Murine Norovirus and Hepatitis A Virus to Electron Beam Irradiation in Oysters and Quantifying the Reduction in Potential Infection Risks

PubMed Central

Praveen, Chandni; Dancho, Brooke A.; Kingsley, David H.; Calci, Kevin R.; Meade, Gloria K.; Mena, Kristina D.

2013-01-01

Consumption of raw oysters is an exposure route for human norovirus (NoV) and hepatitis A virus (HAV). Therefore, efficient postharvest oyster treatment technology is needed to reduce public health risks. This study evaluated the inactivation of HAV and the NoV research surrogate, murine norovirus-1 (MNV-1), in oysters (Crassostrea virginica) by electron beam (E-beam) irradiation. The reduction of potential infection risks was quantified for E-beam irradiation technology employed on raw oysters at various virus contamination levels. The E-beam dose required to reduce the MNV and HAV titer by 90% (D10 value) in whole oysters was 4.05 (standard deviations [SD], ±0.63) and 4.83 (SD, ±0.08) kGy, respectively. Microbial risk assessment suggests that if a typical serving of 12 raw oysters was contaminated with 105 PFU, a 5-kGy treatment would achieve a 12% reduction (from 4.49 out of 10 persons to 3.95 out of 10 persons) in NoV infection and a 16% reduction (from 9.21 out of 10 persons to 7.76 out of 10 persons) in HAV infections. If the serving size contained only 102 PFU of viruses, a 5-kGy treatment would achieve a 26% reduction (2.74 out of 10 persons to 2.03 out of 10 persons) of NoV and 91% reduction (2.1 out of 10 persons to 1.93 out of 100 persons) of HAV infection risks. This study shows that although E-beam processing cannot completely eliminate the risk of viral illness, infection risks can be reduced. PMID:23584781

Susceptibility of murine norovirus and hepatitis A virus to electron beam irradiation in oysters and quantifying the reduction in potential infection risks.

PubMed

Praveen, Chandni; Dancho, Brooke A; Kingsley, David H; Calci, Kevin R; Meade, Gloria K; Mena, Kristina D; Pillai, Suresh D

2013-06-01

Consumption of raw oysters is an exposure route for human norovirus (NoV) and hepatitis A virus (HAV). Therefore, efficient postharvest oyster treatment technology is needed to reduce public health risks. This study evaluated the inactivation of HAV and the NoV research surrogate, murine norovirus-1 (MNV-1), in oysters (Crassostrea virginica) by electron beam (E-beam) irradiation. The reduction of potential infection risks was quantified for E-beam irradiation technology employed on raw oysters at various virus contamination levels. The E-beam dose required to reduce the MNV and HAV titer by 90% (D(10) value) in whole oysters was 4.05 (standard deviations [SD], ±0.63) and 4.83 (SD, ±0.08) kGy, respectively. Microbial risk assessment suggests that if a typical serving of 12 raw oysters was contaminated with 10(5) PFU, a 5-kGy treatment would achieve a 12% reduction (from 4.49 out of 10 persons to 3.95 out of 10 persons) in NoV infection and a 16% reduction (from 9.21 out of 10 persons to 7.76 out of 10 persons) in HAV infections. If the serving size contained only 10(2) PFU of viruses, a 5-kGy treatment would achieve a 26% reduction (2.74 out of 10 persons to 2.03 out of 10 persons) of NoV and 91% reduction (2.1 out of 10 persons to 1.93 out of 100 persons) of HAV infection risks. This study shows that although E-beam processing cannot completely eliminate the risk of viral illness, infection risks can be reduced.

SU-F-J-17: Patient Localization Using MRI-Guided Soft Tissue for Head-And-Neck Radiotherapy: Indication for Margin Reduction and Its Feasibility

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

Qi, X; Yang, Y; Jack, N

Purpose: On-board MRI provides superior soft-tissue contrast, allowing patient alignment using tumor or nearby critical structures. This study aims to study H&N MRI-guided IGRT to analyze inter-fraction patient setup variations using soft-tissue targets and design appropriate CTV-to-PTV margin and clinical implication. Methods: 282 MR images for 10 H&N IMRT patients treated on a ViewRay system were retrospectively analyzed. Patients were immobilized using a thermoplastic mask on a customized headrest fitted in a radiofrequency coil and positioned to soft-tissue targets. The inter-fraction patient displacements were recorded to compute the PTV margins using the recipe: 2.5∑+0.7σ. New IMRT plans optimized on themore » revised PTVs were generated to evaluate the delivered dose distributions. An in-house dose deformation registration tool was used to assess the resulting dosimetric consequences when margin adaption is performed based on weekly MR images. The cumulative doses were compared to the reduced margin plans for targets and critical structures. Results: The inter-fraction displacements (and standard deviations), ∑ and σ were tabulated for MRI and compared to kVCBCT. The computed CTV-to-PTV margin was 3.5mm for soft-tissue based registration. There were minimal differences between the planned and delivered doses when comparing clinical and the PTV reduced margin plans: the paired t-tests yielded p=0.38 and 0.66 between the planned and delivered doses for the adapted margin plans for the maximum cord and mean parotid dose, respectively. Target V95 received comparable doses as planned for the reduced margin plans. Conclusion: The 0.35T MRI offers acceptable soft-tissue contrast and good spatial resolution for patient alignment and target visualization. Better tumor conspicuity from MRI allows soft-tissue based alignments with potentially improved accuracy, suggesting a benefit of margin reduction for H&N radiotherapy. The reduced margin plans (i.e., 2 mm) resulted in improved normal structure sparing and accurate dose delivery to achieve intended treatment goal under MR guidance.« less

Reduction of radiation exposure while maintaining high-quality fluoroscopic images during interventional cardiology using novel x-ray tube technology with extra beam filtering.

PubMed

den Boer, A; de Feyter, P J; Hummel, W A; Keane, D; Roelandt, J R

1994-06-01

Radiographic technology plays an integral role in interventional cardiology. The number of interventions continues to increase, and the associated radiation exposure to patients and personnel is of major concern. This study was undertaken to determine whether a newly developed x-ray tube deploying grid-switched pulsed fluoroscopy and extra beam filtering can achieve a reduction in radiation exposure while maintaining fluoroscopic images of high quality. Three fluoroscopic techniques were compared: continuous fluoroscopy, pulsed fluoroscopy, and a newly developed high-output pulsed fluoroscopy with extra filtering. To ascertain differences in the quality of images and to determine differences in patient entrance and investigator radiation exposure, the radiated volume curve was measured to determine the required high voltage levels (kVpeak) for different object sizes for each fluoroscopic mode. The fluoroscopic data of 124 patient procedures were combined. The data were analyzed for radiographic projections, image intensifier field size, and x-ray tube kilovoltage levels (kVpeak). On the basis of this analysis, a reference procedure was constructed. The reference procedure was tested on a phantom or dummy patient by all three fluoroscopic modes. The phantom was so designed that the kilovoltage requirements for each projection were comparable to those needed for the average patient. Radiation exposure of the operator and patient was measured during each mode. The patient entrance dose was measured in air, and the operator dose was measured by 18 dosimeters on a dummy operator. Pulsed compared with continuous fluoroscopy could be performed with improved image quality at lower kilovoltages. The patient entrance dose was reduced by 21% and the operator dose by 54%. High-output pulsed fluoroscopy with extra beam filtering compared with continuous fluoroscopy improved the image quality, lowered the kilovoltage requirements, and reduced the patient entrance dose by 55% and the operator dose by 69%. High-output pulsed fluoroscopy with a grid-switched tube and extra filtering improves the image quality and significantly reduces both the operator dose and patient dose.

A qualitative and quantitative analysis of radiation dose and image quality of computed tomography images using adaptive statistical iterative reconstruction.

PubMed

Hussain, Fahad Ahmed; Mail, Noor; Shamy, Abdulrahman M; Suliman, Alghamdi; Saoudi, Abdelhamid

2016-05-08

Image quality is a key issue in radiology, particularly in a clinical setting where it is important to achieve accurate diagnoses while minimizing radiation dose. Some computed tomography (CT) manufacturers have introduced algorithms that claim significant dose reduction. In this study, we assessed CT image quality produced by two reconstruction algorithms provided with GE Healthcare's Discovery 690 Elite positron emission tomography (PET) CT scanner. Image quality was measured for images obtained at various doses with both conventional filtered back-projection (FBP) and adaptive statistical iterative reconstruction (ASIR) algorithms. A stan-dard CT dose index (CTDI) phantom and a pencil ionization chamber were used to measure the CT dose at 120 kVp and an exposure of 260 mAs. Image quality was assessed using two phantoms. CT images of both phantoms were acquired at tube voltage (kV) of 120 with exposures ranging from 25 mAs to 400 mAs. Images were reconstructed using FBP and ASIR ranging from 10% to 100%, then analyzed for noise, low-contrast detectability, contrast-to-noise ratio (CNR), and modulation transfer function (MTF). Noise was 4.6 HU in water phantom images acquired at 260 mAs/FBP 120 kV and 130 mAs/50% ASIR 120 kV. The large objects (fre-quency < 7 lp/cm) retained fairly acceptable image quality at 130 mAs/50% ASIR, compared to 260 mAs/FBP. The application of ASIR for small objects (frequency >7 lp/cm) showed poor visibility compared to FBP at 260 mAs and even worse for images acquired at less than 130 mAs. ASIR blending more than 50% at low dose tends to reduce contrast of small objects (frequency >7 lp/cm). We concluded that dose reduction and ASIR should be applied with close attention if the objects to be detected or diagnosed are small (frequency > 7 lp/cm). Further investigations are required to correlate the small objects (frequency > 7 lp/cm) to patient anatomy and clinical diagnosis.

Evaluation of dexamethasone phosphate delivered by ocular iontophoresis for treating noninfectious anterior uveitis.

PubMed

Cohen, Amy E; Assang, Carol; Patane, Michael A; From, Stephen; Korenfeld, Michael

2012-01-01

Determine safe, effective, iontophoretic dose(s) of EGP-437 (dexamethasone phosphate formulated for iontophoresis) in patients with noninfectious anterior uveitis; evaluate systemic drug exposures. Prospective, phase I/II, multicenter, double-masked, parallel group, randomized clinical trial. Forty outpatients with anterior uveitis. Forty of 42 randomized patients received an iontophoresis treatment in 1 qualifying eye and completed the study. Patients were randomized into 1 of 4 iontophoresis dose groups (1.6, 4.8, 10.0, or 14.0 mA-min), treated with EGP-437 via the EyeGate II Delivery System (EGDS), and followed until day 28. The main outcome measures were anterior chamber cell (ACC) scores at days 14 and 28; time to ACC score of zero; proportion of patients with an ACC score reduction from baseline of ≥ 0.5 at day 28; mean change from baseline in ACC score at day 28; and the systemic exposures of dexamethasone and dexamethasone phosphate after EGP-437 treatment with the EGDS. After a single EGP-437 treatment, 19 of 40 patients (48%) achieved an ACC score of zero at day 14. By day 28, 24 of 40 patients (60%) achieved an ACC score of zero. A Kaplan-Meier analysis demonstrated that the 1.6 mA-min dose was the most effective and revealed an inverse dose response; median days to an ACC score of zero were 11.5 days in the 1.6 mA-min group versus 31 days in the 14.0 mA-min group. Twenty-six patients (65%) had an ACC score reduction from baseline of ≥ 0.5 at day 28. The mean change in ACC score from baseline to day 28 was -2.14 with a median of -2.00. Throughout the study, the mean intraocular pressure remained within normal range and mean best-corrected visual acuity at 4 meters remained relatively stable. Most adverse events were mild; no serious adverse events were reported. Pharmacokinetics results showed low short-term systemic exposure to dexamethasone after iontophoresis; no nonocular systemic corticosteroid-mediated effects were observed. Approximately two thirds of the patients reached an ACC score of zero within 28 days, after only receiving 1 iontophoresis treatment. The lower doses seemed to be the most effective, and treatments were well-tolerated. Proprietary or commercial disclosure may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Evaluation of an iterative model-based reconstruction of pediatric abdominal CT with regard to image quality and radiation dose.

PubMed

Aurumskjöld, Marie-Louise; Söderberg, Marcus; Stålhammar, Fredrik; von Steyern, Kristina Vult; Tingberg, Anders; Ydström, Kristina

2018-06-01

Background In pediatric patients, computed tomography (CT) is important in the medical chain of diagnosing and monitoring various diseases. Because children are more radiosensitive than adults, they require minimal radiation exposure. One way to achieve this goal is to implement new technical solutions, like iterative reconstruction. Purpose To evaluate the potential of a new, iterative, model-based method for reconstructing (IMR) pediatric abdominal CT at a low radiation dose and determine whether it maintains or improves image quality, compared to the current reconstruction method. Material and Methods Forty pediatric patients underwent abdominal CT. Twenty patients were examined with the standard dose settings and 20 patients were examined with a 32% lower radiation dose. Images from the standard examination were reconstructed with a hybrid iterative reconstruction method (iDose 4 ), and images from the low-dose examinations were reconstructed with both iDose 4 and IMR. Image quality was evaluated subjectively by three observers, according to modified EU image quality criteria, and evaluated objectively based on the noise observed in liver images. Results Visual grading characteristics analyses showed no difference in image quality between the standard dose examination reconstructed with iDose 4 and the low dose examination reconstructed with IMR. IMR showed lower image noise in the liver compared to iDose 4 images. Inter- and intra-observer variance was low: the intraclass coefficient was 0.66 (95% confidence interval = 0.60-0.71) for the three observers. Conclusion IMR provided image quality equivalent or superior to the standard iDose 4 method for evaluating pediatric abdominal CT, even with a 32% dose reduction.

Comparison of a new noncoplanar intensity-modulated radiation therapy technique for craniospinal irradiation with 3 coplanar techniques

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

Hansen, Anders T., E-mail: andehans@rm.dk; Lukacova, Slavka; Lassen-Ramshad, Yasmin

2015-01-01

When standard conformal x-ray technique for craniospinal irradiation is used, it is a challenge to achieve satisfactory dose coverage of the target including the area of the cribriform plate, while sparing organs at risk. We present a new intensity-modulated radiation therapy (IMRT), noncoplanar technique, for delivering irradiation to the cranial part and compare it with 3 other techniques and previously published results. A total of 13 patients who had previously received craniospinal irradiation with standard conformal x-ray technique were reviewed. New treatment plans were generated for each patient using the noncoplanar IMRT-based technique, a coplanar IMRT-based technique, and a coplanarmore » volumetric-modulated arch therapy (VMAT) technique. Dosimetry data for all patients were compared with the corresponding data from the conventional treatment plans. The new noncoplanar IMRT technique substantially reduced the mean dose to organs at risk compared with the standard radiation technique. The 2 other coplanar techniques also reduced the mean dose to some of the critical organs. However, this reduction was not as substantial as the reduction obtained by the noncoplanar technique. Furthermore, compared with the standard technique, the IMRT techniques reduced the total calculated radiation dose that was delivered to the normal tissue, whereas the VMAT technique increased this dose. Additionally, the coverage of the target was significantly improved by the noncoplanar IMRT technique. Compared with the standard technique, the coplanar IMRT and the VMAT technique did not improve the coverage of the target significantly. All the new planning techniques increased the number of monitor units (MU) used—the noncoplanar IMRT technique by 99%, the coplanar IMRT technique by 122%, and the VMAT technique by 26%—causing concern for leak radiation. The noncoplanar IMRT technique covered the target better and decreased doses to organs at risk compared with the other techniques. All the new techniques increased the number of MU compared with the standard technique.« less

Dose of physical activity, physical functioning and disability risk in mobility-limited older adults: Results from the LIFE study randomized trial

PubMed Central

Guralnik, Jack M.; King, Abby C.; Pahor, Marco; McDermott, Mary M.; Tudor-Locke, Catrine; Manini, Todd M.; Glynn, Nancy W.; Marsh, Anthony P.; Axtell, Robert S.; Hsu, Fang-Chi; Rejeski, W. Jack

2017-01-01

Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70–89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P < 0.001) (highest versus the lowest quartile of physical activity change HR 0.23 ((95% CI:0.10–0.52) P = 0.001) in the physical activity arm. We observed a dose-dependent effect of objectively monitored physical activity on physical functioning and onset of major mobility disability. Relatively small increases (> 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes. Trial registration: ClinicalsTrials.gov NCT00116194 PMID:28820909

Dose of physical activity, physical functioning and disability risk in mobility-limited older adults: Results from the LIFE study randomized trial.

PubMed

Fielding, Roger A; Guralnik, Jack M; King, Abby C; Pahor, Marco; McDermott, Mary M; Tudor-Locke, Catrine; Manini, Todd M; Glynn, Nancy W; Marsh, Anthony P; Axtell, Robert S; Hsu, Fang-Chi; Rejeski, W Jack

2017-01-01

Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70-89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P < 0.001) (highest versus the lowest quartile of physical activity change HR 0.23 ((95% CI:0.10-0.52) P = 0.001) in the physical activity arm. We observed a dose-dependent effect of objectively monitored physical activity on physical functioning and onset of major mobility disability. Relatively small increases (> 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes. ClinicalsTrials.gov NCT00116194.

Influence of post exposure bake time on EUV photoresist RLS trade-off

NASA Astrophysics Data System (ADS)

Vesters, Yannick; De Simone, Danilo; De Gendt, Stefan

2017-03-01

To achieve high volume manufacturing, EUV photoresists need to push back the "RLS trade-off" by simultaneously improving Resolution, Line-Width Roughness and Sensitivity (exposure dose). Acid diffusion in chemically amplified resist is known to impact these performances. This work studies the diffusion of acid in chemically amplified resist by varying the post exposure bake duration while monitoring the evolution of CD and LWR for 6 chemically amplified EUV photoresists (CAR). We observed a first regime where both CD and LWR quickly decrease during the first 30s of post exposure bake (PEB). This can be related to the deprotection reaction taking place in the exposed part of the resist. After 60s the decrease in CD and LWR slows down significantly, likely related to a regime of acid diffusion from exposed to unexposed region, and acid-quencher neutralization at the interface of these two regions. We tested two resists with different protecting group and the one having lower activation energy shows a faster CD change in the second regime, resulting in a worsening of LWR for longer PEB time. On the contrary, a resist with a high quencher loading shows reduced net diffusion of acid towards the unexposed region and controls the resist edge profile. In other words longer PEB does not degrade LWR, but as it reduces the line CD, sensitivity is impacted. With an appropriate ratio selection of quencher to PAG, an EUV dose reduction of up to 12% can be achieved with a change from a standard 60 second to a 240 second PEB time, while keeping LWR and resolution constant and therefore pushing the RLS performances. Finally, we confirmed that the observations on positive tone development (PTD) resist could be applied to negative tone development (NTD) resist: with a high quencher NTD resist we observed a dose reduction of 8% for longer PEB time, keeping LWR and resolution constant.

Systematic Evaluation of the Efficacy of Chlorine Dioxide in Decontamination of Building Interior Surfaces Contaminated with Anthrax Spores▿

PubMed Central

Rastogi, Vipin K.; Ryan, Shawn P.; Wallace, Lalena; Smith, Lisa S.; Shah, Saumil S.; Martin, G. Blair

2010-01-01

Efficacy of chlorine dioxide (CD) gas generated by two distinct generation systems, Sabre (wet system with gas generated in water) and ClorDiSys (dry system with gas generated in air), was evaluated for inactivation of Bacillus anthracis spores on six building interior surfaces. The six building materials included carpet, acoustic ceiling tile, unpainted cinder block, painted I-beam steel, painted wallboard, and unpainted pinewood. There was no statistically significant difference in the data due to the CD generation technology at a 95% confidence level. Note that a common method of CD gas measurement was used for both wet and dry CD generation types. Doses generated by combinations of different concentrations of CD gas (500, 1,000, 1,500, or 3,000 parts per million of volume [ppmv]) and exposure times (ranging between 0.5 and 12 h) were used to evaluate the relative role of fumigant exposure period and total dose in the decontamination of building surfaces. The results showed that the time required to achieve at least a 6-log reduction in viable spores is clearly a function of the material type on which the spores are inoculated. The wood and cinder block coupons required a longer exposure time to achieve a 6-log reduction. The only material showing a clear statistical difference in rate of decay of viable spores as a function of concentration was cinder block. For all other materials, the profile of spore kill (i.e., change in number of viable spores with exposure time) was not dependent upon fumigant concentration (500 to 3,000 ppmv). The CD dose required for complete spore kill on biological indicators (typically, 1E6 spores of Bacillus atrophaeus on stainless steel) was significantly less than that required for decontamination of most of the building materials tested. PMID:20305025

Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes.

PubMed

Chua, Benjamin; Min, Myo; Wood, Maree; Edwards, Sarah; Hoffmann, Matthew; Greenham, Stuart; Kovendy, Andrew; McKay, Michael J; Shakespeare, Thomas P

2013-08-01

There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. Seventy-five eligible patients received either 64 Gy (19%) or 66 Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy < 60% and V60Gy < 40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy < 35% and V65Gy < 17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy < 50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastroinestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

Systematic evaluation of the efficacy of chlorine dioxide in decontamination of building interior surfaces contaminated with anthrax spores.

PubMed

Rastogi, Vipin K; Ryan, Shawn P; Wallace, Lalena; Smith, Lisa S; Shah, Saumil S; Martin, G Blair

2010-05-01

Efficacy of chlorine dioxide (CD) gas generated by two distinct generation systems, Sabre (wet system with gas generated in water) and ClorDiSys (dry system with gas generated in air), was evaluated for inactivation of Bacillus anthracis spores on six building interior surfaces. The six building materials included carpet, acoustic ceiling tile, unpainted cinder block, painted I-beam steel, painted wallboard, and unpainted pinewood. There was no statistically significant difference in the data due to the CD generation technology at a 95% confidence level. Note that a common method of CD gas measurement was used for both wet and dry CD generation types. Doses generated by combinations of different concentrations of CD gas (500, 1,000, 1,500, or 3,000 parts per million of volume [ppmv]) and exposure times (ranging between 0.5 and 12 h) were used to evaluate the relative role of fumigant exposure period and total dose in the decontamination of building surfaces. The results showed that the time required to achieve at least a 6-log reduction in viable spores is clearly a function of the material type on which the spores are inoculated. The wood and cinder block coupons required a longer exposure time to achieve a 6-log reduction. The only material showing a clear statistical difference in rate of decay of viable spores as a function of concentration was cinder block. For all other materials, the profile of spore kill (i.e., change in number of viable spores with exposure time) was not dependent upon fumigant concentration (500 to 3,000 ppmv). The CD dose required for complete spore kill on biological indicators (typically, 1E6 spores of Bacillus atrophaeus on stainless steel) was significantly less than that required for decontamination of most of the building materials tested.

SparseCT: interrupted-beam acquisition and sparse reconstruction for radiation dose reduction

NASA Astrophysics Data System (ADS)

Koesters, Thomas; Knoll, Florian; Sodickson, Aaron; Sodickson, Daniel K.; Otazo, Ricardo

2017-03-01

State-of-the-art low-dose CT methods reduce the x-ray tube current and use iterative reconstruction methods to denoise the resulting images. However, due to compromises between denoising and image quality, only moderate dose reductions up to 30-40% are accepted in clinical practice. An alternative approach is to reduce the number of x-ray projections and use compressed sensing to reconstruct the full-tube-current undersampled data. This idea was recognized in the early days of compressed sensing and proposals for CT dose reduction appeared soon afterwards. However, no practical means of undersampling has yet been demonstrated in the challenging environment of a rapidly rotating CT gantry. In this work, we propose a moving multislit collimator as a practical incoherent undersampling scheme for compressed sensing CT and evaluate its application for radiation dose reduction. The proposed collimator is composed of narrow slits and moves linearly along the slice dimension (z), to interrupt the incident beam in different slices for each x-ray tube angle (θ). The reduced projection dataset is then reconstructed using a sparse approach, where 3D image gradients are employed to enforce sparsity. The effects of the collimator slits on the beam profile were measured and represented as a continuous slice profile. SparseCT was tested using retrospective undersampling and compared against commercial current-reduction techniques on phantoms and in vivo studies. Initial results suggest that SparseCT may enable higher performance than current-reduction, particularly for high dose reduction factors.

Bortezomib for acute humoral rejection treatment at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City: an update.

PubMed

Leyva, Sergio; Marino, Lluvia A; Alberú, Josefina; Morales-Buenrostro, Luis E

2010-01-01

The use of bortezomib as a treatment modality of AHR improved and stabilized graft function (clinical response) in the majority of patients. Its use in single dose, even combined with rituximab, does not seem to be useful to obtain a sustained clinical response, or to reduce HLAabs level. The use of 4 doses of bortezomib in days 1, 4, 7, and 10 (1.3 mg/m2 BSA each) plus plasmapheresis produced both a good clinical response and a reduction in DSA. Moving forward, it will be necessary to define the long-term effectiveness of bortezomib and whether rituximab administration is indispensable to achieve this goal. Until now, it is evident that many patients needed retreatment and they were well tolerated.

Overcoming adaptive resistance in mucoepidermoid carcinoma through inhibition of the IKK-β/IκBα/NFκB axis

PubMed Central

Wagner, Vivian P.; Martins, Marco A.T.; Martins, Manoela D.; Warner, Kristy A.; Webber, Liana P.; Squarize, Cristiane H.; Nör, Jacques E.; Castilho, Rogerio M.

2016-01-01

Patients with mucoepidermoid carcinoma (MEC) experience low survival rates and high morbidity following treatment, yet the intrinsic resistance of MEC cells to ionizing radiation (IR) and the mechanisms underlying acquired resistance remain unexplored. Herein, we demonstrated that low doses of IR intrinsically activated NFκB in resistant MEC cell lines. Moreover, resistance was significantly enhanced in IR-sensitive cell lines when NFκB pathway was stimulated. Pharmacological inhibition of the IKK-β/IκBα/NFκB axis, using a single dose of FDA-approved Emetine, led to a striking sensitization of MEC cells to IR and a reduction in cancer stem cells. We achieved a major step towards better understanding the basic mechanisms involved in IR-adaptive resistance in MEC cell lines and how to efficiently overcome this critical problem. PMID:27682876

Low-dose CT for quantitative analysis in acute respiratory distress syndrome

PubMed Central

2013-01-01

Introduction The clinical use of serial quantitative computed tomography (CT) to characterize lung disease and guide the optimization of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) is limited by the risk of cumulative radiation exposure and by the difficulties and risks related to transferring patients to the CT room. We evaluated the effects of tube current-time product (mAs) variations on quantitative results in healthy lungs and in experimental ARDS in order to support the use of low-dose CT for quantitative analysis. Methods In 14 sheep chest CT was performed at baseline and after the induction of ARDS via intravenous oleic acid injection. For each CT session, two consecutive scans were obtained applying two different mAs: 60 mAs was paired with 140, 15 or 7.5 mAs. All other CT parameters were kept unaltered (tube voltage 120 kVp, collimation 32 × 0.5 mm, pitch 0.85, matrix 512 × 512, pixel size 0.625 × 0.625 mm). Quantitative results obtained at different mAs were compared via Bland-Altman analysis. Results Good agreement was observed between 60 mAs and 140 mAs and between 60 mAs and 15 mAs (all biases less than 1%). A further reduction of mAs to 7.5 mAs caused an increase in the bias of poorly aerated and nonaerated tissue (-2.9% and 2.4%, respectively) and determined a significant widening of the limits of agreement for the same compartments (-10.5% to 4.8% for poorly aerated tissue and -5.9% to 10.8% for nonaerated tissue). Estimated mean effective dose at 140, 60, 15 and 7.5 mAs corresponded to 17.8, 7.4, 2.0 and 0.9 mSv, respectively. Image noise of scans performed at 140, 60, 15 and 7.5 mAs corresponded to 10, 16, 38 and 74 Hounsfield units, respectively. Conclusions A reduction of effective dose up to 70% has been achieved with minimal effects on lung quantitative results. Low-dose computed tomography provides accurate quantitative results and could be used to characterize lung compartment distribution and possibly monitor time-course of ARDS with a lower risk of exposure to ionizing radiation. A further radiation dose reduction is associated with lower accuracy in quantitative results. PMID:24004842

Mathematical models of cervical cancer prevention in Latin America and the Caribbean.

PubMed

Goldie, Sue J; Diaz, Mireia; Constenla, Dagna; Alvis, Nelson; Andrus, Jon Kim; Kim, Sun-Young

2008-08-19

Using population and epidemiologic data for 33 countries in Latin America and the Caribbean (LAC), a model-based approach estimated averted cervical cancer cases and deaths, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (I$/DALY averted) for human papillomavirus (HPV) vaccination of young adolescent girls. Absolute reduction in lifetime cancer risk varied between countries, depending on incidence, proportion attributable to HPV-16 and 18, and population age-structure; for example, with 70% coverage, cancer reduction ranged from 40% in Mexico to more than 50% in Argentina. Screening of women over age 30 three times per lifetime, after vaccinating them as pre-adolescents, is expected to provide a relative increase of 25% to 30% in mortality reduction. Countries with the highest risk of cancer (age-standardized rate > 33.6) accounted for only 34% of deaths averted with vaccination, highlighting why a regional universal vaccination approach will be most effective in reducing the overall global burden. At I$25 per vaccinated girl ($5 per dose), for all 33 countries, the cost per DALY averted is less than I$400; at I$10 ($2 per dose) the vaccine is cost saving in 26 out of 33 countries. For all countries, ratios become less attractive (i.e., increase) as the cost of the vaccine increases. For example, at current vaccine prices ($120 per dose), the cost per DALY averted is I$7,300 in Mexico, I$3,700 in Nicaragua, and I$6,300 in Costa Rica. Vaccine price has an even greater effect on predicted affordability. For the 33 countries, vaccinating 5 consecutive birth cohorts at 70% coverage would cost $360 million at $5.00 per dose, $811 million at $12.25 per dose, and $1.26 billion at $19.50 per dose. In the LAC region, if effective delivery mechanisms can achieve high coverage rates in young adolescent girls, vaccination against HPV-16 and 18 will provide similar health value for resources invested as other new vaccines such as rotavirus. If the cost per vaccinated girl is less than I$25 HPV-16/18 vaccination would be very cost-effective in all 33 countries; for it to be affordable, costs may need to be lower.

Evaluating strategies for reducing scattered radiation in fixed-imaging hybrid operating suites.

PubMed

Miller, Claire; Kendrick, Daniel; Shevitz, Andrew; Kim, Ann; Baele, Henry; Jordan, David; Kashyap, Vikram S

2018-04-01

High-resolution fixed C-arm fluoroscopic systems allow high-quality endovascular imaging but come at a cost of greater scatter radiation generation and increased occupational exposure for surgeons. The purpose of this study was to evaluate the efficacy of two methods in reducing scattered radiation exposure. There were 164 endovascular cases analyzed in three phases. In phase 1 (P1), baseline radiation exposure was calculated. In phase 2 (P2), staff used real-time radiation dose monitoring (dosimetry badges [RaySafe; Unfors, Hopkinton, Mass]). In phase 3 (P3), a software imaging algorithm was installed that reduced radiation (EcoDose software; Philips Healthcare, Best, The Netherlands). A total of 72 cases in P1, 34 cases in P2, and 58 cases in P3 were analyzed. Total mean dose-area product decreased across each phase, with statistical significance achieved for P1 vs P3 (mean ± standard error of the mean, 186,173 ± 16,754 mGy/cm 2 vs 121,536 ± 11,971 mGy/cm 2 ; P = .002) and P2 vs P3 (171,921 ± 26,276 mGy/cm 2 vs 121,536 ± 11,971 mGy/cm 2 ; P = .04), whereas total mean fluoroscopy time did not significantly differ across any phase. The radiation exposure to the primary operator did not change significantly from P1 to P2 but fell significantly in P3 (0.08 ± 0.02 mSv vs 0.03 ± 0.01 mSv; P = .02). The addition of dose reduction software had the most impact on endovascular aneurysm repair, with reductions in median room dose (P = .03) and primary operator exposure (P2 vs P3; 0.19 ± 0.04 mSv vs 0.03 ± 0.02 mSv; P < .01). Dose reduction software may be an effective technique to lower radiation exposure. Implementation of system-based strategies to reduce radiation is needed to reduce lifetime occupational radiation exposure for endovascular staff and to improve patient safety. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Investigation on γ-irradiated PP/ethylene acrylic elastomer TPVs by rheological and thermal approaches

NASA Astrophysics Data System (ADS)

Dutta, Anindya; Ghosh, Anup K.

2018-03-01

Polypropylene (PP) was melt blended with varying concentration of ethylene acrylic elastomer (AEM) in a twin screw extruder and then γ-irradiated at several radiation doses to achieve a series of thermoplastic vulcanizates (TPV). The effect of AEM concentration and γ-irradiation on flow characteristics, crystallization and thermal degradation of blends were explained using melt dynamic rheology, differential scanning calorimetry and thermogravimetric analysis. Gel content values and dynamic rheological data of PP and AEM at different radiation doses confirmed the incessant scissioning of PP chains with radiation doses except for highest radiation dose, where crosslinking of PP chains took place and the incessant crosslinking of AEM chains irrespective of radiation doses. Oxidative degradation of PP was confirmed by FTIR spectroscopy, which also exhibited absence of any chemical interaction between two constituent polymers. Normalized crystallinity and melting point of compositions, obtained from DSC, decreased with the radiation doses. Furthermore, with the radiation doses clear shifts of maxima of the melting peak towards the lower temperature were observed for neat PP and blends. Thermal stability of PP and blends, as observed by TGA, reduced significantly with irradiation; whereas for AEM, no discernable change was observed. Enhanced chain scissioning of PP in presence of AEM reduced the thermal stability of blends, especially at lower irradiation. This reduction of thermal stability was established by "rule of mixture", applied to the activation energy of thermal degradation. Thus, optimization of radiation doses to prepare TPVs was established.

Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

PubMed Central

Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

2013-01-01

Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT. PMID:26229621

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short-Acting β-Agonist Formulations.

PubMed

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai; Ahrens, Richard C

2018-04-01

Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration-recommended 3-by-1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3-by-1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90-μg test dose and a 720-μg reference dose (42% cost reduction). Combining a 180-μg test dose and a 720-μg reference dose produced an estimated 36% cost reduction. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Design of a practical model-observer-based image quality assessment method for CT imaging systems

NASA Astrophysics Data System (ADS)

Tseng, Hsin-Wu; Fan, Jiahua; Cao, Guangzhi; Kupinski, Matthew A.; Sainath, Paavana

2014-03-01

The channelized Hotelling observer (CHO) is a powerful method for quantitative image quality evaluations of CT systems and their image reconstruction algorithms. It has recently been used to validate the dose reduction capability of iterative image-reconstruction algorithms implemented on CT imaging systems. The use of the CHO for routine and frequent system evaluations is desirable both for quality assurance evaluations as well as further system optimizations. The use of channels substantially reduces the amount of data required to achieve accurate estimates of observer performance. However, the number of scans required is still large even with the use of channels. This work explores different data reduction schemes and designs a new approach that requires only a few CT scans of a phantom. For this work, the leave-one-out likelihood (LOOL) method developed by Hoffbeck and Landgrebe is studied as an efficient method of estimating the covariance matrices needed to compute CHO performance. Three different kinds of approaches are included in the study: a conventional CHO estimation technique with a large sample size, a conventional technique with fewer samples, and the new LOOL-based approach with fewer samples. The mean value and standard deviation of area under ROC curve (AUC) is estimated by shuffle method. Both simulation and real data results indicate that an 80% data reduction can be achieved without loss of accuracy. This data reduction makes the proposed approach a practical tool for routine CT system assessment.

SU-C-BRF-01: Correlation of DIBH Breath Hold Amplitude with Dosimetric Sparing of Heart and Left Anterior Descending Artery in Left Breast Radiotherapy

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

Kim, Taeho; Reardon, Kelli; Sukovich, Kaitlyn

Purpose: A 7.4% increase in major coronary events per 1 Gy increase in mean heart dose has been reported from the population-based analysis of radiation-induced cardiac toxicity following treatment of left sided breast cancer. Deep inhalation breath-hold (DIBH) is clinically utilized to reduce radiation dose to heart and left anterior descending artery (LAD). We investigated the correlation of dose sparing in heart and LAD with internal DIBH amplitude to develop a quantitative predictive model for expected dose to heart and LAD based on internal breath hold amplitude. Methods: A treatment planning study (Prescription Dose = 50 Gy) was performed onmore » 50 left breast cancer patients underwent DIBH whole breast radiotherapy. Two CT datasets, free breathing (FB) and DIBH, were utilized for treatment planning and for determination of the internal anatomy DIBH amplitude (difference between sternum position at FB and DIBH). The heart and LAD dose between FB and DIBH plans was compared and dose to the heart and LAD as a function of breath hold amplitude was determined. Results: Average DIBH amplitude using internal anatomy was 13.9±4.2 mm. The DIBH amplitude-mean dose reduction correlation is 20%/5mm (0.3 Gy/5mm) for the heart and 18%/5mm (1.1 Gy/5mm) for LAD. The correlation with max dose reduction is 12%/5mm (3.8 Gy/5mm) for the heart and 16%/5mm (3.2 Gy/5mm) for LAD. We found that average dose reductions to LAD from 6.0±6.5 Gy to 2.0±1.6 Gy with DIBH (4.0 Gy reduction: -67%, p < 0.001) and average dose reduction to the heart from 1.3±0.7 Gy to 0.7±0.2 Gy with DIBH (0.6 Gy reduction: -46%, p < 0.001). That suggests using DIBH may reduce the risk of the major coronary event for left sided breast cancer patients. Conclusion: The correlation between breath hold amplitude and dosimetric sparing suggests that dose sparing linearly increases with internal DIBH amplitude.« less

Disinfection of bacteriophage MS2 by copper in water.

PubMed

Armstrong, Andrew M; Sobsey, Mark D; Casanova, Lisa M

2017-09-01

Households that lack piped water supply are often forced to meet water needs by storing in the home, leaving water vulnerable to contamination by viruses. Storage in copper containers can potentially prevent this type of contamination, but the inactivation kinetics of viruses by copper need to be described to make appropriate storage recommendations. This work characterized inactivation kinetics of bacteriophage MS2 as a surrogate for enteric viruses by dissolved ionic copper in water. Reduction of MS2 increased with increasing doses of copper. At 0.3 mg/L, there was a 1.8-log 10 reduction of MS2 within 6 h. At 1 and 3 mg/L, 2-2.5 log 10 inactivation could be achieved between 6 and 24 h. Parameters for the Chick-Watson, Hom, and One Hit-Two Population models of inactivation were calculated and evaluated, all of which demonstrated strong goodness-of-fit and predictability at various contact times. Copper inactivates MS2 under controlled conditions at doses between 0.3 and 3 mg/L. Although requiring longer contact times than conventional disinfectants, it is a candidate for improving the safety of stored drinking water.

[Dosimetric evaluation of eye lense shieldings in computed tomography examination--measurements and Monte Carlo simulations].

PubMed

Wulff, Jorg; Keil, Boris; Auvanis, Diyala; Heverhagen, Johannes T; Klose, Klaus Jochen; Zink, Klemens

2008-01-01

The present study aims at the investigation of eye lens shielding of different composition for the use in computed tomography examinations. Measurements with thermo-luminescent dosimeters and a simple cylindrical waterfilled phantom were performed as well as Monte Carlo simulations with an equivalent geometry. Besides conventional shielding made of Bismuth coated latex, a new shielding with a mixture of metallic components was analyzed. This new material leads to an increased dose reduction compared to the Bismuth shielding. Measured and Monte Carlo simulated dose reductions are in good agreement and amount to 34% for the Bismuth shielding and 46% for the new material. For simulations the EGSnrc code system was used and a new application CTDOSPP was developed for the simulation of the computed tomography examination. The investigations show that a satisfying agreement between simulation and measurement with the chosen geometries of this study could only be achieved, when transport of secondary electrons was accounted for in the simulation. The amount of scattered radiation due to the protector by fluorescent photons was analyzed and is larger for the new material due to the smaller atomic number of the metallic components.

T Cell Activation Thresholds are Affected by Gravitational

NASA Technical Reports Server (NTRS)

Adams, Charley; Gonzalez, M.; Nelman-Gonzalez, M.

1999-01-01

T cells stimulated in space flight by various mitogenic signals show a dramatic reduction in proliferation and expression of early activation markers. Similar results are also obtained in a ground based model of microgravity, clinorotation, which provides a vector-averaged reduction of the apparent gravity on cells without significant shear force. Here we demonstrate that T cell inhibition is due to an increase in the required threshold for activation. Dose response curves indicate that cells activated during clinorotation require higher stimulation to achieve the same level of activation, as measured by CD69 expression. Interleukin 2 receptor expression, and DNA synthesis. The amount of stimulation necessary for 50% activation is 5 fold in the clinostat relative to static. Correlation of TCR internalization with activation also exhibit a dramatic right shift in clinorotation, demonstrating unequivocally that signal transduction mechanism independent of TCR triggering account for the increased activation threshold. Previous results from space flight experiments are consistent with the dose response curves obtained for clinorotation. Activation thresholds are important aspects of T cell memory, autoimmunity and tolerance Clinorotation is a useful, noninvasive tool for the study of cellular and biochemical event regulating T cell activation threshold and the effects of gravitation forces on these systems.

Difference in EUV photoresist design towards reduction of LWR and LCDU

NASA Astrophysics Data System (ADS)

Jiang, Jing; De Simone, Danilo; Vandenberghe, Geert

2017-03-01

Pattern fidelity of EUV lithography is crucial for high resolution features, since small variation can affect device performance and even cause short or open circuit. For 1D features, dense lines and contact holes are the most common features for active, metal and contact layer, therefore line width roughness (LWR) and local critical dimension uniformity (LCDU) are important indexes to monitor. Both LWR and LCDU are greatly influenced by photon and acid shot noise. In addition, LWR is also affected by resist mechanical properties, like pattern collapse. In this study, we studied the influence of different chemically amplified resist components, such as polymer, PAG and quencher for both types and concentrations in order to understand the relative extent of influences of deprotection, acid diffusion, and base neutralization on pattern fidelity. However, conventional methods to approach higher resolution or low LWR/LCDU by sacrificing the dose are not sustainable. In order to continue to improve resist performance, a new component, metal salt sensitizer, is introduced into the resist system. This metal salt is able to achieve 30% dose reduction by increasing EUV absorption, maintaining LWR. We believe metal sensitizer might give us a new way to challenge the RLS trade-off.

Towards tracer dose reduction in PET studies: Simulation of dose reduction by retrospective randomized undersampling of list-mode data.

PubMed

Gatidis, Sergios; Würslin, Christian; Seith, Ferdinand; Schäfer, Jürgen F; la Fougère, Christian; Nikolaou, Konstantin; Schwenzer, Nina F; Schmidt, Holger

2016-01-01

Optimization of tracer dose regimes in positron emission tomography (PET) imaging is a trade-off between diagnostic image quality and radiation exposure. The challenge lies in defining minimal tracer doses that still result in sufficient diagnostic image quality. In order to find such minimal doses, it would be useful to simulate tracer dose reduction as this would enable to study the effects of tracer dose reduction on image quality in single patients without repeated injections of different amounts of tracer. The aim of our study was to introduce and validate a method for simulation of low-dose PET images enabling direct comparison of different tracer doses in single patients and under constant influencing factors. (18)F-fluoride PET data were acquired on a combined PET/magnetic resonance imaging (MRI) scanner. PET data were stored together with the temporal information of the occurrence of single events (list-mode format). A predefined proportion of PET events were then randomly deleted resulting in undersampled PET data. These data sets were subsequently reconstructed resulting in simulated low-dose PET images (retrospective undersampling of list-mode data). This approach was validated in phantom experiments by visual inspection and by comparison of PET quality metrics contrast recovery coefficient (CRC), background-variability (BV) and signal-to-noise ratio (SNR) of measured and simulated PET images for different activity concentrations. In addition, reduced-dose PET images of a clinical (18)F-FDG PET dataset were simulated using the proposed approach. (18)F-PET image quality degraded with decreasing activity concentrations with comparable visual image characteristics in measured and in corresponding simulated PET images. This result was confirmed by quantification of image quality metrics. CRC, SNR and BV showed concordant behavior with decreasing activity concentrations for measured and for corresponding simulated PET images. Simulation of dose-reduced datasets based on clinical (18)F-FDG PET data demonstrated the clinical applicability of the proposed data. Simulation of PET tracer dose reduction is possible with retrospective undersampling of list-mode data. Resulting simulated low-dose images have equivalent characteristics with PET images actually measured at lower doses and can be used to derive optimal tracer dose regimes.

Dynamic CT for Parathyroid Adenoma Detection: How Does Radiation Dose Compare With Nuclear Medicine?

PubMed

Czarnecki, Caroline A; Einsiedel, Paul F; Phal, Pramit M; Miller, Julie A; Lichtenstein, Meir; Stella, Damien L

2018-05-01

Dynamic CT is increasingly used for preoperative localization of parathyroid adenomas, but concerns remain about the radiation effective dose of CT compared with that of 99m Tc-sestamibi scintigraphy. The purpose of this study was to compare the radiation dose delivered by three-phase dynamic CT with that delivered by 99m Tc-sestamibi SPECT/CT performed in accordance with our current protocols and to assess the possible reduction in effective dose achieved by decreasing the scan length (i.e., z-axis) of two phases of the dynamic CT protocol. The effective dose of a 99m Tc-sestamibi nuclear medicine parathyroid study performed with and without coregistration CT was calculated and compared with the effective dose of our current three-phase dynamic CT protocol as well as a proposed protocol involving CT with reduced scan length. The median effective dose for a 99m Tc-sestamibi nuclear medicine study was 5.6 mSv. This increased to 12.4 mSv with the addition of coregistration CT, which is higher than the median effective dose of 9.3 mSv associated with the dynamic CT protocol. Reducing the scan length of two phases in the dynamic CT protocol could reduce the median effective dose to 6.1 mSv, which would be similar to that of the dose from the 99m Tc-sestamibi study alone. Dynamic CT used for the detection of parathyroid adenoma can deliver a lower radiation dose than 99m Tc-sestamibi SPECT/CT. It may be possible to reduce the dose further by decreasing the scan length of two of the phases, although whether this has an impact on accuracy of the localization needs further investigation.

Radiation dose reduction in thoracic and lumbar spine instrumentation using navigation based on an intraoperative cone beam CT imaging system: a prospective randomized clinical trial.

PubMed

Pireau, Nathalie; Cordemans, Virginie; Banse, Xavier; Irda, Nadia; Lichtherte, Sébastien; Kaminski, Ludovic

2017-11-01

Spine surgery still remains a challenge for every spine surgeon, aware of the potential serious outcomes of misplaced instrumentation. Though many studies have highlighted that using intraoperative cone beam CT imaging and navigation systems provides higher accuracy than conventional freehand methods for placement of pedicle screws in spine surgery, few studies are concerned about how to reduce radiation exposure for patients with the use of such technology. One of the main focuses of this study is based on the ALARA principle (as low as reasonably achievable). A prospective randomized trial was conducted in the hybrid operating room between December 2015 and December 2016, including 50 patients operated on for posterior instrumented thoracic and/or lumbar spinal fusion. Patients were randomized to intraoperative 3D acquisition high-dose (standard dose) or low-dose protocol, and a total of 216 pedicle screws were analyzed in terms of screw position. Two different methods were used to measure ionizing radiation: the total skin dose (derived from the dose-area product) and the radiation dose evaluated by thermoluminescent dosimeters on the surgical field. According to Gertzbein and Heary classifications, low-dose protocol provided a significant higher accuracy of pedicle screw placement than the high-dose protocol (96.1 versus 92%, respectively). Seven screws (3.2%), all implanted with the high-dose protocol, needed to be revised intraoperatively. The use of low-dose acquisition protocols reduced patient exposure by a factor of five. This study emphasizes the paramount importance of using low-dose protocols for intraoperative cone beam CT imaging coupled with the navigation system, as it at least does not affect the accuracy of pedicle screw placement and irradiates drastically less.

Randomised controlled trials define shape of dose-response for Pollinex Quattro Birch allergoid immunotherapy.

PubMed

Worm, Margitta; Higenbottam, Tim; Pfaar, Oliver; Mösges, Ralph; Aberer, Werner; Gunawardena, Kulasiri; Wessiepe, Dorothea; Lee, Denise; Kramer, Matthias F; Skinner, Murray; Lees, Bev; Zielen, Stefan

2018-05-19

The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX ® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed two phase II studies to determine its optimal cumulative dose. The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction of Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modelling analysis was used to test for the dose-response, shape of the curve, and estimation of the median effective dose (ED 50 ), a measure of potency. Statistically significant dose-responses (p<0.01 & 0.001) were seen respectively. The highest cumulative dose in PQBirch204 (27300 standardised units [SU]) approached a plateau. Potency of the PQ Birch was demonstrated by an ED 50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups. Increasing the cumulative dose of PQ Birch 5.5-fold from 5100 to 27300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase of efficacy of 50%, without compromising safety. The cumulative dose-response was confirmed to be curvilinear in shape. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

UK Renal Registry 16th annual report: chapter 9 adequacy of haemodialysis in UK adult patients in 2012: national and centre-specific analyses.

PubMed

Shaw, Catriona; Steenkamp, Retha; Davenport, Andrew

2013-01-01

Outcomes in patients treated with haemodialysis (HD) are influenced by the delivered dose of dialysis. The UK Renal Association (RA) publishes clinical practice guidelines which include recommendations for dialysis dose. The urea reduction ratio (URR) is a widely used measure of dialysis dose and has historically been the measure of adequacy reported by the UKRR. This chapter aims to determine the extent to which patients achieved the recommended UK target. All 71 UK renal centres submitted data to the UK Renal Registry (UKRR). Two groups of patients were included in the analyses: the prevalent HD patient population on 30st September 2012 and the incident HD patient population for 2011. Centres returning data on <50% of their patient population or centres with <20 patients were excluded from centrespecific comparisons. Data regarding URR were available from 63 renal centres in the UK. Forty nine centres provided URR data on more than 90% of prevalent HD patients. The proportion of patients in the UK who met the UK clinical practice guideline for URR (>65%) increased from 69% in 2000 to 88% in 2012. There was persistent variation observed between centres, with 21 centres attaining the RA clinical practice guideline in >90% of patients, 38 centres attaining the guideline in 70-90% of patients and one centre in less than 70% of patients. The overall proportion of prevalent HD patients with a URR >65% has continued to improve over time. The delivered dose of HD, as measured by URR for patients with established renal failure, has increased over the last decade. Whilst the majority of UK patients achieved the target URR there was considerable variation between centres in the percentage of patients achieving the current guideline. © 2014 S. Karger AG, Basel.

Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation.

PubMed

Segovia, Javier; Gerosa, Gino; Almenar, Luis; Livi, Ugolino; Viganò, Mario; Arizón, Jose Maria; Yonan, Nizar; Di Salvo, Thomas G; Renlund, Dale G; Kobashigawa, Jon A

2008-01-01

Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.

SU-F-J-48: Effect of Scan Length On Magnitude of Imaging Dose in KV CBCT

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

Deshpande, S; Naidu, S; Sutar, A

Purpose: To study effect of scan length on magnitude of imaging dose deposition in Varian kV CBCT for head & neck and pelvis CBCT. Methods: To study effect of scan length we measured imaging dose at depth of 8 cm for head and neck Cone Beam Computed Tomography (CBCT) acquisition ( X ray beam energy is used 100kV and 200 degree of gantry rotation) and at 16 cm depth for pelvis CBCT acquisition ( X ray beam energy used is 125 kV and 360 degree of gantry rotation) in specially designed phantom. We used farmer chamber which was calibrated inmore » kV X ray range for measurements .Dose was measured with default field size, and reducing field size along y direction to 10 cm and 5 cm. Results: As the energy of the beam decreases the scattered radiation increases and this contributes significantly to the dose deposited in the patient. By reducing the scan length to 10 Cm from default 20.6 cm we found a dose reduction of 14% for head and neck CBCT protocol and a reduction of 26% for pelvis CBCT protocol. Similarly for a scan length of 5cm compared to default the dose reduction in head and neck CBCT protocol is 36% while in the pelvis CBCT protocol the dose reduction is 50%. Conclusion: By limiting the scan length we can control the scatter radiation generated and hence the dose to the patient. However the variation in dose reduction for same length used in two protocols is because of the scan geometry. The pelvis CBCT protocol uses a full rotation and head and neck CBCT protocol uses partial rotation.« less

Evaluating the effect of increased pitch, iterative reconstruction and dual source CT on dose reduction and image quality.

PubMed

Gariani, Joanna; Martin, Steve P; Botsikas, Diomidis; Becker, Christoph D; Montet, Xavier

2018-06-14

To compare radiation dose and image quality of thoracoabdominal scans obtained with a high-pitch protocol (pitch 3.2) and iterative reconstruction (Sinogram Affirmed Iterative Reconstruction) in comparison to standard pitch reconstructed with filtered back projection (FBP) using dual source CT. 114 CT scans (Somatom Definition Flash, Siemens Healthineers, Erlangen, Germany), 39 thoracic scans, 54 thoracoabdominal scans and 21 abdominal scans were performed. Analysis of three protocols was undertaken; pitch of 1 reconstructed with FBP, pitch of 3.2 reconstructed with SAFIRE, pitch of 3.2 with stellar detectors reconstructed with SAFIRE. Objective and subjective image analysis were performed. Dose differences of the protocols used were compared. Dose was reduced when comparing scans with a pitch of 1 reconstructed with FBP to high-pitch scans with a pitch of 3.2 reconstructed with SAFIRE with a reduction of volume CT dose index of 75% for thoracic scans, 64% for thoracoabdominal scans and 67% for abdominal scans. There was a further reduction after the implementation of stellar detectors reflected in a reduction of 36% of the dose-length product for thoracic scans. This was not at the detriment of image quality, contrast-to-noise ratio, signal-to-noise ratio and the qualitative image analysis revealed a superior image quality in the high-pitch protocols. The combination of a high pitch protocol with iterative reconstruction allows significant dose reduction in routine chest and abdominal scans whilst maintaining or improving diagnostic image quality, with a further reduction in thoracic scans with stellar detectors. Advances in knowledge: High pitch imaging with iterative reconstruction is a tool that can be used to reduce dose without sacrificing image quality.

Three-Dimensional Radiobiologic Dosimetry: Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging–Based Internal Dosimetry

PubMed Central

Prideaux, Andrew R.; Song, Hong; Hobbs, Robert F.; He, Bin; Frey, Eric C.; Ladenson, Paul W.; Wahl, Richard L.; Sgouros, George

2010-01-01

Phantom-based and patient-specific imaging-based dosimetry methodologies have traditionally yielded mean organ-absorbed doses or spatial dose distributions over tumors and normal organs. In this work, radiobiologic modeling is introduced to convert the spatial distribution of absorbed dose into biologically effective dose and equivalent uniform dose parameters. The methodology is illustrated using data from a thyroid cancer patient treated with radioiodine. Methods Three registered SPECT/CT scans were used to generate 3-dimensional images of radionuclide kinetics (clearance rate) and cumulated activity. The cumulated activity image and corresponding CT scan were provided as input into an EGSnrc-based Monte Carlo calculation: The cumulated activity image was used to define the distribution of decays, and an attenuation image derived from CT was used to define the corresponding spatial tissue density and composition distribution. The rate images were used to convert the spatial absorbed dose distribution to a biologically effective dose distribution, which was then used to estimate a single equivalent uniform dose for segmented volumes of interest. Equivalent uniform dose was also calculated from the absorbed dose distribution directly. Results We validate the method using simple models; compare the dose-volume histogram with a previously analyzed clinical case; and give the mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for an illustrative case of a pediatric thyroid cancer patient with diffuse lung metastases. The mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for the tumor were 57.7, 58.5, and 25.0 Gy, respectively. Corresponding values for normal lung tissue were 9.5, 9.8, and 8.3 Gy, respectively. Conclusion The analysis demonstrates the impact of radiobiologic modeling on response prediction. The 57% reduction in the equivalent dose value for the tumor reflects a high level of dose nonuniformity in the tumor and a corresponding reduced likelihood of achieving a tumor response. Such analyses are expected to be useful in treatment planning for radionuclide therapy. PMID:17504874

Radiation dose reduction in a neonatal intensive care unit in computed radiography.

PubMed

Frayre, A S; Torres, P; Gaona, E; Rivera, T; Franco, J; Molina, N

2012-12-01

The purpose of this study was to evaluate the dose received by chest x-rays in neonatal care with thermoluminescent dosimetry and to determine the level of exposure where the quantum noise level does not affect the diagnostic image quality in order to reduce the dose to neonates. In pediatric radiology, especially the prematurely born children are highly sensitive to the radiation because of the highly mitotic state of their cells; in general, the sensitivity of a tissue to radiation is directly proportional to its rate of proliferation. The sample consisted of 208 neonatal chest x-rays of 12 neonates admitted and treated in a Neonatal Intensive Care Unit (NICU). All the neonates were preterm in the range of 28-34 weeks, with a mean of 30.8 weeks. Entrance Surface Doses (ESD) values for chest x-rays are higher than the DRL of 50 μGy proposed by the National Radiological Protection Board (NRPB). In order to reduce the dose to neonates, the optimum image quality was achieved by determining the level of ESD where level noise does not affect the diagnostic image quality. The optimum ESD was estimated for additional 20 chest x-rays increasing kVp and reducing mAs until quantum noise affects image quality. Copyright © 2012 Elsevier Ltd. All rights reserved.

Radiation dose reduction in computed tomography perfusion using spatial-temporal Bayesian methods

NASA Astrophysics Data System (ADS)

Fang, Ruogu; Raj, Ashish; Chen, Tsuhan; Sanelli, Pina C.

2012-03-01

In current computed tomography (CT) examinations, the associated X-ray radiation dose is of significant concern to patients and operators, especially CT perfusion (CTP) imaging that has higher radiation dose due to its cine scanning technique. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) parameter as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and degrade CT perfusion maps greatly if no adequate noise control is applied during image reconstruction. To capture the essential dynamics of CT perfusion, a simple spatial-temporal Bayesian method that uses a piecewise parametric model of the residual function is used, and then the model parameters are estimated from a Bayesian formulation of prior smoothness constraints on perfusion parameters. From the fitted residual function, reliable CTP parameter maps are obtained from low dose CT data. The merit of this scheme exists in the combination of analytical piecewise residual function with Bayesian framework using a simpler prior spatial constrain for CT perfusion application. On a dataset of 22 patients, this dynamic spatial-temporal Bayesian model yielded an increase in signal-tonoise-ratio (SNR) of 78% and a decrease in mean-square-error (MSE) of 40% at low dose radiation of 43mA.

Comparison of two doses of intravenous temsirolimus in patients with relapsed/refractory mantle cell lymphoma.

PubMed

Jurczak, Wojciech; Ramanathan, Sundra; Giri, Pratyush; Romano, Alessandra; Mocikova, Heidi; Clancy, Jill; Lechuga, Mariajose; Casey, Michelle; Boni, Joseph; Giza, Agnieszka; Hess, Georg

2018-03-01

Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly intravenously dosed (175/75 mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75 mg without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n = 47) or 75 mg (n = 42). Treatment continued until objective disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Median PFS was 4.3 versus 4.5 months (hazard ratio [HR] 0.731; 80% confidence interval [CI], 0.520-1.027), and median OS 18.7 versus 11.0 months (HR 0.681; 80% CI, 0.472-0.982) with 175/75 mg versus 75 mg. There were fewer patients with serious AEs, dose reduction, or death with 175/75 mg (57.4%, 48.9%, and 48.9%) versus 75 mg (73.8%, 64.3%, and 65.1%). Temsirolimus 175/75 mg remains the preferred dosing regimen for relapsed/refractory MCL.

Randomized, 6-Week, Placebo-Controlled Study of Treatment for Adult Attention-Deficit/Hyperactivity Disorder: Individualized Dosing of Osmotic-Release Oral System (OROS) Methylphenidate With a Goal of Symptom Remission.

PubMed

Goodman, David W; Starr, H Lynn; Ma, Yi-Wen; Rostain, Anthony L; Ascher, Steve; Armstrong, Robert B

2017-01-01

To evaluate the efficacy and safety of individualized dosing within the approved dose range for osmotic-release oral system (OROS) methylphenidate hydrochloride in adults with attention-deficit/hyperactivity disorder (ADHD). A double-blind, 6-week trial was conducted between July 2009 and February 2010 at 35 US sites. Adults with ADHD (DSM-IV diagnostic criteria) and a screening ADHD Investigator Symptom Rating Scale (AISRS) score > 24 were randomly assigned to OROS methylphenidate 18 mg or matching placebo. Treatment dose could be increased at 18 mg increments, up to 72 mg/d, until an optimal dose was achieved. AISRS score changes from baseline to end point (primary outcome) were analyzed using analysis of covariance. At baseline, the intent-to-treat population of 169 OROS methylphenidate and 172 placebo subjects (mean age = 35.8 years) had mean (standard deviation [SD]) AISRS scores of 37.8 (6.94) and 37.0 (7.51), respectively. OROS methylphenidate-treated subjects exhibited a significantly greater mean (SD) AISRS score improvement than placebo subjects (-17.1 [12.44] vs -11.7 [13.30]; P < .001). In general, OROS methylphenidate-treated subjects experienced greater improvements than placebo subjects in secondary measures of symptom frequency, cognitive function, work productivity, and quality-of-life. Little effect of OROS methylphenidate was observed in exploratory sleep assessments. The adverse event pattern was similar to previous reports of stimulants in adults with ADHD. OROS methylphenidate treatment with individualized doses titrated to achieve symptom remission demonstrated greater ADHD symptom reduction than placebo treatment. These data support the overall efficacy of OROS methylphenidate treatment in the management of adults with ADHD and provide new possibilities for additional intervention. ClinicalTrials.gov identifier: NCT00937040. © Copyright 2017 Physicians Postgraduate Press, Inc.

A review of the efficacy of rosuvastatin in patients with type 2 diabetes.

PubMed

Tuomilehto, J; Leiter, L A; Kallend, D

2004-10-01

It has been estimated that 92% of individuals with type 2 diabetes, without cardiovascular disease (CVD), have a dyslipidaemic profile. Several guidelines on cardiovascular risk now recommend that patients with diabetes should be considered at high risk of CVD and should thus receive lipid-lowering therapy to reduce low-density lipoprotein cholesterol (LDL-C) to below 2.5 mmol/L. Since their introduction in 1987, statins have revolutionized the management of CVD. The most recent statin to be introduced, rosuvastatin, has been shown to be the most effective at lowering LDL-C, as well as consistently raising HDL-C across the 10-40 mg dose range. This has been confirmed by many studies, including the Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study in which rosuvastatin 10 mg was shown to be more effective than commonly used doses of other statins, both for LDL-C reduction and achieving treatment target goals. The effectiveness of rosuvastatin has also been studied in type 2 diabetes patients in three studies: the URANUS (Use of Rosuvastatin vs. Atorvastatin iN type 2 diabetes mellitUS), ANDROMEDA (A raNdomized, Double-blind study to compare Rosuvastatin [10 & 20 mg] and atOrvastatin [10 & 20 Mg] in patiEnts with type II DiAbetes) and CORALL (COmpare Rosuvastatin [10-40 mg] with Atorvastatin [20-80 mg] on apo B/apo A-1 ratio in patients with type 2 diabetes meLLitus and dyslipidaemia) studies. URANUS and ANDROMEDA showed rosuvastatin to be more effective than atorvastatin at reducing LDL-C and achieving treatment target goals. CORALL demonstrated rosuvastatin 10, 20 and 40 mg to be more effective at lowering LDL-C than 20, 40 and 80 mg of atorvastatin, respectively. Ongoing studies will evaluate whether these properties of rosuvastatin translate into beneficial effects on atherosclerosis and significant reductions in cardiovascular events.

Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells

NASA Astrophysics Data System (ADS)

Coverdale, James P. C.; Romero-Canelón, Isolda; Sanchez-Cano, Carlos; Clarkson, Guy J.; Habtemariam, Abraha; Wills, Martin; Sadler, Peter J.

2018-03-01

Catalytic anticancer metallodrugs active at low doses could minimize side-effects, introduce novel mechanisms of action that combat resistance and widen the spectrum of anticancer-drug activity. Here we use highly stable chiral half-sandwich organometallic Os(II) arene sulfonyl diamine complexes, [Os(arene)(TsDPEN)] (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), to achieve a highly enantioselective reduction of pyruvate, a key intermediate in metabolic pathways. Reduction is shown both in aqueous model systems and in human cancer cells, with non-toxic concentrations of sodium formate used as a hydride source. The catalytic mechanism generates selectivity towards ovarian cancer cells versus non-cancerous fibroblasts (both ovarian and lung), which are commonly used as models of healthy proliferating cells. The formate precursor N-formylmethionine was explored as an alternative to formate in PC3 prostate cancer cells, which are known to overexpress a deformylase enzyme. Transfer-hydrogenation catalysts that generate reductive stress in cancer cells offer a new approach to cancer therapy.

X-ray dose reduction in abdominal computed tomography using advanced iterative reconstruction algorithms.

PubMed

Ning, Peigang; Zhu, Shaocheng; Shi, Dapeng; Guo, Ying; Sun, Minghua

2014-01-01

This work aims to explore the effects of adaptive statistical iterative reconstruction (ASiR) and model-based iterative reconstruction (MBIR) algorithms in reducing computed tomography (CT) radiation dosages in abdominal imaging. CT scans on a standard male phantom were performed at different tube currents. Images at the different tube currents were reconstructed with the filtered back-projection (FBP), 50% ASiR and MBIR algorithms and compared. The CT value, image noise and contrast-to-noise ratios (CNRs) of the reconstructed abdominal images were measured. Volumetric CT dose indexes (CTDIvol) were recorded. At different tube currents, 50% ASiR and MBIR significantly reduced image noise and increased the CNR when compared with FBP. The minimal tube current values required by FBP, 50% ASiR, and MBIR to achieve acceptable image quality using this phantom were 200, 140, and 80 mA, respectively. At the identical image quality, 50% ASiR and MBIR reduced the radiation dose by 35.9% and 59.9% respectively when compared with FBP. Advanced iterative reconstruction techniques are able to reduce image noise and increase image CNRs. Compared with FBP, 50% ASiR and MBIR reduced radiation doses by 35.9% and 59.9%, respectively.

CT dose minimization using personalized protocol optimization and aggressive bowtie

NASA Astrophysics Data System (ADS)

Wang, Hui; Yin, Zhye; Jin, Yannan; Wu, Mingye; Yao, Yangyang; Tao, Kun; Kalra, Mannudeep K.; De Man, Bruno

2016-03-01

In this study, we propose to use patient-specific x-ray fluence control to reduce the radiation dose to sensitive organs while still achieving the desired image quality (IQ) in the region of interest (ROI). The mA modulation profile is optimized view by view, based on the sensitive organs and the ROI, which are obtained from an ultra-low-dose volumetric CT scout scan [1]. We use a clinical chest CT scan to demonstrate the feasibility of the proposed concept: the breast region is selected as the sensitive organ region while the cardiac region is selected as IQ ROI. Two groups of simulations are performed based on the clinical CT dataset: (1) a constant mA scan adjusted based on the patient attenuation (120 kVp, 300 mA), which serves as baseline; (2) an optimized scan with aggressive bowtie and ROI centering combined with patient-specific mA modulation. The results shows that the combination of the aggressive bowtie and the optimized mA modulation can result in 40% dose reduction in the breast region, while the IQ in the cardiac region is maintained. More generally, this paper demonstrates the general concept of using a 3D scout scan for optimal scan planning.

Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.

PubMed

Fortin, Israël; Fortin, Bernard; Lambert, Louise; Clavel, Sébastien; Alizadeh, Moein; Filion, Edith J; Soulières, Denis; Bélair, Manon; Guertin, Louis; Nguyen-Tan, Phuc Felix

2014-09-01

In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction. The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60). Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months. This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria. Copyright © 2013 Wiley Periodicals, Inc.

CT brush and CancerZap!: two video games for computed tomography dose minimization.

PubMed

Alvare, Graham; Gordon, Richard

2015-05-12

X-ray dose from computed tomography (CT) scanners has become a significant public health concern. All CT scanners spray x-ray photons across a patient, including those using compressive sensing algorithms. New technologies make it possible to aim x-ray beams where they are most needed to form a diagnostic or screening image. We have designed a computer game, CT Brush, that takes advantage of this new flexibility. It uses a standard MART algorithm (Multiplicative Algebraic Reconstruction Technique), but with a user defined dynamically selected subset of the rays. The image appears as the player moves the CT brush over an initially blank scene, with dose accumulating with every "mouse down" move. The goal is to find the "tumor" with as few moves (least dose) as possible. We have successfully implemented CT Brush in Java and made it available publicly, requesting crowdsourced feedback on improving the open source code. With this experience, we also outline a "shoot 'em up game" CancerZap! for photon limited CT. We anticipate that human computing games like these, analyzed by methods similar to those used to understand eye tracking, will lead to new object dependent CT algorithms that will require significantly less dose than object independent nonlinear and compressive sensing algorithms that depend on sprayed photons. Preliminary results suggest substantial dose reduction is achievable.

Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

PubMed Central

Bozic, Iva; Savic, Danijela; Jovanovic, Marija; Bjelobaba, Ivana; Laketa, Danijela; Nedeljkovic, Nadezda; Stojiljkovic, Mirjana; Pekovic, Sanja; Lavrnja, Irena

2015-01-01

Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation. PMID:26413464

Clinical assessment of the jaw-tracking function in IMRT for a brain tumor

NASA Astrophysics Data System (ADS)

Kim, Jin-Young; Kim, Shin-Wook; Choe, Bo-Young; Suh, Tae-Suk; Park, Sung-Kwang; Jo, Sun-Mi; Oh, Won-Yong; Shin, Jung-Wook; Cho, Gyu-Seok; Nam, Sang-Hee; Chung, Jin-Beom; Kim, Jung-Ki; Lee, Young-Kyu

2015-01-01

Intensity-modulated radiotherapy (IMRT) improves dose conformity and saves critical organs. IMRT is widely used in cases of head and neck, prostate, and brain cancer due to the close location of the targets to critical structures. However, because IMRT has a larger amount of radiation exposure than 3 dimensional-conformal radiation therapy (3D-CRT), it has disadvantages such as increases in the low dose irradiation to normal tissues and in the accumulated dose for the whole volume due to leakage and transmission of the multi-leaf collimator (MLC). The increased accumulated dose and the larger low dose may increase the occurrence of secondary malignant neoplasms. For these reasons, the jaw-tracking function of the TrueBeam (Varian Medical Systems, Palo Alto, CA) was developed to reduce the leakage and the transmission dose of the MLC with linear accelerators. However, the change in the superficial dose has not been verified with a quantitative analysis of the dose reduction in a brain tumor. Therefore, in the present study, we intended to verify the clinical possibility of utilizing the jaw-tracking function for a brain tumor by comparing treatment plans and superficial doses. To accomplish this, we made three types of original treatment plans using Eclipse11 (Varian Medical Systems, Palo Alto, CA): 1) farther than 2 cm from the organs at risk (OAR); 2) within 2 cm of the OAR; and 3) intersecting with the OAR. Jaw-tracking treatment plans were also made with copies of the original treatment plan using Smart LMC Version 11.0.31 (Varian Medical Systems, Palo Alto, CA). A comparison between the original treatment plans and jaw-tracking treatment plans was performed using the difference of the mean dose and maximum dose to the OARs in cumulative Dose Volume Histogram (DVH). In addition, the dependencies of the effects of transmission and the scattering doses according to jaw motion were assessed through the difference in the surface doses. In the DVH comparison, a maximum dose difference of 0.4% was observed between the planning methods in the case of over 2 cm distance, and the maximum dose of 0.6% was obtained for within the 2 cm distance. For the case intersecting with the OAR, the maximum dose difference of 2.3% was achieved. According to these results, the differences in the mean doses and the maximum doses to the OARs ware larger when the OARs and the planning target volume (PTV) were closer. In addition, small differences in the surface dose measurements were observed. In the case of the inside field, the differences were under 2% of the prescription dose while the difference was under 0.1% in the case of the outside field. Therefore, treatment plans with the jaw-tracking function consistently affected the dose reduction for a brain tumor, and the clinical possibility could be verified as the surface dose was not increased.

Physiological and performance effects of pyridostigmine bromide in healthy volunteers: a dose-response study.

PubMed

Cook, Mary R; Graham, Charles; Sastre, Antonio; Gerkovich, Mary M

2002-07-01

Questions have been raised about the role pyridostigmine bromide (PB) plays in the etiology of Gulf War veterans' illnesses. There is a need to understand better the physiological and behavioral effects of this drug, particularly at the 30-mg/8-h regimen recommended by the US Military. OBJECTIVE. To perform a double-blind, cross-over, dose-response study of PB in 67 healthy, young volunteers (31 women, 36 men). Volunteers were initially trained on a standardized test battery. Supervised administration of placebo (PL) and PB (every 8 h/5 days) occurred in each of two dosing weeks, separated by a non-dosing week. One group received 30 mg PB and PL, and the other 60 mg PB and PL. In each dosing week, the battery was performed after the first pill and again when steady-state plasma PB levels were achieved. PB was associated with an overall improvement in reaction time on tests of memory and attention, and with a reduction in RMS error on a tracking task. PB slowed heart rate and decreased the high frequency component of heart rate variability (HF HRV). Dose-response effects were found only for HF HRV, and RMS error. The extent of cholinesterase inhibition was directly related to the magnitude of the HF HRV decrease, and was predicted by the weight-normalized PB dose. Cholinesterase inhibition was not related to the extent or severity of reported drug side effects. PB does not appear to have detrimental physiological or performance consequences at the recommended 30-mg dose, or at twice that dose, when evaluated under non-stressful laboratory conditions.

Assessment of phase based dose modulation for improved dose efficiency in cardiac CT on an anthropomorphic motion phantom

NASA Astrophysics Data System (ADS)

Budde, Adam; Nilsen, Roy; Nett, Brian

2014-03-01

State of the art automatic exposure control modulates the tube current across view angle and Z based on patient anatomy for use in axial full scan reconstructions. Cardiac CT, however, uses a fundamentally different image reconstruction that applies a temporal weighting to reduce motion artifacts. This paper describes a phase based mA modulation that goes beyond axial and ECG modulation; it uses knowledge of the temporal view weighting applied within the reconstruction algorithm to improve dose efficiency in cardiac CT scanning. Using physical phantoms and synthetic noise emulation, we measure how knowledge of sinogram temporal weighting and the prescribed cardiac phase can be used to improve dose efficiency. First, we validated that a synthetic CT noise emulation method produced realistic image noise. Next, we used the CT noise emulation method to simulate mA modulation on scans of a physical anthropomorphic phantom where a motion profile corresponding to a heart rate of 60 beats per minute was used. The CT noise emulation method matched noise to lower dose scans across the image within 1.5% relative error. Using this noise emulation method to simulate modulating the mA while keeping the total dose constant, the image variance was reduced by an average of 11.9% on a scan with 50 msec padding, demonstrating improved dose efficiency. Radiation dose reduction in cardiac CT can be achieved while maintaining the same level of image noise through phase based dose modulation that incorporates knowledge of the cardiac reconstruction algorithm.

The evolution of systolic blood pressure as a strong predictor of cardiovascular risk and the effectiveness of fixed-dose ARB/CCB combinations in lowering levels of this preferential target

PubMed Central

Mourad, Jean-Jacques

2008-01-01

Elevated blood pressure is an important cardiovascular risk factor. Although targets for both diastolic blood pressure (DBP) and systolic blood pressure (SBP) are defined by current guidelines, DBP has historically taken precedence in hypertension management. However, there is strong evidence that SBP is superior to DBP as a predictor of cardiovascular events. Moreover, achieving control of SBP is assuming greater importance amongst an aging population. In spite of the growing recognition of the importance of SBP in reducing cardiovascular risk and the emphasis by current guidelines on SBP control, a substantial proportion of patients still fail to achieve SBP targets, and SBP control is achieved much less frequently than DBP control. Thus, new approaches to the management of hypertension are required in order to control SBP and minimize cardiovascular risk. Fixed-dose combination (FDC) therapy is an approach that offers the advantages of multiple drug administration and a reduction in regimen complexity that favors compliance. We have reviewed the latest evidence demonstrating the efficacy in targeting SBP of the most recent FDC products; combinations of the calcium channel blocker (CCB), amlodipine, with angiotensin receptor blockers (ARBs), valsartan or olmesartan. In addition, results from studies with new classes of agent are outlined. PMID:19337545

Sensitivity of disease parameters to flexible budesonide/formoterol treatment in an allergic rat model.

PubMed

Brange, Charlotte; Smailagic, Amir; Jansson, Anne-Helene; Middleton, Brian; Miller-Larsson, Anna; Taylor, John D; Silberstein, David S; Lal, Harbans

2009-02-01

Clinical studies show that flexible dosing (maintenance and symptom-driven dose adjustments) of budesonide and formoterol (BUD/FORM) improves control of asthma exacerbations as compared to fixed maintenance dosing protocols (maintenance therapy) even when the latter utilize higher BUD/FORM doses. This suggests that dose-response relationships for certain pathobiologic mechanisms in asthma shift over time. Here, we have conducted animal studies to address this issue. (1) To test in an animal asthma-like model whether it is possible to achieve the same or greater pharmacological control over bronchoconstriction and airway/lung inflammation, and with less total drug used, by flexible BUD/FORM dosing (upward adjustment of doses) in association with allergen challenges. (2) To determine whether the benefit requires adjustment of both drug components. Rats sensitized on days 0 and 7 were challenged intratracheally with ovalbumin on days 14 and 21. On days 13-21, rats were treated intratracheally with fixed maintenance or flexible BUD/FORM combinations. On day 22, rats were challenged with methacholine and lungs were harvested for analysis. A flexible BUD/FORM dosing regimen (using 3.3 times less total drug than the fixed maintenance high dose regimen), delivered the same or greater reductions of excised lung gas volume (a measure of gas trapped in lung by bronchoconstriction) and lung weight (a measure of inflammatory oedema). When either BUD or FORM alone was increased on days of challenge, the benefit of the flexible dose upward adjustment was lost. Flexible dosing of the BUD/FORM combination improves the pharmacological inhibition of allergen-induced bronchoconstriction and an inflammatory oedema in an allergic asthma-like rat model.

Higher Dose Imatinib for Children With De Novo Chronic Phase Chronic Myelogenous Leukemia: A Report From the Children’s Oncology Group

PubMed Central

Champagne, Martin A.; Fu, Cecilia H.; Chang, Myron; Chen, Helen; Gerbing, Robert B.; Alonzo, Todd A.; Cooley, Linda D.; Heerema, Nyla A.; Oehler, Vivian; Wood, Charlotte; French, Mary Ellen; Arceci, Robert J.; Smith, Franklin O.; Bernstein, Mark L.

2016-01-01

Purpose To determine the efficacy of imatinib in children with newly diagnosed chronic phase (CP) chronic myelogenous leukemia (CML). Methods This was an open label, multi-center phase II clinical trial. Courses were defined as consecutive 28-day intervals. Oral imatinib was administered daily at 340 mg/m2 without interruption in the absence of toxicity. Results Fifty-one children received 978 28-day courses of imatinib. The most common toxicities encountered were hematologic. Forty-one patients (80%) achieved a complete hematologic response by the end of course 2. Nineteen children (38%) obtained a complete cytogenetic response (CCyR) at the end of course 3. Overall, 72% achieved CCyR at a median time of 5.6 months. The rate of complete molecular response (>3 log reduction) was 27%. Progression-free and overall survival at 3 years were 72% ± 6.4% and 92% ± 3.9%, respectively. Conclusions Daily oral imatinib at a dose of 340 mg/m2 is well tolerated in children. In addition, imatinib therapy is effective in inducing a high percent of hematologic, cytogenetic and molecular responses, comparable to adults with CML. PMID:21465636

Bioleaching of zinc and manganese from spent Zn-Mn batteries and mechanism exploration.

PubMed

Xin, Baoping; Jiang, Wenfeng; Aslam, Hina; Zhang, Kai; Liu, Changhao; Wang, Renqing; Wang, Yutao

2012-02-01

In this work, bioleaching was used to extract valuable Zn and Mn from spent Zn-Mn batteries. The results showed that 96% of Zn extraction was achieved within 24h regardless of energy source types and bioleaching bacteria species. However, initial pH had a remarkable influence on Zn release, extraction dose sharply decreased from 2200 to 500mg/l when the initial pH value increased from 1.5 to 3.0 or higher. In contrast to Zn, all the tested factors evidently affected Mn extraction; the maximum released dose of 3020mg/l was obtained under the optimum conditions. The acidic dissolution by biogenic H(2)SO(4) by the non-contact mechanism was responsible for Zn extraction, while Mn extraction was owed to both contact/biological and non-contact mechanisms. The combined action of acidic dissolution of soluble Mn(2+) by biogenic H(2)SO(4) and reductive dissolution of insoluble Mn(4+) by Fe(2+) resulted in 60% of Mn extraction, while contact of microbial cells with the spent battery material and incubation for more than 7days was required to achieve the maximum extraction of Mn. Copyright © 2011 Elsevier Ltd. All rights reserved.

Magnitudes of biomarker reductions in response to controlled reductions in cigarettes smoked per day: a one-week clinical confinement study.

PubMed

Theophilus, Eugenia H; Coggins, Christopher R E; Chen, Peter; Schmidt, Eckhardt; Borgerding, Michael F

2015-03-01

Tobacco toxicant-related exposure reduction is an important tool in harm reduction. Cigarette per day reduction (CPDR) occurs as smokers migrate from smoking cigarettes to using alternative tobacco/nicotine products, or quit smoking. Few reports characterize the dose-response relationships between CPDR and effects on exposure biomarkers, especially at the low end of CPD exposure (e.g., 5 CPD). We present data on CPDR by characterizing magnitudes of biomarker reductions. We present data from a well-controlled, one-week clinical confinement study in healthy smokers who were switched from smoking 19-25 CPD to smoking 20, 10, 5 or 0 CPD. Biomarkers were measured in blood, plasma, urine, and breath, and included smoke-related toxicants, urine mutagenicity, smoked cigarette filter analyses (mouth level exposure), and vital signs. Many of the biomarkers (e.g., plasma nicotine) showed strong CPDR dose-response reductions, while others (e.g., plasma thiocyanate) showed weaker dose-response reductions. Factors that lead to lower biomarker reductions include non-CPD related contributors to the measured response (e.g., other exposure sources from environment, life style, occupation; inter-individual variability). This study confirms CPDR dose-responsive biomarkers and suggests that a one-week design is appropriate for characterizing exposure reductions when smokers switch from cigarettes to new tobacco products. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

NMOS contact resistance reduction with selenium implant into NiPt silicide

NASA Astrophysics Data System (ADS)

Rao, K. V.; Khaja, F. A.; Ni, C. N.; Muthukrishnan, S.; Darlark, A.; Lei, J.; Peidous, I.; Brand, A.; Henry, T.; Variam, N.; Erokhin, Y.

2012-11-01

A 25% reduction in NMOS contact resistance (Rc) was achieved by Selenium implantation into NiPt silicide film in VIISta Trident high-current single-wafer implanter. The Trident implanter is designed for shallow high-dose implants with high beam currents to maintain high throughput (for low CoO), with improved micro-uniformity and no energy contamination. The integration of Se implant was realized using a test chip dedicated to investigating silicide/junction related electrical properties and testable after silicidation. The silicide module processes were optimized, including the pre-clean (prior to RF PVD NiPt dep) and pre- and post-implant anneals. A 270°C soak anneal was used for RTP1, whereas a msec laser anneal was employed for RTP2 with sufficient process window (800-850°C), while maintaining excellent junction characteristics without Rs degradation.

Enhancement of IVR images by combining an ICA shrinkage filter with a multi-scale filter

NASA Astrophysics Data System (ADS)

Chen, Yen-Wei; Matsuo, Kiyotaka; Han, Xianhua; Shimizu, Atsumoto; Shibata, Koichi; Mishina, Yukio; Mukuta, Yoshihiro

2007-11-01

Interventional Radiology (IVR) is an important technique to visualize and diagnosis the vascular disease. In real medical application, a weak x-ray radiation source is used for imaging in order to reduce the radiation dose, resulting in a low contrast noisy image. It is important to develop a method to smooth out the noise while enhance the vascular structure. In this paper, we propose to combine an ICA Shrinkage filter with a multiscale filter for enhancement of IVR images. The ICA shrinkage filter is used for noise reduction and the multiscale filter is used for enhancement of vascular structure. Experimental results show that the quality of the image can be dramatically improved without any blurring in edge by the proposed method. Simultaneous noise reduction and vessel enhancement have been achieved.

Efficacy of a radiation absorbing shield in reducing dose to the interventionalist during peripheral endovascular procedures: a single centre pilot study.

PubMed

Power, S; Mirza, M; Thakorlal, A; Ganai, B; Gavagan, L D; Given, M F; Lee, M J

2015-06-01

This prospective pilot study was undertaken to evaluate the feasibility and effectiveness of using a radiation absorbing shield to reduce operator dose from scatter during lower limb endovascular procedures. A commercially available bismuth shield system (RADPAD) was used. Sixty consecutive patients undergoing lower limb angioplasty were included. Thirty procedures were performed without the RADPAD (control group) and thirty with the RADPAD (study group). Two separate methods were used to measure dose to a single operator. Thermoluminescent dosimeter (TLD) badges were used to measure hand, eye, and unshielded body dose. A direct dosimeter with digital readout was also used to measure eye and unshielded body dose. To allow for variation between control and study groups, dose per unit time was calculated. TLD results demonstrated a significant reduction in median body dose per unit time for the study group compared with controls (p = 0.001), corresponding to a mean dose reduction rate of 65 %. Median eye and hand dose per unit time were also reduced in the study group compared with control group, however, this was not statistically significant (p = 0.081 for eye, p = 0.628 for hand). Direct dosimeter readings also showed statistically significant reduction in median unshielded body dose rate for the study group compared with controls (p = 0.037). Eye dose rate was reduced for the study group but this was not statistically significant (p = 0.142). Initial results are encouraging. Use of the shield resulted in a statistically significant reduction in unshielded dose to the operator's body. Measured dose to the eye and hand of operator were also reduced but did not reach statistical significance in this pilot study.

Method for simulating dose reduction in digital mammography using the Anscombe transformation

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

Borges, Lucas R., E-mail: lucas.rodrigues.borges@usp.br; Oliveira, Helder C. R. de; Nunes, Polyana F.

2016-06-15

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtainedmore » by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.« less

Method for simulating dose reduction in digital mammography using the Anscombe transformation

PubMed Central

Borges, Lucas R.; de Oliveira, Helder C. R.; Nunes, Polyana F.; Bakic, Predrag R.; Maidment, Andrew D. A.; Vieira, Marcelo A. C.

2016-01-01

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions. PMID:27277017

Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?

PubMed

Craven, Meghan; Frank, Graeme R

2018-06-27

Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability. The recommended starting dose of levothyroxine (LT4) is between 10 and 15 μg/kg, an extremely wide range. We hypothesized that a sizable proportion of newborns treated for CH at the higher end of the dosage range become biochemically hyperthyroid at a follow-up visit. This study is a retrospective chart review of infants with CH between 2002 and 2012. Of the 104 patients included in this analysis, the average age at diagnosis was 11 days and the average starting dose of LT4 was 12±2.5 μg/kg. At follow-up, 36.5% required a dose reduction because of iatrogenic hyperthyroxinemia, 51% required no dose adjustment and 12.5% required a dose increase due to an elevated thyroid stimulating hormone (TSH). The starting doses of LT4 for those requiring a dose reduction, those not requiring an adjustment and those requiring an increase in the dose were 13.2±2.4, 11.5±2.1 and 10.3±2.6 μg/kg/day, respectively (p≤0.0001). Of the 34% of infants treated with an initial dose of >12.5 μg/day, 57.1% required a dose reduction at follow-up, compared to 26.1% of those whose initial starting dose was ≤12.5 μg/kg/day (p=0.007). Following the guidelines for initiating therapy for CH, 36.5% of the infants required a dose reduction for iatrogenic hyperthyroxinemia. These infants received a higher dose of LT4 than the infants who either required no adjustment or required an increase in the dose. A narrower range for initial dosing in CH may be appropriate.

SU-E-T-625: Potential for Reduced Radiation Induced Toxicity for the Treatment of Inoperable Non-Small-Cell Lung Cancer Using RapidArc Planning

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

Pokhrel, D; Sood, S; Badkul, R

2015-06-15

Purpose: To investigate the feasibility of using RapidArc (RA) treatment planning to reduce irradiation volume of normal lung and other organs at risk (OARs) in the treatment of inoperable non-small-cell lung cancer (NSCLC) patients. Methods: A retrospective treatment planning and delivery study was performed to compare target coverage and the volumes of the normal lung, spinal cord, heart and esophagus on 4D-CT scan above their dose tolerances delivered by RA vs. IMRT for ten inoperable NSCLC patients (Stage I-IIIB). RA plans consisted of either one-full or two-partial co-planar arcs used to treat 95% of the planning target volume (PTV) withmore » 6MV beam to a prescription of 66Gy in 33 fractions. IMRT plans were generated using 5–7 co-planar fields with 6MV beam. PTV coverage, dose-volume histograms, homogeneity/conformity indices (CI), total number of monitor units(MUs), beam-on time and delivery accuracy were compared between the two treatment plans. Results: Similar target coverage was obtained between the two techniques. RA (CI=1.02) provided more conformal plans without loss of homogeneity compared to IMRT plans (CI=1.12). Compared to IMRT, RA achieved a significant median dose reduction in V10 (3%), V20 (8%), and mean lung dose (3%) on average, respectively. On average, V5 was comparable between the two treatment plans. RA reduced mean esophagus (6%), mean heart (18%), and maximum spinal cord dose (7%), on average, respectively. Total number of MUs and beam-on time were each reduced almost by a factor of 2 when compared to IMRT-patient comfort, reduced intra-fraction-motion and leakage dose. The average IMRT and RA QA pass rate was about 98% for both types of plans for 3%/3mm criterion. Conclusion: Compared to IMRT plans, RA provided not only comparable target coverage, but also improved conformity, treatment time, and significant reduction in irradiation of OARs. This may potentially allow for target dose escalation without increase in normal tissue toxicity.« less

Physical aspects of total-body irradiation at the Middlesex Hospital (UCL group of hospitals), London 1988 - 1993: II. In vivo planning and dosimetry

NASA Astrophysics Data System (ADS)

Planskoy, B.; Tapper, P. D.; Bedford, A. M.; Davis, F. M.

1996-11-01

Part II of this paper gives the results of applying the TBI methods described in part I, to in vivo patient planning and dosimetry. Patients are planned on nine CT based body slices, five of which pass through the lungs. Planned doses are verified with ten silicon diodes applied bi-laterally to five body sites, at each treatment. LiF TLDs are applied to seven other body sites at the first treatment only. For 84 patients and at least 1016 measurements per body site with the diodes, the mean measured total doses agreed with planned doses within at most 2% except at lung levels, where the mean measured dose was 3% too low. Standard deviations of the measurements about the mean were between 2.4 and 3.1%. For the LiF TLDs, the mean measured doses for all seven body sites were within of planned doses. A separate assessment of measured entrance and transmitted doses showed that the former agreed well with planned doses, but that the latter tended to be low, especially over the lungs, and that they had a wider dispersion. Possible reasons for this are discussed. These results show measurement uncertainties similar to those for non-TBI treatments of Nilsson et al, Leunens et al and Essers et al. An analysis of the treatment plans showed a mean dose inhomogeneity in the body (75 patients, nine slices) of (1 s.d.) and in the lungs (40 patients, five slices) of (1 s.d.). The conclusions are that, overall, the methods are reasonably satisfactory but that, with an extra effort, even closer agreement between measured and planned doses and a further limited reduction in the body dose inhomogeneity could be obtained. However, if it were thought desirable to make a substantial reduction in the dose inhomogeneity in the body and lungs, this could only be achieved with the available equipment by changing from lateral to anterior - posterior irradiation and any potential advantages of this change would have to be balanced against a likely deterioration in patient comfort and an increase in treatment set-up times.

Required ozone doses for removing pharmaceuticals from wastewater effluents.

PubMed

Antoniou, Maria G; Hey, Gerly; Rodríguez Vega, Sergio; Spiliotopoulou, Aikaterini; Fick, Jerker; Tysklind, Mats; la Cour Jansen, Jes; Andersen, Henrik Rasmus

2013-07-01

The aim of the this study was to investigate the ozone dosage required to remove active pharmaceutical ingredients (APIs) from biologically treated wastewater of varying quality, originated from different raw wastewater and wastewater treatment processes. Secondary effluents from six Swedish wastewater treatment plants (WWTP) were spiked with 42 APIs (nominal concentration μg/L) and treated with different O₃ doses (0.5-12.0 mg/L ozone) in bench-scale experiments. In order to compare the sensitivity of APIs in each matrix, the specific dose of ozone required to achieve reduction by one decade of each investigated API (DDO₃) was determined for each effluent by fitting a first order equation to the remaining concentration of API at each applied ozone dose. Ozone dose requirements were found to vary significantly between effluents depending on their matrix characteristics. The specific ozone dose was then normalized to the dissolved organic carbon (DOC) of each effluent. The DDO₃/DOC ratios were comparable for each API between the effluents. 15 of the 42 investigated APIs could be classified as easily degradable (DDO₃/DOC ≤ 0.7), while 19 were moderately degradable (0.7 < DDO₃/DOC ≤ 1.4), and 8 were recalcitrant towards O₃-treatment (DDO₃/DOC >1.4). Furthermore, we predict that a reasonable estimate of the ozone dose required to remove any of the investigated APIs may be attained by multiplying the experimental average DDO₃/DOC obtained with the actual DOC of any effluent. Copyright © 2013 Elsevier B.V. All rights reserved.

Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 μg.

PubMed

Penin, Manuel; Trigo, Cristina; López, Yolanda; Barragáns, María

2014-01-01

Treatment of hypothyroid pregnant women is usually calculated based on weight (1 μg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 μg/day. All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 μg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/ml. A woman had a TSH level less than 0.3 mUI/ml in a test; reduction of thyroxine dose to 50 μg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml in one test; in all of them, increase in thyroxine dose to 100 μg/day allowed for maintaining the level within the desired range until delivery. Fixed daily doses of thyroxine 75 μg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Optimizing Radiation Doses for Computed Tomography Across Institutions: Dose Auditing and Best Practices.

PubMed

Demb, Joshua; Chu, Philip; Nelson, Thomas; Hall, David; Seibert, Anthony; Lamba, Ramit; Boone, John; Krishnam, Mayil; Cagnon, Christopher; Bostani, Maryam; Gould, Robert; Miglioretti, Diana; Smith-Bindman, Rebecca

2017-06-01

Radiation doses for computed tomography (CT) vary substantially across institutions. To assess the impact of institutional-level audit and collaborative efforts to share best practices on CT radiation doses across 5 University of California (UC) medical centers. In this before/after interventional study, we prospectively collected radiation dose metrics on all diagnostic CT examinations performed between October 1, 2013, and December 31, 2014, at 5 medical centers. Using data from January to March (baseline), we created audit reports detailing the distribution of radiation dose metrics for chest, abdomen, and head CT scans. In April, we shared reports with the medical centers and invited radiology professionals from the centers to a 1.5-day in-person meeting to review reports and share best practices. We calculated changes in mean effective dose 12 weeks before and after the audits and meeting, excluding a 12-week implementation period when medical centers could make changes. We compared proportions of examinations exceeding previously published benchmarks at baseline and following the audit and meeting, and calculated changes in proportion of examinations exceeding benchmarks. Of 158 274 diagnostic CT scans performed in the study period, 29 594 CT scans were performed in the 3 months before and 32 839 CT scans were performed 12 to 24 weeks after the audit and meeting. Reductions in mean effective dose were considerable for chest and abdomen. Mean effective dose for chest CT decreased from 13.2 to 10.7 mSv (18.9% reduction; 95% CI, 18.0%-19.8%). Reductions at individual medical centers ranged from 3.8% to 23.5%. The mean effective dose for abdominal CT decreased from 20.0 to 15.0 mSv (25.0% reduction; 95% CI, 24.3%-25.8%). Reductions at individual medical centers ranged from 10.8% to 34.7%. The number of CT scans that had an effective dose measurement that exceeded benchmarks was reduced considerably by 48% and 54% for chest and abdomen, respectively. After the audit and meeting, head CT doses varied less, although some institutions increased and some decreased mean head CT doses and the proportion above benchmarks. Reviewing institutional doses and sharing dose-optimization best practices resulted in lower radiation doses for chest and abdominal CT and more consistent doses for head CT.

A comprehensive study on decreasing the kilovoltage cone-beam CT dose by reducing the projection number.

PubMed

Lu, Bo; Lu, Haibin; Palta, Jatinder

2010-05-12

The objective of this study was to evaluate the effect of kilovoltage cone-beam computed tomography (CBCT) on registration accuracy and image qualities with a reduced number of planar projections used in volumetric imaging reconstruction. The ultimate goal is to evaluate the possibility of reducing the patient dose while maintaining registration accuracy under different projection-number schemes for various clinical sites. An Elekta Synergy Linear accelerator with an onboard CBCT system was used in this study. The quality of the Elekta XVI cone-beam three-dimensional volumetric images reconstructed with a decreasing number of projections was quantitatively evaluated by a Catphan phantom. Subsequently, we tested the registration accuracy of imaging data sets on three rigid anthropomorphic phantoms and three real patient sites under the reduced projection-number (as low as 1/6th) reconstruction of CBCT data with different rectilinear shifts and rota-tions. CBCT scan results of the Catphan phantom indicated the CBCT images got noisier when the number of projections was reduced, but their spatial resolution and uniformity were hardly affected. The maximum registration errors under the small amount transformation of the reference CT images were found to be within 0.7 mm translation and 0.3 masculine rotation. However, when the projection number was lower than one-fourth of the full set with a large amount of transformation of reference CT images, the registration could easily be trapped into local minima solutions for a nonrigid anatomy. We concluded, by using projection-number reduction strategy under conscientious care, imaging-guided localization procedure could achieve a lower patient dose without losing the registration accuracy for various clinical sites and situations. A faster scanning time is the main advantage compared to the mA decrease-based, dose-reduction method.

Development of a Chlorine Dosing Strategy for Fresh Produce Washing Process to Maintain Microbial Food Safety and Minimize Residual Chlorine.

PubMed

Chen, Xi; Hung, Yen-Con

2018-06-01

The residual free chlorine level in fresh produce wash solution is closely correlated to the chemical and microbial safety of produce. Excess amount of free chlorine can quickly react with organic matters to form hazardous disinfection by-products (DBPs) above EPA-permitted levels, whereas deficiency of residual chlorine in produce wash solution may result in incompletely removing pathogens on produce. The purpose of this study was to develop a chlorine dosing strategy to optimize the chlorine dosage during produce washing process without impacting the microbial safety of fresh produce. Prediction equations were developed to estimate free chlorine needed to reach targeted residual chlorine at various sanitizer pH and organic loads, and then validated using fresh-cut iceberg lettuce and whole strawberries in an automated produce washer. Validation results showed that equations successfully predicted the initial chlorine concentration needed to achieve residual chlorine at 10, 30, 60, and 90 mg/L for both lettuce and strawberry washing processes, with the root mean squared error at 4.45 mg/L. The Escherichia coli O157:H7 reductions only slightly increased on iceberg lettuce and strawberries with residual chlorine increasing from 10 to 90 mg/L, indicating that lowering residual chlorine to 10 mg/L would not compromise the antimicrobial efficacy of chlorine-based sanitizer. Based on the prediction equations and E. coli O157:H7 reduction results, a chlorine dosing strategy was developed to help the produce industry to maintain microbial inactivation efficacy without adding excess amount of free chlorine. The chlorine dosing strategy can be used for fresh produce washing process to enhance the microbial food safety and minimize the DBPs formation potential. © 2018 Institute of Food Technologists®.

Rescue Sedation With Intranasal Dexmedetomidine for Pediatric Ophthalmic Examination After Chloral Hydrate Failure: A Randomized, Controlled Trial.

PubMed

Gan, Xiaoliang; Lin, Haotian; Chen, Jingjing; Lin, Zhuoling; Lin, Yiquan; Chen, Weirong

2016-06-01

It is a challenge to rescue ophthalmology examinations performed in children in the sedation room after initial chloral hydrate failure. Intranasal dexmedetomidine can be used in rescue sedation in children undergoing computed tomography. The present study aimed to assess the efficacy and tolerability of intranasal dexmedetomidine use in children undergoing ophthalmic examination after chloral hydrate failure. Sixty uncooperative pediatric patients with cataract (aged 5-36 months; weight, 7-15 kg) presented for follow-up ophthalmic examination. Patients who experienced chloral hydrate failure were randomized to 1 of 2 groups to receive intranasal dexmedetomidine 1 or 2 μg/kg for rescue sedation. Each group contained 30 patients. The primary outcome was the rate of a successful ophthalmic examination. Secondary outcomes included sedation onset time, recovery time, duration of examination, discharge time, and adverse events, including percentage of heart rate reduction, respiratory depression, vomiting, and postsedative agitation. A successful ophthalmic examination was achieved in 93.3% (28/30) of patients in the 2-μg/kg dose group and in 66.7% (20/30) of patients in the 1-μg/kg dose group (P = 0.021). The onset time, recovery time, and discharge time did not significantly differ between the 2 groups. None of the patients required clinical intervention due to heart rate reduction, and none of the patients in either group experienced vomiting, respiratory depression, or agitation after the administration of dexmedetomidine. In children undergoing ophthalmic examination, intranasal dexmedetomidine can be administered in the sedation room for rescue sedation after chloral hydrate failure, with the 2-μg/kg dose being more efficacious than the 1-μg/kg dose, as measured by success rate. ClinicalTrials.gov identifier: NCT02077712. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Factor XII full and partial null in rat confers robust antithrombotic efficacy with no bleeding.

PubMed

Cai, Tian-Quan; Wu, Weizhen; Shin, Myung K; Xu, Yiming; Jochnowitz, Nina; Zhou, Yuchen; Hoos, Lizbeth; Bentley, Ross; Strapps, Walter; Thankappan, Anil; Metzger, Joseph M; Ogletree, Martin L; Tadin-Strapps, Marija; Seiffert, Dietmar A; Chen, Zhu

2015-12-01

This report aims at exploring quantitatively the relationship between FXII inhibition and thromboprotection. FXII full and partial null in rats were established via zinc finger nuclease-mediated knockout and siRNA-mediated knockdown, respectively. The rats were subsequently characterized in thrombosis and hemostasis models. Knockout rats exhibited complete thromboprotection in both the arteriovenous shunt model (∼100% clot weight reduction) and the FeCl3-induced arterial thrombosis model (no reduction in blood flow), without any increase in cuticle bleeding time compared with wild-type control rats. Ex-vivo aPTT and the ellagic acid-triggered thrombin generation assay (TGA) exhibited anticoagulant changes. In contrast, ex-vivo PT or high tissue factor-triggered TGA was indistinguishable from control. Rats receiving single doses (0, 0.01, 0.03, 0.1, 0.3, 1 mg/kg) of FXII siRNA exhibited dose-dependent knockdown in liver FXII mRNA and plasma FXII protein (95 and 99%, respectively, at 1 mg/kg) at day 7 post dosing. FXII knockdown was associated with dose-dependent thromboprotection (maximal efficacy achieved with 1 mg/kg in both models) and negligible change in cuticle bleeding times. Ex-vivo TGA triggered with low-level (0.5 μmol/l) ellagic acid tracked best with the knockdown levels and efficacy. Our findings confirm and extend literature reports of an attractive benefit-to-risk profile of targeting FXII for antithrombotic therapies. Titrating of FXII is instructive for its pharmacological inhibition. The knockout rat is valuable for evaluating both mechanism-based safety concerns and off-target effects of FXII(a) inhibitors. Detailed TGA analyses will inform on optimal trigger conditions in studying pharmacodynamic effects of FXII(a) inhibition.

Pharmacokinetics and Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Neutropenic Murine Pneumonia Model

PubMed Central

Zhou, Jian; Ledesma, Kimberly R.; Chang, Kai-Tai; Abodakpi, Henrietta; Gao, Song

2017-01-01

ABSTRACT Multidrug-resistant (MDR) Acinetobacter baumannii is increasingly more prevalent in nosocomial infections. Although in vitro susceptibility of A. baumannii to minocycline is promising, the in vivo efficacy of minocycline has not been well established. In this study, the in vivo activity of minocycline was evaluated in a neutropenic murine pneumonia model. Specifically, we investigated the relationship between minocycline exposure and bactericidal activity using five A. baumannii isolates with a broad range of susceptibility (MIC ranged from 0.25 mg/liter to 16 mg/liter). The pharmacokinetics of minocycline (single dose of 25 mg/kg of body weight, 50 mg/kg, 100 mg/kg, and a humanized regimen, given intraperitoneally) in serum and epithelial lining fluid (ELF) were characterized. Dose linearity was observed for doses up to 50 mg/kg and pulmonary penetration ratios (area under the concentration-time curve in ELF from 0 to 24 h [AUCELF,0–24]/area under the concentration time curve in serum from 0 to 24 h [AUCserum,0–24]) ranged from 2.5 to 2.8. Pharmacokinetic-pharmacodynamics (PK-PD) index values in ELF for various dose regimens against different A. baumannii isolates were calculated. The maximum efficacy at 24 h was approximately 1.5-log-unit reduction of pulmonary bacterial burdens from baseline. The AUC/MIC ratio was the PK-PD index most closely correlating to the bacterial burden (r2 = 0.81). The required AUCELF,0–24/MIC for maintaining stasis and achieving 1-log-unit reduction were 140 and 410, respectively. These findings could guide the treatment of infections caused by A. baumannii using minocycline in the future. Additional studies to examine resistance development during therapy are warranted. PMID:28264853

Pharmacokinetics and Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Neutropenic Murine Pneumonia Model.

PubMed

Zhou, Jian; Ledesma, Kimberly R; Chang, Kai-Tai; Abodakpi, Henrietta; Gao, Song; Tam, Vincent H

2017-05-01

Multidrug-resistant (MDR) Acinetobacter baumannii is increasingly more prevalent in nosocomial infections. Although in vitro susceptibility of A. baumannii to minocycline is promising, the in vivo efficacy of minocycline has not been well established. In this study, the in vivo activity of minocycline was evaluated in a neutropenic murine pneumonia model. Specifically, we investigated the relationship between minocycline exposure and bactericidal activity using five A. baumannii isolates with a broad range of susceptibility (MIC ranged from 0.25 mg/liter to 16 mg/liter). The pharmacokinetics of minocycline (single dose of 25 mg/kg of body weight, 50 mg/kg, 100 mg/kg, and a humanized regimen, given intraperitoneally) in serum and epithelial lining fluid (ELF) were characterized. Dose linearity was observed for doses up to 50 mg/kg and pulmonary penetration ratios (area under the concentration-time curve in ELF from 0 to 24 h [AUC ELF,0-24 ]/area under the concentration time curve in serum from 0 to 24 h [AUC serum,0-24 ]) ranged from 2.5 to 2.8. Pharmacokinetic-pharmacodynamics (PK-PD) index values in ELF for various dose regimens against different A. baumannii isolates were calculated. The maximum efficacy at 24 h was approximately 1.5-log-unit reduction of pulmonary bacterial burdens from baseline. The AUC/MIC ratio was the PK-PD index most closely correlating to the bacterial burden ( r 2 = 0.81). The required AUC ELF,0-24 /MIC for maintaining stasis and achieving 1-log-unit reduction were 140 and 410, respectively. These findings could guide the treatment of infections caused by A. baumannii using minocycline in the future. Additional studies to examine resistance development during therapy are warranted. Copyright © 2017 American Society for Microbiology.

Is sympathetic neural vasoconstriction blunted in the vascular bed of exercising human muscle?

PubMed

Tschakovsky, Michael E; Sujirattanawimol, Kittiphong; Ruble, Stephen B; Valic, Zoran; Joyner, Michael J

2002-06-01

Sympathetic vasoconstriction of muscle vascular beds is important in the regulation of systemic blood pressure. However, vasoconstriction during exercise can also compromise blood flow support of muscle metabolism. This study tested the hypothesis that local factors in exercising muscle blunt vessel responsiveness to sympathetic vasoconstriction. We performed selective infusions of three doses of tyramine into the brachial artery (n = 8) to evoke endogenous release of noradrenaline (norepinephrine) at rest and during moderate and heavy rhythmic handgrip exercise. In separate experiments, tyramine was administered during two doses of adenosine infusion (n = 7) and two doses of sodium nitroprusside (SNP) infusion (n = 8). Vasoconstrictor effectiveness across conditions was assessed as the percentage reduction in forearm vascular conductance (FVC), calculated from invasive blood pressure and non-invasive Doppler ultrasound blood flow measurements at the brachial artery. Tyramine evoked a similar dose-dependent vasoconstriction at rest in all three groups, with the highest dose resulting in a 42-46 % reduction in FVC. This vasoconstriction was blunted with increasing exercise intensity (e.g. tyramine high dose percentage reduction in FVC; rest -43.4 +/- 3.7 %, moderate exercise -27.5 +/- 2.3 %, heavy exercise -16.7 +/- 3.6 %; P < 0.05). In contrast, tyramine infusion resulted in a greater percentage reduction in FVC during both doses of adenosine vs. rest (P < 0.05). Finally, percentage change in FVC was greater during low dose SNP infusion vs. rest (P < 0.05), but not different from rest at the high dose of SNP infusion (P = 0.507). A blunted percentage reduction in FVC during endogenous noradrenaline release in exercise but not vasodilator infusion indicates that sympathetic vasoconstriction is blunted in exercising muscle. This blunting appears to be exercise intensity-dependent.

Optimizing mini-ridge filter thickness to reduce proton treatment times in a spot-scanning synchrotron system.

PubMed

Courneyea, Lorraine; Beltran, Chris; Tseung, Hok Seum Wan Chan; Yu, Juan; Herman, Michael G

2014-06-01

Study the contributors to treatment time as a function of Mini-Ridge Filter (MRF) thickness to determine the optimal choice for breath-hold treatment of lung tumors in a synchrotron-based spot-scanning proton machine. Five different spot-scanning nozzles were simulated in TOPAS: four with MRFs of varying maximal thicknesses (6.15-24.6 mm) and one with no MRF. The MRFs were designed with ridges aligned along orthogonal directions transverse to the beam, with the number of ridges (4-16) increasing with MRF thickness. The material thickness given by these ridges approximately followed a Gaussian distribution. Using these simulations, Monte Carlo data were generated for treatment planning commissioning. For each nozzle, standard and stereotactic (SR) lung phantom treatment plans were created and assessed for delivery time and plan quality. Use of a MRF resulted in a reduction of the number of energy layers needed in treatment plans, decreasing the number of synchrotron spills needed and hence the treatment time. For standard plans, the treatment time per field without a MRF was 67.0 ± 0.1 s, whereas three of the four MRF plans had treatment times of less than 20 s per field; considered sufficiently low for a single breath-hold. For SR plans, the shortest treatment time achieved was 57.7 ± 1.9 s per field, compared to 95.5 ± 0.5 s without a MRF. There were diminishing gains in time reduction as the MRF thickness increased. Dose uniformity of the PTV was comparable across all plans; however, when the plans were normalized to have the same coverage, dose conformality decreased with MRF thickness, as measured by the lung V20%. Single breath-hold treatment times for plans with standard fractionation can be achieved through the use of a MRF, making this a viable option for motion mitigation in lung tumors. For stereotactic plans, while a MRF can reduce treatment times, multiple breath-holds would still be necessary due to the limit imposed by the proton extraction time. To balance treatment time and normal tissue dose, the ideal MRF choice was shown to be the thinnest option that is able to achieve the desired breath-hold timing.

Dose Reduction Study in Vaginal Balloon Packing Filled With Contrast for HDR Brachytherapy Treatment;HDR; Uterine cervix cancer; Vaginal balloon packing; Contrast; Monte Carlo

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

Saini, Amarjit S.; Zhang, Geoffrey G., E-mail: geoffrey.zhang@moffitt.org; Finkelstein, Steven E.

2011-07-15

Purpose: Vaginal balloon packing is a means to displace organs at risk during high dose rate brachytherapy of the uterine cervix. We tested the hypothesis that contrast-filled vaginal balloon packing reduces radiation dose to organs at risk, such as the bladder and rectum, in comparison to water- or air-filled balloons. Methods and Materials: In a phantom study, semispherical vaginal packing balloons were filled with air, saline solution, and contrast agents. A high dose rate iridium-192 source was placed on the anterior surface of the balloon, and the diode detector was placed on the posterior surface. Dose ratios were taken withmore » each material in the balloon. Monte Carlo (MC) simulations, by use of the MC computer program DOSXYZnrc, were performed to study dose reduction vs. balloon size and contrast material, including commercially available iodine- and gadolinium-based contrast agents. Results: Measured dose ratios on the phantom with the balloon radius of 3.4 cm were 0.922 {+-} 0.002 for contrast/saline solution and 0.808 {+-} 0.001 for contrast/air. The corresponding ratios by MC simulations were 0.895 {+-} 0.010 and 0.781 {+-} 0.010. The iodine concentration in the contrast was 23.3% by weight. The dose reduction of contrast-filled balloon ranges from 6% to 15% compared with water-filled balloon and 11% to 26% compared with air-filled balloon, with a balloon size range between 1.4 and 3.8 cm, and iodine concentration in contrast of 24.9%. The dose reduction was proportional to the contrast agent concentration. The gadolinium-based contrast agents showed less dose reduction because of much lower concentrations in their solutions. Conclusions: The dose to the posterior wall of the bladder and the anterior wall of the rectum can be reduced if the vaginal balloon is filled with contrast agent in comparison to vaginal balloons filled with saline solution or air.« less

Field-scale reduction of PCB bioavailability with activated carbon amendment to river sediments.

PubMed

Beckingham, Barbara; Ghosh, Upal

2011-12-15

Remediation of contaminated sediments remains a technological challenge because traditional approaches do not always achieve risk reduction goals for human health and ecosystem protection and can even be destructive for natural resources. Recent work has shown that uptake of persistent organic pollutants such as polychlorinated biphenyls (PCBs) in the food web is strongly influenced by the nature of contaminant binding, especially to black carbon surfaces in sediments. We demonstrate for the first time in a contaminated river that application of activated carbon to sediments in the field reduces biouptake of PCBs in benthic organisms. After treatment with activated carbon applied at a dose similar to the native organic carbon of sediment, bioaccumulation in freshwater oligochaete worms was reduced compared to preamendment conditions by 69 to 99%, and concentrations of PCBs in water at equilibrium with the sediment were reduced by greater than 93% at all treatment sites for up to three years of monitoring. By comparing measured reductions in bioaccumulation of tetra- and penta-chlorinated PCB congeners resulting from field application of activated carbon to a laboratory study where PCBs were preloaded onto activated carbon, it is evident that equilibrium sorption had not been achieved in the field. Although other remedies may be appropriate for some highly contaminated sites, we show through this pilot study that PCB exposure from moderately contaminated river sediments may be managed effectively through activated carbon amendment in sediments.

Validation of Fully Automated VMAT Plan Generation for Library-Based Plan-of-the-Day Cervical Cancer Radiotherapy

PubMed Central

Breedveld, Sebastiaan; Voet, Peter W. J.; Heijkoop, Sabrina T.; Mens, Jan-Willem M.; Hoogeman, Mischa S.; Heijmen, Ben J. M.

2016-01-01

Purpose To develop and validate fully automated generation of VMAT plan-libraries for plan-of-the-day adaptive radiotherapy in locally-advanced cervical cancer. Material and Methods Our framework for fully automated treatment plan generation (Erasmus-iCycle) was adapted to create dual-arc VMAT treatment plan libraries for cervical cancer patients. For each of 34 patients, automatically generated VMAT plans (autoVMAT) were compared to manually generated, clinically delivered 9-beam IMRT plans (CLINICAL), and to dual-arc VMAT plans generated manually by an expert planner (manVMAT). Furthermore, all plans were benchmarked against 20-beam equi-angular IMRT plans (autoIMRT). For all plans, a PTV coverage of 99.5% by at least 95% of the prescribed dose (46 Gy) had the highest planning priority, followed by minimization of V45Gy for small bowel (SB). Other OARs considered were bladder, rectum, and sigmoid. Results All plans had a highly similar PTV coverage, within the clinical constraints (above). After plan normalizations for exactly equal median PTV doses in corresponding plans, all evaluated OAR parameters in autoVMAT plans were on average lower than in the CLINICAL plans with an average reduction in SB V45Gy of 34.6% (p<0.001). For 41/44 autoVMAT plans, SB V45Gy was lower than for manVMAT (p<0.001, average reduction 30.3%), while SB V15Gy increased by 2.3% (p = 0.011). AutoIMRT reduced SB V45Gy by another 2.7% compared to autoVMAT, while also resulting in a 9.0% reduction in SB V15Gy (p<0.001), but with a prolonged delivery time. Differences between manVMAT and autoVMAT in bladder, rectal and sigmoid doses were ≤ 1%. Improvements in SB dose delivery with autoVMAT instead of manVMAT were higher for empty bladder PTVs compared to full bladder PTVs, due to differences in concavity of the PTVs. Conclusions Quality of automatically generated VMAT plans was superior to manually generated plans. Automatic VMAT plan generation for cervical cancer has been implemented in our clinical routine. Due to the achieved workload reduction, extension of plan libraries has become feasible. PMID:28033342

Mesoscopic in vivo 3-D tracking of sparse cell populations using angular multiplexed optical projection tomography

PubMed Central

Chen, Lingling; Alexandrov, Yuriy; Kumar, Sunil; Andrews, Natalie; Dallman, Margaret J.; French, Paul M. W.; McGinty, James

2015-01-01

We describe an angular multiplexed imaging technique for 3-D in vivo cell tracking of sparse cell distributions and optical projection tomography (OPT) with superior time-lapse resolution and a significantly reduced light dose compared to volumetric time-lapse techniques. We demonstrate that using dual axis OPT, where two images are acquired simultaneously at different projection angles, can enable localization and tracking of features in 3-D with a time resolution equal to the camera frame rate. This is achieved with a 200x reduction in light dose compared to an equivalent volumetric time-lapse single camera OPT acquisition with 200 projection angles. We demonstrate the application of this technique to mapping the 3-D neutrophil migration pattern observed over ~25.5 minutes in a live 2 day post-fertilisation transgenic LysC:GFP zebrafish embryo following a tail wound. PMID:25909009

Use of orbital floor steroids in the management of patients with uniocular non-necrotising scleritis.

PubMed Central

Hakin, K N; Ham, J; Lightman, S L

1991-01-01

Most cases of non-necrotising scleritis can be successfully treated with non-steroidal anti-inflammatory drugs. If these are ineffective, then high-dose systemic corticosteroids, with all their attendant side-effects, are usually required. We have used orbital floor injections of depot steroid in the management of nine patients with non-necrotising scleritis in an attempt to avoid the use of systemic steroids, or to allow the dose of steroids to be reduced while maintaining disease control. A temporary reduction in inflammation was achieved in all cases, which allowed the use of systemic steroids to be avoided altogether in two patients and delayed in the others. Non-steroidal anti-inflammatory drugs and systemic corticosteroids remain the mainstay of treatment for non-necrotising scleritis, but orbital floor injections may be a useful adjunct in certain cases. Images PMID:2043574

Microbial decontamination of cosmetic raw materials and personal care products by irradiation

NASA Astrophysics Data System (ADS)

Katušin-Ražem, Branka; Mihaljević, Branka; Ražem, Dušan

2003-03-01

Typical levels of sporadically occurring (dynamic) microbial contamination of cosmetic raw materials: pigments, abrasives and liposomes, as well as of final products for personal care: toothpaste, crayons, shampoos, cleansers and creams, were evaluated. In most cases the contamination was dominated by a single population of microorganisms, either Gram-negative bacteria or molds. The feasibility of microbial decontamination by irradiation was studied by determining the resistance to gamma radiation of contaminating microflora in situ. It was expressed as a dose required for the first 90% reduction, D first 90% red . The values in the range 1-2 kGy for molds and 0.1-0.6 kGy for Gram-negative bacteria were obtained. This relatively high susceptibility to irradiation allowed inactivation factors close to 6 to be achieved with doses generally not exceeding 3 kGy, and yielding endpoint contamination less than 10/g.

Mesoscopic in vivo 3-D tracking of sparse cell populations using angular multiplexed optical projection tomography.

PubMed

Chen, Lingling; Alexandrov, Yuriy; Kumar, Sunil; Andrews, Natalie; Dallman, Margaret J; French, Paul M W; McGinty, James

2015-04-01

We describe an angular multiplexed imaging technique for 3-D in vivo cell tracking of sparse cell distributions and optical projection tomography (OPT) with superior time-lapse resolution and a significantly reduced light dose compared to volumetric time-lapse techniques. We demonstrate that using dual axis OPT, where two images are acquired simultaneously at different projection angles, can enable localization and tracking of features in 3-D with a time resolution equal to the camera frame rate. This is achieved with a 200x reduction in light dose compared to an equivalent volumetric time-lapse single camera OPT acquisition with 200 projection angles. We demonstrate the application of this technique to mapping the 3-D neutrophil migration pattern observed over ~25.5 minutes in a live 2 day post-fertilisation transgenic LysC:GFP zebrafish embryo following a tail wound.

Is multidetector CT-based bone mineral density and quantitative bone microstructure assessment at the spine still feasible using ultra-low tube current and sparse sampling?

PubMed

Mei, Kai; Kopp, Felix K; Bippus, Rolf; Köhler, Thomas; Schwaiger, Benedikt J; Gersing, Alexandra S; Fehringer, Andreas; Sauter, Andreas; Münzel, Daniela; Pfeiffer, Franz; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B; Baum, Thomas

2017-12-01

Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment. Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5. Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05). In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use. • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

A novel design for a dose finding, safety, and drug interaction study of an antiepileptic drug (retigabine) in early clinical development.

PubMed

Sachdeo, Rajesh; Partiot, Arnaud; Biton, Victor; Rosenfeld, William E; Nohria, Virinder; Tompson, Debra; DeRossett, Sarah; Porter, Roger J

2014-06-01

To obtain information on the acceptable doses of the antiepileptic drug (AED) retigabine (RTG), the maximum tolerated dose (MTD), drug interactions, safety and tolerability, and preliminary evidence of efficacy when administered as adjunctive therapy and as monotherapy. Study 202 was an open-label, add-on study in patients with partial or generalized epilepsy treated with valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), or topiramate (TPM) as monotherapy. Following baseline assessments, patients entered a dose titration phase of 28 – 56 days. The initial daily RTG dose was 100 or 200 mg (2 or 3 × daily). The RTG dose was increased every 1 - 2 weeks by 50 - 200 mg to a maximum of 1,600 mg/day. Once the RTG MTD had been attained, patients entered a 14-day maintenance period. Following this, the patient's background AED dose could be reduced, with the possibility of achieving RTG monotherapy. The final dosing regimen attained was maintained for an additional 14 days. Patients who completed study 202 could choose to continue treatment with RTG (with or without other AEDs) in study 208, the long-term extension of study 202. Safety assessments included adverse event (AE) monitoring, clinical laboratory evaluations, electrocardiograms, and physical and neurologic examinations. Patients' seizure diaries to assess the frequency and type of seizures, the percentage change in seizure rate, and the responder rate (>= 50% reduction in seizure rate from baseline) were evaluated. 60 patients (mean age 37.2, range 16 - 64 years) were enrolled in study 202, and 47 (78%) continued treatment with RTG in the extension study (208). In study 202, the most commonly reported AEs were: dizziness (53%), asthenia (42%), somnolence (33%), nausea (27%), speech disorder (27%), and tremor (27%). In the extension study, AEs were similar and included dizziness, somnolence, diplopia, feeling "drunk", confusion, fatigue, and dysarthria. The median percent reductions in 28-day seizure rate, relative to baseline in Studies 202 and 208, were ~ 20% and 47%, respectively. RTG did not alter the pharmacokinetics of the four monotherapy AEDs investigated. CBZ and PHT increased RTG clearance by 27% and 36%, respectively, whereas TPM and VPA had no effect on RTG clearance. Studies 202 and 208 provided critical information on RTG safety and tolerability, and reductions in seizure rates towards the design and conduct of subsequent pivotal clinical trials. Likewise, information regarding the appropriate dosage of RTG with VPA, CBZ, PHT, or TPM was obtained, which permitted the subsequent pivotal trials to be performed appropriately. *Currently at Shire Pharmaceuticals, Behavioral Health Business Unit, Wayne, PA, USA **Currently at University of Pennsylvania, Department of Neurology, Philadelphia, PA, USA.

Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low–dose rate delivery techniques

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

Li, Jie; Lang, Jinyi; Wang, Pei

2014-01-01

Reirradiation of patients who were previously treated with radiotherapy is vastly challenging. Pulsed low–dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while providing significant tumor control for recurrent cancers. This work investigates treatment planning techniques for intensity-modulated radiation therapy (IMRT)-based PLDR treatment of various sites, including cases with pancreatic and prostate cancer. A total of 20 patients with clinical recurrence were selected for this study, including 10 cases with pancreatic cancer and 10 with prostate cancer. Large variations in the target volume were included to test the ability of IMRT using the existing treatmentmore » planning system and optimization algorithm to deliver uniform doses in individual gantry angles/fields for PLDR treatments. Treatment plans were generated with 10 gantry angles using the step-and-shoot IMRT delivery technique, which can be delivered in 3-minute intervals to achieve an effective low dose rate of 6.7 cGy/min. Instead of dose constraints on critical structures, ring structures were mainly used in PLDR-IMRT optimization. In this study, the PLDR-IMRT plans were compared with the PLDR-3-dimensional conformal radiation therapy (3DCRT) plans and the PLDR-RapidArc plans. For the 10 cases with pancreatic cancer that were investigated, the mean planning target volume (PTV) dose for each gantry angle in the PLDR-IMRT plans ranged from 17.6 to 22.4 cGy. The maximum doses ranged between 22.9 and 34.8 cGy. The minimum doses ranged from 8.2 to 17.5 cGy. For the 10 cases with prostate cancer that were investigated, the mean PTV doses for individual gantry angles ranged from 18.8 to 22.6 cGy. The maximum doses per gantry angle were between 24.0 and 34.7 cGy. The minimum doses per gantry angle ranged from 4.4 to 17.4 cGy. A significant reduction in the organ at risk (OAR) dose was observed with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. The volume receiving an 18-Gy (V{sub 18}) dose for the left and right kidneys was reduced by 10.6% and 12.5%, respectively, for the pancreatic plans. The volume receiving a 45-Gy (V{sub 45}) dose for the small bowel decreased from 65.3% to 45.5%. For the cases with prostate cancer, the volume receiving a 40-Gy (V{sub 40}) dose for the bladder and the rectum was reduced significantly by 25.1% and 51.2%, respectively. When compared with the RapidArc technique, the volume receiving a 30-Gy (V{sub 30}) dose for the left and the right kidneys was lower in the IMRT plans. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. These results clearly demonstrated that the PLDR-IMRT plan was suitable for PLDR pancreatic and prostate cancer treatments in terms of the overall plan quality. A significant reduction in the OAR dose was achieved with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. When compared with the PLDR-3DCRT plan, the PLDR-IMRT plan could provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent pancreatic and prostate cancers. The PLDR-IMRT plan is an effective treatment choice for recurrent cancers in most cancer centers.« less

SU-G-IeP3-05: Effects of Image Receptor Technology and Dose Reduction Software On Radiation Dose Estimates for Fluoroscopically-Guided Interventional (FGI) Procedures

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

Merritt, Z; Dave, J; Eschelman, D

Purpose: To investigate the effects of image receptor technology and dose reduction software on radiation dose estimates for most frequently performed fluoroscopically-guided interventional (FGI) procedures at a tertiary health care center. Methods: IRB approval was obtained for retrospective analysis of FGI procedures performed in the interventional radiology suites between January-2011 and December-2015. This included procedures performed using image-intensifier (II) based systems which were subsequently replaced, flat-panel-detector (FPD) based systems which were later upgraded with ClarityIQ dose reduction software (Philips Healthcare) and relatively new FPD system already equipped with ClarityIQ. Post procedure, technologists entered system-reported cumulative air kerma (CAK) and kerma-areamore » product (KAP; only KAP for II based systems) in RIS; these values were analyzed. Data pre-processing included correcting typographical errors and cross-verifying CAK and KAP. The most frequent high and low dose FGI procedures were identified and corresponding CAK and KAP values were compared. Results: Out of 27,251 procedures within this time period, most frequent high and low dose procedures were chemo/immuno-embolization (n=1967) and abscess drainage (n=1821). Mean KAP for embolization and abscess drainage procedures were 260,657, 310,304 and 94,908 mGycm{sup 2}, and 14,497, 15,040 and 6307 mGycm{sup 2} using II-, FPD- and FPD with ClarityIQ- based systems, respectively. Statistically significant differences were observed in KAP values for embolization procedures with respect to different systems but for abscess drainage procedures significant differences were only noted between systems with FPD and FPD with ClarityIQ (p<0.05). Mean CAK reduced significantly from 823 to 308 mGy and from 43 to 21 mGy for embolization and abscess drainage procedures, respectively, in transitioning to FPD systems with ClarityIQ (p<0.05). Conclusion: While transitioning from II- to FPD- based systems was not associated with dose reduction for the most frequently performed FGI procedures, substantial dose reduction was noted with relatively newer systems and dose reduction software.« less

A Novel Pairwise Comparison-Based Method to Determine Radiation Dose Reduction Potentials of Iterative Reconstruction Algorithms, Exemplified Through Circle of Willis Computed Tomography Angiography.

PubMed

Ellmann, Stephan; Kammerer, Ferdinand; Brand, Michael; Allmendinger, Thomas; May, Matthias S; Uder, Michael; Lell, Michael M; Kramer, Manuel

2016-05-01

The aim of this study was to determine the dose reduction potential of iterative reconstruction (IR) algorithms in computed tomography angiography (CTA) of the circle of Willis using a novel method of evaluating the quality of radiation dose-reduced images. This study relied on ReconCT, a proprietary reconstruction software that allows simulating CT scans acquired with reduced radiation dose based on the raw data of true scans. To evaluate the performance of ReconCT in this regard, a phantom study was performed to compare the image noise of true and simulated scans within simulated vessels of a head phantom. That followed, 10 patients scheduled for CTA of the circle of Willis were scanned according to our institute's standard protocol (100 kV, 145 reference mAs). Subsequently, CTA images of these patients were reconstructed as either a full-dose weighted filtered back projection or with radiation dose reductions down to 10% of the full-dose level and Sinogram-Affirmed Iterative Reconstruction (SAFIRE) with either strength 3 or 5. Images were marked with arrows pointing on vessels of different sizes, and image pairs were presented to observers. Five readers assessed image quality with 2-alternative forced choice comparisons. In the phantom study, no significant differences were observed between the noise levels of simulated and true scans in filtered back projection, SAFIRE 3, and SAFIRE 5 reconstructions.The dose reduction potential for patient scans showed a strong dependence on IR strength as well as on the size of the vessel of interest. Thus, the potential radiation dose reductions ranged from 84.4% for the evaluation of great vessels reconstructed with SAFIRE 5 to 40.9% for the evaluation of small vessels reconstructed with SAFIRE 3. This study provides a novel image quality evaluation method based on 2-alternative forced choice comparisons. In CTA of the circle of Willis, higher IR strengths and greater vessel sizes allowed higher degrees of radiation dose reduction.

Monte Carlo simulations to assess the effects of tube current modulation on breast dose for multidetector CT

NASA Astrophysics Data System (ADS)

Angel, Erin; Yaghmai, Nazanin; Matilda Jude, Cecilia; DeMarco, John J.; Cagnon, Christopher H.; Goldin, Jonathan G.; Primak, Andrew N.; Stevens, Donna M.; Cody, Dianna D.; McCollough, Cynthia H.; McNitt-Gray, Michael F.

2009-02-01

Tube current modulation was designed to reduce radiation dose in CT imaging while maintaining overall image quality. This study aims to develop a method for evaluating the effects of tube current modulation (TCM) on organ dose in CT exams of actual patient anatomy. This method was validated by simulating a TCM and a fixed tube current chest CT exam on 30 voxelized patient models and estimating the radiation dose to each patient's glandular breast tissue. This new method for estimating organ dose was compared with other conventional estimates of dose reduction. Thirty detailed voxelized models of patient anatomy were created based on image data from female patients who had previously undergone clinically indicated CT scans including the chest area. As an indicator of patient size, the perimeter of the patient was measured on the image containing at least one nipple using a semi-automated technique. The breasts were contoured on each image set by a radiologist and glandular tissue was semi-automatically segmented from this region. Previously validated Monte Carlo models of two multidetector CT scanners were used, taking into account details about the source spectra, filtration, collimation and geometry of the scanner. TCM data were obtained from each patient's clinical scan and factored into the model to simulate the effects of TCM. For each patient model, two exams were simulated: a fixed tube current chest CT and a tube current modulated chest CT. X-ray photons were transported through the anatomy of the voxelized patient models, and radiation dose was tallied in the glandular breast tissue. The resulting doses from the tube current modulated simulations were compared to the results obtained from simulations performed using a fixed mA value. The average radiation dose to the glandular breast tissue from a fixed tube current scan across all patient models was 19 mGy. The average reduction in breast dose using the tube current modulated scan was 17%. Results were size dependent with smaller patients getting better dose reduction (up to 64% reduction) and larger patients getting a smaller reduction, and in some cases the dose actually increased when using tube current modulation (up to 41% increase). The results indicate that radiation dose to glandular breast tissue generally decreases with the use of tube current modulated CT acquisition, but that patient size (and in some cases patient positioning) may affect dose reduction.

Bioavailability of curcumin and curcumin glucuronide in the central nervous system of mice after oral delivery of nano-curcumin.

PubMed

Szymusiak, Magdalena; Hu, Xiaoyu; Leon Plata, Paola A; Ciupinski, Paulina; Wang, Zaijie Jim; Liu, Ying

2016-09-10

Curcumin is a bioactive molecule extracted from Turmeric roots that has been recognized to possess a wide variety of important biological activities. Despite its great pharmacological activities, curcumin is highly hydrophobic, which results in poor bioavailability. We have formulated this hydrophobic compound into stable polymeric nanoparticles (nano-curcumin) to enhance its oral absorption. Pharmacokinetic analysis after oral delivery of nano-curcumin in mice demonstrated approximately 20-fold reduction in dose requirement when compared to unformulated curcumin to achieve comparable plasma and central nervous system (CNS) tissue concentrations. This investigation corroborated our previous study of curcumin functionality of attenuating opioid tolerance and dependence, which shows equivalent efficacy of low-dose (20mg/kg) nano-curcumin and high-dose (400mg/kg) pure curcumin in mice. Furthermore, the highly selective and validated liquid chromatography-mass spectrometry (LC-MS) method was developed to quantify curcumin glucuronide, the major metabolite of curcumin. The results suggest that the presence of curcumin in the CNS is essential for prevention and reversal of opioid tolerance and dependence. Copyright © 2016 Elsevier B.V. All rights reserved.

Quality Assurance: Patient Chart Reviews

NASA Astrophysics Data System (ADS)

Oginni, B. M.; Odero, D. O.

2009-07-01

Recent developments in radiation therapy have immensely impacted the way the radiation dose is delivered to patients undergoing radiation treatments. However, the fundamental quality assurance (QA) issues underlying the radiation therapy still remain the accuracy of the radiation dose and the radiation safety. One of the major duties of clinical medical physicists in the radiation therapy departments still revolves around ensuring the accuracy of dose delivery to the planning target volume (PTV), the reduction of unintended radiation to normal organs and minimization of the radiation exposure to the medical personnel based on ALARA (as low as reasonably achievable) principle. Many of the errors in radiation therapy can be minimized through a comprehensive program of periodic checks. One of the QA procedures on the patient comes in the form of chart reviews which could be in either electronic or paper-based format. We present the quality assurance procedures that have to be performed on the patient records from the beginning and periodically to the end of the treatment, based on the guidelines from the American Association of Physicists in Medicine (AAPM) and American College of Physicians (ACP).

Efficiency and Safety of Prolonged Levosimendan Infusion in Patients with Acute Heart Failure

PubMed Central

Aidonidis, Georgios; Kanonidis, Ioannis; Koutsimanis, Vasileios; Neumann, Till; Erbel, Raimund; Sakadamis, Georgios

2011-01-01

Background. Levosimendan is an inotropic drug with unique pharmacological advantages in patients with acute heart failure. Scope of this study is to determine whether longer infusion patterns without the hypotension-inducing loading dose could justify an effective and safe alternative approach. Methods. 70 patients admitted to the emergencies with decompensated chronic heart failure received intravenously levosimendan without a loading dose up to 72 hours. Clinical parameters, BNP (Brain Natriuretic Peptide) and signal-averaged-ECG data (SAECG) were recorded up to 72 hours. Results. The 48-hour group demonstrated a statistically significant BNP decrease (P < .001) after 48 hours, which also maintained after 72 hours. The 72-hour group demonstrated a bordeline decrease of BNP after 48 hours (P = .039), necessitating an additional 24-hour infusion to achieve significant reduction after 72 hours (P < .004). SAECG data demonstrated a statistically significant decrease after 72 hours (P < .04). Apart from two deaths due to advanced heart failure, no major complications were observed. Conclusion. Prolonged infusion of levosimendan without a loading dose is associated with an acceptable clinical and neurohumoral response. PMID:21559263

The Efficacy of Reduced-dose Dasatinib as a Subsequent Therapy in Patients with Chronic Myeloid Leukemia in the Chronic Phase: The LD-CML Study of the Kanto CML Study Group

PubMed Central

Iriyama, Noriyoshi; Ohashi, Kazuteru; Hashino, Satoshi; Kimura, Shinya; Nakaseko, Chiaki; Takano, Hina; Hino, Masayuki; Uchiyama, Michihiro; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

2017-01-01

Objective The aim of this study was to prospectively investigate the efficacy and safety profiles of low-dose dasatinib therapy (50 mg once daily). Methods Patients with chronic myeloid leukemia in the chronic phase (CML-CP) who were being treated with low-dose imatinib (≤200 mg/day), but were resistant to this agent were enrolled in the current study (referred to as the LD-CML study). Results There subjects included 9 patients (4 men and 5 women); all were treated with dasatinib at a dose of 50 mg once daily. Among 8 patients who had not experienced major molecular response (MMR; BCR-ABL1 transcript ≤0.1% according to International Scale [IS]) at study enrollment, 5 attained MMR by 12 months. In particular, 3 of 9 patients demonstrated a deep molecular response (DMR; IS ≤0.0069%) by 18 months. Five patients developed lymphocytosis accompanied by cytotoxic lymphocyte predominance. There was no mortality or disease progression, and all continue to receive dasatinib therapy at 18 months with only 2 patients requiring dose reduction. Toxicities were mild-to-moderate, and pleural effusion was observed in 1 patient (grade 1). Conclusion Low-dose dasatinib can attain MMR and DMR without severe toxicity in patients with CML-CP who are unable to achieve MMR with low-dose imatinib. Switching to low-dose dasatinib should therefore be considered for patients in this setting, especially if they are otherwise considering a cessation of treatment. PMID:29033428

Intratympanic treatment of intractable unilateral Meniere disease: gentamicin or dexamethasone? A randomized controlled trial.

PubMed

Casani, Augusto Pietro; Piaggi, Paolo; Cerchiai, Niccolò; Seccia, Veronica; Franceschini, Stefano Sellari; Dallan, Iacopo

2012-03-01

To determine the efficacy and safety of low-dose intratympanic gentamicin (ITG) compared with intratympanic dexamethasone (ITD) in patients with intractable unilateral Ménière disease (MD). Open prospective randomized controlled study. Tertiary referral center. Sixty patients affected by definite unilateral MD were enrolled between January 1, 2007, and June 30, 2008. Thirty-two patients were treated with a buffered gentamicin solution injected in the middle ear (maximum of 2 injections); 28 patients were treated with ITD (4 mg/mL, 3 injections at intervals of 1 every 3 days). Mean outcome measurements consisted of control of vertigo attacks, pure tone average (PTA), speech discrimination score, functional disability score, and statistical analysis using repeated measures analysis of variance. In the ITG group at 2-year follow-up, complete control of vertigo (class A) was achieved in 26 patients (81%) and substantial control of vertigo (class B) in 4 patients (12.5%). In the ITD group, class A was achieved in 12 (43%), and class B in 5 (18%) patients. In the gentamicin group, 4 patients showed a reduction in PTA of ≥10 dB. In the ITD group, PTA was unchanged or slightly improved in 16 patients (belonging to class A-B) and worse in 12. Low-dose ITG achieved better outcome than ITD in the control of vertigo attacks in patients suffering from unilateral MD, with a very low incidence of hearing deterioration. ITD offers poorer vertigo control rate, and hearing preservation is achieved only in cases with no vertigo recurrences.

Management of dyslipidemia and hyperglycemia with a fixed-dose combination of sitagliptin and simvastatin

PubMed Central

Steinberg, Helmut; Anderson, Matt S; Musliner, Thomas; Hanson, Mary E; Engel, Samuel S

2013-01-01

The risk of death due to heart disease and stroke is up to four times higher in individuals with diabetes compared to individuals without diabetes. Most guidelines that address treatment of dyslipidemia in patients with diabetes consider diabetes a cardiovascular disease (CVD) “risk equivalent” and recommend intensive treatment of dyslipidemia for the purpose of CVD prevention. Statins (3-hydroxy 3-methylglutaryl coenzyme A reductase [HMG-CoA reductase] inhibitors) are first-line agents in achieving lipid goals as an adjunct to diet and exercise and should be used in most patients. In addition to lipid management and blood pressure control, glycemic control is a basic component in the management of diabetes. Glycemic control is achieved by combining diabetes self-management education, diet and exercise, and, where required, antihyperglycemic agents (OHAs). Persistence and adherence to therapy are critical in achieving recommended treatment goals. However, overall compliance with concomitantly prescribed OHAs and statins is low in patients with type 2 diabetes. Fixed-dose combination (FDC) therapies have been shown to improve adherence by reducing pill burden, the complexity of treatment regimen, and, potentially, cost. Based on the available evidence regarding the pharmacokinetics and the efficacy and safety profiles of each component drug, the sitagliptin/simvastatin FDC may provide a rational and well-tolerated approach to achieving better adherence to multiple-drug therapy and improved lipid lowering and glycemic control, with consequent reduction in cardiovascular risk, diabetic microvascular disease, and mortality in diabetic patients for whom treatment with both compounds is appropriate. PMID:23761972

[Home Hemodialysis: Experience and Preliminary Results Of The First Center In Campania].

PubMed

Brancaccio, Stefania; Capuano, Alfredo; Memoli, Andrea; Sorrentino, Livia Maria; Pirro, Laura; Federico, Stefano

2015-12-01

The Home Hemodialysis (HHD) is an uncommon dialytic option that can offer better clinical outcomes and a more satisfactory quality of life. The Health Plan of the Region Campania 2011-2013 states that" the system of home care for regional planning is particularly important". From August 2014 to March 2015 two patients, on standard dialysis (HD) as inpatients at Dialysis Centre of the University "Federico II" of Naples, started Short Daily Home Hemodialysis (SDHD) (4-6 dialysis treatments%week, 2.5 hours per session) using the portable cycler NxStage System One). The data collected showed that the clinical benefits described in the literature were confirmed in patients enrolled in this HHD program. Shorter and more frequent hemodialysis sessions allowed a significant reduction in interdialytic weight gain and greater intradialytic hemodynamic stability. A significant reduction in blood pressure and anti-hypertensive drugs were obtained. The control of phosphorus appeared better and hemoglobin was to target with a lower dose of weekly erythropoetin. The patients reported a greater well-being and a reduction in post-dialytic asthenia. No problem has been reported in using the vascular access (CVC and FAV) by the patient%caregiver. The dialysis adequacy and efficiency were comparable between SDHD and HD. The experience with the HHD is encouraging as the patients achieved an adequate dialysis dose without any complications reporting an improving sense of well-being and a better quality of life. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Quantitative Analysis of the Effect of Iterative Reconstruction Using a Phantom: Determining the Appropriate Blending Percentage

PubMed Central

Kim, Hyun Gi; Lee, Young Han; Choi, Jin-Young; Park, Mi-Suk; Kim, Myeong-Jin; Kim, Ki Whang

2015-01-01

Purpose To investigate the optimal blending percentage of adaptive statistical iterative reconstruction (ASIR) in a reduced radiation dose while preserving a degree of image quality and texture that is similar to that of standard-dose computed tomography (CT). Materials and Methods The CT performance phantom was scanned with standard and dose reduction protocols including reduced mAs or kVp. Image quality parameters including noise, spatial, and low-contrast resolution, as well as image texture, were quantitatively evaluated after applying various blending percentages of ASIR. The optimal blending percentage of ASIR that preserved image quality and texture compared to standard dose CT was investigated in each radiation dose reduction protocol. Results As the percentage of ASIR increased, noise and spatial-resolution decreased, whereas low-contrast resolution increased. In the texture analysis, an increasing percentage of ASIR resulted in an increase of angular second moment, inverse difference moment, and correlation and in a decrease of contrast and entropy. The 20% and 40% dose reduction protocols with 20% and 40% ASIR blending, respectively, resulted in an optimal quality of images with preservation of the image texture. Conclusion Blending the 40% ASIR to the 40% reduced tube-current product can maximize radiation dose reduction and preserve adequate image quality and texture. PMID:25510772

[Effectiveness and safety of losartan and its combination with hydrochlorothiazide in patients with hypertension: in result study].

PubMed

Glezer, M G; Saĭgitov, R T

2012-01-01

There are limited data on the results of Russia's use of losartan in clinical practice for the treatment of patients with arterial hypertension (AH). The purpose of the study was to assess the efficacy and safety of losartan and its fixed combination with hydrochlorothiazide (HCTZ) in patients with hypertension. Primary care physicians (n=644) for 8 weeks evaluated outcomes of treatment of hypertensive patients who were assigned to losartan monotherapy (12.5, 25, 50 or 100 mg) or a fixed combination with hydrochlorothiazide (losartan 50 mg/hydrochlorothiazide 12.5 mg , losartan 100 mg/hydrochlorothiazide 25 mg). The effectiveness of treatment was assessed by size reduction of systolic/diastolic blood pressure (SBP/DBP), and the frequency of achieving target blood pressure (<140/90 or <130/80 mm Hg in patients with diabetes). Losartan at a dose 12.5 mg was assigned to 382 (3.8%), at a dose of 25 mg - to 1061 (10.7%), at a dose of 50 mg - to 3545 (35.6%), at a dose of 100 mg - to 3247 (32.6%), at a dose of 50 mg / hydrochlorothiazide 12.5 mg - to 893 (9.0%), at a dose of 100 mg / hydrochlorothiazide 25 mg - to 820 (8.2%) of 9948 patients included in the study. According to multivariate analysis, dose selection of losartan was determined by an attending physician, mainly (85% according to the estimate of the explained variance), based on the baseline SBP. As a result of treatment (41 to 53% of patients received losartan only or in combination with HCTZ) SBP decrease in the groups ranged from 20 to 38 mm Hg, DBP - from 10 to 17 mm Hg, the target blood pressure is achieved in 29-66% of patients. At least one adverse event occurred in 141 (1.4%) patients, with lower frequency in patients receiving losartan 50 mg (adjusted odds ratio 0.34, 95% confidence interval 0.19 to 0.63; the reference group - patients receiving losartan 100 mg/hydrochlorothiazide 25 mg). Thus losartan as monotherapy or in fixed combination with HCTZ for hypertensive patients is characterized by high antihypertensive efficacy and safety.

Clinically Relevant Reduction in Persistent Facial Erythema of Rosacea on the First Day of Treatment With Oxymetazoline Cream 1.0.

PubMed

Tanghetti, Emil A; Dover, Jeffrey S; Goldberg, David J; Dhawan, Sunil S; Luo, Lei; Berk, David R; Ahluwalia, Gurpreet; Alvandi, Nancy

2018-06-01

Persistent facial erythema is a clinically challenging feature of rosacea. To evaluate persistent erythema reduction on the first day of treatment from pooled data from two pivotal trials of topical oxymetazoline cream 1.0% (oxymetazoline) in persistent facial erythema of rosacea. In two identically designed, phase 3, multicenter trials, adults with moderate to severe persistent facial erythema of rosacea (Clinician Erythema Assessment [CEA] grade ≥3 and Subject Self-Assessment [SSA] grade ≥3) were randomized 1:1 to once-daily topical oxymetazoline or vehicle; the primary efficacy endpoint was ≥2-grade composite CEA and SSA improvement from baseline on day 29. This post hoc analysis evaluated the proportion of patients achieving ≥1-grade composite and individual CEA and SSA improvement at 1, 3, 6, 9, and 12 hours postdose on day 1 (N=885). Significantly more patients achieved ≥1-grade composite and individual CEA and SSA improvement with the first application of oxymetazoline than with vehicle (P less than 0.001) at all postdose time points, beginning with hour 1. Day 1 safety assessments were similar between treatments. Short-term, post hoc analysis. A ≥1-grade improvement in persistent erythema achieved after the first dose of once-daily topical oxymetazoline demonstrated clinically meaningful improvement from the beginning of therapy. J Drugs Dermatol. 2018;17(6):621-626.

Biological groundwater treatment for chromium removal at low hexavalent chromium concentrations.

PubMed

Mamais, Daniel; Noutsopoulos, Constantinos; Kavallari, Ioanna; Nyktari, Eleni; Kaldis, Apostolos; Panousi, Eleni; Nikitopoulos, George; Antoniou, Kornilia; Nasioka, Maria

2016-06-01

The objective of this work is to develop and evaluate biological groundwater treatment systems that will achieve hexavalent chromium reduction and total chromium removal from groundwater at hexavalent chromium (Cr(VI)) groundwater concentrations in the 0-200 μg/L range. Three lab-scale units operated, as sequencing batch reactors (SBR) under aerobic, anaerobic and anaerobic-aerobic conditions. All systems received groundwater with a Cr(VI) content of 200 μg/L. In order to support biological growth, groundwater was supplemented with milk, liquid cheese whey or a mixture of sugar and milk to achieve a COD concentration of 200 mg/L. The results demonstrate that a fully anaerobic system or an anaerobic-aerobic system dosed with simple or complex external organic carbon sources can lead to practically complete Cr(VI) reduction to Cr(III). The temperature dependency of maximum Cr(VI) removal rates can be described by the Arrhenius relationship. Total chromium removal in the biological treatment systems was not complete because a significant portion of Cr(III) remained in solution. An integrated system comprising of an anaerobic SBR followed by a sand filter achieved more than 95% total chromium removal thus resulting in average effluent total and dissolved chromium concentrations of 7 μg/L and 3 μg/L, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Safety, pharmacokinetics, and antitumor activity of AMG 386, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors.

PubMed

Herbst, Roy S; Hong, David; Chap, Linnea; Kurzrock, Razelle; Jackson, Edward; Silverman, Jeffrey M; Rasmussen, Erik; Sun, Yu-Nien; Zhong, Don; Hwang, Yuying C; Evelhoch, Jeffrey L; Oliner, Jonathan D; Le, Ngocdiep; Rosen, Lee S

2009-07-20

PURPOSE AMG 386 is an investigational peptide-Fc fusion protein (ie, peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 with their receptor, Tie2. This first-in-human study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors. PATIENTS AND METHODS Patients in sequential cohorts received weekly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg. Results Thirty-two patients were enrolled on the study and received AMG 386. One occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden that was possibly related to AMG 386. The most common toxicities were fatigue and peripheral edema. Proteinuria (n = 11) was observed without clinical sequelae. Only four patients (12%) experienced treatment-related toxicities greater than grade 1. A maximum-tolerated dose was not reached. PK was dose-linear and the mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days. Serum AMG 386 levels appeared to reach steady-state after four weekly doses, and there was minimal accumulation. No anti-AMG 386 neutralizing antibodies were detected. Reductions in volume transfer constant (K(trans); measured by dynamic contrast-enhanced magnetic resonance imaging) were observed in 10 patients (13 lesions) 48 hours to 8 weeks after treatment. One patient with refractory ovarian cancer achieved a confirmed partial response (ie, 32.5% reduction by Response Evaluation Criteria in Solid Tumors) and withdrew from the study with a partial response after 156 weeks of treatment; four patients experienced stable disease for at least 16 weeks. CONCLUSION Weekly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor-axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this patient population.

Modelling the Ozone-Based Treatments for Inactivation of Microorganisms.

PubMed

Brodowska, Agnieszka Joanna; Nowak, Agnieszka; Kondratiuk-Janyska, Alina; Piątkowski, Marcin; Śmigielski, Krzysztof

2017-10-09

The paper presents the development of a model for ozone treatment in a dynamic bed of different microorganisms ( Bacillus subtilis , B. cereus , B. pumilus , Escherichia coli , Pseudomonas fluorescens , Aspergillus niger , Eupenicillium cinnamopurpureum ) on a heterogeneous matrix (juniper berries, cardamom seeds) initially treated with numerous ozone doses during various contact times was studied. Taking into account various microorganism susceptibility to ozone, it was of great importance to develop a sufficiently effective ozone dose to preserve food products using different strains based on the microbial model. For this purpose, we have chosen the Weibull model to describe the survival curves of different microorganisms. Based on the results of microorganism survival modelling after ozone treatment and considering the least susceptible strains to ozone, we selected the critical ones. Among tested strains, those from genus Bacillus were recognized as the most critical strains. In particular, B. subtilis and B. pumilus possessed the highest resistance to ozone treatment because the time needed to achieve the lowest level of its survival was the longest (up to 17.04 min and 16.89 min for B. pumilus reduction on juniper berry and cardamom seed matrix, respectively). Ozone treatment allow inactivate microorganisms to achieving lower survival rates by ozone dose (20.0 g O₃/m³ O₂, with a flow rate of 0.4 L/min) and contact time (up to 20 min). The results demonstrated that a linear correlation between parameters p and k in Weibull distribution, providing an opportunity to calculate a fitted equation of the process.

The Biphasic Effect of Vitamin D on the Musculoskeletal and Cardiovascular System

PubMed Central

2017-01-01

This narrative review summarizes beneficial and harmful vitamin D effects on the musculoskeletal and cardiovascular system. Special attention is paid to the dose-response relationship of vitamin D with clinical outcomes. In infants and adults, the risk of musculoskeletal diseases is highest at circulating 25-hydroxyvitamin D (25OHD) concentrations below 25 nmol/L and is low if 40–60 nmol/L are achieved. However, evidence is also accumulating that in elderly people the risk of falls and fractures increases again at circulating 25OHD levels > 100 nmol/L. Cohort studies report a progressive increase in cardiovascular disease (CVD) events at 25OHD levels < 50 nmol/L. Nevertheless, meta-analyses of randomized controlled trials suggest only small beneficial effects of vitamin D supplements on surrogate parameters of CVD risk and no reduction in CVD events. Evidence is accumulating for adverse vitamin D effects on CVD outcomes at 25OHD levels > 100 nmol/L, but the threshold may be influenced by the level of physical activity. In conclusion, dose-response relationships indicate deleterious effects on the musculoskeletal system and probably on the cardiovascular system at circulating 25OHD levels < 40–60 nmol/L and >100 nmol/L. Future studies should focus on populations with 25OHD levels < 40 nmol/L and should avoid vitamin D doses achieving 25OHD levels > 100 nmol/L. PMID:28912809

The Biphasic Effect of Vitamin D on the Musculoskeletal and Cardiovascular System.

PubMed

Zittermann, Armin

2017-01-01

This narrative review summarizes beneficial and harmful vitamin D effects on the musculoskeletal and cardiovascular system. Special attention is paid to the dose-response relationship of vitamin D with clinical outcomes. In infants and adults, the risk of musculoskeletal diseases is highest at circulating 25-hydroxyvitamin D (25OHD) concentrations below 25 nmol/L and is low if 40-60 nmol/L are achieved. However, evidence is also accumulating that in elderly people the risk of falls and fractures increases again at circulating 25OHD levels > 100 nmol/L. Cohort studies report a progressive increase in cardiovascular disease (CVD) events at 25OHD levels < 50 nmol/L. Nevertheless, meta-analyses of randomized controlled trials suggest only small beneficial effects of vitamin D supplements on surrogate parameters of CVD risk and no reduction in CVD events. Evidence is accumulating for adverse vitamin D effects on CVD outcomes at 25OHD levels > 100 nmol/L, but the threshold may be influenced by the level of physical activity. In conclusion, dose-response relationships indicate deleterious effects on the musculoskeletal system and probably on the cardiovascular system at circulating 25OHD levels < 40-60 nmol/L and >100 nmol/L. Future studies should focus on populations with 25OHD levels < 40 nmol/L and should avoid vitamin D doses achieving 25OHD levels > 100 nmol/L.

WE-EF-303-08: Proton Radiography Using Pencil Beam Scanning and Novel Micromegas Detectors

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

Dolney, D; Lustig, R; Teo, B

Purpose: While the energy of therapeutic proton beams can be adjusted to penetrate to any given depth in water, range uncertainties arise in patients due in part to imprecise knowledge of the stopping power of protons in human tissues. Proton radiography is one approach to reduce the beam range uncertainty, thereby allowing for a reduction in treatment margins and dose escalation. Methods: The authors have adapted a novel detector technology based on Micromesh Gaseous Structure (“Micromegas”) for proton therapy beams and have demonstrated fine spatial and time resolution of magnetically scanned proton pencil beams, as well as wide dynamic rangemore » for dosimetry. In this work, proton radiographs were obtained using Micromegas 2D planes positioned downstream of solid water assemblies. The position-sensitive monitor chambers in the IBA proton delivery nozzle provide the beam entrance position. Results: Radiography with Micromegas detectors and actively scanned beams provide spatial resolution of up to 300 µm and water-equivalent thickness (WET) resolution as good as 0.02% (60 µm out of 31 cm total thickness), with the dose delivered to the patient kept below 2 cGy. The spatial resolution as a function of sample rate and number of delivered protons is found to be near the theoretical Cramer-Rao lower bound. Using the CR bound, we argue that the imaging dose could be further lowered to 1 mGy, while still achieving sub-mm spatial resolution, by relatively simple instrumentation upgrades and beam delivery modifications. Conclusion: For proton radiography, high spatial and WET resolution can be achieved, with minimal additional dose to patient, by using magnetically scanned proton pencil beams and Micromegas detectors.« less

IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis.

PubMed

Balak, Deepak M W; van Doorn, Martijn B A; Arbeit, Robert D; Rijneveld, Rianne; Klaassen, Erica; Sullivan, Tim; Brevard, Julie; Thio, Hok Bing; Prens, Errol P; Burggraaf, Jacobus; Rissmann, Robert

2017-01-01

Aberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial. Forty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks. Post-treatment follow-up was seven weeks. Primary outcome was incidence of adverse events. Secondary, exploratory outcomes included changes in psoriasis area and severity index (PASI). IMO-8400 across all dose levels did not cause any serious or severe adverse events. The most common treatment-related adverse events were dose-dependent injection-site reactions. All IMO-8400 groups showed clinical improvement, but a clear dose-response relationship and statistically significant differences with placebo were not observed (P=0.26). Eleven (38%) of 29 subjects on IMO-8400 achieved ≥50% PASI-reduction, compared to 1 (11%) of 9 subjects on placebo. Five (17%) and 2 (7%) IMO-8400-treated subjects achieved PASI-75 and PASI-90, respectively, compared to none on placebo. Short-term IMO-8400-treatment was well tolerated and reduced psoriasis severity. These findings warrant further investigation of endosomal TLR-antagonism as a therapeutic approach in psoriasis and other TLR-mediated IMIDs. EudraCT 2013-000164-28 and Clinicaltrials.govNCT01899729. Copyright © 2016 Elsevier Inc. All rights reserved.

Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis.

PubMed

Jayne, David R W; Bruchfeld, Annette N; Harper, Lorraine; Schaier, Matthias; Venning, Michael C; Hamilton, Patrick; Burst, Volker; Grundmann, Franziska; Jadoul, Michel; Szombati, István; Tesař, Vladimír; Segelmark, Mårten; Potarca, Antonia; Schall, Thomas J; Bekker, Pirow

2017-09-01

Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, -4.3% to 37.1%; P =0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, -11.0% to 32.9%; P =0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis. Copyright © 2017 by the American Society of Nephrology.

Dosimetric feasibility of magnetic resonance imaging-guided tri-cobalt 60 preoperative intensity modulated radiation therapy for soft tissue sarcomas of the extremity.

PubMed

Kishan, Amar U; Cao, Minsong; Mikaeilian, Argin G; Low, Daniel A; Kupelian, Patrick A; Steinberg, Michael L; Kamrava, Mitchell

2015-01-01

The purpose of this study was to investigate the dosimetric differences of delivering preoperative intensity modulated radiation therapy (IMRT) to patients with soft tissue sarcomas of the extremity (ESTS) with a teletherapy system equipped with 3 rotating (60)Co sources and a built-in magnetic resonance imaging and with standard linear accelerator (LINAC)-based IMRT. The primary study population consisted of 9 patients treated with preoperative radiation for ESTS between 2008 and 2014 with LINAC-based static field IMRT. LINAC plans were designed to deliver 50 Gy in 25 fractions to 95% of the planning target volume (PTV). Tri-(60)Co system IMRT plans were designed with ViewRay system software. Tri-(60)Co-based IMRT plans achieved equivalent target coverage and dosimetry for organs at risk (long bone, skin, and skin corridor) compared with LINAC-based IMRT plans. The maximum and minimum PTV doses, heterogeneity indices, and ratio of the dose to 50% of the volume were equivalent for both planning systems. One LINAC plan violated the maximum bone dose constraint, whereas none of the tri-(60)Co plans did. Using a tri-(60)Co system, we were able to achieve equivalent dosimetry to the PTV and organs at risk for patients with ESTS compared with LINAC-based IMRT plans. The tri-(60)Co system may be advantageous over current treatment platforms by allowing PTV reduction and by elimination of the additional radiation dose associated with daily image guidance, but this needs to be evaluated prospectively. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Pharmacokinetics, Safety, and 48-Week Efficacy of Oral Raltegravir in HIV-1–Infected Children Aged 2 Through 18 Years

PubMed Central

Nachman, Sharon; Zheng, Nan; Acosta, Edward P.; Teppler, Hedy; Homony, Brenda; Graham, Bobbie; Fenton, Terence; Xu, Xia; Wenning, Larissa; Spector, Stephen A.; Frenkel, Lisa M.; Alvero, Carmelita; Worrell, Carol; Handelsman, Edward; Wiznia, Andrew; Moultrie, Harry; Kindra, Gurpreet; Sanders, Margaret Ann; Williams, Ruth; Jensen, Jennifer; Acevedo, Midnela; Fabregas, Lizbeth; Jurgrau, Andrea; Foca, Marc; Higgins, Alice; Deville, Jaime G.; Nielsen-Saines, Karin; Carter, Michele F.; Swetnam, John; Wilson, Joan; Donnelly, Margaret; Akleh, Siham; Rigaud, Mona; Kaul, Aditya; Patel, Nehali; Gaur, Aditya; Utech, L. Jill; Cardoso, Edmundo; Moreira, Ana Maria; Santos, Breno; Bobat, Raziya; Mngqibisa, Rosie; Burey, Marlene; Abadi, Jacob; Rosenberg, Michael; Luzuriaga, Katherine; Picard, Donna; Pagano-Therrien, Jessica; Dittmer, Sylvia; Ndiweni, Hilda Ntatule; Patel, Amisha; DelRey, Michelle; McMullen-Jackson, Chivon; Paul, Mary E.; Melvin, Ann; Venema-Weiss, Corry; Lane, Jenna; Beneri, Christy; Ferraro, Denise; Infanzon, Erin; McAuley, James B; Aziz, Mariam; McNichols, Maureen; Pelton, Stephen; McLaud, Deb; Clarke, Diana; Zeichner, Steven; Akar, Arezou; Thompson, Deidre; Douglas, Steven D.; Rutstein, Richard M.; Vincent, Carol A.; Vachon, Mary Elizabeth; Cavallo, Martha; Purswani, Murli Udharam; Masheto, Gaerolwe; Ogwu, Anthony; Kakhu, Tebogo; Viani, Rolando M.; Darcey, Anita,; Norris, Kimberly; Burchett, Sandra K.; Kneut, Catherine; Karthas, Nancy; Casey, Denise; Emmanuel, Patricia; Lujan-Zilbermann, Jorge; Rana, Sohail; Houston, Patricia; Mengistab, Mulu; Rathore, Mobeen; Mirza, Ayesha; Gayton, Tabetha; Barr, Emily; Dunn, Jennifer; Hahn, Kerry; Eysallenne, Zulma; Howard, F. Sholar; Graham, Kathleen; Negra, Marinella Della; Queiroz, Wladimir; Lian, Yu Ching; Wara, Diane; Ruel, Ted; VanDyke, Russell; Reilly, Patricia; Bradford, Sheila; van Rensburg, Anita Janse; Dobbels, Els; Bester, Marietjie; Bamji, Mahrukh; Paul, Santa; Sarza, Mirala; Kovacs, Andrea; Homans, James; Spencer, LaShonda; Hofer, Cristna; Abreu, Thalita; Oliveira, Ricardo; Joao, Esau C.; Pinto, Jorge; Ferreira, Flavia; Kakehasi, Fabiana; Cervi, Maria Celia; Isaac, Marcia De Lima; Losso, Marcelo H.; Stankievich, Erica; Foradori, Irene; Tucker, Diane; Church, Joseph; Belzer, Marvin; Hopkins, Johns; Ellen, Jonathan; Agwu, Allison; Laurel, Borkovic

2014-01-01

Background. IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)–infected youth. Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade ≥3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or ≥1 log10 reduction between baseline and week 24. Results. The targeted pharmacokinetic parameters (AUC0-12h and C12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/µL (4.6%). Conclusions. Raltegravir as a film-coated tablet 400 mg twice daily (6 to <19 years, and ≥25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to <12 years) was well tolerated and showed favorable virologic and immunologic responses. Clinical Trials Registration NCT00485264. PMID:24145879

Safety assessment of Hibiscus sabdariffa after maternal exposure on male reproductive parameters in rats.

PubMed

de Arruda, Aline; Cardoso, Claudia Andrea L; Vieira, Maria do Carmo; Arena, Arielle Cristina

2016-01-01

Hibiscus sabdariffa L. (Malvaceae) is a species widely used in folk medicine for the treatment of some disorders. This study evaluated the effects of H. sabdariffa (HS) on the development of the male reproductive tract in rats following in utero exposure. Pregnant rats received 250 or 500 mg/kg of HS extract or vehicle from gestational day 12 until day 21 of lactation. Both doses of HS increased the body weight of male offspring at weaning, without compromising the puberty onset parameters. At puberty, there was a significant increase in the vas deferens absolute weight and a significant reduction in the relative weight of kidney at higher dose. These animals also presented a significant reduction in the sperm number in the caput/corpus of epididymis after exposure to both doses and a reduction in the sperm number in the cauda epididymis for the lower dose. At adulthood, the highest dose significantly reduced the sperm production in relation to controls and both doses provoked a reduction in the relative sperm number in the epididymis without affecting the sperm morphology. These findings demonstrated that maternal exposure to H. sabdariffa can adversely influence the male reproductive system in rats.

CT breast dose reduction with the use of breast positioning and organ-based tube current modulation.

PubMed

Fu, Wanyi; Tian, Xiaoyu; Sturgeon, Gregory M; Agasthya, Greeshma; Segars, William Paul; Goodsitt, Mitchell M; Kazerooni, Ella A; Samei, Ehsan

2017-02-01

This study aimed to investigate the breast dose reduction potential of a breast-positioning (BP) technique for thoracic CT examinations with organ-based tube current modulation (OTCM). This study included 13 female anthropomorphic computational phantoms (XCAT, age range: 27-65 y.o., weight range: 52-105.8 kg). Each phantom was modified to simulate three breast sizes in standard supine geometry. The modeled breasts were then morphed to emulate BP that constrained the majority of the breast tissue inside the 120° anterior tube current (mA) reduction zone. The OTCM mA value was modeled using a ray-tracing program, which reduced the mA to 20% in the anterior region with a corresponding increase to the posterior region. The organ doses were estimated by a validated Monte Carlo program for a typical clinical CT system (SOMATOM Definition Flash, Siemens Healthcare). The simulated organ doses and organ doses normalized by CTDI vol were used to compare three CT protocols: attenuation-based tube current modulation (ATCM), OTCM, and OTCM with BP (OTCM BP ). On average, compared to ATCM, OTCM reduced breast dose by 19.3 ± 4.5%, whereas OTCM BP reduced breast dose by 38.6 ± 8.1% (an additional 23.8 ± 9.4%). The dose saving of OTCM BP was more significant for larger breasts (on average 33, 38, and 44% reduction for 0.5, 1, and 2 kg breasts, respectively). Compared to ATCM, OTCM BP also reduced thymus and heart dose by 15.1 ± 7.4% and 15.9 ± 6.2% respectively. In thoracic CT examinations, OTCM with a breast-positioning technique can markedly reduce unnecessary exposure to radiosensitive organs in anterior chest wall, specifically breast tissue. The breast dose reduction is more notable for women with larger breasts. © 2016 American Association of Physicists in Medicine.

SU-E-I-49: The Evaluation of Usability of Multileaf Collimator for Diagnostic Radiation in Cephalometric Exposure

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

Han, S; Kim, K; Jung, H

Purpose: This study evaluated usability of Multileaf collimator (MLC) for diagnostic radiation in cephalometric exposure using optical stimulated luminance dosimeters (OSLDs) Methods: The MLC material was made alloy tool steel (SKD-11) and the density of it is 7.89g/m3 that is similar to it of steel (Fe, 7.85 g/m3) and the MLC was attached to general radiography unit (Rex-650R, Listem Inc, Korea) for cephalometric exposure. The OSLDs that used were nanoDotTM Dosimeter (Landauer Inc, Glenwood, USA) and we read out OSLDs with micro star system (Landauer Inc, Glenwood, USA). The Optical annealing system contained fluorescent lamps (Osram lumilux, 24 W, 280more » ∼780 nm). To measure absorbed dose using OSLDs, was carried out dosimetric characteristics of OSLDs. Based on these, we evaluated dose reduction of critical organ (Eyes, Thyroids) with MLC in cephalometric exposure Results: The dosimetric characteristics were following that batch homogeneity was 1.21% and reproducibility was 0.96% of the coefficient of variation The linearity was that the correlation of between dose and count was fitted by linear function (dose,mGy = 0.00029 × Count, R2 =0.997). The range of angular dependence was from −3.6% to 3.7% variation when each degree was normalized by zero degree. The organ dose of Rt. eye, Lt eye, thyroids were 77.8 μGy, 337.0 μGy, 323.1μGy, respectively in open field and the dose reduction of organ dose was 10.6%(8.3μGy), 12.4 %(42 μGy), 87.1%(281.4μGy) with MLC Conclusion: We certified dose reduction of organ dose in cephalometric exposure. The dose reduction of Eye was 11% because of reduction of field size and it of thyroids was 87% by primary beam shielding.« less

Prospective Evaluation of Prior Image Constrained Compressed Sensing (PICCS) Algorithm in Abdominal CT: A comparison of reduced dose with standard dose imaging

PubMed Central

Lubner, Meghan G.; Pickhardt, Perry J.; Kim, David H.; Tang, Jie; Munoz del Rio, Alejandro; Chen, Guang-Hong

2014-01-01

Purpose To prospectively study CT dose reduction using the “prior image constrained compressed sensing” (PICCS) reconstruction technique. Methods Immediately following routine standard dose (SD) abdominal MDCT, 50 patients (mean age, 57.7 years; mean BMI, 28.8) underwent a second reduced-dose (RD) scan (targeted dose reduction, 70-90%). DLP, CTDIvol and SSDE were compared. Several reconstruction algorithms (FBP, ASIR, and PICCS) were applied to the RD series. SD images with FBP served as reference standard. Two blinded readers evaluated each series for subjective image quality and focal lesion detection. Results Mean DLP, CTDIvol, and SSDE for RD series was 140.3 mGy*cm (median 79.4), 3.7 mGy (median 1.8), and 4.2 mGy (median 2.3) compared with 493.7 mGy*cm (median 345.8), 12.9 mGy (median 7.9 mGy) and 14.6 mGy (median 10.1) for SD series, respectively. Mean effective patient diameter was 30.1 cm (median 30), which translates to a mean SSDE reduction of 72% (p<0.001). RD-PICCS image quality score was 2.8±0.5, improved over the RD-FBP (1.7±0.7) and RD-ASIR(1.9±0.8)(p<0.001), but lower than SD (3.5±0.5)(p<0.001). Readers detected 81% (184/228) of focal lesions on RD-PICCS series, versus 67% (153/228) and 65% (149/228) for RD-FBP and RD-ASIR, respectively. Mean image noise was significantly reduced on RD-PICCS series (13.9 HU) compared with RD-FBP (57.2) and RD-ASIR (44.1) (p<0.001). Conclusion PICCS allows for marked dose reduction at abdominal CT with improved image quality and diagnostic performance over reduced-dose FBP and ASIR. Further study is needed to determine indication-specific dose reduction levels that preserve acceptable diagnostic accuracy relative to higher-dose protocols. PMID:24943136

A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

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

Zhou, Rachel; Ng, Angela; Constine, Louis S.

Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohortmore » and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.« less

Dose reduction of risperidone and olanzapine can improve cognitive function and negative symptoms in stable schizophrenic patients: A single-blinded, 52-week, randomized controlled study.

PubMed

Zhou, Yanling; Li, Guannan; Li, Dan; Cui, Hongmei; Ning, Yuping

2018-05-01

The long-term effects of dose reduction of atypical antipsychotics on cognitive function and symptomatology in stable patients with schizophrenia remain unclear. We sought to determine the change in cognitive function and symptomatology after reducing risperidone or olanzapine dosage in stable schizophrenic patients. Seventy-five stabilized schizophrenic patients prescribed risperidone (≥4 mg/day) or olanzapine (≥10 mg/day) were randomly divided into a dose-reduction group ( n=37) and a maintenance group ( n=38). For the dose-reduction group, the dose of antipsychotics was reduced by 50%; for the maintenance group, the dose remained unchanged throughout the whole study. The Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery were measured at baseline, 12, 28, and 52 weeks. Linear mixed models were performed to compare the Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects and MATRICS Consensus Cognitive Battery scores between groups. The linear mixed model showed significant time by group interactions on the Positive and Negative Syndrome Scale negative symptoms, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, attention/vigilance, working memory and total score of MATRICS Consensus Cognitive Battery (all p<0.05). Post hoc analyses showed significant improvement in Positive and Negative Syndrome Scale negative subscale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, working memory and total score of MATRICS Consensus Cognitive Battery for the dose reduction group compared with those for the maintenance group (all p<0.05). This study indicated that a risperidone or olanzapine dose reduction of 50% may not lead to more severe symptomatology but can improve speed of processing, working memory and negative symptoms in patients with stabilized schizophrenia.

Comparative reduction of Norwalk virus, poliovirus type 1, F+ RNA coliphage MS2 and Escherichia coli in miniature soil columns.

PubMed

Meschke, J S; Sobsey, M D

2003-01-01

Norwalk-like viruses (NLVs) are important agents of waterborne illness and have been linked to several groundwater-related outbreaks. The presence of human enteric viruses, in particular the presence of NLVs, is difficult to detect in the environment. Consequently, surrogate organisms are typically used as indicators of viruses from faecal contamination. Whether traditional bacterial indicators are reliable indicators for viral pathogens remains uncertain. Few studies have directly compared mobility and reduction of bacterial indicators (e.g. coliforms, Escherichia coli) and other surrogate indicators (coliphages) with pathogenic human viruses in soil systems. In this study the mobility and comparative reduction of the prototype NLV, Norwalk Virus (NV), was compared to poliovirus 1 (PV1), a bacterial indicator (E coli, EC) and a viral indicator (coliphage MS2) through miniature soil columns. Replicate, 10 cm deep, miniature columns were prepared using three soils representing a range of soil textures (sand, organic muck, and clay). Columns were initially conditioned, then incubated at 10-14 degrees C, dosed twice weekly for 8 weeks with one column pore volume of virus-seeded groundwater per dose, followed by 8 weeks of dosing with one column pore volume per dose of unseeded, simulated rainwater. Columns were allowed to drain after each dosing until an effluent volume equivalent to an applied dose was collected. Column effluents and doses were assayed for all viruses and EC. Rapid mobility with minimal reduction was observed for all organisms in the sand. Similar reductions were observed in organic muck for most organisms but NV showed a greater reduction. No organisms were shown to pass through the clay columns. Elution of viruses, in particular PV1, from the columns was gradual. After cessation of microbe dosing, E. coli was less detectable than viruses in column effluents and, therefore, unreliable as a virus indicator.

Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer.

PubMed

Chow, L W-C; Xu, B; Gupta, S; Freyman, A; Zhao, Y; Abbas, R; Vo Van, M-L; Bondarenko, I

2013-05-28

Neratinib is a potent irreversible pan-ErbB tyrosine kinase inhibitor that has demonstrated antitumour activity and an acceptable safety profile in patients with human epidermal growth factor receptor (HER)-2-positive breast cancer and other solid tumours. This was a phase I/II, open-label, two-part study. Part 1 was a dose-escalation study to determine the maximum tolerated dose (MTD) of neratinib plus paclitaxel in patients with solid tumours. Part 2 evaluated the safety, efficacy, and pharmacokinetics of the combination at the MTD in patients with HER2-positive breast cancer. Eight patients were included in the dose-escalation study; no dose-limiting toxicities were observed, and an MTD of oral neratinib 240 mg once daily plus intravenous paclitaxel 80 mg m(-2) on days 1, 8, and 15 of each 28-day cycle was determined. A total of 102 patients with HER2-positive breast cancer were enrolled in part 2. The overall median treatment duration was 47.9 weeks (range: 0.1-147.3 weeks). Common treatment-emergent adverse events (all grades/grade ≥3) included diarrhoea (92%/29%; none grade 4), peripheral sensory neuropathy (51%/3%), neutropenia (50%/20%), alopecia (46%/0%), leukopenia (41%/18%), anaemia (37%/8%), and nausea (34%/1%). Three (3%) patients discontinued treatment due to an adverse event (mouth ulceration, left ventricular ejection fraction reduction, and acute renal failure). Among the 99 evaluable patients in part 2 of the study, the overall response rate (ORR) was 73% (95% confidence interval (CI): 62.9-81.2%), including 7 (7%) patients who achieved a complete response; an additional 9 (9%) patients achieved stable disease for at least 24 weeks. ORR was 71% among patients with 0/1 prior chemotherapy regimen for metastatic disease and no prior lapatinib, and 77% among those with 2/3 prior chemotherapy regimens for metastatic disease with prior lapatinib permitted. Kaplan-Meier median progression-free survival was 57.0 weeks (95% CI: 47.7-81.6 weeks). Pharmacokinetic analyses indicated no interaction between neratinib and paclitaxel. The combination of neratinib and paclitaxel was associated with higher toxicity than that of neratinib as a single agent, but was manageable with antidiarrhoeal agents and dose reductions in general. The combination therapy also demonstrated a high rate of response in patients with HER2-positive breast cancer. A phase III trial is ongoing to assess the benefit and risk of this combination in the first-line setting.

Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer

PubMed Central

Chow, L W-C; Xu, B; Gupta, S; Freyman, A; Zhao, Y; Abbas, R; Vo Van, M-L; Bondarenko, I

2013-01-01

Introduction: Neratinib is a potent irreversible pan-ErbB tyrosine kinase inhibitor that has demonstrated antitumour activity and an acceptable safety profile in patients with human epidermal growth factor receptor (HER)-2-positive breast cancer and other solid tumours. Methods: This was a phase I/II, open-label, two-part study. Part 1 was a dose-escalation study to determine the maximum tolerated dose (MTD) of neratinib plus paclitaxel in patients with solid tumours. Part 2 evaluated the safety, efficacy, and pharmacokinetics of the combination at the MTD in patients with HER2-positive breast cancer. Results: Eight patients were included in the dose-escalation study; no dose-limiting toxicities were observed, and an MTD of oral neratinib 240 mg once daily plus intravenous paclitaxel 80 mg m−2 on days 1, 8, and 15 of each 28-day cycle was determined. A total of 102 patients with HER2-positive breast cancer were enrolled in part 2. The overall median treatment duration was 47.9 weeks (range: 0.1–147.3 weeks). Common treatment-emergent adverse events (all grades/grade ⩾3) included diarrhoea (92%/29% none grade 4), peripheral sensory neuropathy (51%/3%), neutropenia (50%/20%), alopecia (46%/0%), leukopenia (41%/18%), anaemia (37%/8%), and nausea (34%/1%). Three (3%) patients discontinued treatment due to an adverse event (mouth ulceration, left ventricular ejection fraction reduction, and acute renal failure). Among the 99 evaluable patients in part 2 of the study, the overall response rate (ORR) was 73% (95% confidence interval (CI): 62.9–81.2%), including 7 (7%) patients who achieved a complete response; an additional 9 (9%) patients achieved stable disease for at least 24 weeks. ORR was 71% among patients with 0/1 prior chemotherapy regimen for metastatic disease and no prior lapatinib, and 77% among those with 2/3 prior chemotherapy regimens for metastatic disease with prior lapatinib permitted. Kaplan–Meier median progression-free survival was 57.0 weeks (95% CI: 47.7–81.6 weeks). Pharmacokinetic analyses indicated no interaction between neratinib and paclitaxel. Conclusion: The combination of neratinib and paclitaxel was associated with higher toxicity than that of neratinib as a single agent, but was manageable with antidiarrhoeal agents and dose reductions in general. The combination therapy also demonstrated a high rate of response in patients with HER2-positive breast cancer. A phase III trial is ongoing to assess the benefit and risk of this combination in the first-line setting. PMID:23632474

Residual Viral and Bacterial Contamination of Surfaces after Cleaning and Disinfection

PubMed Central

Tuladhar, Era; Hazeleger, Wilma C.; Koopmans, Marion; Zwietering, Marcel H.; Beumer, Rijkelt R.

2012-01-01

Environmental surfaces contaminated with pathogens can be sources of indirect transmission, and cleaning and disinfection are common interventions focused on reducing contamination levels. We determined the efficacy of cleaning and disinfection procedures for reducing contamination by noroviruses, rotavirus, poliovirus, parechovirus, adenovirus, influenza virus, Staphylococcus aureus, and Salmonella enterica from artificially contaminated stainless steel surfaces. After a single wipe with water, liquid soap, or 250-ppm free chlorine solution, the numbers of infective viruses and bacteria were reduced by 1 log10 for poliovirus and close to 4 log10 for influenza virus. There was no significant difference in residual contamination levels after wiping with water, liquid soap, or 250-ppm chlorine solution. When a single wipe with liquid soap was followed by a second wipe using 250- or 1,000-ppm chlorine, an extra 1- to 3-log10 reduction was achieved, and except for rotavirus and norovirus genogroup I, no significant additional effect of 1,000 ppm compared to 250 ppm was found. A reduced correlation between reduction in PCR units (PCRU) and reduction in infectious particles suggests that at least part of the reduction achieved in the second step is due to inactivation instead of removal alone. We used data on infectious doses and transfer efficiencies to estimate a target level to which the residual contamination should be reduced and found that a single wipe with liquid soap followed by a wipe with 250-ppm free chlorine solution was sufficient to reduce the residual contamination to below the target level for most of the pathogens tested. PMID:22941071

Residual viral and bacterial contamination of surfaces after cleaning and disinfection.

PubMed

Tuladhar, Era; Hazeleger, Wilma C; Koopmans, Marion; Zwietering, Marcel H; Beumer, Rijkelt R; Duizer, Erwin

2012-11-01

Environmental surfaces contaminated with pathogens can be sources of indirect transmission, and cleaning and disinfection are common interventions focused on reducing contamination levels. We determined the efficacy of cleaning and disinfection procedures for reducing contamination by noroviruses, rotavirus, poliovirus, parechovirus, adenovirus, influenza virus, Staphylococcus aureus, and Salmonella enterica from artificially contaminated stainless steel surfaces. After a single wipe with water, liquid soap, or 250-ppm free chlorine solution, the numbers of infective viruses and bacteria were reduced by 1 log(10) for poliovirus and close to 4 log(10) for influenza virus. There was no significant difference in residual contamination levels after wiping with water, liquid soap, or 250-ppm chlorine solution. When a single wipe with liquid soap was followed by a second wipe using 250- or 1,000-ppm chlorine, an extra 1- to 3-log(10) reduction was achieved, and except for rotavirus and norovirus genogroup I, no significant additional effect of 1,000 ppm compared to 250 ppm was found. A reduced correlation between reduction in PCR units (PCRU) and reduction in infectious particles suggests that at least part of the reduction achieved in the second step is due to inactivation instead of removal alone. We used data on infectious doses and transfer efficiencies to estimate a target level to which the residual contamination should be reduced and found that a single wipe with liquid soap followed by a wipe with 250-ppm free chlorine solution was sufficient to reduce the residual contamination to below the target level for most of the pathogens tested.

Intussusception reduction: Effect of air vs. liquid enema on radiation dose.

PubMed

Kaplan, Summer L; Magill, Dennise; Felice, Marc A; Edgar, J Christopher; Anupindi, Sudha A; Zhu, Xiaowei

2017-10-01

Both air and radiopaque liquid contrast are used to reduce ileocolic intussusception under fluoroscopy. Some suggest air lowers radiation dose due to shorter procedure times. However, air enema likely lowers radiation dose regardless of fluoroscopy time due to less density over the automatic exposure control cells. We test the hypothesis that air enema reduction of ileocolic intussusception results in lower radiation dose than liquid contrast enema independent of fluoroscopy time. We describe a role for automatic exposure control in this dose difference. We retrospectively evaluated air and liquid intussusception reductions performed on a single digital fluoroscopic unit during a 26-month period. We compared patient age, weight, gender, exam time of day and year, performing radiologist(s), radiographic image acquisitions, grid and magnification use, fluoroscopy time and dose area product. We compared categorical and continuous variables statistically using chi-square and Mann-Whitney U tests, respectively. The mean dose area product was 2.7-fold lower for air enema, 1.3 ± 0.9 dGy·cm 2 , than for liquid, 3.5 ± 2.5 dGy·cm 2 (P<0.005). The mean fluoroscopy time was similar between techniques. The mean dose area product/min was 2.3-fold lower for air, 0.6 ± 0.2 dGy·cm 2 /min, than for liquid, 1.4 ± 0.5 dGy·cm 2 /min (P<0.001). No group differences were identified in other measured dose parameters. Fluoroscopic intussusception reduction using air enema uses less than half the radiation dose of liquid contrast enema. Dose savings are independent of fluoroscopy time and are likely due to automatic exposure control interaction.

Potential of combining iterative reconstruction with noise efficient detector design: aggressive dose reduction in head CT

PubMed Central

Bender, B; Schabel, C; Fenchel, M; Ernemann, U; Korn, A

2015-01-01

Objective: With further increase of CT numbers and their dominant contribution to medical exposure, there is a recent quest for more effective dose control. While reintroduction of iterative reconstruction (IR) has proved its potential in many applications, a novel focus is placed on more noise efficient detectors. Our purpose was to assess the potential of IR in combination with an integrated circuit detector (ICD) for aggressive dose reduction in head CT. Methods: Non-contrast low-dose head CT [190 mAs; weighted volume CT dose index (CTDIvol), 33.2 mGy] was performed in 50 consecutive patients, using a new noise efficient detector and IR. Images were assessed in terms of quantitative and qualitative image quality and compared with standard dose acquisitions (320 mAs; CTDIvol, 59.7 mGy) using a conventional detector and filtered back projection. Results: By combining ICD and IR in low-dose examinations, the signal to noise was improved by about 13% above the baseline level in the standard-dose control group. Both, contrast-to-noise ratio (2.02 ± 0.6 vs 1.88 ± 0.4; p = 0.18) and objective measurements of image sharpness (695 ± 84 vs 705 ± 151 change in Hounsfield units per pixel; p = 0.79) were fully preserved in the low-dose group. Likewise, there was no significant difference in the grading of several subjective image quality parameters when both noise-reducing strategies were used in low-dose examinations. Conclusion: Combination of noise efficient detector with IR allows for meaningful dose reduction in head CT without compromise of standard image quality. Advances in knowledge: Our study demonstrates the feasibility of almost 50% dose reduction in head CT dose (1.1 mSv per scan) through combination of novel dose-reducing strategies. PMID:25827204

Potential uncertainty reduction in model-averaged benchmark dose estimates informed by an additional dose study.

PubMed

Shao, Kan; Small, Mitchell J

2011-10-01

A methodology is presented for assessing the information value of an additional dosage experiment in existing bioassay studies. The analysis demonstrates the potential reduction in the uncertainty of toxicity metrics derived from expanded studies, providing insights for future studies. Bayesian methods are used to fit alternative dose-response models using Markov chain Monte Carlo (MCMC) simulation for parameter estimation and Bayesian model averaging (BMA) is used to compare and combine the alternative models. BMA predictions for benchmark dose (BMD) are developed, with uncertainty in these predictions used to derive the lower bound BMDL. The MCMC and BMA results provide a basis for a subsequent Monte Carlo analysis that backcasts the dosage where an additional test group would have been most beneficial in reducing the uncertainty in the BMD prediction, along with the magnitude of the expected uncertainty reduction. Uncertainty reductions are measured in terms of reduced interval widths of predicted BMD values and increases in BMDL values that occur as a result of this reduced uncertainty. The methodology is illustrated using two existing data sets for TCDD carcinogenicity, fitted with two alternative dose-response models (logistic and quantal-linear). The example shows that an additional dose at a relatively high value would have been most effective for reducing the uncertainty in BMA BMD estimates, with predicted reductions in the widths of uncertainty intervals of approximately 30%, and expected increases in BMDL values of 5-10%. The results demonstrate that dose selection for studies that subsequently inform dose-response models can benefit from consideration of how these models will be fit, combined, and interpreted. © 2011 Society for Risk Analysis.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.

PubMed

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank; Brand, Eva

2016-03-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. Copyright © 2016 by the American Society of Nephrology.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch–2-Year Follow-Up

PubMed Central

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank

2016-01-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3–0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C–based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. PMID:26185201

Radiation dose reduction: comparative assessment of publication volume between interventional and diagnostic radiology.

PubMed

Hansmann, Jan; Henzler, Thomas; Gaba, Ron C; Morelli, John N

2017-01-01

We aimed to quantify and compare awareness regarding radiation dose reduction within the interventional radiology and diagnostic radiology communities. Abstracts accepted to the annual meetings of the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Radiological Society of North America (RSNA), and the European Congress of Radiology (ECR) between 2005 and 2015 were analyzed using the search terms "interventional/computed tomography" and "radiation dose/radiation dose reduction." A PubMed query using the above-mentioned search terms for the years of 2005-2015 was performed. Between 2005 and 2015, a total of 14 520 abstracts (mean, 660±297 abstracts) and 80 614 abstracts (mean, 3664±1025 abstracts) were presented at interventional and diagnostic radiology meetings, respectively. Significantly fewer abstracts related to radiation dose were presented at the interventional radiology meetings compared with the diagnostic radiology meetings (162 abstracts [1% of total] vs. 2706 [3% of total]; P < 0.001). On average 15±7 interventional radiology abstracts (range, 6-27) and 246±105 diagnostic radiology abstracts (range, 112-389) pertaining to radiation dose were presented at each meeting. The PubMed query revealed an average of 124±39 publications (range, 79-187) and 1205±307 publications (range, 829-1672) related to interventional and diagnostic radiology dose reduction per year, respectively (P < 0.001). The observed increase in the number of abstracts regarding radiation dose reduction in the interventional radiology community over the past 10 years has not mirrored the increased volume seen within diagnostic radiology, suggesting that increased education and discussion about this topic may be warranted.

Radiation dose reduction: comparative assessment of publication volume between interventional and diagnostic radiology

PubMed Central

Hansmann, Jan; Henzler, Thomas; Gaba, Ron C.; Morelli, John N.

2017-01-01

PURPOSE We aimed to quantify and compare awareness regarding radiation dose reduction within the interventional radiology and diagnostic radiology communities. METHODS Abstracts accepted to the annual meetings of the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Radiological Society of North America (RSNA), and the European Congress of Radiology (ECR) between 2005 and 2015 were analyzed using the search terms “interventional/computed tomography” and “radiation dose/radiation dose reduction.” A PubMed query using the above-mentioned search terms for the years of 2005–2015 was performed. RESULTS Between 2005 and 2015, a total of 14 520 abstracts (mean, 660±297 abstracts) and 80 614 abstracts (mean, 3664±1025 abstracts) were presented at interventional and diagnostic radiology meetings, respectively. Significantly fewer abstracts related to radiation dose were presented at the interventional radiology meetings compared with the diagnostic radiology meetings (162 abstracts [1% of total] vs. 2706 [3% of total]; P < 0.001). On average 15±7 interventional radiology abstracts (range, 6–27) and 246±105 diagnostic radiology abstracts (range, 112–389) pertaining to radiation dose were presented at each meeting. The PubMed query revealed an average of 124±39 publications (range, 79–187) and 1205±307 publications (range, 829–1672) related to interventional and diagnostic radiology dose reduction per year, respectively (P < 0.001). CONCLUSION The observed increase in the number of abstracts regarding radiation dose reduction in the interventional radiology community over the past 10 years has not mirrored the increased volume seen within diagnostic radiology, suggesting that increased education and discussion about this topic may be warranted. PMID:28287072

SU-F-I-09: Improvement of Image Registration Using Total-Variation Based Noise Reduction Algorithms for Low-Dose CBCT

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

Mukherjee, S; Farr, J; Merchant, T

Purpose: To study the effect of total-variation based noise reduction algorithms to improve the image registration of low-dose CBCT for patient positioning in radiation therapy. Methods: In low-dose CBCT, the reconstructed image is degraded by excessive quantum noise. In this study, we developed a total-variation based noise reduction algorithm and studied the effect of the algorithm on noise reduction and image registration accuracy. To study the effect of noise reduction, we have calculated the peak signal-to-noise ratio (PSNR). To study the improvement of image registration, we performed image registration between volumetric CT and MV- CBCT images of different head-and-neck patientsmore » and calculated the mutual information (MI) and Pearson correlation coefficient (PCC) as a similarity metric. The PSNR, MI and PCC were calculated for both the noisy and noise-reduced CBCT images. Results: The algorithms were shown to be effective in reducing the noise level and improving the MI and PCC for the low-dose CBCT images tested. For the different head-and-neck patients, a maximum improvement of PSNR of 10 dB with respect to the noisy image was calculated. The improvement of MI and PCC was 9% and 2% respectively. Conclusion: Total-variation based noise reduction algorithm was studied to improve the image registration between CT and low-dose CBCT. The algorithm had shown promising results in reducing the noise from low-dose CBCT images and improving the similarity metric in terms of MI and PCC.« less

Role of triple fixed combination valsartan, amlodipine and hydrochlorothiazide in controlling blood pressure

PubMed Central

Doménech, Monica; Coca, Antonio

2010-01-01

Hypertension is one of the main risk factors for the development of cardiovascular diseases and the search for new therapeutic strategies aimed at optimizing its control remains an ongoing research and clinical challenge. In recent years, there has been a marked increase in the use of combinations of antihypertensive drugs with complementary mechanisms of action, with the aims of reducing blood pressure levels more rapidly and vigorously than strategies employing monotherapy and improving treatment compliance and adhesion. Therefore, as recommended by the 2009 reappraisal of the European Society of Hypertension/European Society of Cardiology Guidelines, the use of a triple combination that combines a calcium channel blocker, an angiotensin II receptor blocker and a thiazide diuretic seems a reasonable and efficacious combination for the management of hypertensive patients with moderate, high or very high risk. This article reviews the clinical trials carried out with the fixed combination of amlodipine/valsartan/hydrochlorothiazide at the doses recommended for each drug in monotherapy. The data show that this combination achieved greater reductions in mean sitting diastolic and systolic blood pressure than amlodipine, valsartan or hydrochlorothiazide in monotherapy, with favorable pharmacodynamic and pharmacokinetic profiles. The triple combination at high single doses should be used with caution in elderly patients and those with renal or liver failure. Although the tolerability and safety of the triple combination are good, the most-frequently reported adverse effects were peripheral edema, headache and dizziness. Analytical alterations were consistent with the already-known biochemical effects of amlodipine, valsartan or hydrochlorothiazide in monotherapy. In summary, triple-therapy with amlodipine/valsartan/hydrochlorothiazide in a single pill contributes additional advantages to fixed -combinations of two drugs, achieving a greater and more rapid reduction in blood pressure levels in a safe, well-tolerated manner. PMID:20517471

Additive effect of ketoconazole and octreotide in the treatment of severe adrenocorticotropin-dependent hypercortisolism.

PubMed

Vignati, F; Loli, P

1996-08-01

Over the last few years ketoconazole and octreotide have been employed in the treatment of pituitary-dependent or ectopic Cushing's syndrome. In four patients (two men and two women, aged 25-64 yr) with severe ACTH-dependent hypercortisolism in whom medical treatment with ketoconazole showed limited effectiveness and/or tolerability, we tried the association with octreotide. In all patients ketoconazole (200-1000 mg) induced a marked decrease in urinary free cortisol (UFC) excretion, but normalization could not be achieved. After ketoconazole discontinuation, three patients received octreotide alone (300-1500 micrograms/day, sc). This drug caused a dramatic decrease in UFC excretion, although not normalization; in all patients, escape from treatment occurred. Combined treatment was carried out for 10-180 days. Urinary cortisol excretion normalized and remained steadily within normal limits in three of four patients in whom normal UFC excretion had never been attained with both single drug regimens; in the fourth patient, UFC excretion decreased to levels lower than those achieved with ketoconazole or octreotide alone. The association with octreotide allowed a reduction in the daily dose of ketoconazole in three patients. Consistent with the steady reduction of cortisol production, a striking clinical improvement occurred in all patients after starting combined treatment. The normalization of UFC in three of four patients treated with both agents suggests that this approach may be useful in the long term treatment of severe forms of hypercortisolism of both pituitary and ectopic origin. In contrast to the limited effectiveness of each drug taken singularly at the same or higher doses, the association of the two drugs had an additive effect in the attainment of normal urinary cortisol excretion.

Auranofin in the treatment of steroid dependent asthma: a double blind study.

PubMed Central

Nierop, G; Gijzel, W P; Bel, E H; Zwinderman, A H; Dijkman, J H

1992-01-01

BACKGROUND: Long term administration of oral corticosteroids in patients with asthma may be associated with serious side effects. Non-steroidal anti-inflammatory drugs, including gold salts, have been shown to reduce the need for systemic corticosteroid treatment in uncontrolled studies. The effect of oral gold (auranofin) on asthma symptoms, lung function, and the need for oral prednisone treatment was investigated. METHODS: A 26 week randomised, double blind, placebo controlled, parallel group trial of auranofin was performed in 32 patients with moderately severe chronic asthma who required an oral corticosteroid dose of at least 5 mg prednisone a day (or equivalent) or 2.5 mg/day prednisone plus more than 800 micrograms/day inhaled corticosteroids. Auranofin was given orally in a dose of 3 mg twice daily. Asthma symptoms, lung function, and adverse effects were assessed at regular intervals. After 12 weeks of treatment prednisone dosage was tapered down by 2.5 mg every two weeks if the patient was clinically stable. Asthma exacerbations were treated with short courses of high doses of oral steroids. RESULTS: Twenty eight of the 32 patients, 13 in the placebo group and 15 in the auranofin group, completed the study. The total corticosteroid reduction achieved after 26 weeks of treatment was significantly greater (4 mg) in the auranofin group than in the placebo group (0.3 mg). The number of exacerbations requiring an increase of steroids was greater in the placebo group (2.1) than in the active group (0.9). A significant increase in FEV1 of 6.4% predicted occurred in the auranofin group during the study and there was a reduction of asthma symptoms such as wheezing and cough. There was no difference between the groups in peak flow measurements or in the number of asthma attacks. The incidence of side effects of auranofin was low, but exacerbations of constitutional eczema were noticeable. CONCLUSION: Auranofin provides an effective adjunct to treatment for steroid dependent asthma, leading to a reduction of oral steroid dose. Images PMID:1609377

Changes in HbA1c, insulin dose and incidence of hypoglycemia in patients with type 1 diabetes after switching to insulin degludec in an outpatient setting: an observational study.

PubMed

Landstedt-Hallin, Lena

2015-08-01

Insulin degludec, a basal insulin with an ultra-long duration of action, became available in Sweden from July 2013. The diabetes team at Danderyd Hospital decided to perform a clinical follow-up of patients with type 1 diabetes switching to insulin degludec to evaluate its clinical performance, using a simple form and available measures, thereby indirectly assessing cost-effectiveness. This was a prospective, open-label, single-arm, observational, clinical follow-up from August 2013 to February 2015 of consecutive patients who switched to insulin degludec according to predefined indications (i.e., currently administering basal insulin twice daily, unacceptable HbA1c, repeated hypoglycemic events and/or unstable glucose, difficulty with fixed-time administration) in conjunction with professional judgment and patient wishes. Information about HbA1c, insulin dose and frequency of hypoglycemia (self-reported by patient recall) was collected at baseline and repeated after 4-6 months. In February 2015, data were available on 357 patients. Median time to follow-up was 20 weeks. Mean (SD) HbA1c decreased from 68.9 (15.7) to 65.8 (14.3) mmol/mol, p < 0.0001, and this improvement was achieved despite less insulin. Median reduction of the total insulin dose (basal + prandial) was 12% (interquartile range [IQR] -20% to -3%). The mean (SD) number of self-reported hypoglycemic events in the previous 4 weeks decreased from 8.2 (8.9) to 6.4 (7.6) events, p < 0.0001, and nocturnal hypoglycemic events were reduced from 1.6 (2.9) to 0.7 (2.0) events, p < 0.0001. Due to improvement in glycemic control, reduction of hypoglycemic events and reduction of insulin dose, we concluded that insulin degludec was clinically useful and economically justifiable for our patients with type 1 diabetes. Not every patient may benefit to the same degree after switching to insulin degludec. Controlled studies are needed to confirm these benefits in a larger sample of real-world patients.

TH-AB-BRA-08: Simulated Tumor Tracking in An MRI Linac for Lung Tumor Lesions Using the Monaco Treatment Planning System

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

Al-Ward, S; Kim, A; McCann, C

2016-06-15

Purpose: To simulate tumor tracking in an Elekta MRI-linac (MRL) and to compare this tracking method with our current ITV approach in terms of OAR sparing for lung cancer patients. Methods: Five SABR-NSCLC patients with central lung tumors were selected for reasons of potential enhancement of tumor-tissue delineation using MRI. The Monaco TPS was used to compare the current clinical ITV approach to a simulated, novel tracking method which used a 7MV MRL beam in the presence of an orthogonal 1.5 T magnetic field (4D-MRL method). In the simulated tracking scenario, achieved using the virtual couch shift (VCS), the PTVmore » was defined using an isotropic 5mm margin applied to the GTV of each phase, as acquired from an 8-phase amplitude-binned 4DCT. These VCS plans were optimized and weighted on each phase. The dose weighting was performed using the patient-specific breathing traces. The doses were accumulated on the inhale phase. The two methods were compared by assessing the OAR DVHs. Results: The 4D-MRL method resulted in a reduced target volume (by an average of 29% over all patients). The benefits of using an MRL tracking system depended on the tumor motion amplitude and the relative OAR motion (ROM) to the target. The reduction in mean doses to parallel organs was up to 3 Gy for the heart and 2.1 Gy for the lung. The reductions in maximum doses to serial organs were up to 9.4 Gy, 5.6 Gy, and 8.7 Gy for the esophagus, spinal cord, and the trachea, respectively. Serial organs benefited from MRL tracking when the ROM was ≥ 0.3 cm despite small tumor motion amplitude in some cases. Conclusions: This work demonstrated the potential benefit for an MRL tracking system to spare OARs in SABR-NSCLC patients with central tumors. The benefits are embodied in the target volume reduction. This project was made possible with the financial support of Elekta.« less

OPTIMIZING LENVATINIB THERAPY IN PATIENTS WITH METASTATIC RADIOACTIVE IODINE-RESISTANT DIFFERENTIATED THYROID CANCERS.

PubMed

Jasim, Sina; Iniguez-Ariza, Nicole M; Hilger, Crystal R; Chintakuntlawar, Ashish V; Ryder, Mabel M; Morris, John C; Bible, Keith C

2017-10-01

Lenvatinib is approved for use in advanced radioactive iodine-resistant differentiated thyroid cancers (RAIR-DTCs). Its efficacy is indisputable, but toxicities are great, creating daunting challenges for patients and providers. Few data regarding early adverse events and impact on quality of life (QOL) exist; we sought to clarify these issues by analyzing our initial postapproval lenvatinib experience. Standardized patient education was implemented, providing detailed instructions and expert provider contacts to facilitate timely reporting of toxicities and guide responsive actions. Early adverse events, QOL outcomes, and response data from 25 consecutively treated DTC patients (02/2015 and 05/2016) were retrospectively analyzed. The median age was 55 years (range 27-81); 52% were female. Fourteen (56%) were on antihypertensive medication(s) at baseline. Most patients (21/25, 84%) developed adverse events during the first month of therapy. Hypertension arose in 16/25 (64%), requiring antihypertensive dose adjustment/addition in 6 (24%)/12 (48%) patients, respectively, during the first month of therapy. Dose reduction was required in 11 (44%) due to multiple adverse events; the median time to first dose reduction was 33 days (range 11-84); 8 (32%) required multiple dose reductions. Therapy interruption >3 weeks occurred in 4 (16%). The median change in patient-reported fatigue score was +2 (worsening, range -2 to +10, P<.007; 0-10 scales), but the median QOL change was 0 (range +4 to -9, P = .57). The mean duration of lenvatinib therapy was 6.5 months (range 1-12); median overall and progression-free survival have not yet been reached. Lenvatinib was discontinued in 7 (28%) patients; among 20 patients with available RECIST (Response Evaluation Criteria In Solid Tumors) measurements, 10 (50%) achieved partial response. Lenvatinib has promising efficacy in RAIR-DTC, but toxicities require frequent early interventions. QOL can be maintained on lenvatinib therapy. DTC = differentiated thyroid cancer; LASA = linear analog self-assessment; PR = partial response; QOL = quality of life; RAI = radioactive iodine; RAIR = RAI-resistant; RECIST = Response Evaluation Criteria In Solid Tumors; Tg = thyroglobulin; VEGFR = vascular endothelial growth factor receptor.

Influence of He implantation on the fatigue properties of stainless steel under different atmospheric conditions

NASA Astrophysics Data System (ADS)

Sonnenberg, K.; Antesberger, G.; Brown, B.

1981-12-01

The influence of He on the fatigue properties of stainless steel was investigated using α-particle implantation. The He influence was compared for different external atmospheres (inert, corrosive), various fatigue temperatures (400-750°C), implantation temperatures (400-950°C), He doses (5-3000 ppm), strain amplitudes (0.5-3%) and fatigue frequencies (0.02-8 Hz). In situ and post-implantation fatigue testing showed that the effect of He implantation is very similar in both cases. The effect of He is small if the fatigue temperature is ≤ 600°C. In these cases the fracture mode remains transgranular and only small reductions of the fatigue life (less than a factor of 2) are observed upon He implantation. For higher fatigue temperatures the He causes a transition from a transgranular to an intergranular fracture mode associated with rather dramatic reductions of the fatigue life. It was shown that this fracture mode must be attributed to a growth of He bubbles at the grain boundaries. The growth is probably achieved by condensation of thermal vacancies, the flux of which is controlled by the external stresses and by grain-boundary diffusion. It was found that the size of the lifetime reduction increases with the He dose and the implantation temperature, because more He reaches the grain boundaries. The lifetime depends more strongly on the strain amplitude for irradiated samples. The lifetime for irradiated samples does not depend on the external atmosphere, in contrast to unirradiated samples which have an order of magnitude longer life in the clean atmosphere. In contrast to failure in a transgranular mode, the number of fatigue cycles until feature, N ƒ, is found to decrease with the fatigue frequency in the case of intergranular mode. The temperature above which intergranular fracture occurs (usually above 700°C) is affected by the He dose and the fatigue frequency. For high doses of ≈ 1000 ppm He and small frequencies of ≈0.02 Hz, the intergranular mode is observed as low as 600°C.

A Pharmacometric Approach to Substitute for a Conventional Dose-Finding Study in Rare Diseases: Example of Phase III Dose Selection for Emicizumab in Hemophilia A.

PubMed

Yoneyama, Koichiro; Schmitt, Christophe; Kotani, Naoki; Levy, Gallia G; Kasai, Ryu; Iida, Satofumi; Shima, Midori; Kawanishi, Takehiko

2017-12-06

Emicizumab (ACE910) is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII. In phase I-I/II studies, emicizumab reduced the bleeding frequency in patients with severe hemophilia A, regardless of the presence of factor VIII inhibitors, at once-weekly subcutaneous doses of 0.3, 1, and 3 mg/kg. Using the phase I-I/II study data, population pharmacokinetic and repeated time-to-event (RTTE) modeling were performed to quantitatively characterize the relationship between the pharmacokinetics of emicizumab and reduction in bleeding frequency. Simulations were then performed to identify the minimal exposure expected to achieve zero bleeding events for 1 year in at least 50% of patients and to select the dosing regimens to be tested in phase III studies. The RTTE model adequately predicted the bleeding onset over time as a function of plasma emicizumab concentration. Simulations suggested that plasma emicizumab concentrations of ≥  45 μg/mL should result in zero bleeding events for 1 year in at least 50% of patients. This efficacious exposure provided the basis for selecting previously untested dosing regimens of 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, and 6 mg/kg every 4 weeks for phase III studies. A pharmacometric approach guided the phase III dose selection of emicizumab in hemophilia A, without conducting a conventional dose-finding study. Phase III studies with the selected dosing regimens are currently ongoing. This case study indicates that a pharmacometric approach can substitute for a conventional dose-finding study in rare diseases and will streamline the drug development process.

Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

PubMed

Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

2007-03-05

Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose.

Priori mask guided image reconstruction (p-MGIR) for ultra-low dose cone-beam computed tomography

NASA Astrophysics Data System (ADS)

Park, Justin C.; Zhang, Hao; Chen, Yunmei; Fan, Qiyong; Kahler, Darren L.; Liu, Chihray; Lu, Bo

2015-11-01

Recently, the compressed sensing (CS) based iterative reconstruction method has received attention because of its ability to reconstruct cone beam computed tomography (CBCT) images with good quality using sparsely sampled or noisy projections, thus enabling dose reduction. However, some challenges remain. In particular, there is always a tradeoff between image resolution and noise/streak artifact reduction based on the amount of regularization weighting that is applied uniformly across the CBCT volume. The purpose of this study is to develop a novel low-dose CBCT reconstruction algorithm framework called priori mask guided image reconstruction (p-MGIR) that allows reconstruction of high-quality low-dose CBCT images while preserving the image resolution. In p-MGIR, the unknown CBCT volume was mathematically modeled as a combination of two regions: (1) where anatomical structures are complex, and (2) where intensities are relatively uniform. The priori mask, which is the key concept of the p-MGIR algorithm, was defined as the matrix that distinguishes between the two separate CBCT regions where the resolution needs to be preserved and where streak or noise needs to be suppressed. We then alternately updated each part of image by solving two sub-minimization problems iteratively, where one minimization was focused on preserving the edge information of the first part while the other concentrated on the removal of noise/artifacts from the latter part. To evaluate the performance of the p-MGIR algorithm, a numerical head-and-neck phantom, a Catphan 600 physical phantom, and a clinical head-and-neck cancer case were used for analysis. The results were compared with the standard Feldkamp-Davis-Kress as well as conventional CS-based algorithms. Examination of the p-MGIR algorithm showed that high-quality low-dose CBCT images can be reconstructed without compromising the image resolution. For both phantom and the patient cases, the p-MGIR is able to achieve a clinically-reasonable image with 60 projections. Therefore, a clinically-viable, high-resolution head-and-neck CBCT image can be obtained while cutting the dose by 83%. Moreover, the image quality obtained using p-MGIR is better than the quality obtained using other algorithms. In this work, we propose a novel low-dose CBCT reconstruction algorithm called p-MGIR. It can be potentially used as a CBCT reconstruction algorithm with low dose scan requests

A qualitative and quantitative analysis of radiation dose and image quality of computed tomography images using adaptive statistical iterative reconstruction

PubMed Central

Mail, Noor; Shamy, Abdulrahman M.; Alghamdi, Suliman; Saoudi, Abdelhamid

2016-01-01

Image quality is a key issue in radiology, particularly in a clinical setting where it is important to achieve accurate diagnoses while minimizing radiation dose. Some computed tomography (CT) manufacturers have introduced algorithms that claim significant dose reduction. In this study, we assessed CT image quality produced by two reconstruction algorithms provided with GE Healthcare's Discovery 690 Elite positron emission tomography (PET) CT scanner. Image quality was measured for images obtained at various doses with both conventional filtered back‐projection (FBP) and adaptive statistical iterative reconstruction (ASIR) algorithms. A standard CT dose index (CTDI) phantom and a pencil ionization chamber were used to measure the CT dose at 120 kVp and an exposure of 260 mAs. Image quality was assessed using two phantoms. CT images of both phantoms were acquired at tube voltage (kV) of 120 with exposures ranging from 25 mAs to 400 mAs. Images were reconstructed using FBP and ASIR ranging from 10% to 100%, then analyzed for noise, low‐contrast detectability, contrast‐to‐noise ratio (CNR), and modulation transfer function (MTF). Noise was 4.6 HU in water phantom images acquired at 260 mAs/FBP 120 kV and 130 mAs/50% ASIR 120 kV. The large objects (frequency<7 lp/cm) retained fairly acceptable image quality at 130 mAs/50% ASIR, compared to 260 mAs/FBP. The application of ASIR for small objects (frequency>7 lp/cm) showed poor visibility compared to FBP at 260 mAs and even worse for images acquired at less than 130 mAs. ASIR blending more than 50% at low dose tends to reduce contrast of small objects (frequency>7 lp/cm). We concluded that dose reduction and ASIR should be applied with close attention if the objects to be detected or diagnosed are small (frequency>7 lp/cm). Further investigations are required to correlate the small objects (frequency>7 lp/cm) to patient anatomy and clinical diagnosis. PACS number(s): 87.57.‐s, 87.57.C, 87.57.cf, 87.57.cj, 87.57.cm, 87.57.cp, 87.57.N, 87.57.nf, 87.57.np, 87.57.nt, 87.57.Q, 87.59.‐e, 87.59.B PMID:27167261

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

PubMed Central

Fitzgerald, Kevin; White, Suellen; Borodovsky, Anna; Bettencourt, Brian R.; Strahs, Andrew; Clausen, Valerie; Wijngaard, Peter; Horton, Jay D.; Taubel, Jorg; Brooks, Ashley; Fernando, Chamikara; Kauffman, Robert S.; Kallend, David; Vaishnaw, Akshay; Simon, Amy

2018-01-01

BACKGROUND Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. METHODS In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442.) PMID:27959715

Longitudinal study of radiation exposure in computed tomography with an in-house developed dose monitoring system

NASA Astrophysics Data System (ADS)

Renger, Bernhard; Rummeny, Ernst J.; Noël, Peter B.

2013-03-01

During the last decades, the reduction of radiation exposure especially in diagnostic computed tomography is one of the most explored topics. In the same time, it seems challenging to quantify the long-term clinical dose reduction with regard to new hardware as well as software solutions. To overcome this challenge, we developed a Dose Monitoring System (DMS), which collects information from PACS, RIS, MPPS and structured reports. The integration of all sources overcomes the weaknesses of single systems. To gather all possible information, we integrated an optical character recognition system to extract, for example, information from the CT-dose-report. All collected data are transferred to a database for further evaluation, e.g., for calculations of effective as well as organ doses. The DMS provides a single database for tracking all essential study and patient specific information across different modality as well as different vendors. As an initial study, we longitudinally investigated the dose reduction in CT examination when employing a noise-suppressing reconstruction algorithm. For this examination type a significant long-term reduction in radiation exposure is reported, when comparing to a CT-system with standard reconstruction. In summary our DMS tool not only enables us to track radiation exposure on daily bases but further enables to analyses the long term effect of new dose saving strategies. In the future the statistical analyses of all retrospective data, which are available in a modern imaging department, will provide a unique overview of advances in reduction of radiation exposure.

Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia.

PubMed

Akdim, Fatima; Tribble, Diane L; Flaim, JoAnn D; Yu, Rosie; Su, John; Geary, Richard S; Baker, Brenda F; Fuhr, Rainard; Wedel, Mark K; Kastelein, John J P

2011-11-01

Mipomersen, an apolipoprotein (apo) B synthesis inhibitor, has been shown to produce potent reductions in apoB and LDL-cholesterol levels in animal models as well as healthy human volunteers. A randomized, double-blind, placebo-controlled, dose-escalation study was designed to evaluate the efficacy and safety of mipomersen monotherapy with or without dose loading in subjects with mild-to-moderate hyperlipidaemia. Fifty subjects with LDL-cholesterol levels between 119 and 266 mg/dL were enrolled into five cohorts at a 4:1 randomization ratio of active to placebo. Two 13-week dose regimens were evaluated at doses ranging from 50 to 400 mg/week. Mipomersen produced dose-dependent reductions in all apoB containing lipoproteins. In the 200 and 300 mg/week dose cohorts, mean reductions from baseline in LDL cholesterol were -45 ± 10% (P= 0.000) and -61 ± 8% (P= 0.000), corresponding to a -46 ± 11% (P= 0.000) and -61 ± 7% (P= 0.000) decrease in apoB levels. Triglyceride levels were also lowered with median reductions up to 53% (P= 0.021). The most common adverse events were injection site reactions. Seven of 40 subjects (18%) showed consecutive transaminase elevations >3× upper limit of normal. Five of these subjects received 400 mg/week, four of whom had apoB levels below the limit of detection. As a consequence, the 400 mg/week cohort was discontinued. Mipomersen administered as monotherapy in subjects with mild-to-moderate hyperlipidaemia produced potent reductions in all apoB-containing lipoproteins. Higher doses were associated with hepatic transaminase increases.

A Review of Update Clinical Results of Carbon Ion Radiotherapy

PubMed Central

Tsujii, Hirohiko; Kamada, Tadashi

2012-01-01

Among various types of ion species, carbon ions are considered to have the most balanced, optimal properties in terms of possessing physically and biologically effective dose localization in the body. This is due to the fact that when compared with photon beams, carbon ion beams offer improved dose distribution, leading to the concentration of the sufficient dose within a target volume while minimizing the dose in the surrounding normal tissues. In addition, carbon ions, being heavier than protons, provide a higher biological effectiveness, which increases with depth, reaching the maximum at the end of the beam's range. This is practically an ideal property from the standpoint of cancer radiotherapy. Clinical studies have been carried out in the world to confirm the efficacy of carbon ions against a variety of tumors as well as to develop effective techniques for delivering an efficient dose to the tumor. Through clinical experiences of carbon ion radiotherapy at the National Institute of Radiological Sciences and Gesellschaft für Schwerionenforschung, a significant reduction in the overall treatment time with acceptable toxicities has been obtained in almost all types of tumors. This means that carbon ion radiotherapy has meanwhile achieved for itself a solid place in general practice. This review describes clinical results of carbon ion radiotherapy together with physical, biological and technological aspects of carbon ions. PMID:22798685

Quantification of Acute Vocal Fold Epithelial Surface Damage with Increasing Time and Magnitude Doses of Vibration Exposure

PubMed Central

Kojima, Tsuyoshi; Van Deusen, Mark; Jerome, W. Gray; Garrett, C. Gaelyn; Sivasankar, M. Preeti; Novaleski, Carolyn K.; Rousseau, Bernard

2014-01-01

Because the vocal folds undergo repeated trauma during continuous cycles of vibration, the epithelium is routinely susceptible to damage during phonation. Excessive and prolonged vibration exposure is considered a significant predisposing factor in the development of vocal fold pathology. The purpose of the present study was to quantify the extent of epithelial surface damage following increased time and magnitude doses of vibration exposure using an in vivo rabbit phonation model. Forty-five New Zealand white breeder rabbits were randomized to nine groups and received varying phonation time-doses (30, 60, or 120 minutes) and magnitude-doses (control, modal intensity phonation, or raised intensity phonation) of vibration exposure. Scanning electron microscopy and transmission electron microscopy was used to quantify the degree of epithelial surface damage. Results revealed a significant reduction in microprojection density, microprojection height, and depth of the epithelial surface with increasing time and phonation magnitudes doses, signifying increased epithelial surface damage risk with excessive and prolonged vibration exposure. Destruction to the epithelial cell surface may provide significant insight into the disruption of cell function following prolonged vibration exposure. One important goal achieved in the present study was the quantification of epithelial surface damage using objective imaging criteria. These data provide an important foundation for future studies of long-term tissue recovery from excessive and prolonged vibration exposure. PMID:24626217

Transitional polytherapy: tricks of the trade for monotherapy to monotherapy AED conversions.

PubMed

Garnett, William R; St Louis, Erik K; Henry, Thomas R; Bramley, Thomas

2009-06-01

The goal of epilepsy therapy is to help patients achieve seizure freedom without adverse effects. While monotherapy is preferable in epilepsy treatment, many patients fail a first drug due to lack of efficacy or failure to tolerate an initial medication, necessitating an alteration in therapy. Sudden changes between monotherapies are rarely feasible and sometimes deleterious given potential hazards of acute seizure exacerbation or intolerable adverse effects. The preferred method for converting between monotherapies is transitional polytherapy, a process involving initiation of a new antiepileptic drug (AED) and adjusting it toward a target dose while maintaining or reducing the dose of the baseline medication. A fixed-dose titration strategy of maintaining the baseline drug dose while titrating the new medication is preferable when breakthrough seizures are occurring and no adverse effects are present. However, a flexible titration strategy involving reduction of the baseline drug dose to ensure adequate tolerability of the new adjunctive medication is preferred when patients are already experiencing adverse effects. This article reviews pharmacokinetic considerations pertinent for ensuring successful transitional polytherapy with the standard and newer antiepileptic drugs. Practical consensus recommendations "from an expect panel (SPECTRA, Study by a Panel of Experts Considerations for Therapy Replacement and Antiepileptics) for a successful monotherapy" AED conversions are then summarized. Transitional polytherapy is most successful when clinicians appropriately manage the titration strategy and consider pharmacokinetic factors germane to the baseline and new adjunctive medication.

A dose optimization method for electron radiotherapy using randomized aperture beams

NASA Astrophysics Data System (ADS)

Engel, Konrad; Gauer, Tobias

2009-09-01

The present paper describes the entire optimization process of creating a radiotherapy treatment plan for advanced electron irradiation. Special emphasis is devoted to the selection of beam incidence angles and beam energies as well as to the choice of appropriate subfields generated by a refined version of intensity segmentation and a novel random aperture approach. The algorithms have been implemented in a stand-alone programme using dose calculations from a commercial treatment planning system. For this study, the treatment planning system Pinnacle from Philips has been used and connected to the optimization programme using an ASCII interface. Dose calculations in Pinnacle were performed by Monte Carlo simulations for a remote-controlled electron multileaf collimator (MLC) from Euromechanics. As a result, treatment plans for breast cancer patients could be significantly improved when using randomly generated aperture beams. The combination of beams generated through segmentation and randomization achieved the best results in terms of target coverage and sparing of critical organs. The treatment plans could be further improved by use of a field reduction algorithm. Without a relevant loss in dose distribution, the total number of MLC fields and monitor units could be reduced by up to 20%. In conclusion, using randomized aperture beams is a promising new approach in radiotherapy and exhibits potential for further improvements in dose optimization through a combination of randomized electron and photon aperture beams.

Transfer hydrogenation catalysis in cells as a new approach to anticancer drug design

PubMed Central

Soldevila-Barreda, Joan J.; Romero-Canelón, Isolda; Habtemariam, Abraha; Sadler, Peter J.

2015-01-01

Organometallic complexes are effective hydrogenation catalysts for organic reactions. For example, Noyori-type ruthenium complexes catalyse reduction of ketones by transfer of hydride from formate. Here we show that such catalytic reactions can be achieved in cancer cells, offering a new strategy for the design of safe metal-based anticancer drugs. The activity of ruthenium(II) sulfonamido ethyleneamine complexes towards human ovarian cancer cells is enhanced by up to 50 × in the presence of low non-toxic doses of formate. The extent of conversion of coenzyme NAD+ to NADH in cells is dependent on formate concentration. This novel reductive stress mechanism of cell death does not involve apoptosis or perturbation of mitochondrial membrane potentials. In contrast, iridium cyclopentadienyl catalysts cause cancer cell death by oxidative stress. Organometallic complexes therefore have an extraordinary ability to modulate the redox status of cancer cells. PMID:25791197

Sugar substitutes: their energy values, bulk characteristics, and potential health benefits.

PubMed

Levin, G V; Zehner, L R; Saunders, J P; Beadle, J R

1995-11-01

Restriction of dietary energy extends life and reduces incidences of disease in animals. These benefits would likely extend to humans. However, diet restriction in animals imposes reductions of 30-50% in food intake, which is probably unacceptable to humans. Low-energy sweeteners used in beverages offer minor reductions in energy intake. However, they lack the bulk required for baked goods and other sugar-rich foods. Full-bulk sweeteners providing about one-half the energy of sugar are under development for such uses. Laxation limits their acceptable dose. Even within such limitations, they can help achieve the health benefits for humans indicated by diet restriction. D-Tagatose, a new candidate sweetener, is nearly as sweet as sucrose and has the bulk of sucrose, yet provides zero available energy. We discuss its potential contribution to human diet restriction along with its specific effect in delaying the aging effects of glycosylation.

A feasibility study of dynamic adaptive radiotherapy for nonsmall cell lung cancer

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

Kim, Minsun, E-mail: mk688@uw.edu; Phillips, Mark H.

2016-05-15

Purpose: The final state of the tumor at the end of a radiotherapy course is dependent on the doses given in each fraction during the treatment course. This study investigates the feasibility of using dynamic adaptive radiotherapy (DART) in treating lung cancers assuming CBCT is available to observe midtreatment tumor states. DART adapts treatment plans using a dynamic programming technique to consider the expected changes of the tumor in the optimization process. Methods: DART is constructed using a stochastic control formalism framework. It minimizes the total expected number of tumor cells at the end of a treatment course, which ismore » equivalent to maximizing tumor control probability, subject to the uncertainty inherent in the tumor response. This formulation allows for nonstationary dose distributions as well as nonstationary fractional doses as needed to achieve a series of optimal plans that are conformal to the tumor over time, i.e., spatiotemporally optimal plans. Sixteen phantom cases with various sizes and locations of tumors and organs-at-risk (OAR) were generated using in-house software. Each case was planned with DART and conventional IMRT prescribing 60 Gy in 30 fractions. The observations of the change in the tumor volume over a treatment course were simulated using a two-level cell population model. Monte Carlo simulations of the treatment course for each case were run to account for uncertainty in the tumor response. The same OAR dose constraints were applied for both methods. The frequency of replanning was varied between 1, 2, 5 (weekly), and 29 times (daily). The final average tumor dose and OAR doses have been compared to quantify the potential dosimetric benefits of DART. Results: The average tumor max, min, mean, and D95 doses using DART relative to these using conventional IMRT were 124.0%–125.2%, 102.1%–114.7%, 113.7%–123.4%, and 102.0%–115.9% (range dependent on the frequency of replanning). The average relative maximum doses for the cord and esophagus, mean doses for the heart and lungs, and D05 for the unspecified tissue resulting 84%–102.4%, 99.8%–106.9%, 66.9%–85.6%, 58.2%–78.8%, and 85.2%–94.0%, respectively. Conclusions: It is feasible to apply DART to the treatment of NSCLC using CBCT to observe the midtreatment tumor state. Potential increases in the tumor dose and reductions in the OAR dose, particularly for parallel OARs with mean or dose–volume constraints, could be achieved using DART compared to nonadaptive IMRT.« less

Intensity modulated radiation therapy (IMRT): differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma.

PubMed

Mok, Henry; Crane, Christopher H; Palmer, Matthew B; Briere, Tina M; Beddar, Sam; Delclos, Marc E; Krishnan, Sunil; Das, Prajnan

2011-06-08

A strong dose-volume relationship exists between the amount of small bowel receiving low- to intermediate-doses of radiation and the rates of acute, severe gastrointestinal toxicity, principally diarrhea. There is considerable interest in the application of highly conformal treatment approaches, such as intensity-modulated radiation therapy (IMRT), to reduce dose to adjacent organs-at-risk in the treatment of carcinoma of the rectum. Therefore, we performed a comprehensive dosimetric evaluation of IMRT compared to 3-dimensional conformal radiation therapy (3DCRT) in standard, preoperative treatment for rectal cancer. Using RTOG consensus anorectal contouring guidelines, treatment volumes were generated for ten patients treated preoperatively at our institution for rectal carcinoma, with IMRT plans compared to plans derived from classic anatomic landmarks, as well as 3DCRT plans treating the RTOG consensus volume. The patients were all T3, were node-negative (N = 1) or node-positive (N = 9), and were planned to a total dose of 45-Gy. Pairwise comparisons were made between IMRT and 3DCRT plans with respect to dose-volume histogram parameters. IMRT plans had superior PTV coverage, dose homogeneity, and conformality in treatment of the gross disease and at-risk nodal volume, in comparison to 3DCRT. Additionally, in comparison to the 3DCRT plans, IMRT achieved a concomitant reduction in doses to the bowel (small bowel mean dose: 18.6-Gy IMRT versus 25.2-Gy 3DCRT; p = 0.005), bladder (V40Gy: 56.8% IMRT versus 75.4% 3DCRT; p = 0.005), pelvic bones (V40Gy: 47.0% IMRT versus 56.9% 3DCRT; p = 0.005), and femoral heads (V40Gy: 3.4% IMRT versus 9.1% 3DCRT; p = 0.005), with an improvement in absolute volumes of small bowel receiving dose levels known to induce clinically-relevant acute toxicity (small bowel V15Gy: 138-cc IMRT versus 157-cc 3DCRT; p = 0.005). We found that the IMRT treatment volumes were typically larger than that covered by classic bony landmark-derived fields, without incurring penalty with respect to adjacent organs-at-risk. For rectal carcinoma, IMRT, compared to 3DCRT, yielded plans superior with respect to target coverage, homogeneity, and conformality, while lowering dose to adjacent organs-at-risk. This is achieved despite treating larger volumes, raising the possibility of a clinically-relevant improvement in the therapeutic ratio through the use of IMRT with a belly-board apparatus.

Lorcaserin, a 5-HT2C Agonist, Decreases Nicotine Self-Administration in Female Rats

PubMed Central

Johnson, Joshua E.; Slade, Susan; Wells, Corinne; Cauley, Marty; Petro, Ann; Rose, Jed E.

2011-01-01

Lorcaserin, a selective 5-hydroxytryptamine2C (5-HT2C) agonist, has been shown to facilitate weight loss in obese populations. It was assessed for its efficacy in reducing nicotine self-administration in young adult female Sprague-Dawley rats. The effect of short-term doses (subcutaneous) on nicotine self-administration (0.03 mg/kg per infusion) with a fixed ratio 1 schedule was assessed in 3-h sessions. Short-term lorcaserin doses (0.3125–20 mg/kg) were administered in a counterbalanced order. Significant reduction of nicotine self-administration was achieved with all of the short-term doses in this range. Tests of lorcaserin on locomotor activity detected prominent sedative effects at doses greater than 1.25 mg/kg with more modest transient effects seen at 0.625 to 1.25 mg/kg. Long-term effects of lorcaserin on locomotor activity were tested with repeated injections with 0.625 mg/kg lorcaserin 10 times over 2 weeks. This low lorcaserin dose did not cause an overall change in locomotor activity relative to that of saline-injected controls. Long-term lorcaserin (0.625 mg/kg) significantly reduced nicotine self-administration over a 2-week period of repeated injections. Long-term lorcaserin at this same dose had no significant effects on food self-administration over the same 2-week period of repeated injections. These studies support development of the 5-HT2C agonist lorcaserin to aid tobacco smoking cessation. PMID:21636655