Sample records for fixed dose procedure
-
Bertolaccini, Corinne M; Prazak, Ann Marie B; Agarwal, Jayant; Goodwin, Isak A; Rockwell, W Bradford; Pannucci, Christopher J
2018-05-22
In microvascular surgery, patients often receive unfractionated heparin infusions to minimize risk for microvascular thrombosis. Patients who receive intravenous (IV) heparin are believed to have adequate prophylaxis against venous thromboembolism (VTE). Whether a fixed dose of IV heparin provides detectable levels of anticoagulation, or whether the "one size fits all" approach provides adequate prophylaxis against VTE remains unknown. This study examined the pharmacodynamics of fixed-dose heparin infusions and the effects of real-time, anti-factor Xa (aFXa) level driven heparin dose adjustments. This prospective clinical trial recruited adult microvascular surgery patients placed on a fixed-dose (500 units/h) unfractionated heparin infusion during their initial microsurgical procedure. Steady-state aFXa levels, a marker of unfractionated heparin efficacy and safety, were monitored. Patients with out-of-range aFXa levels received protocol-driven real-time dose adjustments. Outcomes of interest included aFXa levels in response to heparin 500 units/h, number of dose adjustments required to achieve goal aFXa levels, time to reach goal aFXa level, and 90-day clinically relevant bleeding and VTE. Twenty patients were recruited prospectively. None of 20 patients had any detectable level of anticoagulation in response to heparin infusions at 500 units/h. The median number of dose adjustments required to reach goal level was five, and median weight-based dose to reach goal level was 11.8 units/kg/h. Real-time dose adjustments significantly increased the proportion of patients with in-range levels (60 vs. 0%, p = 0.0001). The 90-day VTE rate was 5% and 90-day clinically relevant bleeding rate was 5%. Fixed-dose heparin infusions at a rate of 500 units/h do not provide a detectable level of anticoagulation after microsurgical procedures and are insufficient for the majority of patients who require VTE prophylaxis. Weight-based heparin infusions at 10 to 12 units/kg/h deserve future study in patients undergoing microsurgical procedures to increase the proportion of patients receiving adequate VTE prophylaxis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
-
Svensson, Elin M; Yngman, Gunnar; Denti, Paolo; McIlleron, Helen; Kjellsson, Maria C; Karlsson, Mats O
2018-05-01
Fixed-dose combination formulations where several drugs are included in one tablet are important for the implementation of many long-term multidrug therapies. The selection of optimal dose ratios and tablet content of a fixed-dose combination and the design of individualized dosing regimens is a complex task, requiring multiple simultaneous considerations. In this work, a methodology for the rational design of a fixed-dose combination was developed and applied to the case of a three-drug pediatric anti-tuberculosis formulation individualized on body weight. The optimization methodology synthesizes information about the intended use population, the pharmacokinetic properties of the drugs, therapeutic targets, and practical constraints. A utility function is included to penalize deviations from the targets; a sequential estimation procedure was developed for stable estimation of break-points for individualized dosing. The suggested optimized pediatric anti-tuberculosis fixed-dose combination was compared with the recently launched World Health Organization-endorsed formulation. The optimized fixed-dose combination included 15, 36, and 16% higher amounts of rifampicin, isoniazid, and pyrazinamide, respectively. The optimized fixed-dose combination is expected to result in overall less deviation from the therapeutic targets based on adult exposure and substantially fewer children with underexposure (below half the target). The development of this design tool can aid the implementation of evidence-based formulations, integrating available knowledge and practical considerations, to optimize drug exposures and thereby treatment outcomes.
-
Rawlins, B G; Scheib, C; Tyler, A N; Beamish, D
2012-12-01
Regulatory authorities need ways to estimate natural terrestrial gamma radiation dose rates (nGy h⁻¹) across the landscape accurately, to assess its potential deleterious health effects. The primary method for estimating outdoor dose rate is to use an in situ detector supported 1 m above the ground, but such measurements are costly and cannot capture the landscape-scale variation in dose rates which are associated with changes in soil and parent material mineralogy. We investigate the potential for improving estimates of terrestrial gamma dose rates across Northern Ireland (13,542 km²) using measurements from 168 sites and two sources of ancillary data: (i) a map based on a simplified classification of soil parent material, and (ii) dose estimates from a national-scale, airborne radiometric survey. We used the linear mixed modelling framework in which the two ancillary variables were included in separate models as fixed effects, plus a correlation structure which captures the spatially correlated variance component. We used a cross-validation procedure to determine the magnitude of the prediction errors for the different models. We removed a random subset of 10 terrestrial measurements and formed the model from the remainder (n = 158), and then used the model to predict values at the other 10 sites. We repeated this procedure 50 times. The measurements of terrestrial dose vary between 1 and 103 (nGy h⁻¹). The median absolute model prediction errors (nGy h⁻¹) for the three models declined in the following order: no ancillary data (10.8) > simple geological classification (8.3) > airborne radiometric dose (5.4) as a single fixed effect. Estimates of airborne radiometric gamma dose rate can significantly improve the spatial prediction of terrestrial dose rate.
-
2011-10-01
lung tissue. We were not able to detect sufficient numbers of cells in this manner. We tried a different procedure for fixing the lungs after they...added after 24 hours. The films were fixed and evaluated microscopically. In four trials, 10 random microscopic fields were selected and... dosing by oral gavage once daily with 1.3 mg/kg L-valine-L-boroproline called talabostat (extracellular & intracellular DASH), 13.3 mg/kg L- glutamyl
-
An adaptive two-stage dose-response design method for establishing proof of concept.
Franchetti, Yoko; Anderson, Stewart J; Sampson, Allan R
2013-01-01
We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish "global" PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs.
-
Human salmonellosis: estimation of dose-illness from outbreak data.
Bollaerts, Kaatje; Aerts, Marc; Faes, Christel; Grijspeerdt, Koen; Dewulf, Jeroen; Mintiens, Koen
2008-04-01
The quantification of the relationship between the amount of microbial organisms ingested and a specific outcome such as infection, illness, or mortality is a key aspect of quantitative risk assessment. A main problem in determining such dose-response models is the availability of appropriate data. Human feeding trials have been criticized because only young healthy volunteers are selected to participate and low doses, as often occurring in real life, are typically not considered. Epidemiological outbreak data are considered to be more valuable, but are more subject to data uncertainty. In this article, we model the dose-illness relationship based on data of 20 Salmonella outbreaks, as discussed by the World Health Organization. In particular, we model the dose-illness relationship using generalized linear mixed models and fractional polynomials of dose. The fractional polynomial models are modified to satisfy the properties of different types of dose-illness models as proposed by Teunis et al. Within these models, differences in host susceptibility (susceptible versus normal population) are modeled as fixed effects whereas differences in serovar type and food matrix are modeled as random effects. In addition, two bootstrap procedures are presented. A first procedure accounts for stochastic variability whereas a second procedure accounts for both stochastic variability and data uncertainty. The analyses indicate that the susceptible population has a higher probability of illness at low dose levels when the combination pathogen-food matrix is extremely virulent and at high dose levels when the combination is less virulent. Furthermore, the analyses suggest that immunity exists in the normal population but not in the susceptible population.
-
ASSESSMENT OF EYE LENS DOSES IN INTERVENTIONAL RADIOLOGY: A SIMULATION IN LABORATORY CONDITIONS.
Čemusová, Z; Ekendahl, D; Judas, L
2016-09-01
As workers in interventional radiology belong to one of the most occupationally exposed groups, methods for sufficiently accurate quantification of their external exposure are sought. The objective of the authors' experiment was to investigate the relations between eye lens dose and Hp(10), Hp(3) or Hp(0.07) values measured with a conventional whole-body personal thermoluminescence dosemeter (TLD). Conditions of occupational exposure during common interventional procedures were simulated in laboratory. An anthropomorphic phantom represented a physician. The TLDs were fixed to the phantom in different locations that are common for purposes of personal dosimetry. In order to monitor the dose at the eye lens level during the exposures, a special thermoluminescence eye dosemeter was fixed to the phantom's temple. Correlations between doses measured with the whole-body and the eye dosemeters were found. There are indications that personnel in interventional radiology do not need to be unconditionally equipped with additional eye dosemeters, especially if an appropriate whole-body dosimetry system has been already put into practice. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Cocaine Versus Food Choice Procedure in Rats: Environmental Manipulations and Effects of Amphetamine
Thomsen, Morgane; Barrett, Andrew C.; Negus, S. Stevens; Caine, S. Barak
2014-01-01
We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0–1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. PMID:23319458
-
Li, Mi; McMillan, Donald E
2003-08-22
The experiments showed that sequential drug discriminations can be learned and retained under a fixed-interval (FI) schedule for more than 18 months without additional training under a complex three-choice procedure. Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg D-amphetamine, and saline. After responding stabilized, dose-response curves were determined for other drugs. Subsequently, pentobarbital was replaced with 5 mg/kg morphine as a training drug, and D-amphetamine was replaced with 30 mg/kg caffeine. After the pigeons learned these new discriminations, dose-response curves were redetermined. Initially, chlordiazepoxide substituted for pentobarbital, cocaine substituted for D-amphetamine, and nicotine partially substituted for D-amphetamine. Morphine, Delta9-tetrahydrocannabinol, and caffeine did not substitute for either drug. After retraining with morphine and caffeine, responding occurred on the pentobarbital/morphine key after pentobarbital, chlordiazepoxide and morphine and on the D-amphetamine/caffeine key after D-amphetamine, cocaine and caffeine. After nicotine and Delta9-tetrahyrdocannabinol, responding occurred on the saline key. These data show that drug discriminations learned under fixed-interval schedules are retained for long time periods, even when discrimination training with other drugs occurs during the retention period.
-
Vinnakota, Narayana R; Krishna, V; Viswanath, V; Ahmed, Zaheer; Shaik, Kamal S; Boppana, Naveen K
2016-12-01
To assess the knowledge, attitude, and practices of fixed dose combination drugs among postgraduate dental students. A cross-sectional study was carried out among postgraduate dental students of dental colleges in coastal Andhra Pradesh. Three colleges were randomly selected and students of all the three years were included. Data was collected from the specialities of oral medicine and radiology, oral surgery, endodontics, pedodontics, periodontics, and public health dentistry. The total sample was 90 postgraduate students; informed consent was obtained from the participants, and a pretested questionnaire was distributed to them. Data was analyzed using the Statistical Package for the Social Sciences version 20 software. Out of 90 postgraduates, 33 were males and 57 were females. Thirty-five percent were aware of the essential medical list (EML), among them 11% were from oral medicine and radiology and 6.7% were from pedodontics. However, most of them were unaware of the number of fixed dose combination drugs present in the World Health Organization EML. None of them were able to name at least a single banned fixed dose combination drug. Most of them were unaware of the advantages and disadvantages of using fixed dose combination drugs. Amoxicillin with clavulanic acid was the most common drug prescribed by students (73.3%) followed by ofloxacin with ornidazole (54.4%), ibuprofen with paracetamol (53.3%), and sulfamethoxazole with trimethoprim (6%). Most of them were unaware of the rationality in using fixed dose combination drugs. Common sources of information were medical representatives 43 (47.8%), internet 39 (43.3%), and 12 (13.3%) reported using WHO EML. There is an urgent need to improve knowledge on the rationality for using fixed dose combination, EML, and banned fixed dose combination in India to the promote rational use of fixed dose combination.
-
Ogungbenro, Kayode; Patel, Alkesh; Duncombe, Robert; Nuttall, Richard; Clark, James; Lorigan, Paul
2018-04-01
Pembrolizumab and nivolumab are highly selective anti-programmed cell death 1 (PD-1) antibodies approved for the treatment of advanced malignancies. Variable exposure and significant wastage have been associated with body size dosing of monoclonal antibodies (mAbs). The following dosing strategies were evaluated using simulations: body weight, dose banding, fixed dose, and pharmacokinetic (PK)-based methods. The relative cost to body weight dosing for band, fixed 150 mg and 200 mg, and PK-derived strategies were -15%, -25%, + 7%, and -16% for pembrolizumab and -8%, -6%, and -10% for band, fixed, and PK-derived strategies for nivolumab, respectively. Relative to mg/kg doses, the median exposures were -1.0%, -4.6%, + 27.1%, and +3.0% for band, fixed 150 mg, fixed 200 mg, and PK-derived strategies, respectively, for pembrolizumab and -3.1%, + 1.9%, and +1.4% for band, fixed 240 mg, and PK-derived strategies, respectively, for nivolumab. Significant wastage can be reduced by alternative dosing strategies without compromising exposure and efficacy. © 2017 American Society for Clinical Pharmacology and Therapeutics.
-
Molindone: effects in pigeons responding under conditional discrimination tasks.
Picker, M J; Cleary, J P; Berens, K; Oliveto, A H; Dykstra, L A
1989-02-01
Pigeons were trained to respond under three conditional discrimination procedures; 1) a fixed-consecutive-number procedure with (FCN 8-SD) and without (FCN 8) an added external discriminative stimulus, 2) a delayed matching-to-sample (DMTS) procedure using 0-sec, 2-sec and 8-sec delay intervals, and 3) a repeated acquisition of behavioral chains (RA) procedure using a four-link response chain with three stimulus keys. The atypical neuroleptic agent molindone decreased accuracy under the FCN 8 at doses that had no effect on accuracy under the FCN 8-SD. Under the DMTS procedure, molindone-induced decreases in accuracy were directly related to the delay interval, with the largest relative decrements obtained at the 8-sec delay and the smallest at the 0-sec delay. Under the RA procedure, molindone decreased accuracy at doses that had little or no effect on the number of correct responses emitted. Relative to control values, molindone-induced decreases in accuracy were smallest under the DMTS and FCN 8-SD procedures and largest under the FCN 8 and RA procedures. The differential effects obtained with molindone under each of these procedures illustrate the need to employ a variety of assays when determining the behavioral actions of neuroleptics. In addition, this battery of behavioral tests may provide a useful tool for assessing the different neurochemical actions of neuroleptic compounds.
-
2012-01-01
Background Studies in South-East Asia have suggested that early diagnosis and treatment with artesunate (AS) and mefloquine (MQ) combination therapy may reduce the transmission of Plasmodium falciparum malaria and the progression of MQ resistance. Methods The effectiveness of a fixed-dose combination of AS and MQ (ASMQ) in reducing malaria transmission was tested in isolated communities of the Juruá valley in the Amazon region. Priority municipalities within the Brazilian Legal Amazon area were selected according to pre-specified criteria. Routine national malaria control programmatic procedures were followed. Existing health structures were reinforced and health care workers were trained to treat with ASMQ all confirmed falciparum malaria cases that match inclusion criteria. A local pharmacovigilance structure was implemented. Incidence of malaria and hospitalizations were recorded two years before, during, and after the fixed-dose ASMQ intervention. In total, between July 2006 and December 2008, 23,845 patients received ASMQ. Two statistical modelling approaches were applied to monthly time series of P. falciparum malaria incidence rates, P. falciparum/Plasmodium vivax infection ratio, and malaria hospital admissions rates. All the time series ranged from January 2004 to December 2008, whilst the intervention period span from July 2006 to December 2008. Results The ASMQ intervention had a highly significant impact on the mean level of each time series, adjusted for trend and season, of 0.34 (95%CI 0.20 – 0.58) for the P. falciparum malaria incidence rates, 0.67 (95%CI 0.50 – 0.89) for the P. falciparum/P. vivax infection ratio, and 0.53 (95%CI 0.41 – 0.69) for the hospital admission rates. There was also a significant change in the seasonal (or monthly) pattern of the time series before and after intervention, with the elimination of the malaria seasonal peak in the rainy months of the years following the introduction of ASMQ. No serious adverse events relating to the use of fixed-dose ASMQ were reported. Conclusions In the remote region of the Juruá valley, the early detection of malaria by health care workers and treatment with fixed-dose ASMQ was feasible and efficacious, and significantly reduced the incidence and morbidity of P. falciparum malaria. PMID:22905900
-
Padole, Atul; Deedar Ali Khawaja, Ranish; Otrakji, Alexi; Zhang, Da; Liu, Bob; Xu, X George; Kalra, Mannudeep K
2016-05-01
The aim of this study was to compare the directly measured and the estimated computed tomography (CT) organ doses obtained from commercial radiation dose-tracking (RDT) software for CT performed with modulated tube current or automatic exposure control (AEC) technique and fixed tube current (mAs). With the institutional review board (IRB) approval, the ionization chambers were surgically implanted in a human cadaver (88 years old, male, 68 kg) in six locations such as liver, stomach, colon, left kidney, small intestine, and urinary bladder. The cadaver was scanned with routine abdomen pelvis protocol on a 128-slice, dual-source multidetector computed tomography (MDCT) scanner using both AEC and fixed mAs. The effective and quality reference mAs of 100, 200, and 300 were used for AEC and fixed mAs, respectively. Scanning was repeated three times for each setting, and measured and estimated organ doses (from RDT software) were recorded (N = 3*3*2 = 18). Mean CTDIvol for AEC and fixed mAs were 4, 8, 13 mGy and 7, 14, 21 mGy, respectively. The most estimated organ doses were significantly greater (P < 0.01) than the measured organ doses for both AEC and fixed mAs. At AEC, the mean estimated organ doses (for six organs) were 14.7 mGy compared to mean measured organ doses of 12.3 mGy. Similarly, at fixed mAs, the mean estimated organ doses (for six organs) were 24 mGy compared to measured organ doses of 22.3 mGy. The differences among the measured and estimated organ doses were higher for AEC technique compared to the fixed mAs for most organs (P < 0.01). The most CT organ doses estimated from RDT software are greater compared to directly measured organ doses, particularly when AEC technique is used for CT scanning. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.
-
Ryckmans, V; Kahn, J P; Modell, S; Werner, C; McQuade, R D; Kerselaers, W; Lissens, J; Sanchez, R
2009-05-01
This study evaluated the safety/tolerability and effectiveness of aripiprazole titrated-dose versus fixed-dose switching strategies from risperidone in patients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues. Patients were randomized to an aripiprazole titrated-dose (starting dose 5 mg/day) or fixed-dose (dose 15 mg/day) switching strategy with risperidone down-tapering. Primary endpoint was rate of discontinuation due to adverse events (AEs) during the 12-week study. Secondary endpoints included positive and negative syndrome scale (PANSS), clinical global impressions - improvement of illness scale (CGI-I), preference of medication (POM), subjective well-being under neuroleptics (SWN-K) and GEOPTE (Grupo Español para la Optimización del Tratamiento de la Esquizofrenia) scales. Rates of discontinuations due to AEs were similar between titrated-dose and fixed-dose strategies (3.5% vs. 5.0%; p=0.448). Improvements in mean PANSS total scores were similar between aripiprazole titrated-dose and fixed-dose strategies (-14.8 vs. -17.2; LOCF), as were mean CGI-I scores (2.9 vs. 2.8; p=0.425; LOCF) and SWN-K scores (+8.6 vs.+10.3; OC,+7.8 vs.+9.8; LOCF). Switching can be effectively and safely achieved through a titrated-dose or fixed-dose switching strategy for aripiprazole, with down-titration of risperidone.
-
Kampouraki, Emmanouela; Avery, Peter J; Wynne, Hilary; Biss, Tina; Hanley, John; Talks, Kate; Kamali, Farhad
2017-09-01
Current guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism. We compared the performance of a novel tailored vitamin K dosing regimen to that of a fixed-dose regimen with the primary measure being the proportion of over-anticoagulated patients returning to their target INR within 24 h. One hundred and eighty-one patients with an index INR > 6·0 (asymptomatic or with minor bleeding) were randomly allocated to receive oral administration of either a tailored dose (based upon index INR and body surface area) or a fixed-dose (1 or 2 mg) of vitamin K. A greater proportion of patients treated with the tailored dose returned to within target INR range compared to the fixed-dose regimen (68·9% vs. 52·8%; P = 0·026), whilst a smaller proportion of patients remained above target INR range (12·2% vs. 34·0%; P < 0·001). Individualised vitamin K dosing is more accurate than fixed-dose regimen in lowering INR to within target range in excessively anticoagulated patients. © 2017 John Wiley & Sons Ltd.
-
Thomsen, Morgane; Barrett, Andrew C; Negus, S Stevens; Caine, S Barak
2013-03-01
We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0-1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. © Society for the Experimental Analysis of Behavior.
-
Nilsson, Andreas; Steinvall, Ingrid; Bak, Zoltan; Sjöberg, Folke
2008-11-01
Patient controlled sedation (PCS) enables patients to titrate doses of drugs by themselves during different procedures involving pain or discomfort. We studied it in a prospective crossover design using a fixed protocol without lockout time to examine it as an alternative method of sedation for changing dressings in burned patients. Eleven patients with >10% total burn surface area (TBSA) had their dressings changed, starting with sedation by an anaesthetist (ACS). The second dressing change was done with PCS (propofol/alfentanil) and the third time the patients had to choose ACS or PCS. During the procedures, data on cardiopulmonary variables, sedation (bispectral index), pain intensity (VAS), procedural details, doses of drugs, and patients' preferences were collected to compare the two sedation techniques. The study data indicated that wound care in burned patients is feasible with a standardized PCS protocol. The patients preferred PCS to ACS on the basis of self-control, and because they had less discomfort during the recovery period. Wound care was also considered adequate by the staff during PCS. No respiratory (respiratory rate/transcutaneous PCO(2)) or cardiovascular (heart rate/blood pressure) adverse events were recorded at any time during any of the PCS procedures. The doses of propofol and alfentanil and BIS index decrease were less during PCS than ACS. Procedural pain was higher during PCS but lower after the procedure. We suggest that PCS using a standard protocol is an interesting alternative to anaesthetist-provided sedation during dressing changes. It seems effective, saves resources, is safe, and at same time is preferred by the patients. The strength of these conclusions is, however, hampered by the small size of this investigation and therefore further studies are warranted.
-
Severgnini, Mara; de Denaro, Mario; Bortul, Marina; Vidali, Cristiana; Beorchia, Aulo
2014-01-08
Intraoperative electron radiation therapy (IOERT) cannot usually benefit, as conventional external radiotherapy, from software systems of treatment planning based on computed tomography and from common dose verify procedures. For this reason, in vivo film dosimetry (IVFD) proves to be an effective methodology to evaluate the actual radiation dose delivered to the target. A practical method for IVFD during breast IOERT was carried out to improve information on the dose actually delivered to the tumor target and on the alignment of the shielding disk with respect to the electron beam. Two EBT3 GAFCHROMIC films have been positioned on the two sides of the shielding disk in order to obtain the dose maps at the target and beyond the disk. Moreover the postprocessing analysis of the dose distribution measured on the films provides a quantitative estimate of the misalignment between the collimator and the disk. EBT3 radiochromic films have been demonstrated to be suitable dosimeters for IVD due to their linear dose-optical density response in a narrow range around the prescribed dose, as well as their capability to be fixed to the shielding disk without giving any distortion in the dose distribution. Off-line analysis of the radiochromic film allowed absolute dose measurements and this is indeed a very important verification of the correct exposure to the target organ, as well as an estimate of the dose to the healthy tissue underlying the shielding. These dose maps allow surgeons and radiation oncologists to take advantage of qualitative and quantitative feedback for setting more accurate treatment strategies and further optimized procedures. The proper alignment using elastic bands has improved the absolute dose accuracy and the collimator disk alignment by more than 50%.
-
The development of fixed-ratio performance under the influence of ribonucleic acid12
Gott, C. Thomas; Weiss, Bernard
1972-01-01
The transition from fixed-ratio 1 performance (every response reinforced) to fixed-ratio 30 performance (every thirtieth response reinforced) was studied in nine pigeons. These were divided into three treatment groups given daily oral doses of saline, or 250 mg/kg/day or 500 mg/kg/day of yeast ribonucleic acid. Detailed computer-assisted analyses of how fixed-ratio behavior develops revealed the following typical sequence. After the transition, the first few ratios typically were emitted without long interresponse times within the ratio. Steady responding then ceased, and numerous long interresponse times occurred, with no systematic relationship to ordinal position within the ratio. Gradually, a new pattern evolved, characterized by a consistently long post-reinforcement time, a border region of the next few interresponse times within which the mean interresponse time monotonically decreased, and short interresponse times within the last 80% of the ratio. Long interresponse times were eliminated from this last section of the ratio without regard to proximity to reinforcement. Various analytical procedures suggested that the final pattern can be conceived, in part, as the shaping of a reliable response topography. The group of three pigeons given 250 mg/kg/day of yeast ribonucleic acid responded at higher rates than the saline and 500 mg/kg/day groups. The latter group, in contrast to the saline and lower dose groups, which continued to increase their rates, reached a rate asymptote very early. PMID:4574711
-
de Denaro, Mario; Bortul, Marina; Vidali, Cristiana; Beorchia, Aulo
2014-01-01
Intraoperative electron radiation therapy (IOERT) cannot usually benefit, as conventional external radiotherapy, from software systems of treatment planning based on computed tomography and from common dose verify procedures. For this reason, in vivo film dosimetry (IVFD) proves to be an effective methodology to evaluate the actual radiation dose delivered to the target. A practical method for IVFD during breast IOERT was carried out to improve information on the dose actually delivered to the tumor target and on the alignment of the shielding disk with respect to the electron beam. Two EBT3 GAFCHROMIC films have been positioned on the two sides of the shielding disk in order to obtain the dose maps at the target and beyond the disk. Moreover the postprocessing analysis of the dose distribution measured on the films provides a quantitative estimate of the misalignment between the collimator and the disk. EBT3 radiochromic films have been demonstrated to be suitable dosimeters for IVD due to their linear dose‐optical density response in a narrow range around the prescribed dose, as well as their capability to be fixed to the shielding disk without giving any distortion in the dose distribution. Off‐line analysis of the radiochromic film allowed absolute dose measurements and this is indeed a very important verification of the correct exposure to the target organ, as well as an estimate of the dose to the healthy tissue underlying the shielding. These dose maps allow surgeons and radiation oncologists to take advantage of qualitative and quantitative feedback for setting more accurate treatment strategies and further optimized procedures. The proper alignment using elastic bands has improved the absolute dose accuracy and the collimator disk alignment by more than 50%. PACS number: 87.55.kh
-
Quintano Jiménez, J A; Ginel Mendoza, L; Entrenas Costa, L M; Polo García, J
2016-02-01
The fixed-dose combination fluticasone propionate/formoterol (FPF) is a novel combination of a widely known and used inhaled glucocorticoid (IGC) and a long-acting β2-adrenergic agonist (LABA), available for the first time in a single device. This fixed-dose combination of FPF has a demonstrated efficacy and safety profile in clinical trials compared with its individual components and other fixed-dose combinations of IGC/LABA and is indicated for the treatment of persistent asthma in adults and adolescents. FPF is available in a wide range of doses that can adequately cover the therapeutic steps recommended by treatment guidelines, constituting a fixed-dose combination of GCI/LABA that is effective, rapid, well tolerated and with a reasonable acquisition cost. Various assessment agencies of the Spanish Autonomous Communities consider this combination to be an appropriate alternative therapy for asthma in the primary care setting. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.
-
Kim, Kyung-Jin; Kim, Sang-Hyun; Yoon, Young Won; Rha, Seung-Woon; Hong, Soon-Jun; Kwak, Choong-Hwan; Kim, Weon; Nam, Chang-Wook; Rhee, Moo-Yong; Park, Tae-Ho; Hong, Taek-Jong; Park, Sungha; Ahn, Youngkeun; Lee, Namho; Jeon, Hui-Kyung; Jeon, Dong-Woon; Han, Kyoo-Rok; Moon, Keon-Woong; Chae, In-Ho; Kim, Hyo-Soo
2016-10-01
We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS. © 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.
-
Schwienteck, Kathryn L.; Banks, Matthew L.
2015-01-01
Background Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice.In addition, 7-day cocaine treatment effects were also examined. Methods Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1 mg/kg/h), methylphenidate (0.032-0.32 mg/kg/h), or cocaine (0.1-0.32 mg/kg/h). Results During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1 mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. Conclusions The present subchronic treatment resultssupport the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. PMID:26361713
-
Schwienteck, Kathryn L; Banks, Matthew L
2015-10-01
Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/h), methylphenidate (0.032-0.32mg/kg/h), or cocaine (0.1-0.32mg/kg/h). During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
-
SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram.
Waldinger, M D; Zwinderman, A H; Olivier, B
2001-12-01
Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and ejaculation. However, different SSRIs may differentially delay ejaculation. A double-blind, fixed-dose study in healthy men with lifelong rapid ejaculation was performed to evaluate potential differences between clinically relevant doses of two selective serotonin reuptake inhibitors, paroxetine and citalopram, in their effects on ejaculation. Thirty men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to receive paroxetine (20 mg/day) and citalopram (20 mg/day) for 5 weeks, after taking half the dosage in the first week. During the 1-month baseline and 6-week treatment period, IELTs were measured at home by using a stopwatch procedure. The trial was completed by 23 men. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.0004); the IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds, respectively. Paroxetine 20 mg/day exerted a strong delay (8.9-fold increase), whereas citalopram 20 mg/day mildly delayed ejaculation (1.8-fold increase). These results indicate that paroxetine leads to a significant delay in orgasm and ejaculation, whereas citalopram seems to have less of an effect on it.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Belley, MD; Current Address Rhode Island Hospital, Providence, RI; Faught, A
Purpose: Development of a novel on-line dosimetry tool is needed to move toward patient-specific quality assurance measurements for Ir-192 HDR brachytherapy to verify accurate dose delivery to the intended location. This work describes the development and use of a nano-crystalline yttrium oxide inorganic scintillator based optical-fiber detector capable of acquiring real-time high-precision dose measurements during tandem and ovoid (T&O) gynecological (GYN) applicator Ir-192 HDR brachytherapy procedures. Methods: An optical-fiber detector was calibrated by acquiring light output measurements in liquid water at 3, 5, 7, and 9cm radial source-detector-distances from an Ir-192 HDR source. A regression model was fit to themore » data to describe the relative light output per unit dose (TG-43 derived) as a function of source-detector-distance. Next, the optical-fiber detector was attached to a vaginal balloon fixed to a Varian Fletcher-Suit-Delclos-style applicator (to mimic clinical setup), and localized by acquiring high-resolution computed tomography (CT) images. To compare the physical point dose to the TPS calculated values (TG-43 and Acuros-BV), a phantom measurement was performed, by submerging the T&O applicator in a liquid water bath and delivering a treatment template representative of a clinical T&O procedure. The fiber detector collected scintillation signal as a function of time, and the calibration data was applied to calculate both real-time dose rate, and cumulative dose. Results: Fiber cumulative dose values were 100.0cGy, 94.3cGy, and 348.9cGy from the tandem, left ovoid, and right ovoid dwells, respectively (total of 443.2cGy). A plot of real time dose rate during the treatment was also acquired. The TPS values at the fiber location were 458.4cGy using TG-43, and 437.6cGy using Acuros-BV calculated as Dm,m (per TG-186). Conclusion: The fiber measured dose value agreement was 3% vs TG-43 and −1% vs Acuros-BV. This fiber detector opens up new possibilities for performing patient-specific quality assurance for Ir-192 HDR GYN procedures. Funding from Coulter Foundation, Duke Bio-medical Engineering. Company is being created around the detector technology. Duke holds patents on the technology.« less
-
NASA Astrophysics Data System (ADS)
Heo, Y. J.; Kim, K. T.; Oh, K. M.; Lee, Y. K.; Ahn, K. J.; Cho, H. L.; Kim, J. Y.; Min, B. I.; Mun, C. W.; Park, S. K.
2017-09-01
The most widely used form of radiotherapy to treat tumors uses a linear accelerator, and the apparatus requires regular quality assurance (QA). QA for a linear accelerator demands accuracy throughout, from mock treatment and treatment planning, up to treatment itself. Therefore, verifying a radiation dose is essential to ensure that the radiation is being applied as planned. In current clinical practice, ionization chambers and diodes are used for QA. However, using conventional gaseous ionization chambers presents drawbacks such as complex analytical procedures, difficult measurement procedures, and slow response time. In this study, we discuss the potential of a lead(II) iodide (PbI2)-based radiation dosimeter for radiotherapy QA. PbI2 is a semiconductor material suited to measurements of X-rays and gamma rays, because of its excellent response properties to radiation signals. Our results show that the PbI2-based dosimeter offers outstanding linearity and reproducibility, as well as dose-independent characteristics. In addition, percentage depth dose (PDD) measurements indicate that the error at a fixed reference depth Dmax was 0.3%, very similar to the measurement results obtained using ionization chambers. Based on these results, we confirm that the PbI2-based dosimeter has all the properties required for radiotherapy: stable dose detection, dose linearity, and rapid response time. Based on the evidence of this experimental verification, we believe that the PbI2-based dosimeter could be used commercially in various fields for precise measurements of radiation doses in the human body and for measuring the dose required for stereotactic radiosurgery or localized radiosurgery.
-
Efficacy and Safety of a Single-Pill Fixed-Dose Combination of Azilsartan and Amlodipine.
Motozato, Kota; Miura, Shin-Ichiro; Shiga, Yuhei; Kusumoto, Takaaki; Saku, Keijiro
2016-12-01
Guidelines for the management of hypertension recommend the use of drugs with different mechanisms of action in antihypertensive regimens that include single-pill fixed-dose combinations of medications. There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP). Forty hypertensive patients who were receiving a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day were enrolled. They were randomly divided into two treatment groups, a group that changed to a single-pill fixed-dose combination of azilsartan 20 mg/day and amlodipine 5 mg/day (changeover group) and a group that continued to receive valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day (control group), and treated for 16 weeks. There were no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP) or pulse rate (PR) at 16 weeks between the control and changeover groups. In addition, there were no significant changes in biochemical parameters throughout the study period in both groups. The ability of a single-pill fixed-dose combination of azilsartan and amlodipine to reduce BP may be comparable to that of a combination of valsartan and amlodipine or irbesartan and amlodipine.
-
NASA Astrophysics Data System (ADS)
Giostra, A.; Richetta, E.; Pasquino, M.; Miranti, A.; Cutaia, C.; Brusasco, G.; Pellerito, R. E.; Stasi, M.
2016-06-01
Treatment with radioiodine is a standard procedure for patients with well-differentiated thyroid cancer, but the main approach to the therapy is still empiric, consisting of the administration of fixed activities. A predictive individualized dosimetric study may represent an important tool for physicians to determine the best activity to prescribe. The aim of this work is to compare red marrow and blood absorbed dose values obtained in the pre-treatment (PT) dosimetry phase with those obtained in the in-treatment (IT) dosimetry phase in order to estimate the predictive power of PT trial doses and to determine if they can be used as a decision-making tool to safely administer higher 131I activity to potentially increase the efficacy of treatment. The PT and IT dosimetry for 50 patients has been evaluated using three different dosimetric approaches. In all three approaches blood and red marrow doses, are calculated as the sum of two components, the dose from 131I activity in the blood and the dose from 131I activity located in the remainder of the body (i.e. the blood and whole-body contributions to the total dose). PT and IT dose values to blood and red marrow appear to be well correlated irrespective of the dosimetric approach used. Linear regression analyses of PT and IT total doses, for blood and red marrow, and the whole-body contribution to these doses, showed consistent best fit slope and correlation coefficient values of approximately 0.9 and 0.6, respectively: analyses of the blood dose contribution to the total doses also yielded similar values for the best fit slope but with correlation coefficient values of approximately 0.4 reflecting the greater variance in these dose estimates. These findings suggest that pre-treatment red marrow dose assessments may represent an important tool to personalize metastatic thyroid cancer treatment, removing the constraints of a fixed activity approach and permitting potentially more effective higher 131I activities to be safely used in-treatment.
-
Sahoo, Bijay Kumar; Das, Ayan; Agarwal, Sangita; Bhaumik, Uttam; Bose, Anirbandeep; Ghosh, Debotri; Roy, Bikash; Pal, Tapan Kumar
2009-01-01
The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. Rabeprazole and itopride plasma levels were determined by a validated HPLC method using UV detection. The formulations were compared using the pharmacokinetic parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma concentration (Cmax). General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.
-
A BRST gauge-fixing procedure for Yang Mills theory on sphere
NASA Astrophysics Data System (ADS)
Banerjee, Rabin; Deguchi, Shinichi
2006-01-01
A gauge-fixing procedure for the Yang-Mills theory on an n-dimensional sphere (or a hypersphere) is discussed in a systematic manner. We claim that Adler's gauge-fixing condition used in massless Euclidean QED on a hypersphere is not conventional because of the presence of an extra free index, and hence is unfavorable for the gauge-fixing procedure based on the BRST invariance principle (or simply BRST gauge-fixing procedure). Choosing a suitable gauge condition, which is proved to be equivalent to a generalization of Adler's condition, we apply the BRST gauge-fixing procedure to the Yang-Mills theory on a hypersphere to obtain consistent results. Field equations for the Yang-Mills field and associated fields are derived in manifestly O (n + 1) covariant or invariant forms. In the large radius limit, these equations reproduce the corresponding field equations defined on the n-dimensional flat space.
-
SU-E-T-247: Multi-Leaf Collimator Model Adjustments Improve Small Field Dosimetry in VMAT Plans
DOE Office of Scientific and Technical Information (OSTI.GOV)
Young, L; Yang, F
2014-06-01
Purpose: The Elekta beam modulator linac employs a 4-mm micro multileaf collimator (MLC) backed by a fixed jaw. Out-of-field dose discrepancies between treatment planning system (TPS) calculations and output water phantom measurements are caused by the 1-mm leaf gap required for all moving MLCs in a VMAT arc. In this study, MLC parameters are optimized to improve TPS out-of-field dose approximations. Methods: Static 2.4 cm square fields were created with a 1-mm leaf gap for MLCs that would normally park behind the jaw. Doses in the open field and leaf gap were measured with an A16 micro ion chamber andmore » EDR2 film for comparison with corresponding point doses in the Pinnacle TPS. The MLC offset table and tip radius were adjusted until TPS point doses agreed with photon measurements. Improvements to the beam models were tested using static arcs consisting of square fields ranging from 1.6 to 14.0 cm, with 45° collimator rotation, and 1-mm leaf gap to replicate VMAT conditions. Gamma values for the 3-mm distance, 3% dose difference criteria were evaluated using standard QA procedures with a cylindrical detector array. Results: The best agreement in point doses within the leaf gap and open field was achieved by offsetting the default rounded leaf end table by 0.1 cm and adjusting the leaf tip radius to 13 cm. Improvements in TPS models for 6 and 10 MV photon beams were more significant for smaller field sizes 3.6 cm or less where the initial gamma factors progressively increased as field size decreased, i.e. for a 1.6cm field size, the Gamma increased from 56.1% to 98.8%. Conclusion: The MLC optimization techniques developed will achieve greater dosimetric accuracy in small field VMAT treatment plans for fixed jaw linear accelerators. Accurate predictions of dose to organs at risk may reduce adverse effects of radiotherapy.« less
-
Barrett, J E
1983-04-01
Lever pressing by squirrel monkeys and key pecking by pigeons were maintained under a multiple 3-min fixed-interval (FI), 30-response fixed-ratio (FR) schedule by the presentation of food. These responses, which differed under the two schedules, but were similar for both species, were used to compare the effects of antipsychotic compounds from different pharmacological classes. Except for differences in potency levels, the effects of intermediate doses of haloperidol and molindone were similar in monkeys and pigeons; these compounds decreased responding under the fixed-interval schedule at doses that did not affect fixed-ratio responding. Similar effects also occurred with chlorpromazine, promazine and thiothixene in pigeons. With monkeys, however, intermediate doses of promazine decreased fixed-ratio responding more than responding maintained under the fixed-interval schedule, while chlorpromazine and thiothixene produced similar effects on responding under both schedules. The effects of novel antipsychotic, clozapine, differed from those of the other agents in both monkeys and pigeons. With both species clozapine increased fixed interval responding at doses that did not affect responding under the fixed-ratio schedule. Doses required to reduce responding at least 50% were approximately 5 to 160 times greater for pigeons than for monkeys for all drugs except clozapine which was equipotent in both species. In monkeys the order of potency was haloperidol greater than molindone = thiothixene greater than chlorpromazine greater than clozapine greater than promazine, whereas in pigeons the order was haloperidol greater than thiothixene greater than clozapine greater than molindone greater than promazine greater than chlorpromazine.
-
Efficacy and Safety of a Single-Pill Fixed-Dose Combination of Azilsartan and Amlodipine
Motozato, Kota; Miura, Shin-ichiro; Shiga, Yuhei; Kusumoto, Takaaki; Saku, Keijiro
2016-01-01
Background Guidelines for the management of hypertension recommend the use of drugs with different mechanisms of action in antihypertensive regimens that include single-pill fixed-dose combinations of medications. There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP). Methods Forty hypertensive patients who were receiving a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day were enrolled. They were randomly divided into two treatment groups, a group that changed to a single-pill fixed-dose combination of azilsartan 20 mg/day and amlodipine 5 mg/day (changeover group) and a group that continued to receive valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day (control group), and treated for 16 weeks. Results There were no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP) or pulse rate (PR) at 16 weeks between the control and changeover groups. In addition, there were no significant changes in biochemical parameters throughout the study period in both groups. Conclusion The ability of a single-pill fixed-dose combination of azilsartan and amlodipine to reduce BP may be comparable to that of a combination of valsartan and amlodipine or irbesartan and amlodipine. PMID:27829955
-
Perrin, E; Jackson, M; Grant, R; Lloyd, C; Chinaka, F; Goh, V
2018-02-01
In many centres, a fixed method of contrast-media administration is used for CT regardless of patient body habitus. The aim of this trial was to assess contrast enhancement of the aorta, portal vein, liver and spleen during abdomino-pelvic CT imaging using a weight-adapted contrast media protocol compared to the current fixed dose method. Thirty-nine oncology patients, who had previously undergone CT abdomino-pelvic imaging at the institution using a fixed contrast media dose, were prospectively imaged using a weight-adapted contrast media dose (1.4 ml/kg). The two sets of images were assessed for contrast enhancement levels (HU) at locations in the liver, aorta, portal vein and spleen during portal-venous enhancement phase. The t-test was used to compare the difference in results using a non-inferiority margin of 10 HU. When the contrast dose was tailored to patient weight, contrast enhancement levels were shown to be non-inferior to the fixed dose method (liver p < 0.001; portal vein p = 0.003; aorta p = 0.001; spleen p = 0.001). As a group, patients received a total contrast dose reduction of 165 ml using the weight-adapted method compared to the fixed dose method, with a mean cost per patient of £6.81 and £7.19 respectively. Using a weight-adapted method of contrast media administration was shown to be non-inferior to a fixed dose method of contrast media administration. Patients weighing 76 kg, or less, received a lower contrast dose which may have associated cost savings. A weight-adapted contrast media protocol should be implemented for portal-venous phase abdomino-pelvic CT for oncology patients with adequate renal function (>70 ml/min/1.73 m 2 ). Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
-
Fixed-dose combination therapy for the prevention of cardiovascular disease
de Cates, Angharad N; Farr, Matthew RB; Rees, Karen; Casas, Juan P; Huffman, Mark
2014-01-01
This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world. PMID:25267903
-
Giles, Thomas D; Weber, Michael A; Basile, Jan; Gradman, Alan H; Bharucha, David B; Chen, Wei; Pattathil, Manoj
2014-05-31
The fixed-dose combination of any two antihypertensive drugs from different drug classes is typically more effective in reducing blood pressure than a dose increase of component monotherapy. We assessed the efficacy and safety of a fixed-dose combination of a vasodilating β blocker (nebivolol) and an angiotensin II receptor blocker (valsartan) in adults with hypertension. We did an 8-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group trial at 401 US sites. Participants (age ≥18 years) with hypertension but with blood pressure less than 180/110 mm Hg were randomly assigned (2:2:2:2:2:2:2:1) by a 24-h interactive web response system in blocks of 15 to 4 weeks of double-blind treatment with nebivolol and valsartan fixed-dose combination (5 and 80 mg/day, 5 and 160 mg/day, or 10 and 160 mg/day), nebivolol (5 mg/day or 20 mg/day), valsartan (80 mg/day or 160 mg/day), or placebo. Doses were doubled in weeks 5-8; results are reported according to the final dose. Participants and research staff were masked to treatment allocation. The primary and key secondary endpoints were changes from baseline to week 8 in diastolic and systolic blood pressure, respectively. The primary statistical comparison was between the highest fixed-dose combination dose and the highest monotherapy doses; lower doses were then compared if this comparison was positive (Hochberg method for multiple testing). Efficacy analyses were by intention to treat. Safety assessments included monitoring of adverse events. Continuous efficacy parameters were analysed using an ANCOVA model; binary outcomes were analysed using a logistic regression model. This study is registered with ClinicalTrials.gov, NCT01508026. Between Jan 6, 2012, and March 15, 2013, 4161 patients were randomly assigned (277 to placebo and 554-555 to each active comparator group), 4118 of whom were included in the primary analysis. At week 8, the fixed-dose combination 20 and 320 mg/day group had significantly greater reductions in diastolic blood pressure from baseline than both nebivolol 40 mg/day (least-squares mean difference -1·2 mm Hg, 95% CI -2·3 to -0·1; p=0·030) and valsartan 320 mg/day (-4·4 mm Hg, -5·4 to -3·3; p<0·0001); all other comparisons were also significant, favouring the fixed-dose combinations (all p<0·0001). All systolic blood pressure comparisons were also significant (all p<0·01). At least one treatment-emergent adverse event was experienced by 30-36% of participants in each group. Nebivolol and valsartan fixed-dose combination is an effective and well-tolerated treatment option for patients with hypertension. Forest Research Institute. Copyright © 2014 Elsevier Ltd. All rights reserved.
-
Ryeznik, Yevgen; Sverdlov, Oleksandr
2018-06-04
Randomization designs for multiarm clinical trials are increasingly used in practice, especially in phase II dose-ranging studies. Many new methods have been proposed in the literature; however, there is lack of systematic, head-to-head comparison of the competing designs. In this paper, we systematically investigate statistical properties of various restricted randomization procedures for multiarm trials with fixed and possibly unequal allocation ratios. The design operating characteristics include measures of allocation balance, randomness of treatment assignments, variations in the allocation ratio, and statistical characteristics such as type I error rate and power. The results from the current paper should help clinical investigators select an appropriate randomization procedure for their clinical trial. We also provide a web-based R shiny application that can be used to reproduce all results in this paper and run simulations under additional user-defined experimental scenarios. Copyright © 2018 John Wiley & Sons, Ltd.
-
Paszun, Sylwia K; Stanisz, Beata J; Gradowska, Agnieszka
2013-01-01
The presented study aimed at the evaluation of hydrochlorothiazide influence on cilazapril stability in model mixture and fixed dose tablet formulation. The degradation of cilazapril in the presence of hydrochlorothiazide took place according to autocatalytic reaction kinetic mechanism, described mathematically by Prout-Tompkins equation. Hydrochlorothiazide coexistence with cilazapril in model mixture and fixed dose tablet without blister package accelerated cilazapril degradation in comparison with degradation of cilazapril substance. Values of reaction induction time shortened, while those of observed reaction rate constant increased. Increasing values of relative humidity and temperature have negative impact on cilazapril stability. Determined semi-logarithmic relationships: In k = f(RH) and Arrhenius ln k = f(1/T) are linear and are cilazapril stability predictive. The blister (OPA/Alu/PVC//Alu) package of fixed dose tablets, constitutes absolute moisture protection and prevent cilazapril--hydrochlorothiazide interaction occurrence.
-
Bassinet, Céline; Huet, Christelle; Baumann, Marion; Etard, Cécile; Réhel, Jean-Luc; Boisserie, Gilbert; Debroas, Jacques; Aubert, Bernard; Clairand, Isabelle
2013-04-01
As MOSFET (Metal Oxide Semiconductor Field Effect Transistor) detectors allow dose measurements in real time, the interest in these dosimeters is growing. The aim of this study was to investigate the dosimetric properties of commercially available TN-502RD-H MOSFET silicon detectors (Best Medical Canada, Ottawa, Canada) in order to use them for in vivo dosimetry in interventional radiology and for dose reconstruction in case of overexposure. Reproducibility of the measurements, dose rate dependence, and dose response of the MOSFET detectors have been studied with a Co source. Influence of the dose rate, frequency, and pulse duration on MOSFET responses has also been studied in pulsed x-ray fields. Finally, in order to validate the integrated dose given by MOSFET detectors, MOSFETs and TLDs (LiF:Mg,Cu,P) were fixed on an Alderson-Rando phantom in the conditions of an interventional neuroradiology procedure, and their responses have been compared. The results of this study show the suitability of MOSFET detectors for in vivo dosimetry in interventional radiology and for dose reconstruction in case of accident, provided a well-corrected energy dependence, a pulse duration equal to or higher than 10 ms, and an optimized contact between the detector and the skin of the patient are achieved.
-
Holzhütter, H G; Genschow, E; Diener, W; Schlede, E
2003-05-01
The acute toxic class (ATC) methods were developed for determining LD(50)/LC(50) estimates of chemical substances with significantly fewer animals than needed when applying conventional LD(50)/LC(50) tests. The ATC methods are sequential stepwise procedures with fixed starting doses/concentrations and a maximum of six animals used per dose/concentration. The numbers of dead/moribund animals determine whether further testing is necessary or whether the test is terminated. In recent years we have developed classification procedures for the oral, dermal and inhalation routes of administration by using biometric methods. The biometric approach assumes a probit model for the mortality probability of a single animal and assigns the chemical to that toxicity class for which the best concordance is achieved between the statistically expected and the observed numbers of dead/moribund animals at the various steps of the test procedure. In previous publications we have demonstrated the validity of the biometric ATC methods on the basis of data obtained for the oral ATC method in two-animal ring studies with 15 participants from six countries. Although the test procedures and biometric evaluations for the dermal and inhalation ATC methods have already been published, there was a need for an adaptation of the classification schemes to the starting doses/concentrations of the Globally Harmonized Classification System (GHS) recently adopted by the Organization for Economic Co-operation and Development (OECD). Here we present the biometric evaluation of the dermal and inhalation ATC methods for the starting doses/concentrations of the GHS and of some other international classification systems still in use. We have developed new test procedures and decision rules for the dermal and inhalation ATC methods, which require significantly fewer animals to provide predictions of toxicity classes, that are equally good or even better than those achieved by using the conventional LD(50)/LC(50) methods. In order to cope with rather narrow dose/concentration classes of the GHS we have, as in our previous publications, combined the outcome of all results that can be obtained during testing for the allocation to one of the defined toxicity classes of the GHS. Our results strongly recommend the deletion of the dermal LD(50) and the inhalation LC(50) test as regulatory tests and the adoption of the dermal and inhalation ATC methods as internationally accepted alternatives.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kopp, Robert W.; Duff, Michael, E-mail: mduff@cancercarewny.com; Catalfamo, Frank
2011-01-01
We compared normal tissue radiation dose for the treatment of prostate cancer using 2 different radiation therapy delivery methods: volumetric modulated arc therapy (VMAT) vs. fixed-field intensity-modulated radiation therapy (IMRT). Radiotherapy plans for 292 prostate cancer patients treated with VMAT to a total dose of 7740 cGy were analyzed retrospectively. Fixed-angle, 7-field IMRT plans were created using the same computed tomography datasets and contours. Radiation doses to the planning target volume (PTV) and organs at risk (bladder, rectum, penile bulb, and femoral heads) were measured, means were calculated for both treatment methods, and dose-volume comparisons were made with 2-tailed, pairedmore » t-tests. The mean dose to the bladder was lower with VMAT at all measured volumes: 5, 10, 15, 25, 35, and 50% (p < 0.05). The mean doses to 5 and 10% of the rectum, the high-dose regions, were lower with VMAT (p < 0.05). The mean dose to 15% of the rectal volume was not significantly different (p = 0.95). VMAT exposed larger rectal volumes (25, 35, and 50%) to more radiation than fixed-field IMRT (p < 0.05). Average mean dose to the penile bulb (p < 0.05) and mean dose to 10% of the femoral heads (p < 0.05) were lower with VMAT. VMAT therapy for prostate cancer has dosimetric advantages for critical structures, notably for high-dose regions compared with fixed-field IMRT, without compromising PTV coverage. This may translate into reduced acute and chronic toxicity.« less
-
Banks, Matthew L
2016-08-01
Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.
-
Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios
2016-08-01
Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.
-
Uliana, Gustavo Nadal; Tambara, Elizabeth Milla; Baretta, Giorgio Alfredo Pedroso
2015-01-01
The introduction of propofol (2,6-diisopropylphenol) as a sedative agent has transformed the area of sedation for endoscopic procedures. However, a major drawback of sedation with the use of propofol is its high incidence of injection pain. The most widely used technique in reducing propofol injection pain is through the association of other drugs. The aim of this study was to evaluate the effect of remifentanil-propofol combination on the incidence of propofol injection pain and its influence on the total dose of propofol required for sedation in upper digestive tract endoscopy (UDE) diagnostic tests. One hundred and five patients undergoing upper digestive tract endoscopy were evaluated and randomly divided into 3 groups of 35 patients each. The Control Group received propofol alone; Study-group 1 received remifentanil at a fixed dose of 0.2mg/kg combined with propofol; Study-group 2 received remifentanil at a fixed dose of 0.3mg/kg combined with propofol. The incidence of propofol injection pain and the total dose of propofol required for the test were evaluated. The sample was very similar regarding age, weight, height, sex, and physical status. Statistical analysis was performed according to the nature of the evaluated data. Student's t-test was used to compare the mean of age, weight, height (cm), and dose (mg/kg) variables between groups. The χ(2) test was used to compare sex, physical status, and propofol injection pain between groups. The significance level was α<0.05. There was significant statistical difference between the study groups and the control group regarding the parameters of propofol injection pain and total dose of propofol (mg/kg) used. However, there were no statistical differences between the two study groups for these parameters. We conclude that the use of remifentanil at doses of 0.2mg/kg and 0.3mg/kg was effective for reducing both the propofol injection pain and the total dose of propofol used. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cao, W; Zaghian, M; Lim, G
2015-06-15
Purpose: The current practice of considering the relative biological effectiveness (RBE) of protons in intensity modulated proton therapy (IMPT) planning is to use a generic RBE value of 1.1. However, RBE is indeed a variable depending on the dose per fraction, the linear energy transfer, tissue parameters, etc. In this study, we investigate the impact of using variable RBE based optimization (vRBE-OPT) on IMPT dose distributions compared by conventional fixed RBE based optimization (fRBE-OPT). Methods: Proton plans of three head and neck cancer patients were included for our study. In order to calculate variable RBE, tissue specific parameters were obtainedmore » from the literature and dose averaged LET values were calculated by Monte Carlo simulations. Biological effects were calculated using the linear quadratic model and they were utilized in the variable RBE based optimization. We used a Polak-Ribiere conjugate gradient algorithm to solve the model. In fixed RBE based optimization, we used conventional physical dose optimization to optimize doses weighted by 1.1. IMPT plans for each patient were optimized by both methods (vRBE-OPT and fRBE-OPT). Both variable and fixed RBE weighted dose distributions were calculated for both methods and compared by dosimetric measures. Results: The variable RBE weighted dose distributions were more homogenous within the targets, compared with the fixed RBE weighted dose distributions for the plans created by vRBE-OPT. We observed that there were noticeable deviations between variable and fixed RBE weighted dose distributions if the plan were optimized by fRBE-OPT. For organs at risk sparing, dose distributions from both methods were comparable. Conclusion: Biological dose based optimization rather than conventional physical dose based optimization in IMPT planning may bring benefit in improved tumor control when evaluating biologically equivalent dose, without sacrificing OAR sparing, for head and neck cancer patients. The research is supported in part by National Institutes of Health Grant No. 2U19CA021239-35.« less
-
2014-01-01
Background External cephalic version (ECV) is infrequently performed and 98% of breech presenting fetuses are delivered surgically. Neuraxial analgesia can increase the success rate of ECV significantly, potentially reducing cesarean delivery rates for breech presentation. The current study aims to determine whether the additional cost to the hospital of spinal anesthesia for ECV is offset by cost savings generated by reduced cesarean delivery. Methods In our tertiary hospital, three variables manpower, disposables, and fixed costs were calculated for ECV, ECV plus anesthetic doses of spinal block, vaginal delivery and cesarean delivery. Total procedure costs were compared for possible delivery pathways. Manpower data were obtained from management payroll, fixed costs by calculating cost/lifetime usage rate and disposables were micro-costed in 2008, expressed in 2013 NIS. Results Cesarean delivery is the most expensive option, 11670.54 NIS and vaginal delivery following successful ECV under spinal block costs 5497.2 NIS. ECV alone costs 960.21 NIS, ECV plus spinal anesthesia costs 1386.97 NIS. The highest individual cost items for vaginal, cesarean delivery and ECV were for manpower. Expensive fixed costs for cesarean delivery included operating room trays and postnatal hospitalization (minimum 3 days). ECV with spinal block is cheaper due to lower expected cesarean delivery rate and its lower associated costs. Conclusions The additional cost of the spinal anesthesia is offset by increased success rates for the ECV procedure resulting in reduction in the cesarean delivery rate. PMID:24564984
-
Defining success in clinical trials--profiling pregabalin, the newest AED.
Ryvlin, P
2005-11-01
The efficacy and safety of pregabalin as adjunctive therapy for patients with partial epilepsy with or without secondary generalization has been established by four randomized, 12-week, double-blind, placebo-controlled trials (n = 1396) and four long-term open-label studies (n = 1480). Patients in the three fixed-dose trials were >/=12 years of age, had >/=6 partial seizures and no 4-week seizure-free period during the 8-week baseline period. Seventy-three per cent of patients were taking >/=2 concomitant antiepileptic drugs. Responder rates across the effective doses (150-600 mg/day) ranged from 14% to 51% and demonstrated a significant dose-response relationship. The most common adverse events were central nervous system related, generally mild or moderate, transient, and tended to be dose related. The fourth placebo-controlled trial compared a fixed dose of pregabalin 600 mg/day with a flexible-dose regimen (150-600 mg/day). Responder rates were greater for both the fixed dose (45.3%, P < 0.001) and flexible dose (31.3%, P < 0.001) when compared with placebo (11.0%). Compared with the fixed-dose group, the flexible-dose patients had a lower incidence of adverse events and study discontinuations. In long-term open-label trials, the efficacy of pregabalin was maintained with respect to 50% responder rates suggesting no obvious tolerance developing over 2 years. Seizure-free rates were 8.9% and 5.8% for the last 6 months and 1 year of pregabalin treatment, respectively. Long-term open-label pregabalin treatment was well tolerated.
-
Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody
2015-01-01
Purpose Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Material and methods Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. Results All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans. Conclusions The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy. PMID:26622227
-
Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody; Song, Daniel Y
2015-08-01
Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: (125)I fixed spacing, (125)I variable spacing, (103)Pd fixed spacing, and (103)Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with (103)Pd, and 0.007 and 0.029 with (125)I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with (103)Pd, and 0.012 and 0.037 with (125)I plans. The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy.
-
Yamamoto, Mariko; Nakadate, Hisaya; Iguchi, Umefumi; Masuda, Hiroshi; Sakai, Hirokazu; Ishiguro, Akira
2013-03-01
This report describes the successful management of neurosurgical procedures with continuous infusion of recombinant factor IX (rFIX). A 1-year-old boy with severe hemophilia B was administered prophylactic therapy with rFIX after intracranial bleeding. We found the enlargement of an arachnoid cyst in a follow-up CT scan. He underwent marsupialization of the cyst under the continuous infusion of rFIX. FIX levels were examined in our hospital and the rFIX infusion rate was adjusted in an attempt to keep FIX levels above 90% intraoperatively, and 70% until his 7th post-operative day. We studied the pharmacokinetic profile of rFIX and found a half-time of 25 hours and mean in vivo recovery of 0.69 IU/dl/IU/kg. Reconstituted rFIX also retained at least 95% activity after 72 hours at room temperature. This is the first report of the perioperative management of a child undergoing a neurosurgical procedure under the continuous infusion of rFIX in Japan. Further studies are required before the routine use of this product for continuous infusion.
-
Novel low-kVp beamlet system for choroidal melanoma
Esquivel, Carlos; Fuller, Clifton D; Waggener, Robert G; Wong, Adrian; Meltz, Martin; Blough, Melissa; Eng, Tony Y; Thomas, Charles R
2006-01-01
Background Treatment of choroidal melanoma with radiation often involves placement of customized brachytherapy eye-plaques. However, the dosimetric properties inherent in source-based radiotherapy preclude facile dose optimization to critical ocular structures. Consequently, we have constructed a novel system for utilizing small beam low-energy radiation delivery, the Beamlet Low-kVp X-ray, or "BLOKX" system. This technique relies on an isocentric rotational approach to deliver dose to target volumes within the eye, while potentially sparing normal structures. Methods Monte Carlo N-Particle (MCNP) transport code version 5.0(14) was used to simulate photon interaction with normal and tumor tissues within modeled right eye phantoms. Five modeled dome-shaped tumors with a diameter and apical height of 8 mm and 6 mm, respectively, were simulated distinct positions with respect to the macula iteratively. A single fixed 9 × 9 mm2 beamlet, and a comparison COMS protocol plaque containing eight I-125 seeds (apparent activity of 8 mCi) placed on the scleral surface of the eye adjacent to the tumor, were utilized to determine dosimetric parameters at tumor and adjacent tissues. After MCNP simulation, comparison of dose distribution at each of the 5 tumor positions for each modality (BLOKX vs. eye-plaque) was performed. Results Tumor-base doses ranged from 87.1–102.8 Gy for the BLOKX procedure, and from 335.3–338.6 Gy for the eye-plaque procedure. A reduction of dose of at least 69% to tumor base was noted when using the BLOKX. The BLOKX technique showed a significant reduction of dose, 89.8%, to the macula compared to the episcleral plaque. A minimum 71.0 % decrease in dose to the optic nerve occurred when the BLOKX was used. Conclusion The BLOKX technique allows more favorable dose distribution in comparison to standard COMS brachytherapy, as simulated using a Monte Carlo iterative mathematical modeling. Future series to determine clinical utility of such an approach are warranted. PMID:16965624
-
Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-sequencing offers a promising way to address this problem. Here we evaluated transcriptomic dose responses us...
-
Formalin-fixed paraffin-embedded (FFPE) samples provide a vast untapped resource for chemical safety and translational science. To date, genomic profiling of FFPE samples has been limited by poor RNA quality and inconsistent results with limited utility in dose-response assessmen...
-
Comparative occupational radiation exposure between fixed and mobile imaging systems.
Kendrick, Daniel E; Miller, Claire P; Moorehead, Pamela A; Kim, Ann H; Baele, Henry R; Wong, Virginia L; Jordan, David W; Kashyap, Vikram S
2016-01-01
Endovascular intervention exposes surgical staff to scattered radiation, which varies according to procedure and imaging equipment. The purpose of this study was to determine differences in occupational exposure between procedures performed with fixed imaging (FI) in an endovascular suite compared with conventional mobile imaging (MI) in a standard operating room. A series of 116 endovascular cases were performed over a 4-month interval in a dedicated endovascular suite with FI and conventional operating room with MI. All cases were performed at a single institution and radiation dose was recorded using real-time dosimetry badges from Unfors RaySafe (Hopkinton, Mass). A dosimeter was mounted in each room to establish a radiation baseline. Staff dose was recorded using individual badges worn on the torso lead. Total mean air kerma (Kar; mGy, patient dose) and mean case dose (mSv, scattered radiation) were compared between rooms and across all staff positions for cases of varying complexity. Statistical analyses for all continuous variables were performed using t test and analysis of variance where appropriate. A total of 43 cases with MI and 73 cases with FI were performed by four vascular surgeons. Total mean Kar, and case dose were significantly higher with FI compared with MI. (mean ± standard error of the mean, 523 ± 49 mGy vs 98 ± 19 mGy; P < .00001; 0.77 ± 0.03 mSv vs 0.16 ± 0.08 mSv, P < .00001). Exposure for the primary surgeon and assistant was significantly higher with FI compared with MI. Mean exposure for all cases using either imaging modality, was significantly higher for the primary surgeon and assistant than for support staff (ie, nurse, radiology technologist) beyond 6 feet from the X-ray source, indicated according to one-way analysis of variance (MI: P < .00001; FI: P < .00001). Support staff exposure was negligible and did not differ between FI and MI. Room dose stratified according to case complexity (Kar) showed statistically significantly higher scattered radiation in FI vs MI across all quartiles. The scattered radiation is several-fold higher with FI than MI across all levels of case complexity. Radiation exposure decreases with distance from the radiation source, and is negligible outside of a 6-foot radius. Modern endovascular suites allow high-fidelity imaging, yet additional strategies to minimize exposure and occupational risk are needed. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
-
Morphine tolerance as a function of ratio schedule: response requirement or unit price?
Hughes, Christine E; Sigmon, Stacey C; Pitts, Raymond C; Dykstra, Linda A
2005-05-01
Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, l-methadone, and cocaine dose-dependently decreased overall response rates in each of the components. When a rate decreasing dose of morphine was administered daily, tolerance, as measured by an increase in the dose that reduced response rates to 50% of control (i.e., the ED50 value), developed in each of the components; however, the degree of tolerance was smallest in the fixed-ratio 90 component (i.e., the ED50 value increased the least). When the l-methadone dose-effect curve was redetermined during the chronic morphine phase, the degree of cross-tolerance conferred to l-methadone was similar across components, suggesting that behavioral variables may not influence the degree of cross-tolerance between opioids. During the chronic phase, the cocaine dose-effect curve shifted to the right for 2 pigeons and to the left for 1 pigeon, which is consistent with predictions based on the lack of pharmacological similarity between morphine and cocaine. When the morphine, l-methadone, and cocaine dose-effect curves were redetermined after chronic morphine administration ended, the morphine and l-methadone ED50s replicated those obtained prior to chronic morphine administration. The morphine data suggest that the fixed-ratio value (i.e., the absolute output) determines the degree of tolerance and not the unit price.
-
Lahoud, G Y; Hopkins, P M
2007-02-01
The use of inhalation sedation with sub-anaesthetic concentrations of sevoflurane and nitrous oxide mixture is expected to reduce amounts of intravenous sedative drugs needed to produce a balanced sedation with the benefits of having reduced side-effects. Eighty-two patients requiring endoscopic and/or surgical procedures under conscious sedation and local anaesthesia were recruited for this pilot study. Conscious sedation was induced with a titrated dose of midazolam and propofol given intravenously until the clinical end-point of conscious sedation was achieved. Subsequently, during the procedure, the patient was asked to breathe sevoflurane 0.1-0.3% and a fixed ratio of 40% nitrous oxide in oxygen given through a face mask. In 78 patients (95.1%), the treatment was completed successfully. Patients were discharged back to the wards within 4-16 min (10.1) without significant side-effects. Treatment was satisfactorily accepted by 38 patients (48.7%) and considered excellent by 40 patients (51.3%). The use of titrated doses of intravenous sedative drugs for induction of conscious sedation followed by the use of low concentrations (0.1-0.3%) of sevoflurane combined with 40% nitrous oxide for maintenance of conscious sedation in patients requiring endoscopic and/or surgical procedures under local anaesthesia, has the potential advantages of reducing amounts of intravenous sedative drugs, less likelihood of problems from drug side-effects and fast recovery and discharge time. Further investigations to establish the technique are currently in progress.
-
Markus, Wiebren; de Weert-van Oene, Gerdien H; Woud, Marcella L; Becker, Eni S; DeJong, Cornelis A J
2016-09-01
Experimental research suggests that working memory (WM) taxation reduces craving momentarily. Using a modified Eye Movement Desensitization and Reprocessing (EMDR) procedure, prolonged reductions in craving and relapse rates in alcohol dependence have been demonstrated. Modified EMDR-procedures may also hold promise in smoking cessation attempts. A proof-of-concept study was conducted to narrow the gap between WM-taxation experiments and clinical EMDR studies. To this end the clinical EMDR-procedure was modified for use in a laboratory experiment. Daily smokers (n = 47), abstaining overnight, were allocated (by minimization randomization) to one of two groups using a parallel design. In both cases a modified EMDR-procedure was used. In the experimental group (n = 24) eye movements (EM) were induced while control group participants (n = 23) fixed their gaze (not taxing WM). During 6 min trials, craving-inducing memories were recalled. Craving, vividness of target memories, and smoking behavior were assessed at several variable-specific time-points between baseline (one week pre-intervention) and one week follow-up. The experimental group showed significant immediate reductions of craving and vividness of targeted memories. However, these effects were lost during a one-week follow-up period. A limited dose of WM-taxation, in the form of EM in a modified EMDR-procedure, resulted in transient effects on memory vividness and nicotine craving. EM provide a valuable way of coping with the acute effects of craving during smoking cessation attempts. Other aspects of the EMDR-procedure may provide additional effects. Component and dose-response studies are needed to establish the potential of EMDR-therapy in smoking cessation. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Influence of experimental history on nicotine self-administration in squirrel monkeys.
Desai, Rajeev I; Sullivan, Katherine A; Kohut, Stephen J; Bergman, Jack
2016-06-01
Methods for establishing robust long-term self-administration of intravenous (i.v.) nicotine, the primary psychoactive agent in tobacco, are not well-established in laboratory animals. Here, we examine the use of a fading procedure to establish robust and consistent i.v. nicotine self-administration under second-order schedule conditions in squirrel monkeys. First, self-administration behavior was developed in two groups of male squirrel monkeys using a second-order fixed-interval 5-min schedule with fixed-ratio 5 units (FI 5-min (FR5: S)). Comparable performances were maintained by i.v. cocaine (0.032 mg/kg/injection (inj); group A, n = 3) and the combination of food delivery (20-30 % condensed milk) and 0.01 mg/kg/inj i.v. nicotine (group B, n = 3). Subsequently, the concentration of condensed milk was gradually reduced to zero in the second group and self-administration behavior was maintained by i.v. nicotine alone. Next, self-administration of a range of doses of i.v. nicotine (0.001-0.032 mg/kg/inj) and, in additional experiments, the minor tobacco alkaloid anatabine (0.01-0.18 mg/kg/inj) was studied in both groups. Results show that nicotine and anatabine had reinforcing effects in both groups. However, optimal doses of nicotine and anatabine maintained significantly higher rates of i.v. self-administration behavior in subjects trained with the fading procedure than in subjects provided with a history of cocaine-maintained responding. These results illustrate conditions under which robust i.v. nicotine self-administration can be established in squirrel monkeys and the influence of prior experimental history in the expression of reinforcing effects of nicotine and anatabine.
-
Low-dose fixed-target serial synchrotron crystallography.
Owen, Robin L; Axford, Danny; Sherrell, Darren A; Kuo, Anling; Ernst, Oliver P; Schulz, Eike C; Miller, R J Dwayne; Mueller-Werkmeister, Henrike M
2017-04-01
The development of serial crystallography has been driven by the sample requirements imposed by X-ray free-electron lasers. Serial techniques are now being exploited at synchrotrons. Using a fixed-target approach to high-throughput serial sampling, it is demonstrated that high-quality data can be collected from myoglobin crystals, allowing room-temperature, low-dose structure determination. The combination of fixed-target arrays and a fast, accurate translation system allows high-throughput serial data collection at high hit rates and with low sample consumption.
-
Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 μg.
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.
-
Lima, Glaura C; Silva, Emilia V; Magalhães, Pérola de O; Naves, Janeth S
Tuberculosis, particularly multi-drug-resistant tuberculosis, is a major cause of morbidity and mortality worldwide. To the best of our knowledge, however, no study to date has assessed the combined use of the four available drugs for tuberculosis treatment, which is an issue of great clinical relevance. To determine whether the four-drug fixed-dose combination is safer or more effective than separate drugs for treatment of pulmonary tuberculosis. A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In pooled results from five randomized controlled trials with 3502 patients across Africa, Asia, and Latin America, four-drug fixed-dose combination therapy was no better than separate drugs therapy in terms of culture conversion after 2 and 6 months of treatment. There were no significant differences between the groups in overall incidence of adverse effects. However, the meta-analytic measure (log odds ratio) revealed that separate drugs treatment had a 1.65 [exp (0.5)=1.65] increased chance of gastrointestinal adverse effects compared to four-drug fixed-dose combination treatment. The reviewed studies showed that four-drug fixed-dose combination therapy provides greater patient comfort by reducing the number of pills and the incidence of gastrointestinal adverse effects, as well as simplifying pharmaceutical management at all levels. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.
-
Thurber, Kristina M; Dierkhising, Ross A; Reiland, Sarah A; Pearson, Kristina K; Smith, Steven A; O'Meara, John G
2016-01-01
Carbohydrate counting may improve glycemic control in hospitalized cardiology patients by providing individualized insulin doses tailored to meal consumption. The purpose of this study was to compare glycemic outcomes with mealtime insulin dosed by carbohydrate counting versus fixed dosing in the inpatient setting. This single-center retrospective cohort study included 225 adult medical cardiology patients who received mealtime, basal, and correction-scale insulin concurrently for at least 72 h and up to 7 days in the interval March 1, 2010-November 7, 2013. Mealtime insulin was dosed by carbohydrate counting or with fixed doses determined prior to meal intake. An inpatient diabetes consult service was responsible for insulin management. Exclusion criteria included receipt of an insulin infusion. The primary end point compared mean daily postprandial glucose values, whereas secondary end points included comparison of preprandial glucose values and mean daily rates of hypoglycemia. Mean postprandial glucose level on Day 7 was 204 and 183 mg/dL in the carbohydrate counting and fixed mealtime dose groups, respectively (unadjusted P=0.04, adjusted P=0.12). There were no statistical differences between groups on Days 2-6. Greater rates of preprandial hypoglycemia were observed in the carbohydrate counting cohort on Day 5 (8.6% vs. 1.5%, P=0.02), Day 6 (1.7% vs. 0%, P=0.01), and Day 7 (7.1% vs. 0%, P=0.008). No differences in postprandial hypoglycemia were seen. Mealtime insulin dosing by carbohydrate counting was associated with similar glycemic outcomes as fixed mealtime insulin dosing, except for a greater incidence of preprandial hypoglycemia. Additional comparative studies that include hospital outcomes are needed.
-
Pharmacokinetics and pharmacodynamics of sofosbuvir and ledipasvir for the treatment of hepatitis C.
Cuenca-Lopez, Francisca; Rivero, Antonio; Rivero-Juárez, Antonio
2017-01-01
The sofosbuvir (SOF) plus ledipasvir (LDV) fixed dose combination is the first direct action antiviral (DAA) single-treatment regimen (STR) to be commercialized. It is approved for the treatment of Hepatitis C virus (HCV) genotypes 1,3,4,5 and 6. Following approval in 2014, new pharmacokinetics and pharmacodynamics data were reported, which led to important clinical applications. Areas covered: This article reviews the pharmacokinetic and pharmacodynamic properties of the SOF/LDV fixed dose combination for the treatment of HCV. The topics covered include data regarding the drug´s absorption, distribution, metabolism and excretion and antiviral activity strategies such as the clinical dose selection and treatment duration. Expert opinion: The SOF/LDV fixed dose combination has good pharmacological properties that lead to a high sustained virological response after 12 or 24 weeks of treatment; there is minimal interference with other drugs or associated renal or hepatic impairment, such that dose adjustment is not necessary.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Teoh, May, E-mail: m.teoh@nhs.net; Beveridge, Sabeena; Wood, Katie
2013-04-01
Fluorine-18-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG-PET)–guided focal dose escalation in oropharyngeal cancer may potentially improve local control. We evaluated the feasibility of this approach using volumetric-modulated arc therapy (RapidArc) and compared these plans with fixed-field intensity-modulated radiotherapy (IMRT) focal dose escalation plans. Materials and methods: An initial study of 20 patients compared RapidArc with fixed-field IMRT using standard dose prescriptions. From this cohort, 10 were included in a dose escalation planning study. Dose escalation was applied to {sup 18}F-FDG-PET–positive regions in the primary tumor at dose levels of 5% (DL1), 10% (DL2), and 15% (DL3) above standard radical dose (65 Gymore » in 30 fractions). Fixed-field IMRT and double-arc RapidArc plans were generated for each dataset. Dose-volume histograms were used for plan evaluation and comparison. The Paddick conformity index (CI{sub Paddick}) and monitor units (MU) for each plan were recorded and compared. Both IMRT and RapidArc produced clinically acceptable plans and achieved planning objectives for target volumes. Dose conformity was significantly better in the RapidArc plans, with lower CI{sub Paddick} scores in both primary (PTV1) and elective (PTV2) planning target volumes (largest difference in PTV1 at DL3; 0.81 ± 0.03 [RapidArc] vs. 0.77 ± 0.07 [IMRT], p = 0.04). Maximum dose constraints for spinal cord and brainstem were not exceeded in both RapidArc and IMRT plans, but mean doses were higher with RapidArc (by 2.7 ± 1 Gy for spinal cord and 1.9 ± 1 Gy for brainstem). Contralateral parotid mean dose was lower with RapidArc, which was statistically significant at DL1 (29.0 vs. 29.9 Gy, p = 0.01) and DL2 (29.3 vs. 30.3 Gy, p = 0.03). MU were reduced by 39.8–49.2% with RapidArc (largest difference at DL3, 641 ± 94 vs. 1261 ± 118, p < 0.01). {sup 18}F-FDG-PET–guided focal dose escalation in oropharyngeal cancer is feasible with RapidArc. Compared with conventional fixed-field IMRT, RapidArc can achieve better dose conformity, improve contralateral parotid sparing, and uses fewer MU.« less
-
Monahan, Paul E; Sun, Junjiang; Gui, Tong; Hu, Genlin; Hannah, William B; Wichlan, David G; Wu, Zhijian; Grieger, Joshua C; Li, Chengwen; Suwanmanee, Thipparat; Stafford, Darrel W; Booth, Carmen J; Samulski, Jade J; Kafri, Tal; McPhee, Scott W J; Samulski, R Jude
2015-02-01
Vector capsid dose-dependent inflammation of transduced liver has limited the ability of adeno-associated virus (AAV) factor IX (FIX) gene therapy vectors to reliably convert severe to mild hemophilia B in human clinical trials. These trials also identified the need to understand AAV neutralizing antibodies and empty AAV capsids regarding their impact on clinical success. To address these safety concerns, we have used a scalable manufacturing process to produce GMP-grade AAV8 expressing the FIXR338L gain-of-function variant with minimal (<10%) empty capsid and have performed comprehensive dose-response, biodistribution, and safety evaluations in clinically relevant hemophilia models. The scAAV8.FIXR338L vector produced greater than 6-fold increased FIX specific activity compared with wild-type FIX and demonstrated linear dose responses from doses that produced 2-500% FIX activity, associated with dose-dependent hemostasis in a tail transection bleeding challenge. More importantly, using a bleeding model that closely mimics the clinical morbidity of hemophilic arthropathy, mice that received the scAAV8.FIXR338L vector developed minimal histopathological findings of synovitis after hemarthrosis, when compared with mice that received identical doses of wild-type FIX vector. Hemostatically normal mice (n=20) and hemophilic mice (n=88) developed no FIX antibodies after peripheral intravenous vector delivery. No CD8(+) T cell liver infiltrates were observed, despite the marked tropism of scAAV8.FIXR338L for the liver in a comprehensive biodistribution evaluation (n=60 animals). With respect to the role of empty capsids, we demonstrated that in vivo FIXR338L expression was not influenced by the presence of empty AAV particles, either in the presence or absence of various titers of AAV8-neutralizing antibodies. Necropsy of FIX(-/-) mice 8-10 months after vector delivery revealed no microvascular or macrovascular thrombosis in mice expressing FIXR338L (plasma FIX activity, 100-500%). These preclinical studies demonstrate a safety:efficacy profile supporting an ongoing phase 1/2 human clinical trial of the scAAV8.FIXR338L vector (designated BAX335).
-
López-Tarjuelo, Juan; Bouché-Babiloni, Ana; Santos-Serra, Agustín; Morillo-Macías, Virginia; Calvo, Felipe A; Kubyshin, Yuri; Ferrer-Albiach, Carlos
2014-11-01
Industrial companies use failure mode and effect analysis (FMEA) to improve quality. Our objective was to describe an FMEA and subsequent interventions for an automated intraoperative electron radiotherapy (IOERT) procedure with computed tomography simulation, pre-planning, and a fixed conventional linear accelerator. A process map, an FMEA, and a fault tree analysis are reported. The equipment considered was the radiance treatment planning system (TPS), the Elekta Precise linac, and TN-502RDM-H metal-oxide-semiconductor-field-effect transistor in vivo dosimeters. Computerized order-entry and treatment-automation were also analyzed. Fifty-seven potential modes and effects were identified and classified into 'treatment cancellation' and 'delivering an unintended dose'. They were graded from 'inconvenience' or 'suboptimal treatment' to 'total cancellation' or 'potentially wrong' or 'very wrong administered dose', although these latter effects were never experienced. Risk priority numbers (RPNs) ranged from 3 to 324 and totaled 4804. After interventions such as double checking, interlocking, automation, and structural changes the final total RPN was reduced to 1320. FMEA is crucial for prioritizing risk-reduction interventions. In a semi-surgical procedure like IOERT double checking has the potential to reduce risk and improve quality. Interlocks and automation should also be implemented to increase the safety of the procedure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
-
The feasibility assessment of radiation dose of movement 3D NIPAM gel by magnetic resonance imaging
NASA Astrophysics Data System (ADS)
Hsieh, Chih-Ming; Leung, Joseph Hang; Ng, Yu-Bun; Cheng, Chih-Wu; Sun, Jung-Chang; Lin, Ping-Chin; Hsieh, Bor-Tsung
2015-11-01
NIPAM dosimeter is widely accepted and recommended for its 3D distribution and accuracy in dose absorption. Up to the moment, most research works on dose measurement are based on a fixed irradiation target without the consideration of the effect from physiological motion. We present a study to construct a respiratory motion simulating patient anatomical and dosimetry model for the study of dosimetic effect of organ motion. The dose on fixed and motion targets was measured by MRI after a dose adminstration of 1, 2, 5, 8, and 10 Gy from linear accelerator. Comparison of two situations is made. The average sensitivity of fixed NIPAM was 0.1356 s-1/Gy with linearity R2=0.998. The average sensitivity of movement NIPAM was 0.1366 s-1/Gy with linearity R2=0.998 both having only 0.001 of the sensitivity difference. The difference between the two based on dose rate dependency, position and depth was not significant. There was thus no apparent impact on NIPAM dosimeter from physiological motion. The high sensitivity, linearity and stability of NIPAM dosimeter proved to be an ideal apparatus in the dose measurement in these circumstances.
-
Fixed-dose combination therapy for the prevention of cardiovascular disease
de Cates, Angharad N; Farr, Matthew RB; Wright, Nicola; Jarvis, Morag C; Rees, Karen; Ebrahim, Shah; Huffman, Mark D
2014-01-01
Background Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, yet CVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure and cholesterol lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of CVD by up to 80% given its potential for better adherence and lower costs. Objectives To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD. We also aimed to determine discontinuation rates, adverse events, health-related quality of life, and costs of fixed-dose combination therapy. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library(2013, Issue 6), MEDLINE Ovid (1946 to week 2 July 2013), EMBASE Ovid (1980 to Week 28 2013), ISI Web of Science (1970 to 19 July 2013), and the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), and Health Economics Evaluations Database (HEED) (2011, Issue 4) in The Cochrane Library. We used no language restrictions. Selection criteria We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure lowering and one lipid lowering component versus usual care, placebo, or a single drug active component for any treatment duration in adults ≥ 18 years old with no restrictions on presence or absence of pre-existing cardiovascular disease. Data collection and analysis Three review authors independently selected studies for inclusion and extracted the data. We evaluated risk of bias using the Cochrane risk of bias assessment tool. We sought to include outcome data on all-cause mortality, fatal and non-fatal CVD events, adverse events, changes in systolic and diastolic blood pressure, total and low density lipoprotein (LDL) cholesterol concentrations, discontinuation rates, quality of life, and costs. We calculated risk ratios (RR) for dichotomous data and weighted mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 > 50%). Main results We found nine randomised controlled trials with a total of 7047 participants. Seven of the nine trials evaluated the effects of fixed-dose combination therapy on primary CVD prevention, and the trial length ranged from six weeks to 15 months. We found a moderate to high risk of bias in the domains of selection, performance, detection, attrition, and other types of bias in five of the nine trials. Compared with the comparator groups, the effects of the fixed-dose combination treatment on mortality (1.2% versus 1.0%, RR 1.26, 95% CI 0.67 to 2.38, N = 3465) and cardiovascular events (4.0% versus 2.9%, RR 1.38, 95% CI 0.91 to 2.10, N = 2479) were uncertain (low quality evidence). The low event rates for these outcomes, limited availability of data as only two out of nine trials reported on these outcomes, and a high risk of bias in at least one domain suggest that these results should not be viewed with confidence. Adverse events were common in both the intervention (30%) and comparator (24%) groups, with participants randomised to fixed-dose combination therapy being 20% (95% CI 9% to 30%) more likely to report an adverse event. Notably, no serious adverse events were reported. Compared with placebo, the rate of discontinuation among participants randomised to fixed-dose combination was higher (14% versus 11%, RR 1.26 95% CI 1.02 to 1.55). The weighted mean differences in systolic and diastolic blood pressure between the intervention and control arms were -7.05 mmHg (95% CI -10.18 to -3.87) and -3.65 mmHg (95% CI -5.44 to -1.85), respectively. The weighted mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.75 mmol/L (95% CI -1.05 to -0.46) and -0.81 mmol/L (95% CI -1.09 to -0.53), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 70% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multi-drug strategy by 33% (26% to 41%) compared with usual care, but this comparison was reported in only one study. The effects of fixed-dose combination therapy on quality of life are uncertain, though these results were reported in only one trial. No trials reported costs. Authors' conclusions Compared with placebo, single drug active component, or usual care, the effects of fixed-dose combination therapy on all-cause mortality or CVD events are uncertain; only few trials report these outcomes and the included trials were primarily designed to observe changes in CVD risk factor levels rather than clinical events. Reductions in blood pressure and lipid parameters are generally lower than those previously projected, though substantial heterogeneity of results exists. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, single drug active component, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing trials of fixed-dose combination therapy will likely inform key outcomes. PMID:24737108
-
Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J
2010-01-01
The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate. PMID:20596083
-
Vynckier, An-Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris
2016-05-01
This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed. Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.
-
Bagal, Bhausaheb; Chandrasekharan, Arun; Chougle, Aliya; Khattry, Navin
2018-03-01
Hepatic veno-occlusive disease (VOD) is well recognized potentially serious regimen-related toxicity seen after stem cell transplantation. Severe VOD is associated with poor long-term outcomes with very high mortality. Besides supportive care, only defibrotide has been found to be effective in the management of VOD. The recommended dose of defibrotide is 25mg/kg/d but there has been no classical dose finding study done for this drug. A higher dose of defibrotide is associated with increased risk of bleeding and this drug is prohibitively expensive. We report our experience of using fixed low dose of defibrotide in patients with VOD. We retrospectively evaluated 511 patients who underwent stem cell transplant at our center from November 2007 and December 2015. All patients received ursodeoxycholic acid as VOD prophylaxis. Modified Seattle criterion was used for diagnosis and severity grading of VOD. Patients developing VOD were initially treated with furosemide and adequate analgesia. Defibrotide was started within 12 to 24 hours of diagnosis of VOD. All adult patients received defibrotide at a fixed dose of 200mg twice daily while two children were given dose of 100mg and 50mg twice daily. Nine (1.7%) of our patients developed VOD. Daily dose of defibrotide ranged from 5mg/kg/d to 20mg/kg/d till resolution of VOD. All patients had complete resolution of VOD. None of our patients required ventilator support or dialysis. No episodes of bleeding were observed. No dose response relationship was observed between defibrotide dose and time to resolution of VOD. Low fixed dose defibrotide initiated early seems to be effective and safe in treatment of VOD. This is relevant in a resource limited setting and warrants prospective evaluation. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.
-
Ronga, Giuseppe; Filesi, Mauro; D'Apollo, Rosaria; Toteda, Maria; Di Nicola, Angelo Domenico; Colandrea, Marzia; Travascio, Laura; Vestri, Anna Rita; Montesano, Teresa
2013-05-01
Autonomous functioning thyroid nodules (AFTN), defined as "hot nodules" at thyroid scan, are often cured by radioiodine treatment. The aim of our study was to investigate the long-term outcome in patients treated with an 131I calculated dose, to identify a possible "size-tailored" dose, and to simplify follow-up procedures. Retrospective analysis was carried out on 1402 cases, covering a period of 50 years, of AFTN treated with an 131I calculated dose. Our study focused on nodular size and mean administered dose. Concordance between thyroid scan and serum TSH levels at 3-6 months from treatment was considered. A single 131I dose was effective for the vast majority of patients (93%). The outcome was influenced by nodular size. On the basis of the Italian dose limit for outpatient treatment, our population was divided into subgroups according to administered doses (more or less than 16 mCi) and nodular dimensions: no differences in outcome were observed for each class of nodule size. A dose ≤10 mCi was effective on the smaller nodules (50.1% of our population). The agreement between TSH and scan after treatment was 90.3% at 3 months and 94.5% at 6 months. 131I therapy with a calculated dose is an effective treatment of AFTN. If a fixed dose is chosen, 16 mCi is often resolutive and for nodules <3 cm a dose of 10 mCi can suffice. Nodules >5 cm are eligible for surgery. TSH is the only parameter required to evaluate the outcome.
-
Manno, Catherine S; Pierce, Glenn F; Arruda, Valder R; Glader, Bertil; Ragni, Margaret; Rasko, John J; Rasko, John; Ozelo, Margareth C; Hoots, Keith; Blatt, Philip; Konkle, Barbara; Dake, Michael; Kaye, Robin; Razavi, Mahmood; Zajko, Albert; Zehnder, James; Rustagi, Pradip K; Nakai, Hiroyuki; Chew, Amy; Leonard, Debra; Wright, J Fraser; Lessard, Ruth R; Sommer, Jürg M; Tigges, Michael; Sabatino, Denise; Luk, Alvin; Jiang, Haiyan; Mingozzi, Federico; Couto, Linda; Ertl, Hildegund C; High, Katherine A; Kay, Mark A
2006-03-01
We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B. We carried out a phase 1/2 dose-escalation clinical study to extend this approach to humans with severe hemophilia B. rAAV-2 vector expressing human F.IX was infused through the hepatic artery into seven subjects. The data show that: (i) vector infusion at doses up to 2 x 10(12) vg/kg was not associated with acute or long-lasting toxicity; (ii) therapeutic levels of F.IX were achieved at the highest dose tested; (iii) duration of expression at therapeutic levels was limited to a period of approximately 8 weeks; (iv) a gradual decline in F.IX was accompanied by a transient asymptomatic elevation of liver transaminases that resolved without treatment. Further studies suggested that destruction of transduced hepatocytes by cell-mediated immunity targeting antigens of the AAV capsid caused both the decline in F.IX and the transient transaminitis. We conclude that rAAV-2 vectors can transduce human hepatocytes in vivo to result in therapeutically relevant levels of F.IX, but that future studies in humans may require immunomodulation to achieve long-term expression.
-
Suić, Smiljka Popović; Laus, Katia Novak; Dosen, Vukosava Maricic; Ekert, Miroslav; Mandić, Zdravko; Bojić, Lovro
2010-09-01
An open label, multi-center, 6 months observational study of new fixed combination (travoprost 0.004%/timolol 0.5%), in order to evaluate both efficacy (intraocular pressure lowering) and tolerability (patient and investigator satisfaction) of two dosing regimens--evening (PM) and morning (AM). After screening for enrollment, to 40 patients (79 eyes with primary open angle glaucoma or ocular hypertension), new fixed combination travoprost 0.004%/timolol 0.5% was prescribed once a day in the evening (PM). Patients were enrolled according to each investigator decision on indication for travoprost 0.004%/timolol 0.5% fixed combination once a day, without washout period after previous medication. Intraocular pressure was measured at 9 AM at all time control points: at baseline, after 1 month, after 3 months and after 6 month. After 1 month, screening for nonresponders (criteria: 20% intraocular pressure lowering) and subjects with major side effects was performed. At second control visit, after 3 months PM dosing, intraocular pressure was measured and patients were instructed to continue once a day the same medication, but in the morning (AM) for consequent 3 months. After 1 month, reduction in mean intraocular pressure value was 21.66%. At the visit after 3 month, the mean intraocular pressure was 15.67 +/- 2.17 mm Hg (reduction 21.14%). 3 month after dosing regimen changed to AM (6 month after beginning of travoprost 0.004%/timolol 0.5% combination therapy), reduction in intraocular pressure value was 19.86%. The differences (mean +/- standard deviation) in intraocular pressure values after 1, 3 and 6 month were all highly statistically significant compared to baseline values. The tolerability was evaluated in five steps (Likert scale) ranging from unsatisfactory to excellent by both patient and investigator--taken at 3 and 6 month control visit. 95% of patients and 100% of investigators were satisfied with the possibility of choosing dosing regimen for travoprost 0.004%/timolol 0.5% fixed combination. Travoprost 0.004%/timolol 0.5% fixed combination proved sufficient intraocular pressure control dosed either PM or AM with no statistically significant difference between two dosing regimens. Possibility to choose between two dosing regimens gives each practitioner additional reassurance that glaucoma therapy will be individualised to needs of each patient.
-
Sookpeng, Supawitoo; Butdee, Chitsanupong
2017-06-01
The study aimed to evaluate the image quality in terms of signal-to-noise ratio (SNR) and dose to the lens of the eye and the other nearby organs from the CT brain scan using an automatic tube current modulation (ATCM) system with or without CT gantry tilt is needed. An anthropomorphic phantom was scanned with different settings including use of different ATCM, fixed tube current time product (mAs) settings and degree angles of gantry tilt. Gafchromic film XR-QA2 was used to measure absorbed dose of the organs. Relative doses and SNR for the various scan settings were compared with the reference setting of the fixed 330 mAs. Average absorbed dose for the lens of the eyes varied from 8.7 to 21.7 mGy. The use of the ATCM system with the gantry tilt resulted in up to 60% decrease in the dose to the lens of the eye. SNR significantly decreased while tilting the gantry using the fixed mAs techniques, compared to that of the reference setting. However, there were no statistical significant differences for SNRs between the reference setting and all ATCM settings. Compared to the reference setting of the fixed effective mAs, using the ATCM system and appropriate tilting, the gantry resulted in a substantial decrease in the dose to the lens of the eye while preserving signal-to-noise ratio. CT brain examination should be carefully controlled to optimize dose for lens of the eye and image quality of the examination.
-
Jenkins, Christine R; Eriksson, Göran; Bateman, Eric D; Reddel, Helen K; Sears, Malcolm R; Lindberg, Magnus; O'Byrne, Paul M
2017-04-20
Asthma management may involve a step up in treatment when symptoms are not well controlled. We examined whether budesonide/formoterol maintenance and reliever therapy (MRT) is as effective as higher, fixed-dose budesonide plus as-needed terbutaline in patients requiring step-up from Step 2 treatment (low-dose inhaled corticosteroids), stratified by baseline reliever use. A post-hoc analysis utilized data from three clinical trials of 6-12 months' duration. Patients aged ≥12 years with symptomatic asthma uncontrolled despite Step 2 treatment were included. Severe exacerbation rate, lung function and reliever use were analysed, stratified by baseline reliever use (<1, 1-2 and >2 occasions/day). Overall, 1239 patients were included. Reductions in severe exacerbation rate with budesonide/formoterol MRT versus fixed-dose budesonide were similar across baseline reliever use levels, and were statistically significant in patients using 1-2 (42%, p = 0.01) and >2 (39%, p = 0.02) reliever occasions/day, but not <1 reliever occasion/day (35%, p = 0.11). Both treatments significantly increased mean FEV 1 from baseline; improvements were significantly greater for budesonide/formoterol MRT in all reliever use groups. Reductions in reliever use from baseline were significantly greater with budesonide/formoterol MRT versus fixed-dose budesonide in patients using 1-2 and >2 reliever occasions/day (-0.33 and -0.74 occasions/day, respectively). Treatment benefit with budesonide/formoterol MRT versus higher, fixed-dose budesonide plus short-acting β 2 -agonist was found in Step 2 patients with relatively low reliever use, supporting the proposal that budesonide/formoterol MRT may be useful when asthma is uncontrolled with low-dose inhaled corticosteroid.
-
Bourier, Felix; Reents, Tilko; Ammar-Busch, Sonia; Buiatti, Alessandra; Kottmaier, Marc; Semmler, Verena; Telishevska, Marta; Brkic, Amir; Grebmer, Christian; Lennerz, Carsten; Kolb, Christof; Hessling, Gabriele; Deisenhofer, Isabel
2016-01-01
Aims This study presents and evaluates the impact of a new lowest-dose fluoroscopy protocol (Siemens AG), especially designed for electrophysiology (EP) procedures, on X-ray dose levels. Methods and results From October 2014 to March 2015, 140 patients underwent an EP study on an Artis zee angiography system. The standard low-dose protocol was operated at 23 nGy (fluoroscopy) and at 120 nGy (cine-loop), the new lowest-dose protocol was operated at 8 nGy (fluoroscopy) and at 36 nGy (cine-loop). Procedural data, X-ray times, and doses were analysed in 100 complex left atrial and in 40 standard EP procedures. The resulting dose–area products were 877.9 ± 624.7 µGym² (n = 50 complex procedures, standard low dose), 199 ± 159.6 µGym² (n = 50 complex procedures, lowest dose), 387.7 ± 36.0 µGym² (n = 20 standard procedures, standard low dose), and 90.7 ± 62.3 µGym² (n = 20 standard procedures, lowest dose), P < 0.01. In the low-dose and lowest-dose groups, procedure times were 132.6 ± 35.7 vs. 126.7 ± 34.7 min (P = 0.40, complex procedures) and 72.3 ± 20.9 vs. 85.2 ± 44.1 min (P = 0.24, standard procedures), radiofrequency (RF) times were 53.8 ± 26.1 vs. 50.4 ± 29.4 min (P = 0.54, complex procedures) and 10.1 ± 9.9 vs. 12.2 ± 14.7 min (P = 0.60, standard procedures). One complication occurred in the standard low-dose and lowest-dose groups (P = 1.0). Conclusion The new lowest-dose imaging protocol reduces X-ray dose levels by 77% compared with the currently available standard low-dose protocol. From an operator standpoint, lowest X-ray dose levels create a different, reduced image quality. The new image quality did not significantly affect procedure or RF times and did not result in higher complication rates. Regarding radiological protection, operating at lowest-dose settings should become standard in EP procedures. PMID:26589627
-
Wu, Jiun-Ting; Chiu, Chien-Tung; Wei, Yu-Feng; Lai, Yung-Fa
2015-06-01
Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients' outcomes were analyzed. ClinicalTrials.gov: NCT00979290. A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used.
-
Do fixed-dose combination pills or unit-of-use packaging improve adherence? A systematic review.
Connor, Jennie; Rafter, Natasha; Rodgers, Anthony
2004-01-01
Adequate adherence to medication regimens is central to the successful treatment of communicable and noncommunicable disease. Fixed-dose combination pills and unit-of-use packaging are therapy-related interventions that are designed to simplify medication regimens and so potentially improve adherence. We conducted a systematic review of relevant randomized trials in order to quantify the effects of fixed-dose combination pills and unit-of-use packaging, compared with medications as usually presented, in terms of adherence to treatment and improved outcomes. Only 15 trials met the inclusion criteria; fixed-dose combination pills were investigated in three of these, while unit-of-use packaging was studied in 12 trials. The trials involved treatments for communicable diseases (n = 5), blood pressure lowering medications (n = 3), diabetic patients (n = 1), vitamin supplementation (n = 1) and management of multiple medications by the elderly (n = 5). The results of the trials suggested that there were trends towards improved adherence and/or clinical outcomes in all but three of the trials; this reached statistical significance in four out of seven trials reporting a clinically relevant or intermediate end-point, and in seven out of thirteen trials reporting medication adherence. Measures of outcome were, however, heterogeneous, and interpretation was further limited by methodological issues, particularly small sample size, short duration and loss to follow-up. Overall, the evidence suggests that fixed-dose combination pills and unit-of-use packaging are likely to improve adherence in a range of settings, but the limitations of the available evidence means that uncertainty remains about the size of these benefits. PMID:15654408
-
Su, Jin; Zhu, Liqing; Sherman, Alexandra; Wang, Xiaomei; Lin, Shina; Kamesh, Aditya; Norikane, Joey H.; Streatfield, Stephen J.; Herzog, Roland W.; Daniell, Henry
2015-01-01
Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (~1mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ~2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP+ regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ~870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft2 per annum yielding 24,000–36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs. PMID:26302233
-
Symptom-Triggered vs. Fixed-Dosing Management of Alcohol Withdrawal Syndrome.
Skinner, Reagan T
2014-01-01
A literature review was conducted with the objective of creating evidence-based recommendations for use of symptom-triggered therapy (STT) or fixed-schedule dosing in treating alcohol withdrawal syndrome in inpatients. Use of STT reduced duration of therapy as well as the number of patients requiring treatment or medication, potentially reducing costs and risk of adverse medication reactions.
-
The purpose of this SOP is to describe the general procedures for the operation, calibration, and maintenance of fixed- and adjustable-volume pipette guns. This procedure was followed to ensure consistent data retrieval during the Arizona NHEXAS project and the "Border" study. Ke...
-
Lee, John Y K; Sandhu, Sukhmeet; Miller, Denise; Solberg, Timothy; Dorsey, Jay F; Alonso-Basanta, Michelle
2015-10-01
Gamma Knife radiosurgery (GKRS) utilizes cobalt-60 as its radiation source, and thus dose rate varies as the fixed source decays over its half-life of approximately 5.26 years. This natural decay results in increasing treatment times when delivering the same cumulative dose. It is also possible, however, that the biological effective dose may change based on this dose rate even if the total dose is kept constant. Because patients are generally treated in a uniform manner, radiosurgery for trigeminal neuralgia (TN) represents a clinical model whereby biological efficacy can be tested. The authors hypothesized that higher dose rates would result in earlier and more complete pain relief but only if measured with a sensitive pain assessment tool. One hundred thirty-three patients were treated with the Gamma Knife Model 4C unit at a single center by a single neurosurgeon during a single cobalt life cycle from January 2006 to May 2012. All patients were treated with 80 Gy with a single 4-mm isocenter without blocking. Using an output factor of 0.87, dose rates ranged from 1.28 to 2.95 Gy/min. The Brief Pain Inventory (BPI)-Facial was administered before the procedure and at the first follow-up office visit 1 month from the procedure (mean 1.3 months). Phone calls were made to evaluate patients after their procedures as part of a retrospective study. Univariate and multivariate linear regression was performed on several independent variables, including sex, age in deciles, diagnosis, follow-up duration, prior surgery, and dose rate. In the short-term analysis (mean 1.3 months), patients' self-reported pain intensity at its worst was significantly correlated with dose rate on multivariate analysis (p = 0.028). Similarly, patients' self-reported interference with activities of daily living was closely correlated with dose rate on multivariate analysis (p = 0.067). A 1 Gy/min decrease in dose rate resulted in a 17% decrease in pain intensity at its worst and a 22% decrease in pain interference with activities of daily living. In longer-term follow-up (mean 1.9 years), GKRS with higher dose rates (> 2.0 Gy/min; p = 0.007) and older age in deciles (p = 0.012) were associated with a lower likelihood of recurrence of pain. Prior studies investigating the role of dose rate in Gamma Knife radiosurgical ablation for TN have not used validated outcome tools to measure pain preoperatively. Consequently, differences in pain outcomes have been difficult to measure. By administering pain scales both preoperatively as well as postoperatively, the authors have identified statistically significant differences in pain intensity and pain interference with activities of daily living when comparing higher versus lower dose rates. Radiosurgery with a higher dose rate results in more pain relief at the early follow-up evaluation, and it may result in a lower recurrence rate at later follow-up.
-
Fixed-dose combination of sitagliptin and metformin for the treatment of type 2 diabetes
Reynolds, Jonathan K
2009-01-01
JanumetTM, a fixed dose combination of sitagliptin/metformin HCL manufactured by Merck Pharmaceuticals, has received US Food and Drug Administration approval for treatment of patients with type 2 diabetes, that are inadequately controlled, either by sitagliptin or metformin alone or together in free-dose combination form. Sitagliptin, an inhibitor of the enzyme DDP-4, assists patients with type 2 diabetes mellitus to achieve glycemic control. It has been shown to be safe and effective at 100 mg daily doses. The effect of giving sitagliptin in combination with metformin is thought to have a complimentary and possibly additive effect on glycemic control. PMID:21437126
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meric, S.M.; Rubin, S.I.
The medical records of 62 hyperthyroid cats treated with a fixed dose of 4 mCi of radioactive iodine (131I) were reviewed. In 60 cats, serum thyroxine concentrations were determined after treatment, allowing evaluation of treatment success. Eighty-four percent of the cats had normal serum thyroxine concentrations after treatment. Five of the 60 cats (8%) remained hyperthyroxinemic after treatment. Five cats (8%) were hypothyroxinemic when evaluated within 60 days of treatment. Three of these cats had normal serum thyroxine concentrations 6 months after treatment, and none had clinical signs of hypothyroidism. The administration of a fixed dose of 4 mCi ofmore » 131I was determined to be an effective treatment for feline hyperthyroidism.« less
-
Bourier, Felix; Reents, Tilko; Ammar-Busch, Sonia; Buiatti, Alessandra; Kottmaier, Marc; Semmler, Verena; Telishevska, Marta; Brkic, Amir; Grebmer, Christian; Lennerz, Carsten; Kolb, Christof; Hessling, Gabriele; Deisenhofer, Isabel
2016-09-01
This study presents and evaluates the impact of a new lowest-dose fluoroscopy protocol (Siemens AG), especially designed for electrophysiology (EP) procedures, on X-ray dose levels. From October 2014 to March 2015, 140 patients underwent an EP study on an Artis zee angiography system. The standard low-dose protocol was operated at 23 nGy (fluoroscopy) and at 120 nGy (cine-loop), the new lowest-dose protocol was operated at 8 nGy (fluoroscopy) and at 36 nGy (cine-loop). Procedural data, X-ray times, and doses were analysed in 100 complex left atrial and in 40 standard EP procedures. The resulting dose-area products were 877.9 ± 624.7 µGym² (n = 50 complex procedures, standard low dose), 199 ± 159.6 µGym² (n = 50 complex procedures, lowest dose), 387.7 ± 36.0 µGym² (n = 20 standard procedures, standard low dose), and 90.7 ± 62.3 µGym² (n = 20 standard procedures, lowest dose), P < 0.01. In the low-dose and lowest-dose groups, procedure times were 132.6 ± 35.7 vs. 126.7 ± 34.7 min (P = 0.40, complex procedures) and 72.3 ± 20.9 vs. 85.2 ± 44.1 min (P = 0.24, standard procedures), radiofrequency (RF) times were 53.8 ± 26.1 vs. 50.4 ± 29.4 min (P = 0.54, complex procedures) and 10.1 ± 9.9 vs. 12.2 ± 14.7 min (P = 0.60, standard procedures). One complication occurred in the standard low-dose and lowest-dose groups (P = 1.0). The new lowest-dose imaging protocol reduces X-ray dose levels by 77% compared with the currently available standard low-dose protocol. From an operator standpoint, lowest X-ray dose levels create a different, reduced image quality. The new image quality did not significantly affect procedure or RF times and did not result in higher complication rates. Regarding radiological protection, operating at lowest-dose settings should become standard in EP procedures. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
-
Baran, Timothy M; Foster, Thomas H
2014-02-01
For interstitial photodynamic therapy (iPDT) of bulky tumors, careful treatment planning is required in order to ensure that a therapeutic dose is delivered to the tumor, while minimizing damage to surrounding normal tissue. In clinical contexts, iPDT has typically been performed with either flat cleaved or cylindrical diffusing optical fibers as light sources. Here, the authors directly compare these two source geometries in terms of the number of fibers and duration of treatment required to deliver a prescribed light dose to a tumor volume. Treatment planning software for iPDT was developed based on graphics processing unit enhanced Monte Carlo simulations. This software was used to optimize the number of fibers, total energy delivered by each fiber, and the position of individual fibers in order to deliver a target light dose (D90) to 90% of the tumor volume. Treatment plans were developed using both flat cleaved and cylindrical diffusing fibers, based on tissue volumes derived from CT data from a head and neck cancer patient. Plans were created for four cases: fixed energy per fiber, fixed number of fibers, and in cases where both or neither of these factors were fixed. When the number of source fibers was fixed at eight, treatment plans based on flat cleaved fibers required each to deliver 7180-8080 J in order to deposit 90 J/cm(2) in 90% of the tumor volume. For diffusers, each fiber was required to deliver 2270-2350 J (333-1178 J/cm) in order to achieve this same result. For the case of fibers delivering a fixed 900 J, 13 diffusers or 19 flat cleaved fibers at a spacing of 1 cm were required to deliver the desired dose. With energy per fiber fixed at 2400 J and the number of fibers fixed at eight, diffuser fibers delivered the desired dose to 93% of the tumor volume, while flat cleaved fibers delivered this dose to 79%. With both energy and number of fibers allowed to vary, six diffusers delivering 3485-3600 J were required, compared to ten flat cleaved fibers delivering 2780-3600 J. For the same number of fibers, cylindrical diffusers allow for a shorter treatment duration compared to flat cleaved fibers. For the same energy delivered per fiber, diffusers allow for the insertion of fewer fibers in order to deliver the same light dose to a target volume.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Baran, Timothy M., E-mail: timothy.baran@rochester.edu; Foster, Thomas H.
Purpose: For interstitial photodynamic therapy (iPDT) of bulky tumors, careful treatment planning is required in order to ensure that a therapeutic dose is delivered to the tumor, while minimizing damage to surrounding normal tissue. In clinical contexts, iPDT has typically been performed with either flat cleaved or cylindrical diffusing optical fibers as light sources. Here, the authors directly compare these two source geometries in terms of the number of fibers and duration of treatment required to deliver a prescribed light dose to a tumor volume. Methods: Treatment planning software for iPDT was developed based on graphics processing unit enhanced Montemore » Carlo simulations. This software was used to optimize the number of fibers, total energy delivered by each fiber, and the position of individual fibers in order to deliver a target light dose (D{sub 90}) to 90% of the tumor volume. Treatment plans were developed using both flat cleaved and cylindrical diffusing fibers, based on tissue volumes derived from CT data from a head and neck cancer patient. Plans were created for four cases: fixed energy per fiber, fixed number of fibers, and in cases where both or neither of these factors were fixed. Results: When the number of source fibers was fixed at eight, treatment plans based on flat cleaved fibers required each to deliver 7180–8080 J in order to deposit 90 J/cm{sup 2} in 90% of the tumor volume. For diffusers, each fiber was required to deliver 2270–2350 J (333–1178 J/cm) in order to achieve this same result. For the case of fibers delivering a fixed 900 J, 13 diffusers or 19 flat cleaved fibers at a spacing of 1 cm were required to deliver the desired dose. With energy per fiber fixed at 2400 J and the number of fibers fixed at eight, diffuser fibers delivered the desired dose to 93% of the tumor volume, while flat cleaved fibers delivered this dose to 79%. With both energy and number of fibers allowed to vary, six diffusers delivering 3485–3600 J were required, compared to ten flat cleaved fibers delivering 2780–3600 J. Conclusions: For the same number of fibers, cylindrical diffusers allow for a shorter treatment duration compared to flat cleaved fibers. For the same energy delivered per fiber, diffusers allow for the insertion of fewer fibers in order to deliver the same light dose to a target volume.« less
-
Moustafa, Moustafa; Lehrner, Lawrence; Al-Saghir, Fahd; Smith, Mark; Goyal, Sunita; Dillon, Maureen; Hunter, John; Holmes-Farley, Randy
2014-01-01
Genz-644470 is a new, nonabsorbed phosphate binding polymer. In an in vitro competitive phosphate binding assay, Genz-644470 bound significantly more phosphate per gram than sevelamer. As a consequence, this clinical study evaluated the ability of Genz-644470 to lower serum phosphorus in patients on hemodialysis and compared serum phosphorus lowering of Genz-644470 with sevelamer carbonate and placebo. Because three different fixed doses of Genz-644470 and sevelamer carbonate were used, phosphate-lowering dose-responses of each agent were also analyzed. A randomized, double-blind, dose-ranging study was conducted. After a 2-week phosphate binder washout, 349 hyperphosphatemic (serum phosphorus >5.5 mg/dL) hemodialysis patients were randomized to one of seven fixed-dose groups: placebo, Genz-644470 2.4 g/day, Genz-644470 4.8 g/day, Genz-644470 7.2 g/day, sevelamer carbonate 2.4 g/day, sevelamer carbonate 4.8 g/day, or sevelamer carbonate 7.2 g/day. Indicated total daily doses were administered in fixed divided doses three times a day with meals for 3 weeks. The change in serum phosphorus during the treatment period and its dose-response patterns were assessed. Dose-dependent reductions in serum phosphorus were observed with both Genz-644470 and sevelamer carbonate. Serum phosphorus-lowering responses to fixed doses of sevelamer carbonate and Genz-644470 were enhanced in a roughly linear fashion with increasing doses over a threefold range after 3 weeks of treatment. Genz-644470 did not show any advantage in phosphorus lowering per gram of binder compared with sevelamer carbonate. Overall toler-ability was similar between active treatment groups. The tolerability of sevelamer carbonate was consistent with prior studies and with the established safety profile of sevelamer. Both Genz-644470 and sevelamer carbonate effectively lowered serum phosphate levels in a dose-dependent fashion in patients with chronic kidney disease on hemodialysis. However, Genz-644470 did not provide any advantage over sevelamer carbonate in phosphate lowering in vivo, as had been demonstrated in vitro.
-
NASA Astrophysics Data System (ADS)
Moteabbed, M.; Trofimov, A.; Sharp, G. C.; Wang, Y.; Zietman, A. L.; Efstathiou, J. A.; Lu, H.-M.
2017-03-01
Proton therapy of prostate by anterior beams could offer an attractive option for treating patients with hip prosthesis and limiting the high-dose exposure to the rectum. We investigated the impact of setup and anatomy variations on the anterior-oblique (AO) proton plan dose, and strategies to manage these effects via range verification and adaptive delivery. Ten patients treated by bilateral (BL) passive-scattering proton therapy (79.2 Gy in 44 fractions) who underwent weekly verification CT scans were selected. Plans with AO beams were additionally created. To isolate the effect of daily variations, initial AO plans did not include range uncertainty margins. The use of fixed planning margins and adaptive range adjustments to manage these effects was investigated. For each case, the planned dose was recalculated on weekly CTs, and accumulated on the simulation CT using deformable registration to approximate the delivered dose. Planned and accumulated doses were compared for each scenario to quantify dose deviations induced by variations. The possibility of estimating the necessary range adjustments before each treatment was explored by simulating the procedure of a diode-based in vivo range verification technique, which would potentially be used clinically. The average planned rectum, penile bulb and femoral heads mean doses were smaller for initial AO compared to BL plans (by 8.3, 16.1 and 25.9 Gy, respectively). After considering interfractional variations in AO plans, the target coverage was substantially reduced. The maximum reduction of V 79.2/D 95/D mean/EUD for AO (without distal margins) (25.3%/10.7/1.6/4.9 Gy, respectively) was considerably larger than BL plans. The loss of coverage was mainly related to changes in water equivalent path length of the prostate after fiducial-based setup, caused by discrepancies in patient anterior surface and bony-anatomy alignment. Target coverage was recovered partially when using fixed planning margins, and fully when applying adaptive range adjustments. The accumulated organs-at-risk dose for AO beams after range adjustment demonstrated full sparing of femoral heads and superior sparing of penile bulb and rectum compared to the conventional BL cases. Our study indicates that using AO beams makes prostate treatment more susceptible to target underdose induced by interfractional variations. Adaptive range verification/adjustment may facilitate the use of anterior beam approaches, and ensure adequate target coverage in every fraction of the treatment.
-
The purpose of this SOP is to describe the general procedures for the operation, calibration, and maintenance of fixed- and adjustable-volume pipette guns. This procedure was followed to ensure consistent data retrieval during the Arizona NHEXAS project and the Border study. Keyw...
-
Holló, Gábor; Ropo, Auli
2015-01-01
We investigated the intraocular pressure (IOP) lowering efficacy of preservative-free fixed and non-fixed combination of tafluprost 0.0015% and timolol 0.5% in pseudoexfoliative glaucoma (XFG). A per protocol worse eye analysis was made on all XFG patients who participated in a recent 6 month, prospective, randomized, double-masked, parallel group, multicenter phase III study. The mean time-wise IOP decreased by 8.62 to 10.25 mmHg (31.8 to 36.7%) in the fixed dose combination arm (15 patients) and by 5.38 to 11.35 mmHg (21.3 to 41.2%) in the non-fixed combination arm (13 patients), respectively (p < 0.001 for all comparisons). The results show that a preservative-free fixed dose combination of tafluprost and timolol provides a clinically significant IOP reduction in XFG, and may offer an advantage for the XFG patients with dry eye, due to its preservative-free nature.
-
Ali Khawaja, Ranish Deedar; Singh, Sarabjeet; Padole, Atul; Otrakji, Alexi; Lira, Diego; Zhang, Da; Liu, Bob; Primak, Andrew; Xu, George; Kalra, Mannudeep K
2017-08-01
To determine the effect of patient off-centering on point organ radiation dose measurements in a human cadaver scanned with routine abdominal CT protocol. A human cadaver (88 years, body-mass-index 20 kg/m2) was scanned with routine abdominal CT protocol on 128-slice dual source MDCT (Definition Flash, Siemens). A total of 18 scans were performed using two scan protocols (a) 120 kV-200 mAs fixed-mA (CTDIvol 14 mGy) (b) 120 kV-125 ref mAs (7 mGy) with automatic exposure control (AEC, CareDose 4D) at three different positions (a) gantry isocenter, (b) upward off-centering and (c) downward off-centering. Scanning was repeated three times at each position. Six thimble (in liver, stomach, kidney, pancreas, colon and urinary bladder) and four MOSFET dosimeters (on cornea, thyroid, testicle and breast) were placed for calculation of measured point organ doses. Organ dose estimations were retrieved from dose-tracking software (eXposure, Radimetrics). Statistical analysis was performed using analysis of variance. There was a significant difference between the trends of point organ doses with AEC and fixed-mA at all three positions (p < 0.01). Variation in point doses between fixed-mA and AEC protocols were statistically significant across all organs at all Table positions (p < 0.001). There was up to 5-6% decrease in point doses with upward off-centering and in downward off-centering. There were statistical significant differences in point doses from dosimeters and dose-tracking software (mean difference for internal organs, 5-36% for fixed-mA & 7-48% for AEC protocols; p < 0.001; mean difference for surface organs, >92% for both protocols; p < 0.0001). For both protocols, the highest mean difference in point doses was found for stomach and lowest for colon. Measured absorbed point doses in abdominal CT vary with patient-centering in the gantry isocenter. Due to lack of consideration of patient positioning in the dose estimation on automatic software-over estimation of the doses up to 92% was reported. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Effect of radiation protraction on BED in the case of large fraction dose
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kuperman, V. Y.
2013-08-15
Purpose: To investigate the effect of radiation protraction on biologically effective dose (BED) in the case when dose per fraction is significantly greater than the standard dose of 2 Gy.Methods: By using the modified linear-quadratic model with monoexponential repair, the authors investigate the effect of long treatment times combined with dose escalation.Results: The dependences of the protraction factor and the corresponding BED on fraction time were determined for different doses per fraction typical for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). In the calculations, the authors consider changes in the BED to the normal tissue under the conditionmore » of fixed BED to the target.Conclusion: The obtained results demonstrate that simultaneous increase in fraction time and dose per fraction can be beneficial for SRS and SBRT because of the related decrease in BED to normal structures while BED to the target is fixed.« less
-
Adjuik, Martin A; Allan, Richard; Anvikar, Anupkumar R; Ashley, Elizabeth A; Ba, Mamadou S; Barennes, Hubert; Barnes, Karen I; Bassat, Quique; Baudin, Elisabeth; Björkman, Anders; Bompart, François; Bonnet, Maryline; Borrmann, Steffen; Brasseur, Philippe; Bukirwa, Hasifa; Checchi, Francesco; Cot, Michel; Dahal, Prabin; D'Alessandro, Umberto; Deloron, Philippe; Desai, Meghna; Diap, Graciela; Djimde, Abdoulaye A; Dorsey, Grant; Doumbo, Ogobara K; Espié, Emmanuelle; Etard, Jean-Francois; Fanello, Caterina I; Faucher, Jean-François; Faye, Babacar; Flegg, Jennifer A; Gaye, Oumar; Gething, Peter W; González, Raquel; Grandesso, Francesco; Guerin, Philippe J; Guthmann, Jean-Paul; Hamour, Sally; Hasugian, Armedy Ronny; Hay, Simon I; Humphreys, Georgina S; Jullien, Vincent; Juma, Elizabeth; Kamya, Moses R; Karema, Corine; Kiechel, Jean R; Kremsner, Peter G; Krishna, Sanjeev; Lameyre, Valérie; Ibrahim, Laminou M; Lee, Sue J; Lell, Bertrand; Mårtensson, Andreas; Massougbodji, Achille; Menan, Hervé; Ménard, Didier; Menéndez, Clara; Meremikwu, Martin; Moreira, Clarissa; Nabasumba, Carolyn; Nambozi, Michael; Ndiaye, Jean-Louis; Nikiema, Frederic; Nsanzabana, Christian; Ntoumi, Francine; Ogutu, Bernhards R; Olliaro, Piero; Osorio, Lyda; Ouédraogo, Jean-Bosco; Penali, Louis K; Pene, Mbaye; Pinoges, Loretxu; Piola, Patrice; Price, Ric N; Roper, Cally; Rosenthal, Philip J; Rwagacondo, Claude Emile; Same-Ekobo, Albert; Schramm, Birgit; Seck, Amadou; Sharma, Bhawna; Sibley, Carol Hopkins; Sinou, Véronique; Sirima, Sodiomon B; Smith, Jeffery J; Smithuis, Frank; Somé, Fabrice A; Sow, Doudou; Staedke, Sarah G; Stepniewska, Kasia; Swarthout, Todd D; Sylla, Khadime; Talisuna, Ambrose O; Tarning, Joel; Taylor, Walter R J; Temu, Emmanuel A; Thwing, Julie I; Tjitra, Emiliana; Tine, Roger C K; Tinto, Halidou; Vaillant, Michel T; Valecha, Neena; Van den Broek, Ingrid; White, Nicholas J; Yeka, Adoke; Zongo, Issaka
2015-03-31
Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.
-
Crudele, Julie M; Finn, Jonathan D; Siner, Joshua I; Martin, Nicholas B; Niemeyer, Glenn P; Zhou, Shangzhen; Mingozzi, Federico; Lothrop, Clinton D; Arruda, Valder R
2015-03-05
Emerging successful clinical data on gene therapy using adeno-associated viral (AAV) vector for hemophilia B (HB) showed that the risk of cellular immune response to vector capsid is clearly dose dependent. To decrease the vector dose, we explored AAV-8 (1-3 × 10(12) vg/kg) encoding a hyperfunctional factor IX (FIX-Padua, arginine 338 to leucine) in FIX inhibitor-prone HB dogs. Two naïve HB dogs showed sustained expression of FIX-Padua with an 8- to 12-fold increased specific activity reaching 25% to 40% activity without antibody formation to FIX. A third dog with preexisting FIX inhibitors exhibited a transient anamnestic response (5 Bethesda units) at 2 weeks after vector delivery following by spontaneous eradication of the antibody to FIX by day 70. In this dog, sustained FIX expression reached ∼200% and 30% of activity and antigen levels, respectively. Immune tolerance was confirmed in all dogs after challenges with plasma-derived FIX concentrate. Shortening of the clotting times and lack of bleeding episodes support the phenotypic correction of the severe phenotype, with no clinical or laboratory evidence of risk of thrombosis. Provocative studies in mice showed that FIX-Padua exhibits similar immunogenicity and thrombogenicity compared with FIX wild type. Collectively, these data support the potential translation of gene-based strategies using FIX-Padua for HB. © 2015 by The American Society of Hematology.
-
Fixed-interval performance and self-control in children.
Darcheville, J C; Rivière, V; Wearden, J H
1992-01-01
Operant responses of 16 children (mean age 6 years and 1 month) were reinforced according to different fixed-interval schedules (with interreinforcer intervals of 20, 30, or 40 s) in which the reinforcers were either 20-s or 40-s presentations of a cartoon. In another procedure, they received training on a self-control paradigm in which both reinforcer delay (0.5 s or 40 s) and reinforcer duration (20 s or 40 s of cartoons) varied, and subjects were offered a choice between various combinations of delay and duration. Individual differences in behavior under the self-control procedure were precisely mirrored by individual differences under the fixed-interval schedule. Children who chose the smaller immediate reinforcer on the self-control procedure (impulsive) produced short postreinforcement pauses and high response rates in the fixed-interval conditions, and both measures changed little with changes in fixed-interval value. Conversely, children who chose the larger delayed reinforcer in the self-control condition (the self-controlled subjects) exhibited lower response rates and long postreinforcement pauses, which changed systematically with changes in the interval, in their fixed-interval performances. PMID:1573372
-
Su, Jin; Zhu, Liqing; Sherman, Alexandra; Wang, Xiaomei; Lin, Shina; Kamesh, Aditya; Norikane, Joey H; Streatfield, Stephen J; Herzog, Roland W; Daniell, Henry
2015-11-01
Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (∼1 mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ∼2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP(+) regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ∼870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft(2) per annum yielding 24,000-36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
-
Varrassi, Giustino; Hanna, Magdi; Macheras, Giorgos; Montero, Antonio; Montes Perez, Antonio; Meissner, Winfried; Perrot, Serge; Scarpignato, Carmelo
2017-06-01
Untreated and under-treated pain represent one of the most pervasive health problems, which is worsening as the population ages and accrues risk for pain. Multiple treatment options are available, most of which have one mechanism of action, and cannot be prescribed at unlimited doses due to the ceiling of efficacy and/or safety concerns. Another limitation of single-agent analgesia is that, in general, pain is due to multiple causes. Combining drugs from different classes, with different and complementary mechanism(s) of action, provides a better opportunity for effective analgesia at reduced doses of individual agents. Therefore, there is a potential reduction of adverse events, often dose-related. Analgesic combinations are recommended by several organizations and are used in clinical practice. Provided the two agents are combined in a fixed-dose ratio, the resulting medication may offer advantages over extemporaneous combinations. Dexketoprofen/tramadol (25 mg/75 mg) is a new oral fixed-dose combination offering a comprehensive multimodal approach to moderate-to-severe acute pain that encompasses central analgesic action, peripheral analgesic effect and anti-inflammatory activity, together with a good tolerability profile. The analgesic efficacy of dexketoprofen/tramadol combination is complemented by a favorable pharmacokinetic and pharmacodynamic profile, characterized by rapid onset and long duration of action. This has been well documented in both somatic- and visceral-pain human models. This review discusses the available clinical evidence and the future possible applications of dexketoprofen/tramadol fixed-dose combination that may play an important role in the management of moderate-to-severe acute pain.
-
Chromatid Paints: A New Method for Detecting Tumor-Specific Chromosomal Inversions
1999-10-01
chromosomal DNA as a template for DNA polymerization. The cloning procedure requires copying DNA from fixed cells attached to a glass substrate. Any...achieved by initially fixing cells in methanol and adding acetic acid just before dropping cells onto coverslips. The procedure itself is a novel and...human hybrid cells containing one human #11 chromosome were fixed and dropped onto microscope coverslips. These cells had been synchronized by mitotic
-
Inactivation of Lactobacillus rhamnosus GG by fixation modifies its probiotic properties.
Markowicz, C; Kubiak, P; Grajek, W; Schmidt, M T
2016-01-01
Probiotics are microorganisms that have beneficial effects on the host and are safe for oral intake in a suitable dose. However, there are situations in which the administration of living microorganisms poses a risk for immunocompromised host. The objective of this study was to evaluate the influence of several fixation methods on selected biological properties of Lactobacillus rhamnosus GG that are relevant to its probiotic action. Fixation of the bacterial cells with ethanol, 2-propanol, glutaraldehyde, paraformaldehyde, and heat treatment resulted in a significant decrease of alkaline phosphatase, peroxidase, and β-galactosidase activities. Most of the fixation procedures reduced bacterial cell hydrophobicity and increased adhesion capacity. The fixation procedures resulted in a different perception of the bacterial cells by enterocytes, which was shown as changes in gene expression in enterocytes. The results show that some procedures of inactivation allow a fraction of the enzymatic activity to be maintained. The adhesion properties of the bacterial cells were enhanced, but the response of enterocytes to fixed cells was different than to live bacteria. Inactivation allows maintenance and modification of some of the properties of the bacterial cells.
-
Real-Time Patient and Staff Radiation Dose Monitoring in IR Practice
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sailer, Anna M., E-mail: karmanna@stanford.edu; Paulis, Leonie, E-mail: leonie.paulis@mumc.nl; Vergoossen, Laura
PurposeKnowledge of medical radiation exposure permits application of radiation protection principles. In our center, the first dedicated real-time, automated patient and staff dose monitoring system (DoseWise Portal, Philips Healthcare) was installed. Aim of this study was to obtain insight in the procedural and occupational doses.Materials and MethodsAll interventional radiologists, vascular surgeons, and technicians wore personal dose meters (PDMs, DoseAware, Philips Healthcare). The dose monitoring system simultaneously registered for each procedure dose-related data as the dose area product (DAP) and effective staff dose (E) from PDMs. Use and type of shielding were recorded separately. All procedures were analyzed according to proceduremore » type; these included among others cerebral interventions (n = 112), iliac and/or caval venous recanalization procedures (n = 68), endovascular aortic repair procedures (n = 63), biliary duct interventions (n = 58), and percutaneous gastrostomy procedure (n = 28).ResultsMedian (±IQR) DAP doses ranged from 2.0 (0.8–3.1) (percutaneous gastrostomy) to 84 (53–147) Gy cm{sup 2} (aortic repair procedures). Median (±IQR) first operator doses ranged from 1.6 (1.1–5.0) μSv to 33.4 (12.1–125.0) for these procedures, respectively. The relative exposure, determined as first operator dose normalized to procedural DAP, ranged from 1.9 in biliary interventions to 0.1 μSv/Gy cm{sup 2} in cerebral interventions, indicating large variation in staff dose per unit DAP among the procedure types.ConclusionReal-time dose monitoring was able to identify the types of interventions with either an absolute or relatively high staff dose, and may allow for specific optimization of radiation protection.« less
-
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.
-
NASA Astrophysics Data System (ADS)
Zeng, Lu-Chuan; Yao, Jen-Chih
2006-09-01
Recently, Agarwal, Cho, Li and Huang [R.P. Agarwal, Y.J. Cho, J. Li, N.J. Huang, Stability of iterative procedures with errors approximating common fixed points for a couple of quasi-contractive mappings in q-uniformly smooth Banach spaces, J. Math. Anal. Appl. 272 (2002) 435-447] introduced the new iterative procedures with errors for approximating the common fixed point of a couple of quasi-contractive mappings and showed the stability of these iterative procedures with errors in Banach spaces. In this paper, we introduce a new concept of a couple of q-contractive-like mappings (q>1) in a Banach space and apply these iterative procedures with errors for approximating the common fixed point of the couple of q-contractive-like mappings. The results established in this paper improve, extend and unify the corresponding ones of Agarwal, Cho, Li and Huang [R.P. Agarwal, Y.J. Cho, J. Li, N.J. Huang, Stability of iterative procedures with errors approximating common fixed points for a couple of quasi-contractive mappings in q-uniformly smooth Banach spaces, J. Math. Anal. Appl. 272 (2002) 435-447], Chidume [C.E. Chidume, Approximation of fixed points of quasi-contractive mappings in Lp spaces, Indian J. Pure Appl. Math. 22 (1991) 273-386], Chidume and Osilike [C.E. Chidume, M.O. Osilike, Fixed points iterations for quasi-contractive maps in uniformly smooth Banach spaces, Bull. Korean Math. Soc. 30 (1993) 201-212], Liu [Q.H. Liu, On Naimpally and Singh's open questions, J. Math. Anal. Appl. 124 (1987) 157-164; Q.H. Liu, A convergence theorem of the sequence of Ishikawa iterates for quasi-contractive mappings, J. Math. Anal. Appl. 146 (1990) 301-305], Osilike [M.O. Osilike, A stable iteration procedure for quasi-contractive maps, Indian J. Pure Appl. Math. 27 (1996) 25-34; M.O. Osilike, Stability of the Ishikawa iteration method for quasi-contractive maps, Indian J. Pure Appl. Math. 28 (1997) 1251-1265] and many others in the literature.
-
Aerobic exercise decreases the positive-reinforcing effects of cocaine.
Smith, Mark A; Schmidt, Karl T; Iordanou, Jordan C; Mustroph, Martina L
2008-11-01
Aerobic exercise can serve as an alternative, non-drug reinforcer in laboratory animals and has been recommended as a potential intervention for substance abusing populations. Unfortunately, relatively little empirical data have been collected that specifically address the possible protective effects of voluntary, long-term exercise on measures of drug self-administration. The purpose of the present study was to examine the effects of chronic exercise on sensitivity to the positive-reinforcing effects of cocaine in the drug self-administration procedure. Female rats were obtained at weaning and immediately divided into two groups. Sedentary rats were housed individually in standard laboratory cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed individually in modified cages equipped with a running wheel. After 6 weeks under these conditions, rats were surgically implanted with venous catheters and trained to self-administer cocaine on a fixed-ratio schedule of reinforcement. Once self-administration was acquired, cocaine was made available on a progressive ratio schedule and breakpoints were obtained for various doses of cocaine. Sedentary and exercising rats did not differ in the time to acquire cocaine self-administration or responding on the fixed-ratio schedule of reinforcement. However, on the progressive ratio schedule, breakpoints were significantly lower in exercising rats than sedentary rats when responding was maintained by both low (0.3mg/kg/infusion) and high (1.0mg/kg/infusion) doses of cocaine. In exercising rats, greater exercise output prior to catheter implantation was associated with lower breakpoints at the high dose of cocaine. These data indicate that chronic exercise decreases the positive-reinforcing effects of cocaine and support the possibility that exercise may be an effective intervention in drug abuse prevention and treatment programs.
-
Shen, Jie; Goodkin, Margot L; Tong, Warren; Attar, Mayssa
2017-01-01
Purpose Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed. Methods New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. Results Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation. Conclusion Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties), formulations of bimatoprost 0.01% can be administered once or twice daily. These findings support development of bimatoprost 0.01%-based fixed-dose combination therapies administered twice daily for patients who require multiple adjunctive medications to control their IOP. PMID:29026287
-
47 CFR 101.91 - Involuntary relocation procedures.
Code of Federal Regulations, 2013 CFR
2013-10-01
... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses Policies Governing Fixed Service Relocation from the 18.58-19.30 Ghz Band § 101.91 Involuntary relocation procedures. (a) If no agreement is... Commission's rules. FSS licensees are obligated to pay to relocate only the specific microwave links from...
-
47 CFR 101.91 - Involuntary relocation procedures.
Code of Federal Regulations, 2014 CFR
2014-10-01
... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses Policies Governing Fixed Service Relocation from the 18.58-19.30 Ghz Band § 101.91 Involuntary relocation procedures. (a) If no agreement is... Commission's rules. FSS licensees are obligated to pay to relocate only the specific microwave links from...
-
47 CFR 101.91 - Involuntary relocation procedures.
Code of Federal Regulations, 2012 CFR
2012-10-01
... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses Policies Governing Fixed Service Relocation from the 18.58-19.30 Ghz Band § 101.91 Involuntary relocation procedures. (a) If no agreement is... Commission's rules. FSS licensees are obligated to pay to relocate only the specific microwave links from...
-
47 CFR 101.91 - Involuntary relocation procedures.
Code of Federal Regulations, 2011 CFR
2011-10-01
... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses Policies Governing Fixed Service Relocation from the 18.58-19.30 Ghz Band § 101.91 Involuntary relocation procedures. (a) If no agreement is... Commission's rules. FSS licensees are obligated to pay to relocate only the specific microwave links from...
-
The financial and service implications of splitting fixed-dose antiretroviral drugs - a case study.
Taylor, R; Carlin, E; Sadique, Z; Ahmed, I; Adams, E J
2015-02-01
In 2010/2011, regional commissioners withdrew payment for the fixed-dose combination Combivir, forcing a switch to component drugs. This was deemed clinically acceptable and annual savings of £44 k expected. We estimated the true costs of switching and examined patient outcomes. Information for 46 patients using Combivir was extracted from case notes for each clinical contact in the 12 months pre- and post-switch (clinician seen, tests, antiretrovirals). Post-switch care costs £93/patient more annually versus pre-switch (95% CI £424 to £609), yielding £4278/year more post-switch for all patients. Drug and pathology costs were more expensive post-switch and extra clinical visits required. None of these results were statistically significant. Forty-two per cent of patients switched directly or in the subsequent year to an alternative fixed-dose combination rather than generics. Costs in this group were significantly higher post-switch driven by drug cost. Six patients (13%) reported problems with the switch including confusion around dosing and new side effects. As less-expensive generic antiretroviral drugs become available, it may appear cheaper to switch from fixed-dose combinations to component drugs. However, the additional clinical costs involved may outweigh the initial cost savings of the drugs and switching may cause confusion for some patients, risking loss of adherence. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
-
WE-G-BRE-08: Radiosensitization by Olaparib Eluting Nanospheres
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tangutoori, S; Kumar, R; Sridhar, S
2014-06-15
Purpose: Permanent prostate brachytherapy often uses inert bio-absorbable spacers to achieve the desired geometric distribution of sources within the prostate. Transforming these spacers into implantable nanoplatforms for chemo-radiation therapy (INCeRT) provides a means of providing sustained in-situ release of radiosensitizers in the prostate to enhance the therapeutic ratio of the procedure. Olaparib, a PARP inhibitor, suppresses DNA repair processes present during low dose rate continuous irradiation. This work investigates the radiosensitizing/DNA damage repair inhibition by NanoOlaparib eluting nanospheres. Methods: Human cell line PC3 (from ATCC), was maintained in F12-k medium supplemented with fetal bovine serum. Clonogenic assay kit (from Fischermore » Scientific) was used to fix and stain the cells to determine the long term effects of irradiation. Nanoparticle size and zeta potential of nanospheres were determined using a Zeta particle size analyzer. The incorporation of Olaparib in nanospheres was evaluated by HPLC. Irradiation was performed in a small animal irradiator operating at 220 KeV.The long term effects of radio-sensitization with olaparib and nanoolaparib was determined using the clonogenic assay at 2 Gy and 4 Gy doses. The cells were allowed to grow for around 10 doubling cycles, The colonies were fixed and stained using clonogenic assay kit. The excess stain was washed off using DI water and the images were taken using a digital camera. Results: Radiosensitization studies were carried out in prostate cancer cell line, PC3 radiation at 0, 2 and 4Gy doses. Strongest dose response was observed with nanoolaparib treated cells compared to untreated cells. Conclusion: A two stage drug release of drug eluting nanospheres from a biodegradable spacer has been suggested for sustained in-situ release of Olaparib to suppress DNA repair processes during prostate brachytherapy. The Olaparib eluting nanospheres had the same in-vitro radiosensitizing effect as free olaparib. DOD 1R21CA16977501, A. David Mazzone Awards Program 2012PD164.« less
-
NASA Astrophysics Data System (ADS)
Magro, G.; Molinelli, S.; Mairani, A.; Mirandola, A.; Panizza, D.; Russo, S.; Ferrari, A.; Valvo, F.; Fossati, P.; Ciocca, M.
2015-09-01
This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus® chamber. An EBT3® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.
-
Magro, G; Molinelli, S; Mairani, A; Mirandola, A; Panizza, D; Russo, S; Ferrari, A; Valvo, F; Fossati, P; Ciocca, M
2015-09-07
This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo(®) TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus(®) chamber. An EBT3(®) film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.
-
48 CFR 931.102 - Fixed-price contracts.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Fixed-price contracts. 931... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Applicability 931.102 Fixed-price contracts. The intent of... Government in— (a) Pricing fixed-price prime contracts and modifications, (b) Evaluating the reasonableness...
-
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.
-
Husic, Samir; Izic, Senad; Matic, Srecko; Sukalo, Aziz
2015-02-01
The goal of the research was to determine the efficacy of a fixed combination of tramadol and paracetamol (acetaminophen) in the treatment of pain of patients with the advanced stage of cancer. A prospective study was conducted at the Center for Palliative Care, University Clinical Center Tuzla, Bosnia and Herzegovina, from January 1(st) to December 31(st) 2013. A total of 353 patients who were treated with a fixed combination of tramadol and acetaminophen (37.5 mg and 325 mg) at the initial dosage 3x1 tablet (112.5 mg tramadol and 975 mg acetaminophen) for pain intensity 4, up to 4x2 tablets (300 mg of tramadol and 2600 mg paracetamol) for pain intensity 7 and 8. If the patient during previous day has two or more pain episodes that required a "rescue dose" of tramadol, increased was the dose of fixed combination tramadol and acetaminophen to a maximum of 8 tablets daily (300 mg of tramadol and 2600 mg paracetamol). Statistical analysis was performed by biomedical software MedCalc for Windows version 9.4.2.0. The difference was considered significant for P<0.05. The average duration of treatment with a fixed combination tramadol and acetaminophen was 57 days (13-330 days). Already after 24 hours of treatment the average pain score was significantly lower (p<0.0001) compared to the admission day [5.00 (4:00 to 8:00) during the first days versus 2.00 (1:00 to 7:00) during the second day of treatment]. The average dose of the fixed combination tramadol and acetaminophen tablets was 4.8 ± 1.8 (180 mg of tramadol and 1560 mg paracetamol). Side effects, in the treatment of pain with a fixed combination tramadol and acetaminophen, were found in 29.18% of patients, with a predominance of nausea and vomiting. Fixed combination of tramadol and acetaminophen can be used as an effective combination in the treatment of chronic cancer pain, with frequent dose evaluation and mild side effects.
-
The colorimetric analysis of anti-tuberculosis fixed-dose combination tablets and capsules.
Ellard, G A
1999-11-01
The perceived need to demonstrate whether or not the actual amounts of rifampicin, isoniazid and pyrazinamide in fixed-dose combination tablets or capsules correspond to their stated drug contents. To adapt specific, robust and simple colorimetric methods that have been previously applied to measuring plasma and urinary rifampicin, isoniazid, pyrazinamide and ethambutol concentrations to estimate tablet and capsule drug contents. The methods were applied to the analysis of 14 commercially manufactured fixed-dose combinations: two capsule and three tablet formulations containing rifampicin and isoniazid; seven tablet formulations containing rifampicin, isoniazid and pyrazinamide; and two tablet formulations containing rifampicin, isoniazid, pyrazinamide and ethambutol. All the combined formulations contained near to their stated drug contents. Replicate analyses confirmed the excellent precision of the drug analyses. Such methods are not only rapid to perform but should be practical in many Third World situations with relatively modest laboratory facilities.
-
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.
-
Schnapauff, D; Collettini, F; Steffen, I; Wieners, G; Hamm, B; Gebauer, B; Maurer, M H
2016-02-25
To analyse and compare the costs of hepatic tumor ablation with computed tomography (CT)-guided high-dose rate brachytherapy (CT-HDRBT) and CT-guided radiofrequency ablation (CT-RFA) as two alternative minimally invasive treatment options of hepatocellular carcinoma (HCC). An activity based process model was created determining working steps and required staff of CT-RFA and CT-HDRBT. Prorated costs of equipment use (purchase, depreciation, and maintenance), costs of staff, and expenditure for disposables were identified in a sample of 20 patients (10 treated by CT-RFA and 10 by CT-HDRBT) and compared. A sensitivity and break even analysis was performed to analyse the dependence of costs on the number of patients treated annually with both methods. Costs of CT-RFA were nearly stable with mean overall costs of approximately 1909 €, 1847 €, 1816 € and 1801 € per patient when treating 25, 50, 100 or 200 patients annually, as the main factor influencing the costs of this procedure was the single-use RFA probe. Mean costs of CT-HDRBT decreased significantly per patient ablation with a rising number of patients treated annually, with prorated costs of 3442 €, 1962 €, 1222 € and 852 € when treating 25, 50, 100 or 200 patients, due to low costs of single-use disposables compared to high annual fix-costs which proportionally decreased per patient with a higher number of patients treated annually. A break-even between both methods was reached when treating at least 55 patients annually. Although CT-HDRBT is a more complex procedure with more staff involved, it can be performed at lower costs per patient from the perspective of the medical provider when treating more than 55 patients compared to CT-RFA, mainly due to lower costs for disposables and a decreasing percentage of fixed costs with an increasing number of treatments.
-
Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings
Trigo, Jose M.; Lagzdins, Dina; Rehm, Jürgen; Selby, Peter; Gamaleddin, Islam; Fischer, Benedikt; Barnes, Allan J.; Huestis, Marilyn A.; Le Foll, Bernard
2016-01-01
Background There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects. Methods Participants underwent an 8-week double-blind placebo-controlled trial (an ABACADAE design), with four smoke as usual conditions (SAU) (A) separated by four cannabis abstinence conditions (B–E), with administration of either self-titrated/fixed doses of placebo or Sativex (up to 108 mg THC/100 mg CBD). The order of medication administration during abstinence conditions was randomized and counterbalanced. Withdrawal symptoms and craving were assessed using the Cannabis Withdrawal Scale (CWS), Marijuana Withdrawal Checklist (MWC) and Marijuana Craving Questionnaire (MCQ). Medication use was assessed during the study by means of self-reports, vial weight control, toxicology and metabolite analysis. Cannabis use was assessed by means of self-reports. Results High fixed doses of Sativex were well tolerated and significantly reduced cannabis withdrawal during abstinence, but not craving, as compared to placebo. Self-titrated doses were lower and showed limited efficacy as compared to high fixed doses. Participants reported a significantly lower “high” following Sativex or placebo as compared to SAU conditions. Cannabis/medication use along the study, as per self-reports, suggests compliance with the study conditions. Conclusions The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence. PMID:26925704
-
Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.
Trigo, Jose M; Lagzdins, Dina; Rehm, Jürgen; Selby, Peter; Gamaleddin, Islam; Fischer, Benedikt; Barnes, Allan J; Huestis, Marilyn A; Le Foll, Bernard
2016-04-01
There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects. Participants underwent an 8-week double-blind placebo-controlled trial (an ABACADAE design), with four smoke as usual conditions (SAU) (A) separated by four cannabis abstinence conditions (B-E), with administration of either self-titrated/fixed doses of placebo or Sativex (up to 108 mg THC/100 mg CBD). The order of medication administration during abstinence conditions was randomized and counterbalanced. Withdrawal symptoms and craving were assessed using the Cannabis Withdrawal Scale (CWS), Marijuana Withdrawal Checklist (MWC) and Marijuana Craving Questionnaire (MCQ). Medication use was assessed during the study by means of self-reports, vial weight control, toxicology and metabolite analysis. Cannabis use was assessed by means of self-reports. High fixed doses of Sativex were well tolerated and significantly reduced cannabis withdrawal during abstinence, but not craving, as compared to placebo. Self-titrated doses were lower and showed limited efficacy as compared to high fixed doses. Participants reported a significantly lower "high" following Sativex or placebo as compared to SAU conditions. Cannabis/medication use along the study, as per self-reports, suggests compliance with the study conditions. The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
-
OCCUPATIONAL RADIATION DOSES TO OPERATORS PERFORMING FLUOROSCOPICALLY-GUIDED PROCEDURES
Kim, Kwang Pyo; Miller, Donald L.; de Gonzalez, Amy Berrington; Balter, Stephen; Kleinerman, Ruth A.; Ostroumova, Evgenia; Simon, Steven L.; Linet, Martha S.
2012-01-01
In the past 30 years, the numbers and types of fluoroscopically-guided (FG) procedures have increased dramatically. The objective of the present study is to provide estimated radiation doses to physician specialists, other than cardiologists, who perform FG procedures. We searched Medline to identify English-language journal articles reporting radiation exposures to these physicians. We then identified several primarily therapeutic FG procedures that met specific criteria: well-defined procedures for which there were at least five published reports of estimated radiation doses to the operator, procedures performed frequently in current medical practice, and inclusion of physicians from multiple medical specialties. These procedures were percutaneous nephrolithotomy (PCNL), vertebroplasty, orthopedic extremity nailing for treatment of fractures, biliary tract procedures, transjugular intrahepatic portosystemic shunt creation (TIPS), head/neck endovascular therapeutic procedures, and endoscopic retrograde cholangiopancreatography (ERCP). We abstracted radiation doses and other associated data, and estimated effective dose to operators. Operators received estimated doses per patient procedure equivalent to doses received by interventional cardiologists. The estimated effective dose per case ranged from 1.7 – 56μSv for PCNL, 0.1 – 101 μSv for vertebroplasty, 2.5 – 88μSv for orthopedic extremity nailing, 2.0 – 46μSv for biliary tract procedures, 2.5 – 74μSv for TIPS, 1.8 – 53μSv for head/neck endovascular therapeutic procedures, and 0.2 – 49μSv for ERCP. Overall, mean operator radiation dose per case measured over personal protective devices at different anatomic sites on the head and body ranged from 19 – 800 (median = 113) μSv at eye level, 6 – 1180 (median = 75)μSv at the neck, and 2 – 1600 (median = 302) μSv at the trunk. Operators’ hands often received greater doses than the eyes, neck or trunk. Large variations in operator doses suggest that optimizing procedure protocols and proper use of protective devices and shields might reduce occupational radiation dose substantially. PMID:22647920
-
Barnwal, Neeraj Kumar; Umbarkar, Sanjeeta Rajendra; Sarkar, Manjula Sudeep; Dias, Raylene J
2017-01-01
Background: Pulmonary hypertension secondary to congenital heart disease is a common problem in pediatric patients presenting for open heart surgery. Milrinone has been shown to reduce pulmonary vascular resistance and pulmonary artery pressure in pediatric patients and neonates postcardiac surgery. We aimed to evaluate the postoperative outcome in such patients with three different fixed maintenance doses of milrinone. Methodology: Patients were randomized into three groups. All patients received fixed bolus dose of milrinone 50 μg/kg on pump during rewarming. Following this, patients in low-dose group received infusion of milrinone at the rate of 0.375 μg/kg/min, medium-dose group received 0.5 μg/kg/min, and high-dose group received 0.75 μg/kg/min over 24 h. Heart rate, mean arterial pressure (MAP), mean airway pressure (MaP), oxygenation index (OI), and central venous pressure (CVP) were compared at baseline and 24 h postoperatively. Dose of inotropic requirement, duration of ventilatory support and Intensive Care Unit (ICU) stay were noted. Results: MAP, MaP, OI, and CVP were comparable in all three groups postoperatively. All patients in the low-dose group required low inotropic support while 70% of patients in the high-dose group needed high inotropic support to manage episodes of hypotension (P = 0.000). Duration of ventilatory support and ICU stay in all three groups was comparable (P = 0.412, P = 0.165). Conclusion: Low-dose infusions while having a clinical impact were more beneficial in avoiding adverse events and decreasing inotropic requirement without affecting duration of ventilatory support and duration of ICU stay. PMID:28701597
-
Barnwal, Neeraj Kumar; Umbarkar, Sanjeeta Rajendra; Sarkar, Manjula Sudeep; Dias, Raylene J
2017-01-01
Pulmonary hypertension secondary to congenital heart disease is a common problem in pediatric patients presenting for open heart surgery. Milrinone has been shown to reduce pulmonary vascular resistance and pulmonary artery pressure in pediatric patients and neonates postcardiac surgery. We aimed to evaluate the postoperative outcome in such patients with three different fixed maintenance doses of milrinone. Patients were randomized into three groups. All patients received fixed bolus dose of milrinone 50 μg/kg on pump during rewarming. Following this, patients in low-dose group received infusion of milrinone at the rate of 0.375 μg/kg/min, medium-dose group received 0.5 μg/kg/min, and high-dose group received 0.75 μg/kg/min over 24 h. Heart rate, mean arterial pressure (MAP), mean airway pressure (MaP), oxygenation index (OI), and central venous pressure (CVP) were compared at baseline and 24 h postoperatively. Dose of inotropic requirement, duration of ventilatory support and Intensive Care Unit (ICU) stay were noted. MAP, MaP, OI, and CVP were comparable in all three groups postoperatively. All patients in the low-dose group required low inotropic support while 70% of patients in the high-dose group needed high inotropic support to manage episodes of hypotension (P = 0.000). Duration of ventilatory support and ICU stay in all three groups was comparable (P = 0.412, P = 0.165). Low-dose infusions while having a clinical impact were more beneficial in avoiding adverse events and decreasing inotropic requirement without affecting duration of ventilatory support and duration of ICU stay.
-
Hagstrom, J N; Couto, L B; Scallan, C; Burton, M; McCleland, M L; Fields, P A; Arruda, V R; Herzog, R W; High, K A
2000-04-15
Hemophilia B is caused by the absence of functional coagulation factor IX (F.IX) and represents an important model for treatment of genetic diseases by gene therapy. Recent studies have shown that intramuscular injection of an adeno-associated viral (AAV) vector into mice and hemophilia B dogs results in vector dose-dependent, long-term expression of biologically active F.IX at therapeutic levels. In this study, we demonstrate that levels of expression of approximately 300 ng/mL (6% of normal human F.IX levels) can be reached by intramuscular injection of mice using a 2- to 4-fold lower vector dose (1 x 10(11) vector genomes/mouse, injected into 4 intramuscular sites) than previously described. This was accomplished through the use of an improved expression cassette that uses the cytomegalovirus (CMV) immediate early enhancer/promoter in combination with a 1.2-kilobase portion of human skeletal actin promoter. These results correlated with enhanced levels of F.IX transcript and secreted F.IX protein in transduced murine C2C12 myotubes. Systemic F.IX expression from constructs containing the CMV enhancer/promoter alone was 120 to 200 ng/mL in mice injected with 1 x 10(11) vector genomes. Muscle-specific promoters performed poorly for F.IX transgene expression in vitro and in vivo. However, the incorporation of a sequence from the alpha-skeletal actin promoter containing at least 1 muscle-specific enhancer and 1 enhancer-like element further improved muscle-derived expression of F.IX from a CMV enhancer/promoter-driven expression cassette over previously published results. These findings will allow the design of a clinical protocol for therapeutic levels of F.IX expression with lower vector doses, thus enhancing efficacy and safety of the protocol. (Blood. 2000;95:2536-2542)
-
Lopez, F; Pereira, C
1985-03-01
Two experiments used response-restriction procedures in order to test the independence of the factors determining response rate and the factors determining the size of the postreinforcement pause on interval schedules. Responding was restricted by response-produced blackout or by retracting the lever. In Experiment 1 with a Conjunctive FR 1 FT schedule, the blackout procedure reduced the postreinforcement pause more than the lever-retraction procedure did, and both procedures produced shorter pauses than did the schedule without response restriction. In Experiment 2 the interreinforcement interval was also manipulated, and the size of the pause was an increasing function of the interreinforcement interval, but the rate of increase was lower than that produced by fixed interval schedules of comparable interval durations. The assumption of functional independence of the postreinforcement pause and terminal rate in fixed interval schedules is questioned since data suggest that pause reductions resulted from constraining variation in response number compared to equivalent periodic schedules in which response number was allowed to vary. Copyright © 1985. Published by Elsevier B.V.
-
Hu, Dayi; Sun, Yihong; Liao, Yuhua; Huang, Jing; Zhao, Ruiping; Yang, Kan
2016-01-01
To assess the blood pressure-lowering efficacy and tolerability of perindopril/amlodipine fixed-dose combinations in Chinese patients with mild-to-moderate essential hypertension not adequately controlled with monotherapy alone. In 2 separate double-blind studies, patients received a 4-week run-in monotherapy of amlodipine 5 mg or perindopril 4 mg, respectively. Those whose blood pressure was uncontrolled were then randomized to receive the fixed-dose combination of perindopril 5 mg/amlodipine 5 mg (Per/Amlo group) or remain on the monotherapy for 8 weeks. Patients who were uncontrolled at the week 8 (W8) visit were up-titrated for the Per/Amlo combination, or received additional treatment if on monotherapy, for a further 4 weeks. The main efficacy assessment was at 8 weeks. After 8 weeks, systolic blood pressure (SBP; primary criterion) was statistically significantly lower in the Per/Amlo group (vs. Amlo 5 mg, p = 0.0095; vs. Per 4 mg, p < 0.0001). Uncontrolled patients at W8 who received an up-titration of the Per/Amlo combination showed a further SBP reduction. These changes were mirrored by reassuring reductions in diastolic blood pressure. The fixed-dose combinations were well tolerated. Single-pill combinations of perindopril and amlodipine provide hypertensive patients with a convenient and effective method of reducing blood pressure. © 2016 S. Karger AG, Basel.
-
Nebivolol and valsartan as a fixed-dose combination for the treatment of hypertension.
Sander, Gary E; Giles, Thomas D
2015-04-01
The fixed-dose combination of nebivolol and valsartan drug has been clinically evaluated and demonstrated to represent a unique combination of nebivolol, a selective β1-adrenoceptor antagonist and a β3-adrenoceptor agonist; β3 receptor activation increases endothelial nitric oxide and produces vasodilation. Valsartan is highly selective angiotensin AT1 receptor blocker and exerts its major pharmacological effect by decreasing angiotensin II-induced vasoconstriction and production of aldosterone. The addition of nebivolol counteracts the effects of increased angiotensin II concentrations resulting from potent AT1 blockade. This review describes a recently completed trial establishing the efficacy of the nebivolol/valsartan combination. This review provides a literature search of pertinent pharmacological and clinical data that describes the mechanisms of both drugs individually and the results of a clinical trial comparing fixed-dose combinations of nebivolol with valsartan as compared with each drug as monotherapy. Fixed-dose combination drugs are intended to improve patient compliance and reduce drug costs, as well as to reduce long-term cardiovascular event rates and block counter-regulatory effects due to monotherapy. The vast majority of hypertensive patients will require at least two medications. We believe that the clinical evidence suggests that the combination of nebivolol with valsartan offers a definite clinical benefit, combining β1-adrenoceptor and angiotensin AT1 receptor blockade with β3 receptor activation and resultant increase in nitric oxide and vasodilation.
-
Neutel, Joel M; Cushman, William C; Lloyd, Eric; Barger, Bruce; Handley, Alison
2017-09-01
This 52-week, randomized, open-label study evaluated long-term safety/tolerability of fixed-dose combination azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs fixed-dose combination olmesartan medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with essential hypertension (stage 2; clinic systolic blood pressure 160-190 mm Hg). Initial AZL-M/CLD 40/12.5 mg/d (n=418) or OLM/HCTZ 20/12.5 mg/d (n=419) could be uptitrated during weeks 4 to 52 (AZL-M/CLD to 80/25 mg; OLM/HCTZ to 40/25 mg [United States] or 20/25 mg [Europe]) to meet blood pressure targets. Treatment-emergent adverse events/serious adverse events occurred in 78.5%/5.7% of patients taking AZL-M/CLD vs 76.4%/6.2% taking OLM/HCTZ. The most frequent adverse events were dizziness (16.3% vs 12.6%), blood creatinine increase (21.5% vs 8.6%), headache (7.4% vs 11.0%), and nasopharyngitis (12.2% vs 11.5%). Hypokalemia was uncommon (1.0% vs 0.7%). Greater blood pressure reductions with AZL-M/CLD by week 2 were maintained throughout the study, despite less uptitration (32.3% vs 48.9% with OLM/HCTZ). Fixed-dose combination AZL-M/CLD showed an encouraging benefit-risk profile when used per standard clinical practice in a titrate-to-target strategy. ©2017 Wiley Periodicals, Inc.
-
Side Effects in Time Discounting Procedures: Fixed Alternatives Become the Reference Point
2016-01-01
Typical research on intertemporal choice utilizes a two-alternative forced choice (2AFC) paradigm requiring participants to choose between a smaller sooner and larger later payoff. In the adjusting-amount procedure (AAP) one of the alternatives is fixed and the other is adjusted according to particular choices made by the participant. Such a method makes the alternatives unequal in status and is speculated to make the fixed alternative a reference point for choices, thereby affecting the decision made. The current study shows that fixing different alternatives in the AAP influences discount rates in intertemporal choices. Specifically, individuals’ (N = 283) choices were affected to just the same extent by merely fixing an alternative as when choices were preceded by scenarios explicitly imposing reference points. PMID:27768759
-
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.
-
Choice with a fixed requirement for food, and the generality of the matching relation
Stubbs, D. Alan; Dreyfus, Leon R.; Fetterman, J. Gregor; Dorman, Lana G.
1986-01-01
Pigeons were trained on choice procedures in which responses on each of two keys were reinforced probabilistically, but only after a schedule requirement had been met. Under one arrangement, a fixed-interval choice procedure was used in which responses were not reinforced until the interval was over; then a response on one key would be reinforced, with the effective key changing irregularly from interval to interval. Under a second, fixed-ratio choice procedure, responses on either key counted towards completion of the ratio and then, once the ratio had been completed, a response on the probabilistically selected key would produce food. In one experiment, the schedule requirements were varied for both fixed-interval and fixed-ratio schedules. In the second experiment, relative reinforcement rate was varied. And in a third experiment, the duration of an intertrial interval separating choices was varied. The results for 11 pigeons across all three experiments indicate that there were often large deviations between relative response rates and relative reinforcement rates. Overall performance measures were characterized by a great deal of variability across conditions. More detailed measures of choice across the schedule requirement were also quite variable across conditions. In spite of this variability, performance was consistent across conditions in its efficiency of producing food. The absence of matching of behavior allocation to reinforcement rate indicates an important difference between the present procedures and other choice procedures; that difference raises questions about the specific conditions that lead to matching as an outcome. PMID:16812452
-
Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.
Yap, Felix Boon-Bin
2017-09-01
Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.
-
Miksys, Nelson; Gordon, Christopher L; Thomas, Karen; Connolly, Bairbre L
2010-05-01
The purpose of this study was to estimate the effective doses received by pediatric patients during interventional radiology procedures and to present those doses in "look-up tables" standardized according to minute of fluoroscopy and frame of digital subtraction angiography (DSA). Organ doses were measured with metal oxide semiconductor field effect transistor (MOSFET) dosimeters inserted within three anthropomorphic phantoms, representing children at ages 1, 5, and 10 years, at locations corresponding to radiosensitive organs. The phantoms were exposed to mock interventional radiology procedures of the head, chest, and abdomen using posteroanterior and lateral geometries, varying magnification, and fluoroscopy or DSA exposures. Effective doses were calculated from organ doses recorded by the MOSFET dosimeters and are presented in look-up tables according to the different age groups. The largest effective dose burden for fluoroscopy was recorded for posteroanterior and lateral abdominal procedures (0.2-1.1 mSv/min of fluoroscopy), whereas procedures of the head resulted in the lowest effective doses (0.02-0.08 mSv/min of fluoroscopy). DSA exposures of the abdomen imparted higher doses (0.02-0.07 mSv/DSA frame) than did those involving the head and chest. Patient doses during interventional procedures vary significantly depending on the type of procedure. User-friendly look-up tables may provide a helpful tool for health care providers in estimating effective doses for an individual procedure.
-
Hackenberg, T D; Hineline, P N
1992-01-01
Pigeons chose between two schedules of food presentation, a fixed-interval schedule and a progressive-interval schedule that began at 0 s and increased by 20 s with each food delivery provided by that schedule. Choosing one schedule disabled the alternate schedule and stimuli until the requirements of the chosen schedule were satisfied, at which point both schedules were again made available. Fixed-interval duration remained constant within individual sessions but varied across conditions. Under reset conditions, completing the fixed-interval schedule not only produced food but also reset the progressive interval to its minimum. Blocks of sessions under the reset procedure were interspersed with sessions under a no-reset procedure, in which the progressive schedule value increased independent of fixed-interval choices. Median points of switching from the progressive to the fixed schedule varied systematically with fixed-interval value, and were consistently lower during reset than during no-reset conditions. Under the latter, each subject's choices of the progressive-interval schedule persisted beyond the point at which its requirements equaled those of the fixed-interval schedule at all but the highest fixed-interval value. Under the reset procedure, switching occurred at or prior to that equality point. These results qualitatively confirm molar analyses of schedule preference and some versions of optimality theory, but they are more adequately characterized by a model of schedule preference based on the cumulated values of multiple reinforcers, weighted in inverse proportion to the delay between the choice and each successive reinforcer. PMID:1548449
-
Perioperative haemostatic management of haemophilic mice using normal mouse plasma.
Tatsumi, K; Ohashi, K; Kanegae, K; Shim, I K; Okano, T
2013-11-01
Intense haemostatic interventions are required to avoid bleeding complications when surgical procedures are performed on haemophilia patients. The objective of this study was to establish an appropriate protocol for perioperative haemostatic management of haemophilic mice. We assessed the prophylactic haemostatic effects of normal mouse plasma (NMP) on haemophilia B (HB) mice for both a skin flap procedure and a laparotomy. When 500 μL of NMP was administered to the mice, plasma factor IX (FIX:C) levels peaked at 15.1% immediately after intravenous (IV) administration, at 6.1% 2 h after intraperitoneal (IP) administration and at 2.7% 6 h after subcutaneous administration. Administering 500 μL of NMP via IP or IV 30 min in advance enabled the skin flap procedure to be performed safely without any complications. After the laparotomy procedure, several mice in the IP administration group exhibited lethal bleeding, but all mice survived in the IV administration group. Anti-mouse FIX inhibitors did not develop, even after repetitive administrations of NMP. However, human FIX concentrates, especially plasma-derived concentrates, elicited the anti-human FIX inhibitors. The results show that administering 500 μL of NMP via IV or IP 30 min in advance enables surgical procedures to be safely performed on HB mice, and that IV administration is more desirable than IP if the procedure requires opening of the abdominal wall. © 2013 John Wiley & Sons Ltd.
-
Björkman, S; Folkesson, A; Berntorp, E
2007-01-01
In vivo recovery (IVR) is traditionally used as a parameter to characterize the pharmacokinetic properties of coagulation factors. It has also been suggested that dosing of factor VIII (FVIII) and factor IX (FIX) can be adjusted according to the need of the individual patient, based on an individually determined IVR value. This approach, however, requires that the individual IVR value is more reliably representative for the patient than the mean value in the population, i.e. that there is less variance within than between the individuals. The aim of this investigation was to compare intra- and interindividual variance in IVR (as U dL1 per U kg1) for FVIII and plasma-derived FIX in a cohort of non-bleeding patients with haemophilia. The data were collected retrospectively from six clinical studies, yielding 297 IVR determinations in 50 patients with haemophilia A and 93 determinations in 13 patients with haemophilia B. For FVIII, the mean variance within patients exceeded the between-patient variance. Thus, an individually determined IVR value is apparently no more informative than an average, or population, value for the dosing of FVIII. There was no apparent relationship between IVR and age of the patient (1.5-67 years). For FIX, the mean variance within patients was lower than the between-patient variance, and there was a significant positive relationship between IVR and age (13-69 years). From these data, it seems probable that using an individual IVR confers little advantage in comparison to using an age-specific population mean value. Dose tailoring of coagulation factor treatment has been applied successfully after determination of the entire single-dose curve of FVIII:C or FIX:C in the patient and calculation of the relevant pharmacokinetic parameters. However, the findings presented here do not support the assumption that dosing of FVIII or FIX can be individualized on the basis of a clinically determined IVR value.
-
Use of radiation protraction to escalate biologically effective dose to the treatment target
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kuperman, V. Y.; Spradlin, G. S.; Department of Mathematics, Embry-Riddle University, Daytona Beach, Florida 32114
2011-12-15
Purpose: The aim of this study is to evaluate how simultaneously increasing fraction time and dose per fraction affect biologically effective dose for the target (BED{sub tar}) while biologically effective dose for the normal tissue (BED{sub nt}) is fixed. Methods: In this investigation, BED{sub tar} and BED{sub nt} were studied by assuming mono-exponential repair of sublethal damage with tissue dependent repair half-time. Results: Our results demonstrate that under certain conditions simultaneously increasing fraction time and dose per fraction result in increased BED{sub tar} while BED{sub nt} is fixed. The dependence of biologically effective dose on fraction time is influenced bymore » the dose rate. In this investigation we analytically determined time-varying dose rate R-tilde which minimizes BED. Changes in BED with fraction time were compared for constant dose rate and for R-tilde. Conclusions: A number of recent experimental and theoretical studies have demonstrated that slow delivery of radiation (known as radiation protraction) leads to reduced therapeutic effect because of increased repair of sublethal damage. In contrast, our analysis shows that under certain conditions simultaneously increasing fraction time and dose per fraction are radiobiologically advantageous.« less
-
Patient doses in the healing arts
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
Determinations of radiation doses to patients from x-ray procedures and radiopharmaceuticals are detailed in this chapter. Instructions are given for estimating doses from x-ray procedures. For selected pediatric procedures, the methodology developed by the Food and Drug Administration is presented. The effect of testicular and ovarian shielding is illustrated in tabular form. Estimates of the Genetically Significant Dose (GSD) and mean annual bone marrow dose from diagnostic x-ray examinations are presented for the US populations (1990). This chapter also provides tables of patient doses from selected nuclear medicine procedures and estimates of fetal doses from {sup 131}I.
-
Liu, Chuanlei; Zhang, Weihua; Ungar, Kurt; Korpach, Ed; White, Brian; Benotto, Mike; Pellerin, Eric
2018-05-07
This work explores the application of Health Canada's Fixed Point Surveillance (FPS) network for cosmic ray monitoring and dose estimation purposes. This network is comprised of RS250 3 inch by 3 inch Sodium Iodide (NaI) spectroscopic dosimeters distributed throughout Canada. The RS250's high channel count rate responds to the electromagnetic and muonic components of cosmic ray shower. These count rates are used to infer cosmic ray doses throughout FPS locations. The derived dose was found to have an accuracy within 6.5% deviation relative to theoretical calculation. The solar cycle effect and meteorologically induced fluctuation can be realistically reflected in the estimated dose. This work may serve as a basis to enable the FPS network to monitor and report both terrestrial and cosmic radiation in quasi-real time. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.
-
Lytle, Allison M; Brown, Harrison C; Paik, Na Yoon; Knight, Kristopher A; Wright, J Fraser; Spencer, H Trent; Doering, Christopher B
2016-01-01
Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV) vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV. PMID:26909355
-
Real-time eye lens dose monitoring during cerebral angiography procedures.
Safari, M J; Wong, J H D; Kadir, K A A; Thorpe, N K; Cutajar, D L; Petasecca, M; Lerch, M L F; Rosenfeld, A B; Ng, K H
2016-01-01
To develop a real-time dose-monitoring system to measure the patient's eye lens dose during neuro-interventional procedures. Radiation dose received at left outer canthus (LOC) and left eyelid (LE) were measured using Metal-Oxide-Semiconductor Field-Effect Transistor dosimeters on 35 patients who underwent diagnostic or cerebral embolization procedures. The radiation dose received at the LOC region was significantly higher than the dose received by the LE. The maximum eye lens dose of 1492 mGy was measured at LOC region for an AVM case, followed by 907 mGy for an aneurysm case and 665 mGy for a diagnostic angiography procedure. Strong correlations (shown as R(2)) were observed between kerma-area-product and measured eye doses (LOC: 0.78, LE: 0.68). Lateral and frontal air-kerma showed strong correlations with measured dose at LOC (AKL: 0.93, AKF: 0.78) and a weak correlation with measured dose at LE. A moderate correlation was observed between fluoroscopic time and dose measured at LE and LOC regions. The MOSkin dose-monitoring system represents a new tool enabling real-time monitoring of eye lens dose during neuro-interventional procedures. This system can provide interventionalists with information needed to adjust the clinical procedure to control the patient's dose. Real-time patient dose monitoring helps interventionalists to monitor doses. Strong correlation was observed between kerma-area-product and measured eye doses. Radiation dose at left outer canthus was higher than at left eyelid.
-
Stepaniak, Pieter S; Vrijland, Wietske W; de Quelerij, Marcel; de Vries, Guus; Heij, Christiaan
2010-12-01
If variation in procedure times could be controlled or better predicted, the cost of surgeries could be reduced through improved scheduling of surgical resources. This study on the impact of similar consecutive cases on the turnover, surgical, and procedure times tests the perception that repeating the same manual tasks reduces the duration of these tasks. We hypothesize that when a fixed team works on similar consecutive cases the result will be shorter turnover and procedure duration as well as less variation as compared with the situation without a fixed team. Case-control study. St Franciscus Hospital, a large general teaching hospital in Rotterdam, the Netherlands. Two procedures, inguinal hernia repair and laparoscopic cholecystectomy, were selected and divided across a control group and a study group. Patients were randomly assigned to the study or control group. Preparation time, surgical time, procedure time, and turnover time. For inguinal hernia repair, we found a significantly lower preparation time and 10 minutes less procedure time in the study group, as compared with the control group. Variation in the study group was lower, as compared with the control group. For laparoscopic cholecystectomy, preparation time was significantly lower in the study group, as compared with the control group. For both procedures, there was a significant decrease in turnover time. Scheduling similar consecutive cases and performing with a fixed team results in lower turnover times and preparation times. The procedure time of the inguinal hernia repair decreased significantly and has practical scheduling implications. For more complex surgery, like laparoscopic cholecystectomy, there is no effect on procedure time.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kainz, K; Prah, D; Ahunbay, E
2014-06-01
Purpose: A novel modulated arc therapy technique, mARC, enables superposition of step-and-shoot IMRT segments upon a subset of the optimization points (OPs) of a continuous-arc delivery. We compare two approaches to mARC planning: one with the number of OPs fixed throughout optimization, and another where the planning system determines the number of OPs in the final plan, subject to an upper limit defined at the outset. Methods: Fixed-OP mARC planning was performed for representative cases using Panther v. 5.01 (Prowess, Inc.), while variable-OP mARC planning used Monaco v. 5.00 (Elekta, Inc.). All Monaco planning used an upper limit of 91more » OPs; those OPs with minimal MU were removed during optimization. Plans were delivered, and delivery times recorded, on a Siemens Artiste accelerator using a flat 6MV beam with 300 MU/min rate. Dose distributions measured using ArcCheck (Sun Nuclear Corporation, Inc.) were compared with the plan calculation; the two were deemed consistent if they agreed to within 3.5% in absolute dose and 3.5 mm in distance-to-agreement among > 95% of the diodes within the direct beam. Results: Example cases included a prostate and a head-and-neck planned with a single arc and fraction doses of 1.8 and 2.0 Gy, respectively. Aside from slightly more uniform target dose for the variable-OP plans, the DVHs for the two techniques were similar. For the fixed-OP technique, the number of OPs was 38 and 39, and the delivery time was 228 and 259 seconds, respectively, for the prostate and head-and-neck cases. For the final variable-OP plans, there were 91 and 85 OPs, and the delivery time was 296 and 440 seconds, correspondingly longer than for fixed-OP. Conclusion: For mARC, both the fixed-OP and variable-OP approaches produced comparable-quality plans whose delivery was successfully verified. To keep delivery time per fraction short, a fixed-OP planning approach is preferred.« less
-
Kirkwood, Melissa L; Guild, Jeffrey B; Arbique, Gary M; Tsai, Shirling; Modrall, J Gregory; Anderson, Jon A; Rectenwald, John; Timaran, Carlos
2016-11-01
A new proprietary image-processing system known as AlluraClarity, developed by Philips Healthcare (Best, The Netherlands) for radiation-based interventional procedures, claims to lower radiation dose while preserving image quality using noise-reduction algorithms. This study determined whether the surgeon and patient radiation dose during complex endovascular procedures (CEPs) is decreased after the implementation of this new operating system. Radiation dose to operators, procedure type, reference air kerma, kerma area product, and patient body mass index were recorded during CEPs on two Philips Allura FD 20 fluoroscopy systems with and without Clarity. Operator dose during CEPs was measured using optically stimulable, luminescent nanoDot (Landauer Inc, Glenwood, Ill) detectors placed outside the lead apron at the left upper chest position. nanoDots were read using a microStar ii (Landauer Inc) medical dosimetry system. For the CEPs in the Clarity group, the radiation dose to surgeons was also measured by the DoseAware (Philips Healthcare) personal dosimetry system. Side-by-side measurements of DoseAware and nanoDots allowed for cross-calibration between systems. Operator effective dose was determined using a modified Niklason algorithm. To control for patient size and case complexity, the average fluoroscopy dose rate and the dose per radiographic frame were adjusted for body mass index differences and then compared between the groups with and without Clarity by procedure. Additional factors, for example, physician practice patterns, that may have affected operator dose were inferred by comparing the ratio of the operator dose to procedural kerma area product with and without Clarity. A one-sided Wilcoxon rank sum test was used to compare groups for radiation doses, reference air kermas, and operating practices for each procedure type. The analysis included 234 CEPs; 95 performed without Clarity and 139 with Clarity. Practice patterns of operators during procedures with and without Clarity were not significantly different. For all cases, procedure radiation dose to the patient and the primary and assistant operators were significantly decreased in the Clarity group by 60% compared with the non-Clarity group. By procedure type, fluorography dose rates decreased from 44% for fenestrated endovascular repair and up to 70% with lower extremity interventions. Fluoroscopy dose rates also significantly decreased, from about 37% to 47%, depending on procedure type. The AlluraClarity system reduces the patient and primary operator's radiation dose by more than half during CEPs. This feature appears to be an effective tool in lowering the radiation dose while maintaining image quality. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
-
Preclinical safety and efficacy of a new recombinant FIX drug product for treatment of hemophilia B.
Dietrich, Barbara; Schiviz, Alexandra; Hoellriegl, Werner; Horling, Frank; Benamara, Karima; Rottensteiner, Hanspeter; Turecek, Peter L; Schwarz, Hans Peter; Scheiflinger, Friedrich; Muchitsch, Eva-Maria
2013-11-01
Baxter has developed a new recombinant factor IX (rFIX) drug product (BAX326) for treating patients with hemophilia B, or congenital FIX deficiency. An extensive preclinical program evaluated the pharmacokinetics, efficacy, and safety of BAX326 in different species. The efficacy of BAX326 was tested in three mouse models of primary pharmacodynamics: tail-tip bleeding, carotid occlusion, and thrombelastography. The pharmacokinetics was evaluated after a single intravenous bolus injection in mice, rats, and macaques. Toxicity was assessed in rats and macaques, safety pharmacology in rabbits and macaques, and immunogenicity in mice. BAX326 was shown to be efficacious in all three primary pharmacodynamic studies (P ≤ 0.0076). Hemostatic efficacy was dose related and similar for the three lots tested. Pharmacokinetic results showed that rFIX activity and rFIX antigen concentrations declined in a bi-phasic manner, similar to a previously licensed rFIX product. BAX326 was well tolerated in rabbits and macaques at all dose levels; no thrombogenic events and no adverse clinical, respiratory, or cardiovascular effects occurred. BAX326 was also shown to have a similar immunogenicity profile to the comparator rFIX product in mice. These results demonstrate that BAX326 has a favorable preclinical safety and efficacy profile, predictive of a comparable effect to that of the previously licensed rFIX in humans.
-
Randomized study of surgical prophylaxis in immunocompromised hosts.
Lopes, D R; Peres, M P S M; Levin, A S
2011-02-01
Although prophylaxis is current practice, there are no randomized controlled studies evaluating preoperative antimicrobial prophylaxis in dental procedures in patients immunocompromised by chemotherapy or organ transplants. To evaluate prophylaxis in dental-invasive procedures in patients with cancer or solid organ transplants, 414 patients were randomized to receive one oral 500-mg dose 2 hours before the procedure (1-dose group) or a 500-mg dose 2 hours before the procedure and an additional dose 8 hours later (2-dose group). Procedures were exodontia or periodontal scaling/root planing. Follow-up was 4 weeks. No deaths or surgical site infections occurred. Six patients (1.4%) presented with use of pain medication > 3 days or hospitalization during follow-up: 4 of 207 (2%) in the 1-dose group and 2 of 207 (1%) in the 2-dose group (relative risk, 2.02; 95% confidence interval, 0.37-11.15). In conclusion, no statistically significant difference occurred in outcome using 1 or 2 doses of prophylactic amoxicillin for invasive dental procedures in immunocompromised patients.
-
Morphine Tolerance as a Function of Ratio Schedule: Response Requirement or Unit Price?
ERIC Educational Resources Information Center
Hughes, Christine; Sigmon, Stacey C.; Pitts, Raymond C.; Dykstra, Linda A.
2005-01-01
Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, "l"-methadone, and cocaine dose-dependently decreased…
-
NASA Astrophysics Data System (ADS)
He, Wenjun; Mah, Eugene; Huda, Walter; Selby, Bayne; Yao, Hai
2011-03-01
Purpose: To investigate the dose distributions in water cylinders simulating patients undergoing Interventional Radiological examinations. Method: The irradiation geometry consisted of an x-ray source, dose-area-product chamber, and image intensifier as currently used in Interventional Radiology. Water cylinders of diameters ranging between 17 and 30 cm were used to simulate patients weighing between 20 and 90 kg. X-ray spectra data with peak x-ray tube voltages ranging from 60 to 120 kV were generated using XCOMP3R. Radiation dose distributions inside the water cylinder (Dw) were obtained using MCNP5. The depth dose distribution along the x-ray beam central axis was normalized to free-in-air air kerma (AK) that is incident on the phantom. Scattered radiation within the water cylinders but outside the directly irradiated region was normalized to the dose at the edge of the radiation field. The total absorbed energy to the directly irradiated volume (Ep) and indirectly irradiated volume (Es) were also determined and investigated as a function of x-ray tube voltage and phantom size. Results: At 80 kV, the average Dw/AK near the x-ray entrance point was 1.3. The ratio of Dw near the entrance point to Dw near the exit point increased from ~ 26 for the 17 cm water cylinder to ~ 290 for the 30 cm water cylinder. At 80 kV, the relative dose for a 17 cm water cylinder fell to 0.1% at 49 cm away from the central ray of the x-ray beam. For a 30 cm water cylinder, the relative dose fell to 0.1% at 53 cm away from the central ray of the x-ray beam. At a fixed x-ray tube voltage of 80 kV, increasing the water cylinder diameter from 17 to 30 cm increased the Es/(Ep+Es) ratio by about 50%. At a fixed water cylinder diameter of 24 cm, increasing the tube voltage from 60 kV to 120 kV increased the Es/(Ep+Es) ratio by about 12%. The absorbed energy from scattered radiation was between 20-30% of the total energy absorbed by the water cylinder, and was affected more by patient size than x-ray beam energy. Conclusion: MCNP offers a powerful tool to study the absorption and transmission of x-ray energy in phantoms that can be designed to represent patients undergoing Interventional Radiological procedures. This ability will permit a systematic investigation of the relationship between patient dose and diagnostic image quality, and thereby keep patient doses As Low As Reasonably Achievable (ALARA).
-
Macaskill, Anne C; Branch, Marc N
2012-01-01
The schedule of reinforcement under which behavior is maintained is an important contributor to whether tolerance to the behavioral effects of cocaine develops. Schedule parameter value (for example, fixed-ratio size) has been shown to affect the development of tolerance under some schedule types but not others, but the specific procedural variables causing this effect remain to be identified. To date, schedule-parameter-related tolerance has developed when a longer pause after reinforcement does not lead to a shorter delay between the response that ends the pause and reinforcement. The current study investigated the importance of this variable in pigeons using a multiple chained Fixed-Ratio 1, Fixed-Time x schedule, in which the first key peck in a trial produced a stimulus change and initiated a delay at the end of which food was presented regardless of whether or not additional pecks were made during the delay. Dose-response curves were assessed before, during and after chronic (daily) administration of cocaine. Tolerance to the pause-increasing effects of cocaine occurred to a similar degree regardless of the scheduled time between the end of the pause and reinforcement. Therefore, the relationship between pause length and delay to reinforcement does not provide an explanation for schedule-parameter-related tolerance. Copyright © 2011 Elsevier Inc. All rights reserved.
-
Zhou, Caicun; Huang, Yunchao; Wang, Donglin; An, Changshan; Zhou, Fuxiang; Li, Yali; Chen, Gongyan; Wu, Changping; He, Jianxing; Wu, Gang; Song, Xia; Gao, Jianfei; Liu, Wei; Li, Baolan; Shi, Jianhua; Huang, Cheng; Yu, Jingrui; Feng, Jueping; Yue, Hongmei; Shi, Meiqi; Xia, Jielai
2016-03-01
Mecapegfilgrastim (code name HHPG-19K) is a biosimilar to pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF). The efficacy and safety of mecapegfilgrastim, using a regimen of once-per-cycle injection of 100-μg/kg or a fixed 6-mg dose, were evaluated for the prophylactic therapy for neutropenia in patients with advanced non-small-cell lung cancer (NSCLC) who were treated with myelosuppressive chemotherapy. Patients were randomized (1:1:1) blindly to 3 treatment arms to receive a single injection of mecapegfilgrastim 100 μg/kg, a 6-mg fixed dose of mecapegfilgrastim, or saline (control) in cycle 1. In cycles 2 to 4 following unblinding at the end of cycle 1, patients in the control arm received daily injections of short-acting rhG-CSF at a dose of 5 μg/kg, whereas patients in the 2 mecapegfilgrastim arms continued the same treatment as in cycle 1. All patients received 4 chemotherapy cycles of docetaxel combined with cisplatin or carboplatin every 21 days. The primary endpoint was the incidence of grade ≥ 3 neutropenia in cycle 1. A single dose of 100 μg/kg or a fixed 6-mg dose of mecapegfilgrastim per cycle effectively reduced chemotherapy-induced neutropenia and was comparable to daily rhG-CSF with regard to all efficacy endpoints, including incidence of grade ≥ 3 neutropenia, incidence of febrile neutropenia, duration of grade ≥ 3 neutropenia, and time to neutrophil recovery. No difference in efficacy parameters was observed between the 2-dose regimens of mecapegfilgrastim across all cycles. Mecapegfilgrastim was well-tolerated and was as safe as daily rhG-CSF. Once-per-cycle injection of mecapegfilgrastim is as effective and safe as daily rhG-CSF for prophylaxis of chemotherapy-induced neutropenia in patients with NSCLC. Mecapegfilgrastim (fixed 6-mg dose) is recommended in clinical practice for its convenient dose management. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.
-
Repaglinide in type 2 diabetes: a 24-week, fixed-dose efficacy and safety study.
Jovanovic, L; Dailey, G; Huang, W C; Strange, P; Goldstein, B J
2000-01-01
In this 24-week multicenter, double-blind, randomized, fixed-dose trial, 361 patients having type 2 diabetes received daily preprandial treatment with placebo (n = 75), repaglinide 1 mg (n = 140), or repaglinide 4 mg (n = 146). By a last-observation carried-forward calculation, repaglinide 1 mg or 4 mg treatment decreased mean fasting plasma glucose (FPG) values (by -47 mg/dL or -49 mg/dL) while the placebo group had increased FPG values (by 19 mg/dL). For the repaglinide treatment groups at the end of the study, changes in HbA1c from baseline values ranged from 1.8 to 1.9 percentage points lower than the placebo group. There were no events of severe hypoglycemia. Nearly all hypoglycemic symptom episodes had blood glucose levels above 45 mg/dL. Repaglinide was well tolerated in a preprandial fixed-dose regimen of 1 mg or 4 mg, assigned without adjustment for clinical parameters.
-
Thomas, Hannah Mary; Kinahan, Paul E; Samuel, James Jebaseelan E; Bowen, Stephen R
2018-02-01
To quantitatively estimate the impact of different methods for both boost volume delineation and respiratory motion compensation of [18F] FDG PET/CT images on the fidelity of planned non-uniform 'dose painting' plans to the prescribed boost dose distribution. Six locally advanced non-small cell lung cancer (NSCLC) patients were retrospectively reviewed. To assess the impact of respiratory motion, time-averaged (3D AVG), respiratory phase-gated (4D GATED) and motion-encompassing (4D MIP) PET images were used. The boost volumes were defined using manual contour (MANUAL), fixed threshold (FIXED) and gradient search algorithm (GRADIENT). The dose painting prescription of 60 Gy base dose to the planning target volume and an integral dose of 14 Gy (total 74 Gy) was discretized into seven treatment planning substructures and linearly redistributed according to the relative SUV at every voxel in the boost volume. Fifty-four dose painting plan combinations were generated and conformity was evaluated using quality index VQ0.95-1.05, which represents the sum of planned dose voxels within 5% deviation from the prescribed dose. Trends in plan quality and magnitude of achievable dose escalation were recorded. Different segmentation techniques produced statistically significant variations in maximum planned dose (P < 0.02), as well as plan quality between segmentation methods for 4D GATED and 4D MIP PET images (P < 0.05). No statistically significant differences in plan quality and maximum dose were observed between motion-compensated PET-based plans (P > 0.75). Low variability in plan quality was observed for FIXED threshold plans, while MANUAL and GRADIENT plans achieved higher dose with lower plan quality indices. The dose painting plans were more sensitive to segmentation of boost volumes than PET motion compensation in this study sample. Careful consideration of boost target delineation and motion compensation strategies should guide the design of NSCLC dose painting trials. © 2017 The Royal Australian and New Zealand College of Radiologists.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Y; Zhang, J; Hu, Q
2014-06-01
Purpose: To investigate the possibility of applying optimized scanning protocols for pediatric CT simulation by quantifying the dosimetric inaccuracy introduced by using a fixed HU to density conversion. Methods: The images of a CIRS electron density reference phantom (Model 062) were acquired by a Siemens CT simulator (Sensation Open) using the following settings of tube voltage and beam current: 120 kV/190mA (the reference protocol used to calibrate CT for our treatment planning system (TPS)); Fixed 190mA combined with all available kV: 80, 100, and 140; fixed 120 kV and various current from 37 to 444 mA (scanner extremes) with intervalmore » of 30 mA. To avoid the HU uncertainty of point sampling in the various inserts of known electron densities, the mean CT numbers of the central cylindrical volume were calculated using DICOMan software. The doses per 100 MU to the reference point (SAD=100cm, Depth=10cm, Field=10X10cm, 6MV photon beam) in a virtual cubic phantom (30X30X30cm) were calculated using Eclipse TPS (calculation model: AcurosXB-11031) by assigning the CT numbers to HU of typical materials acquired by various protocols. Results: For the inserts of densities less than muscle, CT number fluctuations of all protocols were within the tolerance of 10 HU as accepted by AAPM-TG66. For more condensed materials, fixed kV yielded stable HU with any mA combination where largest disparities were found in 1750mg/cc insert: HU{sub reference}=1801(106.6cGy), HU{sub minimum}=1799 (106.6cGy, error{sub dose}=0.00%), HU{sub maximum}=1815 (106.8cGy, error{sub dose}=0.19%). Yet greater disagreements were observed with increasing density when kV was modified: HU{sub minimum}=1646 (104.5cGy, error{sub dose}=- 1.97%), HU{sub maximum}=2487 (116.4cGy, error{sub dose}=9.19%) in 1750mg/cc insert. Conclusion: Without affecting treatment dose calculation, personalized mA optimization of CT simulator can be conducted by fixing kV for a better cost-effectiveness of imaging dose and quality especially for children. Unless recalibrated, kV should be constant for all anatomical sites if diagnostic CT scanner is used as a simulator. This work was partially supported by Capital Medical Development Scientific Research Fund of China.« less
-
Silkosessak, O; Jacobs, R; Bogaerts, R; Bosmans, H; Panmekiate, S
2014-01-01
Objectives: To determine the optimal kVp setting for a particular cone beam CT (CBCT) device by maximizing technical image quality at a fixed radiation dose. Methods: The 3D Accuitomo 170 (J. Morita Mfg. Corp., Kyoto, Japan) CBCT was used. The radiation dose as a function of kVp was measured in a cylindrical polymethyl methacrylate (PMMA) phantom using a small-volume ion chamber. Contrast-to-noise ratio (CNR) was measured using a PMMA phantom containing four materials (air, aluminium, polytetrafluoroethylene and low-density polyethylene), which was scanned using 180 combinations of kVp/mA, ranging from 60/1 to 90/8. The CNR was measured for each material using PMMA as background material. The pure effect of kVp and mAs on the CNR values was analysed. Using a polynomial fit for CNR as a function of mA for each kVp value, the optimal kVp was determined at five dose levels. Results: Absorbed doses ranged between 0.034 mGy mAs−1 (14 × 10 cm, 60 kVp) and 0.108 mGy mAs−1 (14 × 10 cm, 90 kVp). The relation between kVp and dose was quasilinear (R2 > 0.99). The effect of mA and kVp on CNR could be modelled using a second-degree polynomial. At a fixed dose, there was a tendency for higher CNR values at increasing kVp values, especially at low dose levels. A dose reduction through mA was more efficient than an equivalent reduction through kVp in terms of image quality deterioration. Conclusions: For the investigated CBCT model, the most optimal contrast at a fixed dose was found at the highest available kVp setting. There is great potential for dose reduction through mA with a minimal loss in image quality. PMID:24708447
-
NASA Astrophysics Data System (ADS)
Benhayoune, H.; Charlier, D.; Jallot, E.; Laquerriere, P.; Balossier, G.; Bonhomme, P.
2001-01-01
Biomaterials used in dental and orthopaedic surgery to fill bony loss and to coat prostheses are either of natural or synthetic origin. Amongst these biomaterials, hydroxyapatites (HA) offer good properties of biocompatibility and bioactivity when they interact with bone. This interaction depends mainly on the physico-chemical properties of HA particles. In this work, using a scanning transmission electronic microscope equipped with an Si(Li) detector for x-ray analysis, we analysed three kinds of hydroxyapatite: non-sintered particles, 600 °C sintered particles and 1180 °C sintered particles. Then, we determined the Ca/P concentration ratio in order to observe the influence of the temperature processing on this ratio. Concurrently, we carried out measurements on the HA powders by varying the electron irradiation dose either with the current density or with irradiation time. When the electron irradiation dose varied with the current density (at constant and short irradiation time), the Ca/P concentration ratio did not vary. But, at fixed current density and increasing irradiation time, the calcium and phosphorus intensities decreased, leading to an increase of the Ca/P concentration ratio at high electron irradiation dose. This phenomenon represents a mass loss of the specimen during electronic bombardment. We propose an experimental procedure to avoid all these problems.
-
D-optimal experimental designs to test for departure from additivity in a fixed-ratio mixture ray.
Coffey, Todd; Gennings, Chris; Simmons, Jane Ellen; Herr, David W
2005-12-01
Traditional factorial designs for evaluating interactions among chemicals in a mixture may be prohibitive when the number of chemicals is large. Using a mixture of chemicals with a fixed ratio (mixture ray) results in an economical design that allows estimation of additivity or nonadditive interaction for a mixture of interest. This methodology is extended easily to a mixture with a large number of chemicals. Optimal experimental conditions can be chosen that result in increased power to detect departures from additivity. Although these designs are used widely for linear models, optimal designs for nonlinear threshold models are less well known. In the present work, the use of D-optimal designs is demonstrated for nonlinear threshold models applied to a fixed-ratio mixture ray. For a fixed sample size, this design criterion selects the experimental doses and number of subjects per dose level that result in minimum variance of the model parameters and thus increased power to detect departures from additivity. An optimal design is illustrated for a 2:1 ratio (chlorpyrifos:carbaryl) mixture experiment. For this example, and in general, the optimal designs for the nonlinear threshold model depend on prior specification of the slope and dose threshold parameters. Use of a D-optimal criterion produces experimental designs with increased power, whereas standard nonoptimal designs with equally spaced dose groups may result in low power if the active range or threshold is missed.
-
Chapple, Christopher R; Cardozo, Linda; Snijder, Robert; Siddiqui, Emad; Herschorn, Sender
2016-12-15
Patient-level data are available for 11 randomized, controlled, Phase III/Phase IV solifenacin clinical trials. Meta-analyses were conducted to interrogate the data, to broaden knowledge about solifenacin and overactive bladder (OAB) in general. Before integrating data, datasets from individual studies were mapped to a single format using methodology developed by the Clinical Data Interchange Standards Consortium (CDISC). Initially, the data structure was harmonized, to ensure identical categorization, using the CDISC Study Data Tabulation Model (SDTM). To allow for patient level meta-analysis, data were integrated and mapped to analysis datasets. Mapping included adding derived and categorical variables and followed standards described as the Analysis Data Model (ADaM). Mapping to both SDTM and ADaM was performed twice by two independent programming teams, results compared, and inconsistencies corrected in the final output. ADaM analysis sets included assignments of patients to the Safety Analysis Set and the Full Analysis Set. There were three analysis groupings: Analysis group 1 (placebo-controlled, monotherapy, fixed-dose studies, n = 3011); Analysis group 2 (placebo-controlled, monotherapy, pooled, fixed- and flexible-dose, n = 5379); Analysis group 3 (all solifenacin monotherapy-treated patients, n = 6539). Treatment groups were: solifenacin 5 mg fixed dose, solifenacin 5/10 mg flexible dose, solifenacin 10 mg fixed dose and overall solifenacin. Patient were similar enough for data pooling to be acceptable. Creating ADaM datasets provided significant information about individual studies and the derivation decisions made in each study; validated ADaM datasets now exist for medical history, efficacy and AEs. Results from these meta-analyses were similar over time.
-
ERIC Educational Resources Information Center
Blagov, Pavel S.; Bi, Wu; Shedler, Jonathan; Westen, Drew
2012-01-01
The Shedler-Westen Assessment Procedure (SWAP) is a personality assessment instrument designed for use by expert clinical assessors. Critics have raised questions about its psychometrics, most notably its validity across observers and situations, the impact of its fixed score distribution on research findings, and its test-retest reliability. We…
-
McGiff, Thomas J; Danforth, Robert A; Herschaft, Edward E
2012-08-01
Clinical experience indicates that newly available portable hand-held x-ray units provide advantages compared to traditional fixed properly installed and operated x-ray units in dental radiography. However, concern that hand-held x-ray units produce higher operator doses than fixed x-ray units has caused regulatory agencies to mandate requirements for use of hand-held units that go beyond those recommended by the manufacturer and can discourage the use of this technology. To assess the need for additional requirements, a hand-held x-ray unit and a pair of manikins were used to measure the dose to a simulated operator under two conditions: exposures made according to the manufacturer's recommendations and exposures made according to manufacturer's recommendation except for the removal of the x-ray unit's protective backscatter shield. Dose to the simulated operator was determined using an array of personal dosimeters and a pair of pressurized ion chambers. The results indicate that the dose to an operator of this equipment will be less than 0.6 mSv y⁻¹ if the device is used according to the manufacturer's recommendations. This suggests that doses to properly trained operators of well-designed, hand-held dental x-ray units will be below 1.0 mSv y⁻¹ (2% of the annual occupational dose limit) even if additional no additional operational requirements are established by regulatory agencies. This level of annual dose is similar to those reported as typical dental personnel using fixed x-ray units and appears to satisfy the ALARA principal for this class of occupational exposures.
-
Liew, Danny; Park, Hye-Jin; Ko, Su-Kyoung
2009-10-01
In Korea, the treatment of hypertension and dyslipidemia constitutes an important strategy for the prevention of cardiovascular disease (CVD). This study sought to investigate the cost-effectiveness (from the Korean health care system perspective) of prescribing a proprietary formulation single-tablet fixed-dose combination of amlodipine and atorvastatin (at weighted mean doses of 5 mg and 10.25 mg, respectively) to all eligible patients aged > or = 45 years for the primary prevention of CVD (ie, coronary heart disease and ischemic stroke) in Korea, compared with currently observed patterns of blood-pressure and lipid-lowering medication prescription and use. A Markov model was developed with 4 health states: alive without CVD, alive with CVD, dead from CVD, and dead from non-CVD causes. The model population comprised 244 Koreans aged >/=45 years from the 2005 Korean National Health and Nutrition Examination Survey (KNHNES) without a history of myocardial infarction (MI) or stroke who met current criteria for both blood-pressure and lipid-lowering treatment. From a 2008 baseline, follow-up was simulated for 40 years. Cardiovascular risk was estimated for each subject individually using a multivariate, Asian population-specific equation, and updated with ongoing cycles. Decision analysis compared the effects of prescribing the fixed-dose combination to all subjects versus currently observed patterns of treatment. Data regarding the blood-pressure and lipid-lowering efficacies of combination therapy were drawn from the Respond trial. Costs of the fixed-dose combination tablet and CVD were sourced from pharmaceutical pricing lists and Korean Health Insurance Review and Assessment Services estimates, respectively. Utility values for CVD were obtained from a large Korean utility study. In the model, of the 244 treatment-eligible subjects, 126 (51.6%) and 13 (5.3%) were taking blood-pressure and lipid-lowering therapy, respectively. Use of single-tablet fixed-dose combination amlodipine and atorvastatin by all subjects was associated with estimated incremental cost-effectiveness ratios of 7,773,063 Korean won (KRW) per quality-adjusted life-year gained and 10,378,230 KRW per overall life-year gained (1300 KRW approximately US $1). Sensitivity and uncertainty analyses indicated these results to be robust. In this model, based on data from the 2005 KNHNES, hypertension and dyslipidemia were undertreated among Koreans aged > or = 45 years without a history of MI or stroke. The administration of single-tablet fixed-dose combination amlodipine and atorvastatin to all such individuals was likely to represent a cost-effective means of preventing first-onset CVD (ie, coronary heart disease and ischemic stroke) in this subgroup, compared with current patterns of treatment.
-
Ciraj-Bjelac, Olivera; Antic, Vojislav; Selakovic, Jovana; Bozovic, Predrag; Arandjic, Danijela; Pavlovic, Sinisa
2016-12-01
The purpose of this study was to assess the patient exposure and staff eye dose levels during implantation procedures for all types of pacemaker therapy devices performed under fluoroscopic guidance and to investigate potential correlation between patients and staff dose levels. The mean eye dose during pacemaker/defibrillator implementation was 12 µSv for the first operator, 8.7 µSv for the second operator/nurse and 0.50 µSv for radiographer. Corresponding values for cardiac resynchronisation therapy procedures were 30, 26 and 2.0 µSv, respectively. Significant (p < 0.01) correlation between the eye dose and the kerma-area product was found for the first operator and radiographers, but not for other staff categories. The study revealed eye dose per procedure and eye dose normalised to patient dose indices for different staff categories and provided an input for radiation protection in electrophysiology procedures. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Ma, Xiaosu; Chien, Jenny Y; Johnson, Jennal; Malone, James; Sinha, Vikram
2017-08-01
The purpose of this prospective, model-based simulation approach was to evaluate the impact of various rapid-acting mealtime insulin dose-titration algorithms on glycemic control (hemoglobin A1c [HbA1c]). Seven stepwise, glucose-driven insulin dose-titration algorithms were evaluated with a model-based simulation approach by using insulin lispro. Pre-meal blood glucose readings were used to adjust insulin lispro doses. Two control dosing algorithms were included for comparison: no insulin lispro (basal insulin+metformin only) or insulin lispro with fixed doses without titration. Of the seven dosing algorithms assessed, daily adjustment of insulin lispro dose, when glucose targets were met at pre-breakfast, pre-lunch, and pre-dinner, sequentially, demonstrated greater HbA1c reduction at 24 weeks, compared with the other dosing algorithms. Hypoglycemic rates were comparable among the dosing algorithms except for higher rates with the insulin lispro fixed-dose scenario (no titration), as expected. The inferior HbA1c response for the "basal plus metformin only" arm supports the additional glycemic benefit with prandial insulin lispro. Our model-based simulations support a simplified dosing algorithm that does not include carbohydrate counting, but that includes glucose targets for daily dose adjustment to maintain glycemic control with a low risk of hypoglycemia.
-
Peruzzo Cornetto, Andrea; Aimonetto, Stefania; Pisano, Francesco; Giudice, Marcello; Sicuro, Marco; Meloni, Teodoro; Tofani, Santi
2016-01-01
This study evaluates per-procedure, collective and per capita effective dose to the population by interventional cardiology (IC) procedures performed during 2002–11 at the main hospital of Aosta Valley Region that can be considered as representative of the health-care level I countries, as defined by the UNSCEAR, based on its socio-demographic characteristics. IC procedures investigated were often multiple procedures in patients older than 60 y. The median extreme dose-area product values of 300 and 22 908 cGycm2 were found for standard pacemaker implantation and coronary angioplasty, respectively, while the relative mean per-procedure effective dose ranged from 0.7 to 47 mSv. A 3-fold increase in frequency has been observed together with a correlated increase in the delivered per capita dose (0.05–0.27 mSv y−1) and the collective dose (5.8–35 man Sv y−1). Doses increased particularly from 2008 onwards mainly because of the introduction of coronary angioplasty procedures in the authors’ institution. IC practice contributed remarkably in terms of effective dose to the population, delivering ∼10 % of the total dose by medical ionising radiation examination categories. PMID:26012484
-
Gigante, Antonio; Tagarro, Ignacio
2012-04-01
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed agents for rheumatic disorders such as osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Despite the known association between NSAID use and gastropathy, however, only around one-third of patients at risk of NSAID-induced gastrointestinal toxicity receive adequate gastroprotection, and as many as 44% of these patients are non-adherent. We review the co-prescription of proton pump inhibitors (PPIs) for the prevention of NSAID-induced gastropathy, with a particular focus on the first fixed-dose NSAID/PPI formulation: ketoprofen/omeprazole modified-release capsules. The ketoprofen/omeprazole fixed-dose combination is available in doses of 100 mg/20 mg, 150 mg/20 mg or 200 mg/20 mg as a single capsule for once-daily administration. Ketoprofen monotherapy has been shown to be generally equivalent to other NSAIDs when used in the treatment of OA. In RA, ketoprofen has demonstrated equivalent efficacy to diclofenac, indometacin, piroxicam, aceclofenac, phenylbutazone, naproxen and flurbiprofen. Studies comparing ketoprofen with ibuprofen and sulindac in patients with RA have, in general, favoured ketoprofen. Studies in AS have generally reported similar efficacy between ketoprofen and phenylbutazone and pirprofen. Prophylaxis with omeprazole is effective for the prevention of gastroduodenal ulcers, maintenance of remission and alleviation of dyspeptic symptoms in NSAID recipients. Omeprazole is well tolerated, and adverse events are generally gastrointestinal in nature. The fixed-dose combination of ketoprofen and omeprazole has demonstrated bioequivalence to the respective monotherapies. The incidence of digestive symptoms and the need for dose reduction was reported to be lower with the combination than with its components. Ketoprofen/omeprazole modified-release capsules are the first fixed-dose NSAID/PPI formulation to be approved. This formulation ensures compliance with the gastroprotective prophylaxis, as whenever the NSAID is taken, the PPI is co-administered. Additionally, the once-daily formulation has the potential to improve adherence to anti-inflammatory therapy. © 2012 Adis Data Information BV. All rights reserved.
-
Cushman, William C; Bakris, George L; White, William B; Weber, Michael A; Sica, Domenic; Roberts, Andrew; Lloyd, Eric; Kupfer, Stuart
2012-08-01
Azilsartan medoxomil, an effective, long-acting angiotensin II receptor blocker, is a new treatment for hypertension that is also being developed in fixed-dose combinations with chlorthalidone, a potent, long-acting thiazide-like diuretic. We compared once-daily fixed-dose combinations of azilsartan medoxomil/chlorthalidone force titrated to a high dose of either 40/25 mg or 80/25 mg with a fixed-dose combination of the angiotensin II receptor blocker olmesartan medoxomil plus the thiazide diuretic hydrochlorothiazide force titrated to 40/25 mg. The design was a randomized, 3-arm, double-blind, 12-week study of 1071 participants with baseline clinic systolic blood pressure 160 to 190 mm Hg and diastolic blood pressure ≤119 mm Hg. Patients had a mean age of 57 years; 59% were men, 73% were white, and 22% were black. At baseline, mean clinic blood pressure was 165/96 mm Hg and 24-hour mean blood pressure was 150/88 mm Hg. Changes in clinic (primary end point) and ambulatory systolic blood pressures at week 12 were significantly greater in both azilsartan medoxomil/chlorthalidone arms than in the olmesartan/hydrochlorothiazide arm (P<0.001). Changes in clinic systolic blood pressure (mean±SE) were -42.5±0.8, -44.0±0.8, and -37.1±0.8 mm Hg, respectively. Changes in 24-hour ambulatory systolic blood pressure were -33.9±0.8, -36.3±0.8, and -27.5±0.8 mm Hg, respectively. Adverse events leading to permanent drug discontinuation occurred in 7.9%, 14.5%, and 7.1% of the groups given azilsartan medoxomil/chlorthalidone 40/25 mg, azilsartan medoxomil/chlorthalidone 80/25 mg, and olmesartan/hydrochlorothiazide 40/25 mg, respectively. This large, forced-titration study has demonstrated superior antihypertensive efficacy of azilsartan medoxomil/chlorthalidone fixed-dose combinations compared with the maximum approved dose of olmesartan/hydrochlorothiazide.
-
Determining the use of prophylactic antibiotics in breast cancer surgeries: a survey of practice
2012-01-01
Background Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. Methods An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. Results The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). Conclusion Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery. PMID:22937833
-
Determining the use of prophylactic antibiotics in breast cancer surgeries: a survey of practice.
Acuna, Sergio A; Angarita, Fernando A; Escallon, Jaime; Tawil, Mauricio; Torregrosa, Lilian
2012-08-31
Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhou, S; Zhu, X; Zhang, M
Purpose: Randomness in patient internal organ motion phase at the beginning of non-gated radiotherapy delivery may introduce uncertainty to dose received by the patient. Concerns of this dose deviation from the planned one has motivated many researchers to study this phenomenon although unified theoretical framework for computing it is still missing. This study was conducted to develop such framework for analyzing the effect. Methods: Two reasonable assumptions were made: a) patient internal organ motion is stationary and periodic; b) no special arrangement is made to start a non -gated radiotherapy delivery at any specific phase of patient internal organ motion.more » A statistical ensemble was formed consisting of patient’s non-gated radiotherapy deliveries at all equally possible initial organ motion phases. To characterize the patient received dose, statistical ensemble average method is employed to derive formulae for two variables: expected value and variance of dose received by a patient internal point from a non-gated radiotherapy delivery. Fourier Series was utilized to facilitate our analysis. Results: According to our formulae, the two variables can be computed from non-gated radiotherapy generated dose rate time sequences at the point’s corresponding locations on fixed phase 3D CT images sampled evenly in time over one patient internal organ motion period. The expected value of point dose is simply the average of the doses to the point’s corresponding locations on the fixed phase CT images. The variance can be determined by time integration in terms of Fourier Series coefficients of the dose rate time sequences on the same fixed phase 3D CT images. Conclusion: Given a non-gated radiotherapy delivery plan and patient’s 4D CT study, our novel approach can predict the expected value and variance of patient radiation dose. We expect it to play a significant role in determining both quality and robustness of patient non-gated radiotherapy plan.« less
-
Rizza, S A; Nehra, V; Temesgen, Z
2017-08-01
The United States Food and Drug Administration recently approved sofosbuvir and the fixed-dose combination of ledipasvir/sofosbuvir for the treatment of hepatitis C virus (HCV) infection in children ages 12 to 17. These are the first direct-acting antiviral treatments approved for children and adolescents with HCV. Pharmacokinetic data confirm equivalent drug exposure in this population as that found in adults during clinical trials. The efficacy and safety of these drugs has been shown in clinical trials. Copyright 2017 Clarivate Analytics.
-
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
-
Procedures to handle inventory cluster plots that straddle two or more conditions
Jerold T. Hahn; Colin D. MacLean; Stanford L. Arner; William A. Bechtold
1995-01-01
We review the relative merits and field procedures for four basic plot designs to handle forest inventory plots that straddle two or more conditions, given that subplots will not be moved. A cluster design is recommended that combines fixed-area subplots and variable-radius plot (VRP) sampling. Each subplot in a cluster consists of a large fixed-area subplot for...
-
Smith, Blake; Gelover, Edgar; Moignier, Alexandra; Wang, Dongxu; Flynn, Ryan T.; Lin, Liyong; Kirk, Maura; Solberg, Tim; Hyer, Daniel E.
2016-01-01
Purpose: To quantitatively assess the advantages of energy-layer specific dynamic collimation system (DCS) versus a per-field fixed aperture for spot scanning proton therapy (SSPT). Methods: Five brain cancer patients previously planned and treated with SSPT were replanned using an in-house treatment planning system capable of modeling collimated and uncollimated proton beamlets. The uncollimated plans, which served as a baseline for comparison, reproduced the target coverage and organ-at-risk sparing of the clinically delivered plans. The collimator opening for the fixed aperture-based plans was determined from the combined cross sections of the target in the beam’s eye view over all energy layers which included an additional margin equivalent to the maximum beamlet displacement for the respective energy of that energy layer. The DCS-based plans were created by selecting appropriate collimator positions for each row of beam spots during a Raster-style scanning pattern which were optimized to maximize the dose contributions to the target and limited the dose delivered to adjacent normal tissue. Results: The reduction of mean dose to normal tissue adjacent to the target, as defined by a 10 mm ring surrounding the target, averaged 13.65% (range: 11.8%–16.9%) and 5.18% (2.9%–7.1%) for the DCS and fixed aperture plans, respectively. The conformity index, as defined by the ratio of the volume of the 50% isodose line to the target volume, yielded an average improvement of 21.35% (19.4%–22.6%) and 8.38% (4.7%–12.0%) for the DCS and fixed aperture plans, respectively. Conclusions: The ability of the DCS to provide collimation to each energy layer yielded better conformity in comparison to fixed aperture plans. PMID:27487886
-
Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.
Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar
2017-09-07
Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men. Copyright © 2017 by the American Society of Nephrology.
-
SU-E-T-639: Proton Dose Calculation for Irregular Motion Using a Sliding Interface
DOE Office of Scientific and Technical Information (OSTI.GOV)
Phillips, J; Gueorguiev, G; Grassberger, C
2015-06-15
Purpose: While many techniques exist to evaluate dose to regularly moving lung targets, there are few available to calculate dose at tumor positions not present in the 4DCT. We have previously developed a method that extrapolates an existing dose to a new tumor location. In this abstract, we present a novel technique that accounts for relative anatomical shifts at the chest wall interface. We also utilize this procedure to simulate breathing motion functions on a cohort of eleven patients. Amplitudes exceeding the original range of motion were used to evaluate coverage using several aperture and smearing beam settings. Methods: Themore » water-equivalent depth (WED) technique requires an initial dose and CT image at the corresponding tumor position. Each dose volume was converted from its Cartesian geometry into a beam-specific radiological depth space. The sliding chest wall interface was determined by converting the lung contour into this same space. Any dose proximal to the initial boundary of the warped lung contour was held fixed, while the remaining distal dose was moved in the direction of motion along the interface. Results: V95 coverage was computed for each patient using the updated algorithm. Incorporation of the sliding motion yielded large dose differences, with gamma pass rates as low as 69.7% (3mm, 3%) and V95 coverage differences up to 2.0%. Clinical coverage was maintained for most patients with 5 mm excess simulated breathing motion, and up to 10 mm of excess motion was tolerated for a subset of patients and beam settings. Conclusion: We have established a method to determine the maximum allowable excess breathing motion for a given plan on a patient-by-patient basis. By integrating a sliding chest wall interface into our dose calculation technique, we have analyzed the robustness of breathing patterns that differ during treatment from at the time of 4DCT acquisition.« less
-
Banks, Matthew L; Blough, Bruce E
2015-08-01
Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32-1.8 mg/kg/h) and risperidone (0.001-0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01-0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food choice model.
-
[Is Herceptin(®) (trastuzumab) by subcutaneous a mini revolution? Pharmaco-economic study].
Lieutenant, Vincent; Toulza, Émilie; Pommier, Martine; Lortal-Canguilhem, Barbara
2015-03-01
Herceptin(®) injected by intravenous (IV) is one of the key treatment of breast cancer HER2+. The improvement of galenic form allowed a new way of administration, the sub-cutaneous way (SC), authorized by EMEA in 2013. This new way enables a 5-minute infusion, a fixed dose and a fixed volume of preparation. On 2012, saving-time and financial impacts were calculated by extrapolation of the IV way in a cancer treatment center. The study showed a preparing time-saving of 7.5min/loading dose and of 6.5min/maintenance dose, and a nurse time-saving of 4.5min/loading dose and 4.25min/maintenance dose. Moreover, it can be added a saving of consumable of 13,31€ per injection in case of monotherapy. The SC leads to a new adaptation and reorganization in the preparation of monoclonal antibodies and day hospitals. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
-
Halpern, Bruno; Mancini, Marcio C
2017-01-01
Few studies on combination therapies for the treatment of obesity had been conducted until recently, when two fixed-dose combinations, bupropion-naltrexone ER fixed-dose combination and phentermine-topiramate ER titrated-dose combinations were evaluated in clinical studies that ultimately led to FDA approval. Areas covered: In this review, we discuss safety concerns about both combinations, the rationale and history of combination therapies for obesity (including phentermine plus fenfluramine), and possible future new combinations. Expert opinion: Combination therapies are a promising new area in obesity treatment, similar to what occurs with diabetes and hypertension. Safety assessment is highly important due to the high number of potential users on a chronic basis.
-
P.B., Mohite; R.B., Pandhare; S.G., Khanage
2012-01-01
Purpose: Lamivudine is cytosine and zidovudine is cytidine and is used as an antiretroviral agents. Both drugs are available in tablet dosage forms with a dose of 150 mg for LAM and 300 mg ZID respectively. Method: The method employed is based on first order derivative spectroscopy. Wavelengths 279 nm and 300 nm were selected for the estimation of the Lamovudine and Zidovudine respectively by taking the first order derivative spectra. The conc. of both drugs was determined by proposed method. The results of analysis have been validated statistically and by recovery studies as per ICH guidelines. Result: Both the drugs obey Beer’s law in the concentration range 10-50 μg mL-1,for LAM and ZID; with regression 0.9998 and 0.9999, intercept – 0.0677 and – 0.0043 and slope 0.0457 and 0.0391 for LAM and ZID, respectively.The accuracy and reproducibility results are close to 100% with 2% RSD. Conclusion: A simple, accurate, precise, sensitive and economical procedures for simultaneous estimation of Lamovudine and Zidovudine in tablet dosage form have been developed. PMID:24312779
-
Freitas, Kelen; Carroll, F. Ivy; Negus, S. Stevens
2015-01-01
Intracranial self-stimulation (ICSS) is one type of preclinical procedure for research on pharmacological mechanisms that mediate abuse potential of drugs acting at various targets including nicotinic acetylcholine receptors (nAChRs). This study compared effects of the non-selective nAChR agonist nicotine (0.032-1.0 mg/kg) and the α4β2-selective nAChR agonist 5-I-A-85380 (0.01-1.0 mg/kg) on ICSS in male Sprague-Dawley rats. Rats were implanted with electrodes targeting the medial forebrain bundle at the level of the lateral hypothalamus and trained to respond under a fixed-ratio 1 schedule for a range of brain stimulation frequencies (158-56 Hz). A broad range of 5-I-A-85380 doses produced an abuse-related increase (or “facilitation”) of low ICSS rates maintained by low brain-stimulation frequencies, and this effect was blocked by both the nonselective nAChR antagonist mecamylamine and the selective α4β2 antagonist dihyrdo-ß-erythroidine (DHßE). Conversely, nicotine produced weaker ICSS facilitation across a narrower range of doses, and higher nicotine doses decreased high rates of ICSS maintained by high brain- stimulation frequencies. The rate-decreasing effects of a high nicotine dose were blocked by mecamylamine but not DHßE. Chronic nicotine treatment produced selective tolerance to rate-decreasing effects of nicotine but did not alter ICSS rate-increasing effects of nicotine. These results suggest that α4β2 receptors are sufficient to mediate abuse-related rate-increasing effects of nAChR agonists in this ICSS procedure. Conversely, nicotine effects at non-α4β2 nAChRs appear to oppose and limit abuse-related effects mediated by α4β2 receptors, although tolerance can develop to these non-α4β2 effects. Selective α4β2 agonists may have higher abuse potential than nicotine. PMID:26461167
-
NASA Astrophysics Data System (ADS)
Angel, Erin
Advances in Computed Tomography (CT) technology have led to an increase in the modality's diagnostic capabilities and therefore its utilization, which has in turn led to an increase in radiation exposure to the patient population. As a result, CT imaging currently constitutes approximately half of the collective exposure to ionizing radiation from medical procedures. In order to understand the radiation risk, it is necessary to estimate the radiation doses absorbed by patients undergoing CT imaging. The most widely accepted risk models are based on radiosensitive organ dose as opposed to whole body dose. In this research, radiosensitive organ dose was estimated using Monte Carlo based simulations incorporating detailed multidetector CT (MDCT) scanner models, specific scan protocols, and using patient models based on accurate patient anatomy and representing a range of patient sizes. Organ dose estimates were estimated for clinical MDCT exam protocols which pose a specific concern for radiosensitive organs or regions. These dose estimates include estimation of fetal dose for pregnant patients undergoing abdomen pelvis CT exams or undergoing exams to diagnose pulmonary embolism and venous thromboembolism. Breast and lung dose were estimated for patients undergoing coronary CTA imaging, conventional fixed tube current chest CT, and conventional tube current modulated (TCM) chest CT exams. The correlation of organ dose with patient size was quantified for pregnant patients undergoing abdomen/pelvis exams and for all breast and lung dose estimates presented. Novel dose reduction techniques were developed that incorporate organ location and are specifically designed to reduce close to radiosensitive organs during CT acquisition. A generalizable model was created for simulating conventional and novel attenuation-based TCM algorithms which can be used in simulations estimating organ dose for any patient model. The generalizable model is a significant contribution of this work as it lays the foundation for the future of simulating TCM using Monte Carlo methods. As a result of this research organ dose can be estimated for individual patients undergoing specific conventional MDCT exams. This research also brings understanding to conventional and novel close reduction techniques in CT and their effect on organ dose.
-
[Granulomatous sporotrichosis: report of two unusual cases].
Ramírez-Soto, Max; Lizárraga-Trujillo, José
2013-10-01
Sporotrichosis is a subcutaneous mycosis caused by Sporothrix complex, endemic in Abancay, Peru. Is acquired by traumatic inoculation with plant material. Common clinical presentations are lymphatic cutaneous and fixed cutaneous disease. We report 2 cases of fixed cutaneous sporotrichosis with granulomatous appearance. The first case was a patient of 65 years old with no risk factors and the second case was a 67 year old diabetic patient. Subjects underwent mycological culture with Sabouraud agar, with isolation of Sporothrix schenckii and clinical dignosis of fixed cutaneous sporotrichosis with granulomatous appearance. One patient received oral treatment with saturated solution of potassium iodide (SSKI) with a initial dose of 3 drops tid up to a maximum dose of 40 drops tid. Mycological and clinical cure was achieved after 2 months of treatment. We should consider the unusual clinical presentations of fixed cutaneous sporotrichosis with granulomatous appearance that present morphological and clinical features in diabetic and nondiabetic patients older than 60 years from endemic areas and communicate adequate response to treatment with SSKI in one case.
-
NASA Astrophysics Data System (ADS)
Yoo, Seung Hoon; Son, Jae Man; Yoon, Myonggeun; Park, Sung Yong; Shin, Dongho; Min, Byung Jun
2018-06-01
A moving phantom is manufactured for mimicking lung model to study the dose uncertainty from CT number-stopping power conversion and dose calculation in the soft tissue, light lung tissue and bone regions during passive proton irradiation with compensator smearing value. The phantom is scanned with a CT system, and a proton beam irradiation plan is carried out with the use of a treatment planning system (Eclipse). In the case of the moving phantom, a RPM system is used for respiratory gating. The uncertainties in the dose distribution between the measured data and the planned data are investigated by a gamma analysis with 3%-3 mm acceptance criteria. To investigate smearing effect, three smearing values (0.3 cm, 0.7 cm, 1.2 cm) are used to for fixed and moving phantom system. For both fixed and moving phantom, uncertainties in the light lung tissue are severe than those in soft tissue region in which the dose uncertainties are within clinically tolerable ranges. As the smearing value increases, the uncertainty in the proton dose distribution decreases.
-
Kaithwas, Gaurav; Majumdar, Dipak K
2010-06-01
The present study was undertaken to assess the activity/anti-inflammatory potential of Linum usitatissimum fixed oil against castor oil-induced diarrhoea, turpentine oil-induced joint oedema, formaldehyde and Complete Freund's Adjuvant (CFA)-induced arthritis in Wistar albino rats. The oil intraperitoneally, significantly inhibited the castor oil-induced diarrhoea and turpentine oil-induced exudative joint oedema in a dose-dependent manner. Significant inhibitory effect of L. usitatissimum fixed oil was observed in formaldehyde-induced proliferative global oedematous arthritis when given intraperitoneally, with significant checking of the serum glutamic oxaloacetic acid transaminase and serum glutamic pyruvic acid transaminase. Further, L. usitatissimum fixed oil showed a significant dose-dependent protective effect against CFA-induced arthritis as well. Secondary lesions produced by CFA due to a delayed hypersensitivity reaction were also reduced in a significant manner. Anti-inflammatory activity of L. usitatissimum fixed oil can be attributed to the presence of alpha linolenic acid (57.38%, an omega-3 fatty acid, 18:3, n-3) having dual inhibitory effect on arachidonate metabolism resulting in suppressed production of proinflammatory n-6 eicosanoids (PGE(2), LTB(4)) and diminished vascular permeability. These observations suggest possible therapeutic potential of L. usitatissimum fixed oil in inflammatory disorders like rheumatoid arthritis.
-
Schreiber, Shaul; Barak, Yonatan; Hostovsky, Avner; Baratz-Goldstein, Renana; Volis, Ina; Rubovitch, Vardit; Pick, Chaim G
2014-04-01
We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p < 0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn.
-
Automatic dispensing of liquid nitrogen in submilliliter doses
NASA Astrophysics Data System (ADS)
Milner, C. J.
1984-10-01
Well-controlled doses of 0.2 to 0.5 ml of liquid nitrogen are delivered, on electrical signal (not more than once per 5 s), as fills of a miniature bucket raised by an automatic hoist. The bucket is lifted, brimming, from the storage flask and then moved sideways until over the receiver. At this point, a steel ball, which has been resting in and sealing a drain hole in the bucket, is lifted from its seat by a magnet fixed alongside the (now descending) bucket. Design features are outlined: some alternative designs, valving liquid through a short drain tube fixed in the storage flask, are briefly reviewed. In tests the device delivered 74 g (approx. 260 doses) during 63 min, the loss by evaporation meanwhile being 11 g from the bucket, implying a transfer efficiency of 87%. An indirect measure indicated the dose sizes as 354±10 μl approximately.
-
Lens of the eye dose calculation for neuro-interventional procedures and CBCT scans of the head
NASA Astrophysics Data System (ADS)
Xiong, Zhenyu; Vijayan, Sarath; Rana, Vijay; Jain, Amit; Rudin, Stephen; Bednarek, Daniel R.
2016-03-01
The aim of this work is to develop a method to calculate lens dose for fluoroscopically-guided neuro-interventional procedures and for CBCT scans of the head. EGSnrc Monte Carlo software is used to determine the dose to the lens of the eye for the projection geometry and exposure parameters used in these procedures. This information is provided by a digital CAN bus on the Toshiba Infinix C-Arm system which is saved in a log file by the real-time skin-dose tracking system (DTS) we previously developed. The x-ray beam spectra on this machine were simulated using BEAMnrc. These spectra were compared to those determined by SpekCalc and validated through measured percent-depth-dose (PDD) curves and half-value-layer (HVL) measurements. We simulated CBCT procedures in DOSXYZnrc for a CTDI head phantom and compared the surface dose distribution with that measured with Gafchromic film, and also for an SK150 head phantom and compared the lens dose with that measured with an ionization chamber. Both methods demonstrated good agreement. Organ dose calculated for a simulated neuro-interventional-procedure using DOSXYZnrc with the Zubal CT voxel phantom agreed within 10% with that calculated by PCXMC code for most organs. To calculate the lens dose in a neuro-interventional procedure, we developed a library of normalized lens dose values for different projection angles and kVp's. The total lens dose is then calculated by summing the values over all beam projections and can be included on the DTS report at the end of the procedure.
-
DOSE COEFFICIENTS FOR LIVER CHEMOEMBOLISATION PROCEDURES USING MONTE CARLO CODE.
Karavasilis, E; Dimitriadis, A; Gonis, H; Pappas, P; Georgiou, E; Yakoumakis, E
2016-12-01
The aim of the present study is the estimation of radiation burden during liver chemoembolisation procedures. Organ dose and effective dose conversion factors, normalised to dose-area product (DAP), were estimated for chemoembolisation procedures using a Monte Carlo transport code in conjunction with an adult mathematical phantom. Exposure data from 32 patients were used to determine the exposure projections for the simulations. Equivalent organ (H T ) and effective (E) doses were estimated using individual DAP values. The organs receiving the highest amount of doses during these exams were lumbar spine, liver and kidneys. The mean effective dose conversion factor was 1.4 Sv Gy -1 m -2 Dose conversion factors can be useful for patient-specific radiation burden during chemoembolisation procedures. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain
Pergolizzi, Joseph V; van de Laar, Mart; Langford, Richard; Mellinghoff, Hans-Ulrich; Merchante, Ignacio Morón; Nalamachu, Srinivas; O’Brien, Joanne; Perrot, Serge; Raffa, Robert B
2012-01-01
Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a “do ask, do tell” approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with minimal toxicity. PMID:23055775
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rong, Yi, E-mail: yi.rong@osumc.edu; Chen, Yu; Lu, Weiguo
Purpose: Despite superior target dose uniformity, helical tomotherapy{sup ®} (HT) may involve a trade-off between longitudinal dose conformity and beam-on time (BOT), due to the limitation of only three available jaw sizes with the conventional HT (1.0, 2.5, and 5.0 cm). The recently introduced dynamic running-start-stop (RSS) delivery allows smaller jaw opening at the superior and inferior ends of the target when a sharp penumbra is needed. This study compared the dosimetric performance of RSS delivery with the fixed jaw HT delivery. Methods: Twenty patient cases were selected and deidentified prior to treatment planning, including 16 common clinical cases (brain,more » head and neck (HN), lung, and prostate) and four special cases of whole brain with hippocampus avoidance (WBHA) that require a high degree of dose modulation. HT plans were generated for common clinical cases using the fixed 2.5 cm jaw width (HT2.5) and WBHA cases using 1.0 cm (HT1.0). The jaw widths for RSS were preset with a larger size (RSS5.0 vs HT2.5 and RSS2.5 vs HT1.0). Both delivery techniques were planned based on identical contours, prescriptions, and planning objectives. Dose indices for targets and critical organs were compared using dose-volume histograms, BOT, and monitor units. Results: The average BOT was reduced from 4.8 min with HT2.5 to 2.5 min with RSS5.0. Target dose homogeneity with RSS5.0 was shown comparable to HT2.5 for common clinical sites. Superior normal tissue sparing was observed in RSS5.0 for optic nerves and optic chiasm in brain and HN cases. RSS5.0 demonstrated improved dose sparing for cord and esophagus in lung cases, as well as penile bulb in prostate cases. The mean body dose was comparable for both techniques. For the WBHA cases, the target homogeneity was significantly degraded in RSS2.5 without distinct dose sparing for hippocampus, compared to HT1.0. Conclusions: Compared to the fixed jaw HT delivery, RSS combined with a larger jaw width provides faster treatment delivery and improved cranial-caudal target dose conformity. The target coverage achieved by RSS with a large jaw width is comparable to the fixed jaw HT delivery for common cancer sites, but may deteriorate for cases where complex geometry is present in the middle part of the target.« less
-
Opposing Effects of Dopamine D1- and D2-Like Agonists on Intracranial Self-Stimulation in Male Rats
Lazenka, Matthew F.; Legakis, Luke P.; Negus, S. Stevens
2016-01-01
Dopamine acts through dopamine type 1 receptors (comprised of D1 and D5 subtypes) and dopamine type 2 receptors (comprised of D2, D3 and D4 subtypes). Intracranial self-stimulation (ICSS) is one experimental procedure that can be used to evaluate abuse-related effects of drugs targeting dopamine receptors. This study evaluated effects of dopamine receptor ligands on ICSS in rats using experimental procedures that have been used previously to examine abused indirect dopamine agonists such as cocaine and amphetamine. Male Sprague-Dawley rats responded under a fixed-ratio 1 schedule for electrical stimulation of the medial forebrain bundle, and frequency of stimulation varied from 56–158 Hz in 0.05 log increments during each experimental session. Drug potency and time course were determined for the D1 ligands A77636, SKF82958, SKF38393, fenoldopam and SCH39166 and the D2/3 ligands sumanirole, apomorphine, quinpirole, PD128907, pramipexole, aripiprazole, eticolopride and PG01037. The high-efficacy D1 agonists A77636 and SKF82958 produced dose-dependent, time-dependent, and abuse-related facilitation of ICSS. Lower efficacy D1 ligands and all D2/3 ligands failed to facilitate ICSS at any dose or pretreatment time. A mixture of SKF82958 and quinpirole produced a mixture of effects produced by each drug alone. Quinpirole also failed to facilitate ICSS after regimens of repeated treatment with either quinpirole or cocaine. These studies provide more evidence for divergent effects of dopamine D1- and D2-family agonists on ICSS procedure in rats and suggest that ICSS may be a useful complement to other approaches for preclinical abuse potential assessment, in part because of the reproducibility of results. PMID:26987070
-
O'Connor, U; Gallagher, A; Malone, L; O'Reilly, G
2013-02-01
Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure that combines the use of X-ray fluoroscopy and endoscopy for examination of the bile duct. Published data on ERCP doses are limited, including staff eye dose from ERCP. Occupational eye doses are of particular interest now as the International Commission on Radiological Protection (ICRP) has recommended a reduction in the dose limit to the lens of the eye. The aim of this study was to measure occupational eye doses obtained from ERCP procedures. A new eye lens dosemeter (EYE-D(™), Radcard, Krakow, Poland) was used to measure the ERCP eye dose, H(p)(3), at two endoscopy departments in Ireland. A review of radiation protection practice at the two facilities was also carried out. The mean equivalent dose to the lens of the eye of a gastroenterologist is 0.01 mSv per ERCP procedure with an undercouch X-ray tube and 0.09 mSv per ERCP procedure with an overcouch X-ray tube. Staff eye dose normalised to patient kerma area product is also presented. Staff eye doses in ERCP have the potential to exceed the revised ICRP limit of 20 mSv per annum when an overcouch X-ray tube is used. The EYE-D dosemeter was found to be a convenient method for measuring lens dose. Eye doses in areas outside of radiology departments should be kept under review, particularly in light of the new ICRP eye dose limit. Occupational eye lens doses from ERCP procedures have been established using a new commercially available dedicated H(p)(3) dosemeter.
-
PEST reduces bias in forced choice psychophysics.
Taylor, M M; Forbes, S M; Creelman, C D
1983-11-01
Observers performed several different detection tasks using both the PEST adaptive psychophysical procedure and a fixed-level (method of constant stimuli) psychophysical procedure. In two experiments, PEST runs targeted at P (C) = 0.80 were immediately followed by fixed-level detection runs presented at the difficulty level resulting from the PEST run. The fixed-level runs yielded P (C) about 0.75. During the fixed-level runs, the probability of a correct response was greater when the preceding response was correct than when it was wrong. Observers, even highly trained ones, perform in a nonstationary manner. The sequential dependency data can be used to determine a lower bound for the observer's "true" capability when performing optimally; this lower bound is close to the PEST target, and well above the forced choice P (C). The observer's "true" capability is the measure used by most theories of detection performance. A further experiment compared psychometric functions obtained from a set of PEST runs using different targets with those obtained from blocks of fixed-level trials at different levels. PEST results were more stable across observers, performance at all but the highest signal levels was better with PEST, and the PEST psychometric functions had shallower slopes. We hypothesize that PEST permits the observer to keep track of what he is trying to detect, whereas in the fixed-level method performance is disrupted by memory failure. Some recently suggested "more virulent" versions of PEST may be subject to biases similar to those of the fixed-level procedures.(ABSTRACT TRUNCATED AT 250 WORDS)
-
Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Itamura, Rio; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki
2016-01-01
The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75-225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (-10.76; P=0.031), but not in the flexible-dose (-10.37; P=0.106) group compared with placebo (-9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan.
-
Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki
2016-01-01
The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75–225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (−10.76; P=0.031), but not in the flexible-dose (−10.37; P=0.106) group compared with placebo (−9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan. PMID:26513202
-
Bijlsma, Maarten J; Janssen, Fanny; Hak, Eelko
2016-03-01
Accurate measurement of drug adherence is essential for valid risk-benefit assessments of pharmacologic interventions. To date, measures of drug adherence have almost exclusively been applied for a fixed-time interval and without considering changes over time. However, patients with irregular dosing behaviour commonly have a different prognosis than patients with stable dosing behaviour. We propose a method, based on the proportion of days covered (PDC) method, to measure time-varying drug adherence and drug dosage using electronic records. We compare a time-fixed PDC method with the time-varying PDC method through detailed examples and through summary statistics of 100 randomly selected patients on statin therapy. We demonstrate that time-varying PDC method better distinguishes an irregularly dosing patient from a stably dosing patient and demonstrate how the time-fixed method can result in a biassed estimate of drug adherence. Furthermore, the time-varying PDC method may be better used to reduce certain types of confounding and misclassification of exposure. The time-varying PDC method may improve longitudinal and time-to-event studies that associate adherence with a clinical outcome or (intervention) studies that seek to describe changes in adherence over time. Copyright © 2015 John Wiley & Sons, Ltd.
-
SU-E-T-609: Perturbation Effects of Pedicle Screws On Radiotherapy Dose Distributions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bar-Deroma, R; Borzov, E; Nevelsky, A
2015-06-15
Purpose: Radiation therapy in conjunction with surgical implant fixation is a common combined treatment in case of bone metastases. However, metal implants generally used in orthopedic implants perturb radiation dose distributions. Carbon-Fiber Reinforced (CFR) PEEK material has been recently introduced for production of intramedullary screws and plates. Gold powder can be added to the CFR-PEEK material in order to enhance visibility of the screws during intraoperative imaging procedures. In this work, we investigated the perturbation effects of the pedicle screws made of CFR-PEEK, CFR-PEEK with added gold powder (CFR-PEEK-AU) and Titanium (Ti) on radiotherapy dose distributions. Methods: Monte Carlo (MC)more » simulations were performed using the EGSnrc code package for 6MV beams with 10×10 fields at SSD=100cm. By means of MC simulations, dose distributions around titanium, CFR- PEEK and CFR-PEEK-AU screws (manufactured by Carbo-Fix Orthopedics LTD, Israel) placed in a water phantom were calculated. The screw axis was either parallel or perpendicular to the beam axis. Dose perturbation (relative to dose in homogeneous water phantom) was assessed. Results: Maximum overdose due to backscatter was 10% for the Ti screws, 5% for the CFR-PEEK-AU screws and effectively zero for the CFR-PEEK screws. Maximum underdose due to attenuation was 25% for the Ti screws, 15% for the CFR-PEEK-AU screws and 5% for the CFR-PEEK screws. Conclusion: Titanium screws introduce the largest distortion on the radiation dose distribution. The gold powder added to the CFR-PEEK material improves visibility at the cost of increased dose perturbation. CFR-PEEK screws caused minimal alteration on the dose distribution. This can decrease possible over and underdose of adjacent tissue and thus favorably influence treatment efficiency. The use of such implants has potential clinical advantage in the treatment of neoplastic bone disease.« less
-
Husic, Samir; Izic, Senad; Matic, Srecko; Sukalo, Aziz
2015-01-01
Goal: The goal of the research was to determine the efficacy of a fixed combination of tramadol and paracetamol (acetaminophen) in the treatment of pain of patients with the advanced stage of cancer. Material and methods: A prospective study was conducted at the Center for Palliative Care, University Clinical Center Tuzla, Bosnia and Herzegovina, from January 1st to December 31st 2013. A total of 353 patients who were treated with a fixed combination of tramadol and acetaminophen (37.5 mg and 325 mg) at the initial dosage 3x1 tablet (112.5 mg tramadol and 975 mg acetaminophen) for pain intensity 4, up to 4x2 tablets (300 mg of tramadol and 2600 mg paracetamol) for pain intensity 7 and 8. If the patient during previous day has two or more pain episodes that required a “rescue dose” of tramadol, increased was the dose of fixed combination tramadol and acetaminophen to a maximum of 8 tablets daily (300 mg of tramadol and 2600 mg paracetamol). Statistical analysis was performed by biomedical software MedCalc for Windows version 9.4.2.0. The difference was considered significant for P<0.05. Results: The average duration of treatment with a fixed combination tramadol and acetaminophen was 57 days (13-330 days). Already after 24 hours of treatment the average pain score was significantly lower (p<0.0001) compared to the admission day [5.00 (4:00 to 8:00) during the first days versus 2.00 (1:00 to 7:00) during the second day of treatment]. The average dose of the fixed combination tramadol and acetaminophen tablets was 4.8 ± 1.8 (180 mg of tramadol and 1560 mg paracetamol). Side effects, in the treatment of pain with a fixed combination tramadol and acetaminophen, were found in 29.18% of patients, with a predominance of nausea and vomiting. Conclusion: Fixed combination of tramadol and acetaminophen can be used as an effective combination in the treatment of chronic cancer pain, with frequent dose evaluation and mild side effects. PMID:25870531
-
Lai, Priscilla; McNeil, Sarah M; Gordon, Christopher L; Connolly, Bairbre L
2014-12-01
The purpose of this study was to determine the range of effective doses associated with imaging techniques used during interventional radiology procedures on children. A pediatric phantom set (1, 5, and 10 years) coupled with high-sensitivity metal oxide semiconductor field effect transistor (MOSFET) dosimeters was used to calculate effective doses. Twenty MOSFETs were inserted into each phantom at radiosensitive organ locations. The phantoms were exposed to mock head, chest, and abdominal interventional radiology procedures performed with different geometries and magnifications. Fluoroscopy, digital subtraction angiography (DSA), and spin angiography were simulated on each phantom. Road mapping was conducted only on the 5-year-old phantom. International Commission on Radiological Protection publication 103 tissue weights were applied to the organ doses recorded with the MOSFETs to determine effective dose. For easy application to clinical cases, doses were normalized per minute of fluoroscopy and per 10 frames of DSA or spin angiography. Effective doses from DSA, angiography, and fluoroscopy were higher for younger ages because of magnification use and were largest for abdominal procedures. DSA of the head, chest, and abdomen (normalized per 10 frames) imparted doses 2-3 times as high as corresponding doses per minute of fluoroscopy while all other factors remained unchanged (age, projection, collimation, magnification). Three to five frames of DSA imparted an effective dose equal to doses from 1 minute of fluoroscopy. Doses from spin angiography were almost one-half the doses received from an equivalent number of frames of DSA. Patient effective doses during interventional procedures vary substantially depending on procedure type but tend to be higher because of magnification use in younger children and higher in the abdomen.
-
Eye lens exposure to medical staff during endoscopic retrograde cholangiopancreatography.
Zagorska, A; Romanova, K; Hristova-Popova, J; Vassileva, J; Katzarov, K
2015-11-01
The paper presents a study of the radiation doses to eye lens of medical staff during endoscopic retrograde cholangiopancreatography (ERCP) procedures performed in a busy gastroenterology department. For each procedure the dose equivalent to the eye, exposure time, dose rate, Kerma Area Product and fluoroscopy time were recorded. Measurements were performed for a period of two months in four main positions of the operating staff, and then extrapolated to estimate annual doses. The fluoroscopy time per ERCP procedure varied between 1.0 min and 28.8 min, with a mean value of 4.6 min. The calculated mean eye dose per procedure varied between 34.9 μSv and 93.3 μSv. The results demonstrated that if eye protection is not used, annual doses to the eye lens of the gastroenterologist performing the procedure and the anesthesiologist can exceed the dose limit of 20 mSv per year. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Best, R; Harrell, A; Geesey, C
2014-06-15
Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parametersmore » of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%±15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%±15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%±13.8% and 27.5%±12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.2±0.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference trends of more statistical significance.« less
-
Drug discrimination under two concurrent fixed-interval fixed-interval schedules.
McMillan, D E; Li, M
2000-07-01
Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent schedules in which the reinforcement frequency under the schedule components differs only by a factor of two, and that when other drugs are substituted for the training drugs they produce dose-response curves similar to the curves produced by these drugs under other concurrent interval schedules.
-
Hirabayashi, Yoshihiro; Kawakami, Takayuki; Suzuki, Hideo; Igarashi, Takashi; Saitoh, Kazuhiko; Seo, Norimasa
2005-09-01
Syringe swap is an important problem in anesthetic care, causing harm to patients. We examined the effect of colored syringe and a colored sheet on the incidence of syringe swaps during anesthetic management. We determined the color code. The blue-syringe contains local anesthetics; yellow-syringe, sympathomimetic drugs; and white-syringe with a red label fixed opposite the scale, muscle relaxants. The colored sheet displays the photographs of the syringe with drug name, dose and volume. The colored syringe and colored sheet were supplied for use from February 2004. We compared the incidence of syringe swaps during the period from February 2004 to January 2005 with that from February 2003 to January 2004. Although five syringe swaps were recorded from February 2003 to January 2004, in 5901 procedures, we encountered no syringe swaps from February 2004 to January 2005, in 6078 procedures. The colored syringe and colored sheet significantly decreased the incidence of syringe swaps during anesthetic management (P <0.05). The use of the sheet together with colored syringes can prevent syringe swaps during anesthesia.
-
Zeichner, Joshua A; Patel, Rita V; Haddican, Madelaine; Wong, Vicky
2012-06-01
Combination therapy addressing multiple pathogenic factors should be used to achieve optimal outcomes in treating acne. The following study demonstrated both safety and efficacy of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% in the morning with micronized tretinoin 0.05% gel in the evening. Both products were applied to the skin following the use of a ceramide containing moisturizing lotion.
-
Kodama, Y; Furumatsu, T; Fujii, M; Tanaka, T; Miyazawa, S; Ozaki, T
2016-11-01
A medial meniscus posterior root tear (MMPRT) may increase the tibiofemoral contact pressure by decreasing the tibiofemoral contact area. Meniscal dysfunction induced by posterior root injury may lead to the development of osteoarthritic knees. Repair of a MMPRT can restore medial meniscus (MM) function and prevent knee osteoarthritis progression. Several surgical procedures have been reported for treating a MMPRT. However, these procedures are associated with several technical difficulties. Here, we describe a technique to stabilize a torn MM posterior root using the FasT-Fix ® all-inside meniscal suture device and a new aiming device. The uncut free-end of the FasT-Fix ® suture can be used as a thread for transtibial pullout repair. Our procedure might help overcome the technical difficulties in arthroscopic treatment of a MMPRT. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
-
SU-G-IeP3-13: Real-Time Patient and Staff Dose Monitoring in Fluoroscopy Guided Interventions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vergoossen, L; Sailer, A; Paulis, L
Purpose: Interventional radiology procedures involve the use of X-rays, which can pose a large radiation burden on both patients and staff. Although some reports on radiation dose are available, most studies focus on limited types of procedures and only report patient dose. In our cathlabs a dedicated real-time patient and staff monitoring system was installed in November 2015. The aim of this study was to investigate the patient and staff dose exposure for different types of interventions. Methods: Radiologists involved in fluoroscopy guided interventional radiology procedures wore personal dose meters (PDM, DoseAware, Philips) on their lead-apron that measured the personalmore » dose equivalent Hp(10), a measure for the effective dose (E). Furthermore, reference PDMs were installed in the C-arms of the fluoroscopy system (Allura XPer, Philips). Patient dose-area-product (DAP) and PDM doses were retrieved from the monitoring system (DoseWise, Philips) for each procedure. A total of 399 procedures performed between November 2015 and February 2016 were analyzed with respect to the type of intervention. Interventions were grouped by anatomy and radiologist position. Results: The mean DAP for the different types of interventions ranged from 2.86±2.96 Gycm{sup 2} (percutaneous gastrostomy) to 147±178 Gycm{sup 2} (aortic repair procedures). The radiologist dose (E) ranged from 5.39±7.38 µSv (cerebral interventions) to 84.7±106 µSv (abdominal interventions) and strongly correlated with DAP (R{sup 2}=0.83). The E normalized to DAP showed that the relative radiologist dose was higher for interventions in larger body parts (e.g. abdomen) compared to smaller body parts (e.g. head). Conclusion: Using a real-time dose monitoring system we were able to assess the staff and patient dose revealing that the relative staff dose strongly depended on the type of procedure and patient anatomy. This could be explained by the position of the radiologist with respect to the patient and X-ray tube. To facilitate this study L Vergoossen received a scholarship from Philips Medical Systems.« less
-
Radiation Dose Estimation for Pediatric Patients Undergoing Cardiac Catheterization
NASA Astrophysics Data System (ADS)
Wang, Chu
Patients undergoing cardiac catheterization are potentially at risk of radiation-induced health effects from the interventional fluoroscopic X-ray imaging used throughout the clinical procedure. The amount of radiation exposure is highly dependent on the complexity of the procedure and the level of optimization in imaging parameters applied by the clinician. For cardiac catheterization, patient radiation dosimetry, for key organs as well as whole-body effective, is challenging due to the lack of fixed imaging protocols, unlike other common X-ray based imaging modalities. Pediatric patients are at a greater risk compared to adults due to their greater cellular radio-sensitivities as well as longer remaining life-expectancy following the radiation exposure. In terms of radiation dosimetry, they are often more challenging due to greater variation in body size, which often triggers a wider range of imaging parameters in modern imaging systems with automatic dose rate modulation. The overall objective of this dissertation was to develop a comprehensive method of radiation dose estimation for pediatric patients undergoing cardiac catheterization. In this dissertation, the research is divided into two main parts: the Physics Component and the Clinical Component. A proof-of-principle study focused on two patient age groups (Newborn and Five-year-old), one popular biplane imaging system, and the clinical practice of two pediatric cardiologists at one large academic medical center. The Physics Component includes experiments relevant to the physical measurement of patient organ dose using high-sensitivity MOSFET dosimeters placed in anthropomorphic pediatric phantoms. First, the three-dimensional angular dependence of MOSFET detectors in scatter medium under fluoroscopic irradiation was characterized. A custom-made spherical scatter phantom was used to measure response variations in three-dimensional angular orientations. The results were to be used as angular dependence correction factors for the MOSFET organ dose measurements in the following studies. Minor angular dependence (< +/-20% at all angles tested, < +/-10% at clinically relevant angles in cardiac catheterization) was observed. Second, the cardiac dose for common fluoroscopic imaging techniques for pediatric patients in the two age groups was measured. Imaging technique settings with variations of individual key imaging parameters were tested to observe the quantitative effect of imaging optimization or lack thereof. Along with each measurement, the two standard system output indices, the Air Kerma (AK) and Dose-Area Product (DAP), were also recorded and compared to the measured cardiac and skin doses -- the lack of correlation between the indices and the organ doses shed light to the substantial limitation of the indices in representing patient radiation dose, at least within the scope of this dissertation. Third, the effective dose (ED) for Posterior-Anterior and Lateral fluoroscopic imaging techniques for pediatric patients in the two age groups was determined. In addition, the dosimetric effect of removing the anti-scatter grid was studied, for which a factor-of-two ED rate reduction was observed for the imaging techniques. The Clinical Component involved analytical research to develop a validated retrospective cardiac dose reconstruction formulation and to propose the new Optimization Index which evaluates the level of optimization of the clinician's imaging usage during a procedure; and small sample group of actual procedures were used to demonstrate applicability of these formulations. In its entirety, the research represents a first-of-its-kind comprehensive approach in radiation dosimetry for pediatric cardiac catheterization; and separately, it is also modular enough that each individual section can serve as study templates for small-scale dosimetric studies of similar purposes. The data collected and algorithmic formulations developed can be of use in areas of personalized patient dosimetry, clinician training, image quality studies and radiation-associated health effect research.
-
Amphetamine increases schedule-induced drinking reduced by negative punishment procedures.
Pérez-Padilla, Angeles; Pellón, Ricardo
2003-05-01
d-Amphetamine has been reported to increase schedule-induced drinking punished by lick-dependent signalled delays in food delivery. This might reflect a drug-behaviour interaction dependent on the type of punisher, because no such effect has been found when drinking was reduced by lick-contingent electric shocks. However, the anti-punishment effect of amphetamine could be mediated by other behavioural processes, such as a loss of discriminative control or an increase in the value of delayed reinforcers. To test the effects of d-amphetamine on the acquisition and maintenance of schedule-induced drinking reduced by unsignalled delays in food delivery. Rats received 10-s unsignalled delays initiated by each lick after polydipsia was induced by a fixed-time 30-s food reinforcement schedule or from the outset of the experiment. Yoked-control rats received these same delays but independently of their own behaviour. d-Amphetamine (0.1-3.0 mg/kg) was then tested IP. d-Amphetamine dose-dependently increased and then decreased punished schedule-induced drinking. The drug led to dose-dependent reductions when the delays were not contingent or when they were applied from the outset of training. These results support the contention that d-amphetamine has an increasing effect on schedule-induced drinking that has been previously reduced by a negative punishment procedure. This effect cannot be attributed to other potentially involved processes, and therefore support the idea that drug effects on punished behaviour depend on punishment being delays in food or shock deliveries.
-
Ubeda, Carlos; Morales, Claudio; Gutiérrez, Diego; Oliveira, Marcus; Manterola, Carlos
2018-05-11
The objective of this article is to present initial occupational dose values using digital active personal dosimeters for medical staff during adult interventional cardiology procedures in a public hospital in Chile. Personal dose equivalent Hp(10) over the lead apron of physician, nurse and radiographer were measured during 59 procedures. Mean values of occupational dose Hp(10) per procedure were 47.6, 6.2 and 4.3 μSv for physician, nurse and radiographer, respectively. If no protective tools are used, physician dose can exceed the new eye lens dose limit.
-
de Ruiter, Quirina M; Gijsberts, Crystel M; Hazenberg, Constantijn E; Moll, Frans L; van Herwaarden, Joost A
2017-06-01
To determine which patient and C-arm characteristics are the strongest predictors of intraoperative patient radiation dose rates (DRs) during endovascular aneurysm repair (EVAR) procedures and create a patient risk chart. A retrospective analysis was performed of 74 EVAR procedures, including 16,889 X-ray runs using fixed C-arm imaging equipment. Four multivariate log-linear mixed models (with patient as a random effect) were constructed. Mean air kerma DR (DR AK , mGy/s) and the mean dose area product DR (DR DAP , mGycm 2 /s) were the outcome variables utilized for fluoroscopy as differentiated from digital subtraction angiography (DSA). These models were used to predict the maximum radiation duration allowed before a 2-Gy skin threshold (for DR AK ) or a 500-Gycm 2 threshold (for DR DAP ) was reached. The strongest predictor of DR AK and DR DAP for fluoroscopy imaging was the radiation protocol, with an increase of 200% when changing from "low" to "medium" and 410% from "low" to "normal." The strongest predictors of DR AK and DR DAP for DSA were C-arm angulation, with an increase of 47% per 30° of angulation, and body mass index (BMI), with an increase of 58% for every 5-point increase in BMI. Based on these models, a patient with a BMI of 30 kg/m 2 , combined with 45° of rotation and a field size of 800 cm 2 in the medium fluoroscopy protocol has a predicted DR AK of 0.39 mGy/s (or 85.5 minutes until the 2-Gy skin threshold is reached). While using comparable settings but switching the acquisition to a DSA with a "2 frames per second" protocol, the predicted DR AK will be 6.6 mGy/s (or 5.0 minutes until the 2-Gy threshold is reached). X-ray radiation DRs are constantly fluctuating during and between patients based on BMI, the protocols, C-arm position, and the image acquisitions that are used. An instant patient risk chart visualizes these radiation dose fluctuations and provides an overview of the expected duration of X-ray radiation, which can be used to predict when follow-up dose thresholds are reached during abdominal endovascular procedures.
-
Rotary transformer design with fixed magnetizing and/or leakage inductances
NASA Technical Reports Server (NTRS)
Stuart, T. A.; King, R. J.; Shamseddin, H.
1985-01-01
A design algorithm is considered for transformers that must transfer electric power across a rotating interface. Among other features, this procedure allows the designer to minimize either weight or losses for either a fixed magnetizing inductance or a fixed leakage inductance. Numerical results are included to indicate the design trade-offs between various parameters.
-
Picon, Paulo Dornelles; Costa, Marisa Boff; da Veiga Picon, Rafael; Fendt, Lucia Costa Cabral; Suksteris, Maurício Leichter; Saccilotto, Indara Carmanim; Dornelles, Alicia Dorneles; Schmidt, Luis Felipe Carissimi
2013-11-22
The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups. A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. NCT01389518.
-
2013-01-01
Background The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. Methods This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. Results Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups. Conclusion A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. Trial registration NCT01389518 PMID:24261438
-
Hänscheid, Heribert; Lapa, Constantin; Buck, Andreas K; Lassmann, Michael; Werner, Rudolf A
2017-01-01
To retrospectively analyze the accuracy of absorbed dose estimates from a single measurement of the activity concentrations in tumors and relevant organs one to three days after the administration of 177 Lu-DOTA-TATE/TOC assuming tissue specific effective half-lives. Activity kinetics in 54 kidneys, 30 neuroendocrine tumor lesions, 25 livers, and 27 spleens were deduced from series of planar images in 29 patients. After adaptation of mono- or bi-exponential fit functions to the measured data, it was analyzed for each fit function how precise the time integral can be estimated from fixed tissue-specific half-lives and a single measurement at 24, 48, or 72 h after the administration. For the kidneys, assuming a fixed tissue-specific half-life of 50 h, the deviations of the estimate from the actual integral were median (5 % percentile, 95 % percentile): -3 °% (-15 %>; +16 °%) for measurements after 24 h, +2 %> (-9 %>; +12 %>) for measurements after 48 h, and 0 % (-2 %; +12 %) for measurements after 72 h. The corresponding values for the other tissues, assuming fixed tissue-specific half-lives of 67 h for liver and spleen and 77 h for tumors, were +2 % (-25 %; +20 %) for measurements after 24 h, +2 °% (-16 %>; +17 %>) for measurements after 48 h, and +2 %> (-11 %>; +10 %>) for measurements after 72 h. Especially for the kidneys, which often represent the dose limiting organ, but also for liver, spleen, and neuroendocrine tumors, a meaningful absorbed dose estimate is possible from a single measurement after 2, more preferably 3 days after the administration of 177 Lu-DOTA-TATE/-TOC assuming fixed tissue specific effective half-lives. Schattauer GmbH.
-
Bacchim Neto, Fernando Antonio; Alves, Allan Felipe Fattori; Mascarenhas, Yvone Maria; Nicolucci, Patrícia; Pina, Diana Rodrigues de
2016-08-01
To perform a complete evaluation on radiation doses, received by primary and assistant medical staff, while performing different vascular interventional radiology procedures. We evaluated dose received in different body regions during three categories of vascular procedures: lower limb angiography (Angiography), lower limb percutaneous transluminal angioplasty (Angioplasty) and stent graft placement for abdominal aortic aneurysm treatment (A. A. A. Treatment). We positioned the dosimeters near the eye lens, thyroid, chest, abdomen, hands, and feet of the interventional physicians. Equivalent dose was compared with annual dose limits for workers in order to determine the maximum number of procedures per year that each physician could perform. We assessed 90 procedures. We found the highest equivalent doses in the A. A. A. Treatment, in which 90% of the evaluations indicated at least one region receiving more than 1mSv per procedure. Angioplasty was the only procedural modality that provided statistically different doses for different professionals, which is an important aspect on regards to radiological protection strategies. In comparison with the dose limits, the most critical region in all procedures was the eye lens. Since each body region of the interventionist is exposed to different radiation levels, dose distribution measurements are essential for radiological protection strategies. These results indicate that dosimeters placed in abdomen instead of chest may represent more accurately the whole body doses received by the medical staff. Additional dosimeters and a stationary shield for the eye lens are strongly recommended. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
-
Desai, Divyakant; Wang, Jennifer; Wen, Hong; Li, Xuhong; Timmins, Peter
2013-01-01
Fixed dose combination (FDC) products are common in the treatment of hypertension, diabetes, human immunodeficiency virus, and tuberculosis. They make it possible to combine two or more drug molecules with different modes of pharmacological actions in a single dosing unit and optimize the treatment. From a patient perspective, they offer convenience, reduced dosing unit burden, and cost savings. From a clinical perspective, aging population in developed countries will need multiple medications to treat age related diseases and co-morbidities. FDC products simplify dosing regimen and enhance patient compliance. As outlined in the article, the number of FDC products has grown over the years and the trend is likely to continue. This review article gives an overview to pharmaceutical scientists about recent trends in the formulation development of the FDC products and provides decision trees to select most optimum formulation development strategy. While some formulation technologies such as multi-layer tablets, multiparticulate systems, active film coating, and hot-melt granulation are discussed in more detail, a few specialized technologies are also introduced briefly to the readers.
-
Repeated Post- or Presession Cocaine Administration: Roles of Dose and Fixed-Ratio Schedule
ERIC Educational Resources Information Center
Pinkston, Jonathan W.; Branch, Marc N.
2004-01-01
Effects of repeated administration of cocaine to animals behaving under operant contingencies have depended on when the drug is given. Moderate doses given presession have generally led to a decrease in the drug's effect, an outcome usually referred to as tolerance. When these same doses have been given after sessions, the usual result has been no…
-
Organ dose conversion coefficients for tube current modulated CT protocols for an adult population
NASA Astrophysics Data System (ADS)
Fu, Wanyi; Tian, Xiaoyu; Sahbaee, Pooyan; Zhang, Yakun; Segars, William Paul; Samei, Ehsan
2016-03-01
In computed tomography (CT), patient-specific organ dose can be estimated using pre-calculated organ dose conversion coefficients (organ dose normalized by CTDIvol, h factor) database, taking into account patient size and scan coverage. The conversion coefficients have been previously estimated for routine body protocol classes, grouped by scan coverage, across an adult population for fixed tube current modulated CT. The coefficients, however, do not include the widely utilized tube current (mA) modulation scheme, which significantly impacts organ dose. This study aims to extend the h factors and the corresponding dose length product (DLP) to create effective dose conversion coefficients (k factor) database incorporating various tube current modulation strengths. Fifty-eight extended cardiac-torso (XCAT) phantoms were included in this study representing population anatomy variation in clinical practice. Four mA profiles, representing weak to strong mA dependency on body attenuation, were generated for each phantom and protocol class. A validated Monte Carlo program was used to simulate the organ dose. The organ dose and effective dose was further normalized by CTDIvol and DLP to derive the h factors and k factors, respectively. The h factors and k factors were summarized in an exponential regression model as a function of body size. Such a population-based mathematical model can provide a comprehensive organ dose estimation given body size and CTDIvol. The model was integrated into an iPhone app XCATdose version 2, enhancing the 1st version based upon fixed tube current modulation. With the organ dose calculator, physicists, physicians, and patients can conveniently estimate organ dose.
-
Reduced-dose C-arm computed tomography applications at a pediatric institution.
Acord, Michael; Shellikeri, Sphoorti; Vatsky, Seth; Srinivasan, Abhay; Krishnamurthy, Ganesh; Keller, Marc S; Cahill, Anne Marie
2017-12-01
Reduced-dose C-arm computed tomography (CT) uses flat-panel detectors to acquire real-time 3-D images in the interventional radiology suite to assist with anatomical localization and procedure planning. To describe dose-reduction techniques for C-arm CT at a pediatric institution and to provide guidance for implementation. We conducted a 5-year retrospective study on procedures using an institution-specific reduced-dose protocol: 5 or 8 s Dyna Rotation, 248/396 projection images/acquisition and 0.1-0.17 μGy/projection dose at the detector with 0.3/0.6/0.9-mm copper (Cu) filtration. We categorized cases by procedure type and average patient age and calculated C-arm CT and total dose area product (DAP). Two hundred twenty-two C-arm CT-guided procedures were performed with a dose-reduction protocol. The most common procedures were temporomandibular and sacroiliac joint injections (48.6%) and sclerotherapy (34.2%). C-arm CT was utilized in cases of difficult percutaneous access in less common applications such as cecostomy and gastrostomy placement, foreign body retrieval and thoracentesis. C-arm CT accounted for between 9.9% and 80.7% of the total procedural DAP. Dose-reducing techniques can preserve image quality for intervention while reducing radiation exposure to the child. This technology has multiple applications within pediatric interventional radiology and can be considered as an adjunctive imaging tool in a variety of procedures, particularly when percutaneous access is challenging despite routine fluoroscopic or ultrasound guidance.
-
Zotova, R; Vassileva, J; Hristova, J; Pirinen, M; Järvinen, H
2012-06-01
A national study on patient dose values in interventional radiology and cardiology was performed in order to assess current practice in Bulgaria, to estimate the typical patient doses and to propose reference levels for the most common procedures. Fifteen units and more than 1,000 cases were included. Average values of the measured parameters for three procedures-coronary angiography (CA), combined procedure (CA + PCI) and lower limb arteriography (LLA)--were compared with data published in the literature. Substantial variations were observed in equipment and procedure protocols used. This resulted in variations in patient dose: air-kerma area product ranges were 4-339, 6-1,003 and 0.2-288 Gy cm(2) for CA, CA + PCI and LLA respectively. Reference levels for air kerma-area product were proposed: 40 Gy cm(2) for CA, 140 Gy cm(2) for CA + PCI and 45 Gy cm(2) for LLA. Auxiliary reference intervals were proposed for other dose-related parameters: fluoroscopy time, number of images and entrance surface air kerma rate in fluoroscopy and cine mode. There is an apparent necessity for improvement in the classification of peripheral procedures and for standardisation of the protocols applied. It is important that patient doses are routinely recorded and compared with reference levels. • Patient doses in interventional radiology are high and vary greatly • Better standardisation of procedures and techniques is needed to improve practice • Dose reference levels for most common procedures are proposed.
-
Fixed-ratio ray designs have been used for detecting and characterizing interactions of large numbers of chemicals in combination. Single chemical dose-response data are used to predict an “additivity curve” along an environmentally relevant ray. A “mixture curve” is estimated fr...
-
Komemushi, Atsushi; Suzuki, Satoshi; Sano, Akira; Kanno, Shohei; Kariya, Shuji; Nakatani, Miyuki; Yoshida, Rie; Kono, Yumiko; Ikeda, Koshi; Utsunomiya, Keita; Harima, Yoko; Komemushi, Sadao; Tanigawa, Noboru
2014-08-01
To compare radiation exposure of nurses when performing nursing tasks associated with interventional procedures depending on whether or not the nurses called out to the operator before approaching the patient. In a prospective study, 93 interventional radiology procedures were randomly divided into a call group and a no-call group; there were 50 procedures in the call group and 43 procedures in the no-call group. Two monitoring badges were used to calculate effective dose of nurses. In the call group, the nurse first told the operator she was going to approach the patient each time she was about to do so. In the no-call group, the nurse did not say anything to the operator when she was about to approach the patient. In all the nursing tasks, the equivalent dose at the umbilical level inside the lead apron was below the detectable limit. The equivalent dose at the sternal level outside the lead apron was 0.16 μSv ± 0.41 per procedure in the call group and 0.51 μSv ± 1.17 per procedure in the no-call group. The effective dose was 0.018 μSv ± 0.04 per procedure in the call group and 0.056 μSv ± 0.129 per procedure in the no-call group. The call group had a significantly lower radiation dose (P = .034). Radiation doses of nurses were lower in the group in which the nurse called to the operator before she approached the patient. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Swartling, Johannes; Höglund, Odd V.; Hansson, Kerstin; Södersten, Fredrik; Axelsson, Johan; Lagerstedt, Anne-Sofie
2016-02-01
Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2.
-
Liou, Jing-Yang; Ting, Chien-Kun; Mandell, M Susan; Chang, Kuang-Yi; Teng, Wei-Nung; Huang, Yu-Yin; Tsou, Mei-Yung
2016-08-01
Selecting an effective dose of sedative drugs in combined upper and lower gastrointestinal endoscopy is complicated by varying degrees of pain stimulation. We tested the ability of 5 response surface models to predict depth of sedation after administration of midazolam and alfentanil in this complex model. The procedure was divided into 3 phases: esophagogastroduodenoscopy (EGD), colonoscopy, and the time interval between the 2 (intersession). The depth of sedation in 33 adult patients was monitored by Observer Assessment of Alertness/Scores. A total of 218 combinations of midazolam and alfentanil effect-site concentrations derived from pharmacokinetic models were used to test 5 response surface models in each of the 3 phases of endoscopy. Model fit was evaluated with objective function value, corrected Akaike Information Criterion (AICc), and Spearman ranked correlation. A model was arbitrarily defined as accurate if the predicted probability is <0.5 from the observed response. The effect-site concentrations tested ranged from 1 to 76 ng/mL and from 5 to 80 ng/mL for midazolam and alfentanil, respectively. Midazolam and alfentanil had synergistic effects in colonoscopy and EGD, but additivity was observed in the intersession group. Adequate prediction rates were 84% to 85% in the intersession group, 84% to 88% during colonoscopy, and 82% to 87% during EGD. The reduced Greco and Fixed alfentanil concentration required for 50% of the patients to achieve targeted response Hierarchy models performed better with comparable predictive strength. The reduced Greco model had the lowest AICc with strong correlation in all 3 phases of endoscopy. Dynamic, rather than fixed, γ and γalf in the Hierarchy model improved model fit. The reduced Greco model had the lowest objective function value and AICc and thus the best fit. This model was reliable with acceptable predictive ability based on adequate clinical correlation. We suggest that this model has practical clinical value for patients undergoing procedures with varying degrees of stimulation.
-
Radiation dose to technologists per nuclear medicine examination and estimation of annual dose.
Bayram, Tuncay; Yilmaz, A Hakan; Demir, Mustafa; Sonmez, Bircan
2011-03-01
Conventional diagnostic nuclear medicine applications have been continuously increasing in most nuclear medicine departments in Turkey, but to our knowledge no one has studied the doses to technologists who perform nuclear medicine procedures. Most nuclear medicine laboratories do not have separate control rooms for technologists, who are quite close to the patient during data acquisition. Technologists must therefore stay behind lead shields while performing their task if they are to reduce the radiation dose received. The aim of this study was to determine external radiation doses to technologists during nuclear medicine procedures with and without a lead shield. Another aim was to investigate the occupational annual external radiation doses to Turkish technologists. This study used a Geiger-Müller detector to measure dose rates to technologists at various distances from patients (0.25, 0.50, 1, and 2 m and behind a lead shield) and determined the average time spent by technologists at these distances. Deep-dose equivalents to technologists were obtained. The following conventional nuclear medicine procedures were considered: thyroid scintigraphy performed using (99m)Tc pertechnetate, whole-body bone scanning performed using (99m)Tc-methylene diphosphonate, myocardial perfusion scanning performed using (99m)Tc-methoxyisobutyl isonitrile, and (201)Tl (thallous chloride) and renal scanning performed using (99m)Tc-dimercaptosuccinic acid. The measured deep-dose equivalent to technologists per procedure was within the range of 0.13 ± 0.05 to 0.43 ± 0.17 μSv using a lead shield and 0.21 ± 0.07 to 1.01 ± 0.46 μSv without a lead shield. Also, the annual individual dose to a technologist performing only a particular scintigraphic procedure throughout a year was estimated. For a total of 95 clinical cases (71 patients), effective external radiation doses to technologists were found to be within the permissible levels. This study showed that a 2-mm lead shield markedly reduced the external dose to technologists. The doses to technologists varied significantly for different diagnostic applications. Consequently, the estimated annual dose to a technologist performing only a particular scintigraphic procedure is very different from one type of procedure to another. The results of this study should help in determining the rotation time of technologists in different procedures and differences in their individual techniques.
-
Pareek, Anil; Chandurkar, Nitin B; Sharma, Ravishankar; Tiwari, Dharmendra; Gupta, Bhagwan S
2010-01-01
Epidemiological studies and clinical trials have shown that prevention of cardiovascular disease, the ultimate goal of hypertension treatment, requires a sufficient reduction in blood pressure. The primary objective of this study was to compare the mean decrease in systolic (SBP) and diastolic (DBP) blood pressure between metoprolol extended release (XL)/amlodipine fixed-dose combination and losartan plus amlodipine combination in patients with mild-to-moderate essential hypertension. The secondary objectives of this study were to compare the proportion of responders in the two treatment groups and to evaluate the tolerability of the study medications. This was a randomized, parallel-group, multicentre comparative study conducted at the outpatient departments of three teaching hospitals in India. Patients with mild-to-moderate hypertension (defined as DBP 90-109 mmHg) aged between 18 and 75 years were enrolled in this study and followed up for 12 weeks. Response to study treatments was evaluated in terms of mean decrease in SBP and DBP and the response rate (reduction to SBP <140 mmHg and DBP <90 mmHg). Out of 152 patients who underwent a 1-week placebo washout, 148 eligible patients were randomized to receive either metoprolol XL 25 mg/amlodipine 2.5 mg fixed-dose combination (76 patients) or losartan 25 mg plus amlodipine 2.5 mg (72 patients). The two treatment groups were similar with respect to demographic and baseline characteristics. Non-responders after 4 weeks of therapy were escalated to metoprolol XL 50 mg/amlodipine 5 mg fixed-dose combination or losartan 50 mg plus amlodipine 5 mg, respectively. The study was completed by 66 patients in each group, of whom 43 patients in each group responded to the starting doses. After 4 weeks' therapy, both treatments were associated with significant decreases in SBP and DBP from baseline (p < 0.001) and were comparable with respect to mean decrease in SBP (p = 0.304), mean decrease in DBP (p = 0.630) and response rate (p = 1.0). Also, both the step-up therapies were comparable with respect to mean decrease in SBP (p = 0.484), mean decrease in DBP (p = 0.650) and response rate (p = 0.134) at week 12. Both treatments were well tolerated in the studied population. Metoprolol XL/amlodipine fixed-dose combination was found to be as effective and well tolerated as losartan plus amlodipine in the treatment of essential hypertension.
-
Dose-dependent X-ray measurements using a 64×64 hybrid GaAs pixel detector with photon counting
NASA Astrophysics Data System (ADS)
Schwarz, C.; Campbell, M.; Goeppert, R.; Ludwig, J.; Mikulec, B.; Rogalla, M.; Runge, K.; Soeldner-Rembold, A.; Smith, K. M.; Snoeys, W.; Watt, J.
2001-03-01
New developments in medical imaging head towards semiconductor detectors flip-chip bonded to CMOS readout chips. In this work, detectors fabricated on SI-GaAs bulk material were bonded to Photon Counting Chips. This PCC consists of a matrix of 64×64 identical square pixels (170 μm×170 μm) with a 15-bit counter in each cell. We investigated the imaging properties of these detector systems under exposure of a dental X-ray tube. First, a dose calibration of the X-ray tube was performed. Fixed pattern noise in flood exposure images was determined for a fixed dose and an image correction method, which uses a gain map, was applied. For characterising the imaging properties, the signal-to-noise ratio (SNR) was calculated as function of exposure dose. Finally, the dynamic range of the system was estimated. Developed in the framework of the MEDIPIX collaboration: CERN, Universities of Freiburg, Glasgow, Naples and Pisa.
-
Expert opinion on a flexible extended regimen of drospirenone/ethinyl estradiol contraceptive.
Han, Leo; Jensen, Jeffrey T
2014-10-01
Oral contraceptives are often prescribed in extended or continuous forms in order to manage menstrual bleeding and menstrual-related side effects. However, with extended regimens, unscheduled intracycle bleeding can become problematic. Flexible extended dosing of a contraceptive containing drospirenone (DRSP) and ethinyl estradiol (EE) was designed to improve bleeding profiles during extended cycles through active management of bleeding symptoms. We examine the rationale for flexible extended dosing as well as review the dosing regimen. We will focus on the findings of the two most important clinical trials regarding flexible extended DRSP/EE (3 mg/20 μg), including the bleeding profiles of women in those trials. Pharmacology, mechanisms of action, efficacy as well as safety of DRSP containing pills will also be reviewed. Flexible extended dosing of DRSP/EE (3 mg/20 μg) has similar pharmacokinetics and contraceptive efficacy of both conventional and fixed extended regimens. However, it has the added benefit of fewer days of bleeding/spotting compared to conventional and fixed extended regimens.
-
Planchard, David; Brown, Kathryn H; Kim, Dong-Wan; Kim, Sang-We; Ohe, Yuichiro; Felip, Enriqueta; Leese, Philip; Cantarini, Mireille; Vishwanathan, Karthick; Jänne, Pasi A; Ranson, Malcolm; Dickinson, Paul A
2016-04-01
Osimertinib (AZD9291) 80 mg once daily is approved by the US FDA for the treatment of patients with metastatic EGFR T790M-positive NSCLC whose disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was evaluated to define the dose and dosing interval, whether a fixed-dosing approach can be used globally, and the impact of formulation and food on exposure. AURA (NCT01802632): single- and multiple-dose PK of osimertinib (20-240 mg daily) was determined in patients with advanced NSCLC. Bioavailability study (NCT01951599): single-dose PK of osimertinib (20 mg) was determined in healthy volunteers with administration of capsule, solution, or tablet formulations fasted, and as a tablet in the fed and fasted state. Osimertinib was slowly absorbed and displayed dose-proportional increases in exposure from 20 to 240 mg. Distribution was extensive and clearance low to moderate, resulting in a mean half-life of 48.3 h. Steady state was achieved by 15 days of dosing, consistent with single-dose PK, with a peak-to-trough ratio of 1.6. Two active metabolites circulated at ~10 % of osimertinib exposure. Ethnicity did not appear to affect exposure. Osimertinib PK profiles in healthy volunteers were similar to those in patients and were unaffected by formulation. Food caused a clinically insignificant increase in exposure. Osimertinib PK supports once-daily dosing; the same dose for Asian and non-Asian populations; a fixed-dosing approach; a minimal effect of food on exposure; and a switch to tablet formulation without alteration to dose or schedule. Osimertinib plasma concentrations are sustained throughout the dosing period, which is considered optimal for efficacy.
-
Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B
Nathwani, Amit C.; Tuddenham, Edward G.D.; Rangarajan, Savita; Rosales, Cecilia; McIntosh, Jenny; Linch, David C.; Chowdary, Pratima; Riddell, Anne; Pie, Arnulfo Jaquilmac; Harrington, Chris; O’Beirne, James; Smith, Keith; Pasi, John; Glader, Bertil; Rustagi, Pradip; Ng, Catherine Y.C.; Kay, Mark A.; Zhou, Junfang; Spence, Yunyu; Morton, Christopher L.; Allay, James; Coleman, John; Sleep, Susan; Cunningham, John M.; Srivastava, Deokumar; Basner-Tschakarjan, Etiena; Mingozzi, Federico; High, Katherine A.; Gray, John T.; Reiss, Ulrike M.; Nienhuis, Arthur W.; Davidoff, Andrew M.
2012-01-01
BACKGROUND Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder. METHODS We infused a single dose of a serotype-8–pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein in six patients with severe hemophilia B (FIX activity, <1% of normal values). Study participants were enrolled sequentially in one of three cohorts (given a high, intermediate, or low dose of vector), with two participants in each group. Vector was administered without immunosuppressive therapy, and participants were followed for 6 to 16 months. RESULTS AAV-mediated expression of FIX at 2 to 11% of normal levels was observed in all participants. Four of the six discontinued FIX prophylaxis and remained free of spontaneous hemorrhage; in the other two, the interval between prophylactic injections was increased. Of the two participants who received the high dose of vector, one had a transient, asymptomatic elevation of serum aminotransferase levels, which was associated with the detection of AAV8-capsid–specific T cells in the peripheral blood; the other had a slight increase in liver-enzyme levels, the cause of which was less clear. Each of these two participants received a short course of glucocorticoid therapy, which rapidly normalized aminotransferase levels and maintained FIX levels in the range of 3 to 11% of normal values. CONCLUSIONS Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects. Although immune-mediated clearance of AAV-transduced hepatocytes remains a concern, this process may be controlled with a short course of glucocorticoids without loss of transgene expression. (Funded by the Medical Research Council and others; ClinicalTrials.gov number, NCT00979238.) PMID:22149959
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Smith, Blake, E-mail: bsmith34@wisc.edu; Gelover,
Purpose: To quantitatively assess the advantages of energy-layer specific dynamic collimation system (DCS) versus a per-field fixed aperture for spot scanning proton therapy (SSPT). Methods: Five brain cancer patients previously planned and treated with SSPT were replanned using an in-house treatment planning system capable of modeling collimated and uncollimated proton beamlets. The uncollimated plans, which served as a baseline for comparison, reproduced the target coverage and organ-at-risk sparing of the clinically delivered plans. The collimator opening for the fixed aperture-based plans was determined from the combined cross sections of the target in the beam’s eye view over all energy layersmore » which included an additional margin equivalent to the maximum beamlet displacement for the respective energy of that energy layer. The DCS-based plans were created by selecting appropriate collimator positions for each row of beam spots during a Raster-style scanning pattern which were optimized to maximize the dose contributions to the target and limited the dose delivered to adjacent normal tissue. Results: The reduction of mean dose to normal tissue adjacent to the target, as defined by a 10 mm ring surrounding the target, averaged 13.65% (range: 11.8%–16.9%) and 5.18% (2.9%–7.1%) for the DCS and fixed aperture plans, respectively. The conformity index, as defined by the ratio of the volume of the 50% isodose line to the target volume, yielded an average improvement of 21.35% (19.4%–22.6%) and 8.38% (4.7%–12.0%) for the DCS and fixed aperture plans, respectively. Conclusions: The ability of the DCS to provide collimation to each energy layer yielded better conformity in comparison to fixed aperture plans.« less
-
Hecksel, D; Anferov, V; Fitzek, M; Shahnazi, K
2010-06-01
Conventional proton therapy facilities use double scattering nozzles, which are optimized for delivery of a few fixed field sizes. Similarly, uniform scanning nozzles are commissioned for a limited number of field sizes. However, cases invariably occur where the treatment field is significantly different from these fixed field sizes. The purpose of this work was to determine the impact of the radiation field conformity to the patient-specific collimator on the secondary neutron dose equivalent. Using a WENDI-II neutron detector, the authors experimentally investigated how the neutron dose equivalent at a particular point of interest varied with different collimator sizes, while the beam spreading was kept constant. The measurements were performed for different modes of dose delivery in proton therapy, all of which are available at the Midwest Proton Radiotherapy Institute (MPRI): Double scattering, uniform scanning delivering rectangular fields, and uniform scanning delivering circular fields. The authors also studied how the neutron dose equivalent changes when one changes the amplitudes of the scanned field for a fixed collimator size. The secondary neutron dose equivalent was found to decrease linearly with the collimator area for all methods of dose delivery. The relative values of the neutron dose equivalent for a collimator with a 5 cm diameter opening using 88 MeV protons were 1.0 for the double scattering field, 0.76 for rectangular uniform field, and 0.6 for the circular uniform field. Furthermore, when a single circle wobbling was optimized for delivery of a uniform field 5 cm in diameter, the secondary neutron dose equivalent was reduced by a factor of 6 compared to the double scattering nozzle. Additionally, when the collimator size was kept constant, the neutron dose equivalent at the given point of interest increased linearly with the area of the scanned proton beam. The results of these experiments suggest that the patient-specific collimator is a significant contributor to the secondary neutron dose equivalent to a distant organ at risk. Improving conformity of the radiation field to the patient-specific collimator can significantly reduce secondary neutron dose equivalent to the patient. Therefore, it is important to increase the number of available generic field sizes in double scattering systems as well as in uniform scanning nozzles.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sahbaee, P; Zhang, Y; Solomon, J
Purpose: To substantiate the interdependency of contrast dose, radiation dose, and image quality in CT towards the patient- specific optimization of the imaging protocols Methods: The study deployed two phantom platforms. A variable sized (12, 18, 23, 30, 37 cm) phantom (Mercury-3.0) containing an iodinated insert (8.5 mgI/ml) was imaged on a representative CT scanner at multiple CTDI values (0.7–22.6 mGy). The contrast and noise were measured from the reconstructed images for each phantom diameter. Linearly related to iodine-concentration, contrast-to-noise ratio (CNR), were calculated for 16 iodine-concentration levels (0–8.5 mgI/ml). The analysis was extended to a recently developed suit ofmore » 58 virtual human models (5D XCAT) with added contrast dynamics. Emulating a contrast-enhanced abdominal image procedure and targeting a peak-enhancement in aorta, each XCAT phantom was “imaged” using a simulation platform (CatSim, GE). 3D surfaces for each patient/size established the relationship between iodine-concentration, dose, and CNR. The ratios of change in iodine-concentration versus dose (IDR) to yield a constant change in CNR were calculated for each patient size. Results: Mercury phantom results show the image-quality size- dependence on CTDI and IC levels. For desired image-quality values, the iso-contour-lines reflect the trade off between contrast-material and radiation doses. For a fixed iodine-concentration (4 mgI/mL), the IDR values for low (1.4 mGy) and high (11.5 mGy) dose levels were 1.02, 1.07, 1.19, 1.65, 1.54, and 3.14, 3.12, 3.52, 3.76, 4.06, respectively across five sizes. The simulation data from XCAT models confirmed the empirical results from Mercury phantom. Conclusion: The iodine-concentration, image quality, and radiation dose are interdependent. The understanding of the relationships between iodine-concentration, image quality, and radiation dose will allow for a more comprehensive optimization of CT imaging devices and techniques, providing the methodology to balance iodine-concentration and dose based on patient’s attributes.« less
-
Factors influencing discomfort during anterior ultrasound-guided injection for hip arthrography.
Hsu, Yi-Chih; Wu, Yu-Cheng; Kao, Hao-Lun; Pan, Ru-Yu; Lee, Meei-Shyuan; Huang, Guo-Shu
2013-09-01
Although ultrasound (US)-guided injection techniques for magnetic resonance arthrography of the hip have been used with increasing frequency to diagnose internal joint derangements, little is known about patient tolerance, which is relevant information for patients. The objective of this study was to evaluate prospectively the association between possible influencing factors and discomfort felt during the performance of anterior US-guided injection techniques targeting the femoral head-neck junction during hip arthrography. Forty-four consecutive patients (21 women and 23 men; mean age, 41 years) undergoing magnetic resonance hip arthrography were sequentially assigned to receive injection alternating between fixed and freehand US-guided injection. Discomfort was assessed using a visual analog scale and relative ratings. Patient body mass index, extra-articular contrast leakage, the duration of the procedure, the needle advancement distance, and the fixed trajectory of the needle were assessed. Pearson's correlation coefficients and multiple logistic regression analysis were used to determine the association. Puncture was successfully accomplished in all cases, and no relevant complications were reported. The only significant relationships were between discomfort and the time required for needle manipulation (r = 0.8) and fixed US-guided injection (r = 0.6; p < 0.001). Compared with the freehand technique, the fixed technique resulted in significantly less pain and took significantly less time to perform (p < 0.001). The procedure time during needle manipulation in the fixed US-guided injections (4.0 ± 0.9 seconds) was significantly less than that in the freehand US-guided injections (19.4 ± 17.6 seconds; p < 0.001). No significant relationships were found between discomfort and other parameters (r < 0.3, p > 0.05). The procedure time appears to be the most important factor influencing patient discomfort. Fixed US-guided injection is a time-saving technique that alleviates procedure-related discomfort. Copyright © 2013. Published by Elsevier B.V.
-
Pott, Alexander; Kraft, Christoph; Stephan, Tilman; Petscher, Kerstin; Rottbauer, Wolfgang; Dahme, Tillman
2018-03-15
The optimal freeze duration in cryoballoon pulmonary vein isolation (PVI) is unknown. The 3rd generation cryoballoon facilitates observation of the time-to-isolation (TTI) and thereby enables individualized cryoenergy titration. To evaluate the efficacy of an individualized freeze duration we compared the clinical outcome of patients treated with a TTI-guided ablation protocol to the outcome of patients treated with a fixed ablation protocol. We compared 100 patients treated with the 3rd generation cryoballoon applying a TTI-based protocol (TTI group) to 100 patients treated by a fixed freeze protocol (fixed group). In the fixed group a 240s freeze cycle was followed by a 240s bonus freeze after acute PV isolation. In the TTI group freeze duration was 180s if TTI was ≥30s and reduced to only 120s, if TTI was <30s. In case of a TTI >60s a 180s bonus freeze was applied. Freedom from atrial arrhythmia recurrence off class I/III antiarrhythmic drugs after one year was not different between the TTI group (73.6%) and the fixed group (75.7%; p=0.75). Mean procedure duration was 85.8±27.3min in the TTI group compared to 115.7±27.1min in the fixed group (p<0.001). Mean fluoroscopy time was 17.5±6.6min in the TTI group and 22.5±9.8min in the fixed group (p<0.001). TTI-guided cryoenergy titration leads to reduced procedure duration and fluoroscopy time and appears to be as effective as a fixed ablation strategy. A single 2-minute freeze seems to be sufficient in case of short TTI. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
-
Prescription of fixed dose combination drugs for diarrhoea.
Chakrabarti, Amit
2007-01-01
Fixed-dose combinations (FDCs) of an antiprotozoal and an antibacterial, for treatment of diarrhoea, have been available in the Indian pharmaceutical market for about a decade. There is little evidence to substantiate this combination therapy. We evaluated 2,163 physician prescriptions for diarrhoea and found that 59 per cent of prescriptions were for FDCs. This is unethical because prescribing such combinations exposes a patient to higher risks of adverse drug reactions and also increases the chances of drug resistance. Physicians' prescribing practices in India are influenced by socioeconomic factors and the pharmaceutical industry's marketing techniques that include giving incentives to physicians to prescribe certain drugs.
-
Morón Merchante, Ignacio; Pergolizzi, Joseph V.; van de Laar, Mart; Mellinghoff, Hans-Ulrich; O'Brien, Joanne; Perrot, Serge; Raffa, Robert B.
2013-01-01
The family practitioner plays an important role in the prevention, diagnosis, and early management of chronic pain. He/she is generally the first to be consulted, the one most familiar with the patients and their medical history, and is likely the first to be alerted in case of inadequate pain control or safety and tolerability issues. The family practitioner should therefore be at the center of the multidisciplinary team involved in a patient's pain management. The most frequent indications associated with chronic pain in family practice are of musculoskeletal origin, and the pain is often multimechanistic. Fixed-dose combination analgesics combine compounds with different mechanisms of action; their broader analgesic spectrum and potentially synergistic analgesic efficacy and improved benefit/risk ratio might thus be useful. A pain specialist meeting held in November 2010 agreed that the fixed-dose combination tramadol/paracetamol might be a useful pharmacological option for chronic pain management in family practice. The combination is effective in a variety of pain conditions with generally good tolerability. Particularly in elderly patients, it might be considered as an alternative to conventional analgesics such as NSAIDs, which should be used rarely with caution in this population. PMID:24959571
-
Eye dose to staff involved in interventional and procedural fluoroscopy
NASA Astrophysics Data System (ADS)
McLean, D.; Hadaya, D.; Tse, J.
2016-03-01
In 2011 the International Commission on Radiological Protection (ICRP) lowered the occupational eye dose limit from 150 to 20 mSv/yr [1]. While international jurisdictions are in a process of adopting these substantial changes, medical physicists at the clinical level have been advising medical colleagues on specific situations based on dose measurements. Commissioned and calibrated TLDs mounted in commercially available holders designed to simulate the measurement of Hp(3), were applied to staff involved in x-ray procedures for a one month period. During this period clinical procedure data was concurrently collected and subject to audit. The use or not of eye personal protective equipment (PPE) was noted for all staff. Audits were conducted in the cardiac catheterisation laboratory, the interventional angiography rooms and the procedural room where endoscopic retrograde cholangiopancreatography (ERCP) procedures are performed. Significant levels of occupational dose were recorded in the cardiac and interventional procedures, with maximum reading exceeding the new limit for some interventional radiologists. No significant eye doses were measured for staff performing ERCP procedures. One outcome of the studies was increased use of eye PPE for operators of interventional equipment with increased availability also to nursing staff, when standing in close proximity to the patient during procedures.
-
Bouazza, Naïm; Cressey, Tim R; Foissac, Frantz; Bienczak, Andrzej; Denti, Paolo; McIlleron, Helen; Burger, David; Penazzato, Martina; Lallemant, Marc; Capparelli, Edmund V; Treluyer, Jean-Marc; Urien, Saïk
2017-02-01
Child-friendly, low-cost, solid, oral fixed-dose combinations (FDCs) of efavirenz with lamivudine and abacavir are urgently needed to improve clinical management and drug adherence for children. Data were pooled from several clinical trials and therapeutic drug monitoring datasets from different countries. The number of children/observations was 505/3667 for efavirenz. Population pharmacokinetic analyses were performed using a non-linear mixed-effects approach. For abacavir and lamivudine, data from 187 and 920 subjects were available (population pharmacokinetic models previously published). Efavirenz/lamivudine/abacavir FDC strength options assessed were (I) 150/75/150, (II) 120/60/120 and (III) 200/100/200 mg. Monte Carlo simulations of the different FDC strengths were performed to determine the optimal dose within each of the WHO weight bands based on drug efficacy/safety targets. The probability of being within the target efavirenz concentration range 12 h post-dose (1-4 mg/L) varied between 56% and 60%, regardless of FDC option. Option I provided a best possible balance between efavirenz treatment failure and toxicity risks. For abacavir and lamivudine, simulations showed that for option I >75% of subjects were above the efficacy target. According to simulations, a paediatric efavirenz/lamivudine/abacavir fixed-dose formulation of 150 mg efavirenz, 75 mg lamivudine and 150 mg abacavir provided the most effective and safe concentrations across WHO weight bands, with the flexibility of dosage required across the paediatric population. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
-
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-20
...-space) frequency band, operating with Geostationary Satellite Orbit (GSO) Satellites in the Fixed... with Geostationary Orbit (GSO) Satellites in the Fixed- Satellite Service. (a) The following ongoing...
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
McNamara, A; Underwood, T; Wo, J
2016-06-15
Purpose: Anal cancer patients treated using a posterior proton beam may be at risk of vaginal wall injury due to the increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the beam distal edge. We investigate the vaginal dose received. Methods: Five patients treated for anal cancer with proton pencil beam scanning were considered, all treated to a prescription dose of 54 Gy(RBE) over 28–30 fractions. Dose and LET distributions were calculated using the Monte Carlo simulation toolkit TOPAS. In addition to the standard assumption of a fixed RBE of 1.1, variable RBE was considered via the applicationmore » of published models. Dose volume histograms (DVHs) were extracted for the planning treatment volume (PTV) and vagina, the latter being used to calculate the vaginal normal tissue complication probability (NTCP). Results: Compared to the assumption of a fixed RBE of 1.1, the variable RBE model predicts a dose increase of approximately 3.3 ± 1.7 Gy at the end of beam range. NTCP parameters for the vagina are incomplete in the current literature, however, inferring value ranges from the existing data we use D{sub 50} = 50 Gy and LKB model parameters a=1–2 and m=0.2–0.4. We estimate the NTCP for the vagina to be 37–48% and 42–47% for the fixed and variable RBE cases, respectively. Additionally, a difference in the dose distribution was observed between the analytical calculation and Monte Carlo methods. We find that the target dose is overestimated on average by approximately 1–2%. Conclusion: For patients treated with posterior beams, the vaginal wall may coincide with the distal end of the proton beam and may receive a substantial increase in dose if variable RBE models are applied compared to using the current clinical standard of RBE equal to 1.1. This could potentially lead to underestimating toxicities when treating with protons.« less
-
SU-D-209-03: Radiation Dose Reduction Using Real-Time Image Processing in Interventional Radiology
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kanal, K; Moirano, J; Zamora, D
Purpose: To characterize changes in radiation dose after introducing a new real-time image processing technology in interventional radiology systems. Methods: Interventional radiology (IR) procedures are increasingly complex, at times requiring substantial time and radiation dose. The risk of inducing tissue reactions as well as long-term stochastic effects such as radiation-induced cancer is not trivial. To reduce this risk, IR systems are increasingly equipped with dose reduction technologies.Recently, ClarityIQ (Philips Healthcare) technology was installed in our existing neuroradiology IR (NIR) and vascular IR (VIR) suites respectively. ClarityIQ includes real-time image processing that reduces noise/artifacts, enhances images, and sharpens edges while alsomore » reducing radiation dose rates. We reviewed 412 NIR (175 pre- and 237 post-ClarityIQ) procedures and 329 VIR (156 preand 173 post-ClarityIQ) procedures performed at our institution pre- and post-ClarityIQ implementation. NIR procedures were primarily classified as interventional or diagnostic. VIR procedures included drain port, drain placement, tube change, mesenteric, and implanted venous procedures. Air Kerma (AK in units of mGy) was documented for all the cases using a commercial radiation exposure management system. Results: When considering all NIR procedures, median AK decreased from 1194 mGy to 561 mGy. When considering all VIR procedures, median AK decreased from 49 to 14 mGy. Both NIR and VIR exhibited a decrease in AK exceeding 50% after ClarityIQ implementation, a statistically significant (p<0.05) difference. Of the 5 most common VIR procedures, all median AK values decreased, but significance (p<0.05) was only reached in venous access (N=53), angio mesenteric (N=41), and drain placement procedures (N=31). Conclusion: ClarityIQ can reduce dose significantly for both NIR and VIR procedures. Image quality was not assessed in conjunction with the dose reduction.« less
-
Organ dose measurement using Optically Stimulated Luminescence Detector (OSLD) during CT examination
NASA Astrophysics Data System (ADS)
Yusuf, Muhammad; Alothmany, Nazeeh; Abdulrahman Kinsara, Abdulraheem
2017-10-01
This study provides detailed information regarding the imaging doses to patient radiosensitive organs from a kilovoltage computed tomography (CT) scan procedure using OSLD. The study reports discrepancies between the measured dose and the calculated dose from the ImPACT scan, as well as a comparison with the dose from a chest X-ray radiography procedure. OSLDs were inserted in several organs, including the brain, eyes, thyroid, lung, heart, spinal cord, breast, spleen, stomach, liver and ovaries, of the RANDO phantom. Standard clinical scanning protocols were used for each individual site, including the brain, thyroid, lung, breast, stomach, liver and ovaries. The measured absorbed doses were then compared with the simulated dose obtained from the ImPACT scan. Additionally, the equivalent doses for each organ were calculated and compared with the dose from a chest X-ray radiography procedure. Absorbed organ doses measured by OSLD in the RANDO phantom of up to 17 mGy depend on the organ scanned and the scanning protocols used. A maximum 9.82% difference was observed between the target organ dose measured by OSLD and the results from the ImPACT scan. The maximum equivalent organ dose measured during this experiment was equal to 99.899 times the equivalent dose from a chest X-ray radiography procedure. The discrepancies between the measured dose with the OSLD and the calculated dose from the ImPACT scan were within 10%. This report recommends the use of OSLD for measuring the absorbed organ dose during CT examination.
-
Dissolution of cement, root caries, fracture, and retrofit of post and cores.
Rosen, H
1998-10-01
Fixed partial denture abutments severely damaged by dental caries or fracture present a challenge to the dentist. The fixed partial denture may need to be removed for endodontic treatment with post and core fabrication. Frequently, the existing fixed partial denture can be recycled as a provisional restoration. Retrofitting the post and core greatly improves the stabilization of the interim as well as the remake of the definitive fixed partial denture. This article describes a chair side procedure for retrofitting posts and cores and, at the same appointment, converting the original fixed partial denture to an effective provisional restoration.
-
Safari, Mohammad Javad; Wong, Jeannie Hsiu Ding; Jong, Wei Loong; Thorpe, Nathan; Cutajar, Dean; Rosenfeld, Anatoly; Ng, Kwan Hoong
2017-03-01
The purpose of this study was to investigate the effects of routine exposure parameters on patient's dose during neuro-interventional radiology procedures. We scrutinized the routine radiological exposure parameters during 58 clinical neuro-interventional procedures such as, exposure direction, magnification, frame rate, and distance between image receptor to patient's body and evaluate their effects on patient's dose using an anthropomorphic phantom. Radiation dose received by the occipital region, ears and eyes of the phantom were measured using MOSkin detectors. DSA imaging technique is a major contributor to patient's dose (80.9%) even though they are used sparingly (5.3% of total frame number). The occipital region of the brain received high dose largely from the frontal tube constantly placed under couch (73.7% of the total KAP). When rotating the frontal tube away from under the couch, the radiation dose to the occipital reduced by 40%. The use of magnification modes could increase radiation dose by 94%. Changing the image receptor to the phantom surface distance from 10 to 40cm doubled the radiation dose received by the patient's skin at the occipital region. Our findings provided important insights into the contribution of selected fluoroscopic exposure parameters and their impact on patient's dose during neuro-interventional radiology procedures. This study showed that the DSA imaging technique contributed to the highest patient's dose and judicial use of exposure parameters might assist interventional radiologists in effective skin and eye lens dose reduction for patients undergoing neuro-interventional procedures. Copyright © 2017 Associazione Italiana di Fisica Medica. All rights reserved.
-
Dundar, Mine; Gungor, M Ali; Cal, Ebru
2003-04-01
Esthetics is a major concern during restoration of anterior partial edentulous areas. All-ceramic fixed partial dentures may provide better esthetics and biocompatibility in the restoration of anterior teeth. This clinic report describes a multidisciplinary approach and treatment procedures with an IPS Empress 2 fixed partial denture to restore missing anterior teeth.
-
1996-09-07
Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). However, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism. 1044 patients with AF and with at least one thromboembolic risk factor (congestive heart failure or left ventricular fractional shortening < or = 25%, previous thromboembolism, systolic blood pressure of more than 160 mm Hg at study enrollment, or being a woman aged over 75 years) were randomly assigned either a combination of low-intensity, fixed-dose warfarin (international normalised ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open-labelled. The mean INR during follow-up of patients taking combination therapy (n = 521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n = 523). During follow-up, 54% of INRs in patients taking combination therapy were 1.2-1.5 and 34% were less than 1.2. The trial was stopped after a mean, follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism (primary events) in patients given combination therapy (7.9% per year) was significantly higher than in those given adjusted-dose warfarin (1.9% per year) at an interim analysis (p < 0.0001), an absolute reduction of 6.0% per year (95% Cl 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p = 0.0007) and of primary event or vascular death (11.8% vs 6.4%, p = 0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups. Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients.
-
Respiration Induced Heart Motion and Indications of Gated Delivery for Left-Sided Breast Irradiation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Qi, X. Sharon, E-mail: xiangrong.qi@ucdenver.edu; Hu, Angela; Wang Kai
Purpose: To investigate respiration-induced heart motion for left-sided breast irradiation using a four-dimensional computed tomography (4DCT) technique and to determine novel indications to assess heart motion and identify breast patients who may benefit from a gated treatment. Methods and Materials: Images of 4DCT acquired during free breathing for 20 left-sided breast cancer patients, who underwent whole breast irradiation with or without regional nodal irradiation, were analyzed retrospectively. Dose distributions were reconstructed in the phases of 0%, 20%, and 50%. The intrafractional heart displacement was measured in three selected transverse CT slices using D{sub LAD} (the distance from left ascending aortamore » to a fixed line [connecting middle point of sternum and the body] drawn on each slice) and maximum heart depth (MHD, the distance of the forefront of the heart to the line). Linear regression analysis was used to correlate these indices with mean heart dose and heart dose volume at different breathing phases. Results: Respiration-induced heart displacement resulted in observable variations in dose delivered to the heart. During a normal free-breathing cycle, heart-induced motion D{sub LAD} and MHD changed up to 9 and 11 mm respectively, resulting in up to 38% and 39% increases of mean doses and V{sub 25.2} for the heart. MHD and D{sub LAD} were positively correlated with mean heart dose and heart dose volume. Respiratory-adapted gated treatment may better spare heart and ipsilateral-lung compared with the conventional non-gated plan in a subset of patients with large D{sub LAD} or MHD variations. Conclusion: Proposed indices offer novel assessment of heart displacement based on 4DCT images. MHD and D{sub LAD} can be used independently or jointly as selection criteria for respiratory gating procedure before treatment planning. Patients with great intrafractional MHD variations or tumor(s) close to the diaphragm may particularly benefit from the gated treatment.« less
-
Miller, Donald L.; Kwon, Deukwoo; Bonavia, Grant H.
2009-01-01
Purpose: To propose initial values for patient reference levels for fluoroscopically guided procedures in the United States. Materials and Methods: This secondary analysis of data from the Radiation Doses in Interventional Radiology Procedures (RAD-IR) study was conducted under a protocol approved by the institutional review board and was HIPAA compliant. Dose distributions (percentiles) were calculated for each type of procedure in the RAD-IR study where there were data from at least 30 cases. Confidence intervals for the dose distributions were determined by using bootstrap resampling. Weight banding and size correction methods for normalizing dose to patient body habitus were tested. Results: The different methods for normalizing patient radiation dose according to patient weight gave results that were not significantly different (P > .05). The 75th percentile patient radiation doses normalized with weight banding were not significantly different from those that were uncorrected for body habitus. Proposed initial reference levels for various interventional procedures are provided for reference air kerma, kerma-area product, fluoroscopy time, and number of images. Conclusion: Sufficient data exist to permit an initial proposal of values for reference levels for interventional radiologic procedures in the United States. For ease of use, reference levels without correction for body habitus are recommended. A national registry of radiation-dose data for interventional radiologic procedures is a necessary next step to refine these reference levels. © RSNA, 2009 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2533090354/-/DC1 PMID:19789226
-
Baird, Rachel; Maxwell, Scott E
2016-06-01
Time-varying predictors in multilevel models are a useful tool for longitudinal research, whether they are the research variable of interest or they are controlling for variance to allow greater power for other variables. However, standard recommendations to fix the effect of time-varying predictors may make an assumption that is unlikely to hold in reality and may influence results. A simulation study illustrates that treating the time-varying predictor as fixed may allow analyses to converge, but the analyses have poor coverage of the true fixed effect when the time-varying predictor has a random effect in reality. A second simulation study shows that treating the time-varying predictor as random may have poor convergence, except when allowing negative variance estimates. Although negative variance estimates are uninterpretable, results of the simulation show that estimates of the fixed effect of the time-varying predictor are as accurate for these cases as for cases with positive variance estimates, and that treating the time-varying predictor as random and allowing negative variance estimates performs well whether the time-varying predictor is fixed or random in reality. Because of the difficulty of interpreting negative variance estimates, 2 procedures are suggested for selection between fixed-effect and random-effect models: comparing between fixed-effect and constrained random-effect models with a likelihood ratio test or fitting a fixed-effect model when an unconstrained random-effect model produces negative variance estimates. The performance of these 2 procedures is compared. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
-
Pulse-dose radiofrequency treatment in pain management-initial experience.
Ojango, Christine; Raguso, Mario; Fiori, Roberto; Masala, Salvatore
2018-05-01
Radiofrequency procedures have been used for treating various chronic pain conditions for decades. These minimally invasive percutaneous treatments employ an alternating electrical current with oscillating radiofrequency wavelengths to eliminate or alter pain signals from the targeted site. The aim of the continuous radiofrequency procedure is to increase the temperature sufficiently to create an irreversible thermal lesion on nerve fibres and thus permanently interrupt pain signals. The pulsed radiofrequency procedure utilises short pulses of radiofrequency current with intervals of longer pauses to avert a temperature increase to the level of permanent tissue damage. The goal of these pulses is to alter the processing of pain signals, but to avoid relevant structural damage to nerve fibres, as seen in the continuous radiofrequency procedure. The pulse-dose radiofrequency procedure is a technical improvement of the pulsed radiofrequency technique in which the delivery mode of the current is adapted. During the pulse-dose radiofrequency procedure thermal damage is avoided. In addition, the amplitude and width of the consecutive pulses are kept the same. The method ensures that each delivered pulse keeps the same characteristics and therefore the dose is similar between patients. The current review outlines the pulse-dose radiofrequency procedure and presents our institution's chronic pain management studies.
-
Mazón, P; Galve, E; Gómez, J; Gorostidi, M; Górriz, J L; Mediavilla, J D
The opinion of experts (different specialties) on the triple fixed-dose antihypertensive therapy in clinical practice may differ. Online questionnaire with controversial aspects of the triple therapy answered by panel of experts in hypertension (HT) using two-round modified Delphi method. The questionnaire was completed by 158 experts: Internal Medicine (49), Nephrology (26), Cardiology (83). Consensus was reached (agreement) on 27/45 items (60%); 7 items showed differences statistically significant. Consensus was reached regarding: Predictive factors in the need for combination therapy and its efficacy vs. increasing the dose of a pretreatment, and advantage of triple therapy (prescription/adherence/cost/pressure control) vs. free combination. This consensus provides an overview of the clinical use of triple therapy in moderate-severe and resistant/difficult to control HT. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.
-
NASA Technical Reports Server (NTRS)
Buehler, Martin G. (Inventor); Blaes, Brent R. (Inventor)
1994-01-01
A p-MOSFET total dose dosimeter where the gate voltage is proportional to the incident radiation dose. It is configured in an n-WELL of a p-BODY substrate. It is operated in the saturation region which is ensured by connecting the gate to the drain. The n-well is connected to zero bias. Current flow from source to drain, rather than from peripheral leakage, is ensured by configuring the device as an edgeless MOSFET where the source completely surrounds the drain. The drain junction is the only junction not connected to zero bias. The MOSFET is connected as part of the feedback loop of an operational amplifier. The operational amplifier holds the drain current fixed at a level which minimizes temperature dependence and also fixes the drain voltage. The sensitivity to radiation is made maximum by operating the MOSFET in the OFF state during radiation soak.
-
IMRT treatment of anal cancer with a scrotal shield
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hood, Rodney C., E-mail: Rodney.Hood@duke.edu; Wu, Q. Jackie; McMahon, Ryan
The risk of sterility in males undergoing radiotherapy in the pelvic region indicates the use of a shielding device, which offers protection to the testes for patients wishing to maintain fertility. The use of such devices in the realm of intensity-modulated radiotherapy (IMRT) in the pelvic region can pose many obstacles during simulation, treatment planning, and delivery of radiotherapy. This work focuses on the development and execution of an IMRT plan for the treatment of anal cancer using a scrotal shielding device on a clinical patient. An IMRT plan was developed using Eclipse treatment planning system (Varian Medical Systems, Palomore » Alto, CA), using a wide array of gantry angles as well as fixed jaw and fluence editing techniques. When possible, the entire target volume was encompassed by the treatment field. When the beam was incident on the scrotal shield, the jaw was fixed to avoid the device and the collimator rotation optimized to irradiate as much of the target as possible. This technique maximizes genital sparing and allows minimal irradiation of the gonads. When this fixed-jaw technique was found to compromise adequate coverage of the target, manual fluence editing techniques were used to avoid the shielding device. Special procedures for simulation, imaging, and treatment verification were also developed. In vivo dosimetry was used to verify and ensure acceptable dose to the gonads. The combination of these techniques resulted in a highly conformal plan that spares organs and risk and avoids the genitals as well as entrance of primary radiation onto the shielding device.« less
-
Model Comparison of Nonlinear Structural Equation Models with Fixed Covariates.
ERIC Educational Resources Information Center
Lee, Sik-Yum; Song, Xin-Yuan
2003-01-01
Proposed a new nonlinear structural equation model with fixed covariates to deal with some complicated substantive theory and developed a Bayesian path sampling procedure for model comparison. Illustrated the approach with an illustrative example using data from an international study. (SLD)
-
75 FR 15392 - Satellite License Procedures
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-29
... earth station applications must be filed electronically through the International Bureau Filing System... space radio- communication service other than the Fixed Satellite Service. Fixed earth station. An earth... revisions to its satellite and earth station licensing rules. The intended purpose of this proceeding is to...
-
Bioequivalence of fixed-dose combination RIN®-150 to each reference drug in loose combination.
Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Damle, B
2015-03-01
RIN(®)-150 is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg) and isoniazid (INH, 75 mg) developed for the treatment of tuberculosis. This study was conducted at a single center: the Pfizer Clinical Research Unit in Singapore. To demonstrate bioequivalence of each drug component between RIN-150 and individual products in a loose combination. This was a randomized, open-label, single-dose, two-way crossover study. Subjects received single doses of RIN-150 or two individual reference products under fasting conditions in a crossover fashion, with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC). Of 28 subjects enrolled, 26 completed the study. The adjusted geometric mean ratios of Cmax and AUClast between the FDC and single-drug references and 90% confidence intervals were respectively 91.63% (90%CI 83.13-101.01) and 95.45% (90%CI 92.07-98.94) for RMP, and 107.58% (90%CI 96.07-120.47) and 103.45% (90%CI 99.33-107.75) for INH. Both formulations were generally well tolerated in this study. The RIN-150 FDC tablet formulation is bioequivalent to the two single-drug references for RMP and INH at equivalent doses.
-
Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.
Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Naqvi, A; Jafri, I
2013-12-01
Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB). This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore. To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination. In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC). Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study. The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.
-
Skin dosimetry of patients during interventional cardiology procedures in the Czech Republic
NASA Astrophysics Data System (ADS)
Sukupova, Lucie; Novak, Leos
2008-01-01
The aim of the study is to determine distribution of air kerma-area product, fluoro time and number of frames values for the two most frequent procedures in the interventional cardiology, to reconstruct skin dose distributions for some patients undergoing coronarography and percutaneous transluminal coronary angioplasty procedures. Patient dose data were obtained from X-ray unit dose monitoring software report from one hospital and the reconstructions were performed in MATLAB. Dependence of maximum skin dose on air kerma-area product, fluoro time and number of frames was determined to assess trigger levels of these quantities, which can indicate possible exceeding of the 2 Gy skin dose threshold.
-
Zhang, M; Westerly, D C; Mackie, T R
2011-08-07
With on-line image guidance (IG), prostate shifts relative to the bony anatomy can be corrected by realigning the patient with respect to the treatment fields. In image guided intensity modulated proton therapy (IG-IMPT), because the proton range is more sensitive to the material it travels through, the realignment may introduce large dose variations. This effect is studied in this work and an on-line adaptive procedure is proposed to restore the planned dose to the target. A 2D anthropomorphic phantom was constructed from a real prostate patient's CT image. Two-field laterally opposing spot 3D-modulation and 24-field full arc distal edge tracking (DET) plans were generated with a prescription of 70 Gy to the planning target volume. For the simulated delivery, we considered two types of procedures: the non-adaptive procedure and the on-line adaptive procedure. In the non-adaptive procedure, only patient realignment to match the prostate location in the planning CT was performed. In the on-line adaptive procedure, on top of the patient realignment, the kinetic energy for each individual proton pencil beam was re-determined from the on-line CT image acquired after the realignment and subsequently used for delivery. Dose distributions were re-calculated for individual fractions for different plans and different delivery procedures. The results show, without adaptive, that both the 3D-modulation and the DET plans experienced delivered dose degradation by having large cold or hot spots in the prostate. The DET plan had worse dose degradation than the 3D-modulation plan. The adaptive procedure effectively restored the planned dose distribution in the DET plan, with delivered prostate D(98%), D(50%) and D(2%) values less than 1% from the prescription. In the 3D-modulation plan, in certain cases the adaptive procedure was not effective to reduce the delivered dose degradation and yield similar results as the non-adaptive procedure. In conclusion, based on this 2D phantom study, by updating the proton pencil beam energy from the on-line image after realignment, this on-line adaptive procedure is necessary and effective for the DET-based IG-IMPT. Without dose re-calculation and re-optimization, it could be easily incorporated into the clinical workflow.
-
NASA Astrophysics Data System (ADS)
Zhang, M.; Westerly, D. C.; Mackie, T. R.
2011-08-01
With on-line image guidance (IG), prostate shifts relative to the bony anatomy can be corrected by realigning the patient with respect to the treatment fields. In image guided intensity modulated proton therapy (IG-IMPT), because the proton range is more sensitive to the material it travels through, the realignment may introduce large dose variations. This effect is studied in this work and an on-line adaptive procedure is proposed to restore the planned dose to the target. A 2D anthropomorphic phantom was constructed from a real prostate patient's CT image. Two-field laterally opposing spot 3D-modulation and 24-field full arc distal edge tracking (DET) plans were generated with a prescription of 70 Gy to the planning target volume. For the simulated delivery, we considered two types of procedures: the non-adaptive procedure and the on-line adaptive procedure. In the non-adaptive procedure, only patient realignment to match the prostate location in the planning CT was performed. In the on-line adaptive procedure, on top of the patient realignment, the kinetic energy for each individual proton pencil beam was re-determined from the on-line CT image acquired after the realignment and subsequently used for delivery. Dose distributions were re-calculated for individual fractions for different plans and different delivery procedures. The results show, without adaptive, that both the 3D-modulation and the DET plans experienced delivered dose degradation by having large cold or hot spots in the prostate. The DET plan had worse dose degradation than the 3D-modulation plan. The adaptive procedure effectively restored the planned dose distribution in the DET plan, with delivered prostate D98%, D50% and D2% values less than 1% from the prescription. In the 3D-modulation plan, in certain cases the adaptive procedure was not effective to reduce the delivered dose degradation and yield similar results as the non-adaptive procedure. In conclusion, based on this 2D phantom study, by updating the proton pencil beam energy from the on-line image after realignment, this on-line adaptive procedure is necessary and effective for the DET-based IG-IMPT. Without dose re-calculation and re-optimization, it could be easily incorporated into the clinical workflow.
-
A pilot stability study on four-drug fixed-dose combination anti-tuberculosis products.
Singh, S; Mohan, B
2003-03-01
A pilot stability study was carried out on four fixed-dose combination anti-tuberculosis products at 40 degrees C and 75% RH. The strip-packed products were stable, while the blister-packed products showed both physical and chemical changes. The products in unpacked conditions showed severe (approximately 60%) decomposition of rifampicin and extensive physical changes. The main decomposition product in the solid state was isonicotinyl hydrazone of 3-formylrifamycin and isoniazid. It is suggested that attention should be paid to the detection and quantitation of this product in the marketed formulations. The packing material used in the manufacture of FDC products should also be of the highest quality.
-
Freitas, Kelen; Carroll, F Ivy; Negus, S Stevens
2016-02-01
Intracranial self-stimulation (ICSS) is one type of preclinical procedure for research on pharmacological mechanisms that mediate abuse potential of drugs acting at various targets, including nicotinic acetylcholine receptors (nAChRs). This study compared effects of the nonselective nAChR agonist nicotine (0.032-1.0 mg/kg) and the α4β2-selective nAChR agonist 5-I-A-85380 (0.01-1.0 mg/kg) on ICSS in male Sprague-Dawley rats. Rats were implanted with electrodes targeting the medial forebrain bundle at the level of the lateral hypothalamus and trained to respond under a fixed-ratio 1 schedule for a range of brain stimulation frequencies (158-56 Hz). A broad range of 5-I-A-85380 doses produced an abuse-related increase (or "facilitation") of low ICSS rates maintained by low brain-stimulation frequencies, and this effect was blocked by both the nonselective nAChR antagonist mecamylamine and the selective α4β2 antagonist dihyrdo-β-erythroidine (DHβE). Conversely, nicotine produced weaker ICSS facilitation across a narrower range of doses, and higher nicotine doses decreased high rates of ICSS maintained by high brain-stimulation frequencies. The rate-decreasing effects of a high nicotine dose were blocked by mecamylamine but not DHβE. Chronic nicotine treatment produced selective tolerance to rate-decreasing effects of nicotine but did not alter ICSS rate-increasing effects of nicotine. These results suggest that α4β2 receptors are sufficient to mediate abuse-related rate-increasing effects of nAChR agonists in this ICSS procedure. Conversely, nicotine effects at non-α4β2 nAChRs appear to oppose and limit abuse-related effects mediated by α4β2 receptors, although tolerance can develop to these non-α4β2 effects. Selective α4β2 agonists may have higher abuse potential than nicotine. PsycINFO Database Record (c) 2016 APA, all rights reserved.
-
Watanabe, Yoshinori; Asami, Yuko; Hirano, Yoko; Kuribayashi, Kazuhiko; Itamura, Rio; Imaeda, Takayuki
2018-01-01
Purpose To explore the potential factors impacting the efficacy of venlafaxine extended release (ER) and treatment differences between 75 mg/day and 75–225 mg/day dose in patients with major depressive disorder (MDD). Methods We performed exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study conducted in Japan. A total of 538 outpatients aged 20 years or older with a primary diagnosis of MDD who experienced single or recurrent episodes were randomized into three groups: fixed-dose, flexible-dose, or placebo. Venlafaxine ER was initiated at 37.5 mg/day and titrated to 75 mg/day for both fixed-dose and flexible-dose group, and to 225 mg/day for flexible-dose group (if well tolerated). Efficacy endpoints were changes from baseline at Week 8 using the Hamilton Rating Scale for Depression–17 items (HAM-D17) total score, Hamilton Rating Scale for Depression–6 items score, and Montgomery–Asberg Depression Rating Scale total score. The following factors were considered in the subgroup analyses: sex, age, HAM-D17 total score at baseline, duration of MDD, duration of current depressive episode, history of previous depressive episodes, history of previous medications for MDD, and CYP2D6 phenotype. For each subgroup, an analysis of covariance model was fitted and the adjusted mean of the treatment effect and corresponding 95% CI were computed. Due to the exploratory nature of the investigation, no statistical hypothesis testing was used. Results Venlafaxine ER improved symptoms of MDD compared with placebo in most subgroups. The subgroup with a long duration of MDD (>22 months) consistently showed greater treatment benefits in the flexible-dose group than in the fixed-dose group. Conclusion These results suggest that a greater treatment response to venlafaxine ER (up to 225 mg/day) can be seen in patients with a longer duration of MDD. Further investigations are needed to identify additional factors impacting the efficacy of venlafaxine ER. PMID:29844674
-
Watanabe, Yoshinori; Asami, Yuko; Hirano, Yoko; Kuribayashi, Kazuhiko; Itamura, Rio; Imaeda, Takayuki
2018-01-01
To explore the potential factors impacting the efficacy of venlafaxine extended release (ER) and treatment differences between 75 mg/day and 75-225 mg/day dose in patients with major depressive disorder (MDD). We performed exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study conducted in Japan. A total of 538 outpatients aged 20 years or older with a primary diagnosis of MDD who experienced single or recurrent episodes were randomized into three groups: fixed-dose, flexible-dose, or placebo. Venlafaxine ER was initiated at 37.5 mg/day and titrated to 75 mg/day for both fixed-dose and flexible-dose group, and to 225 mg/day for flexible-dose group (if well tolerated). Efficacy endpoints were changes from baseline at Week 8 using the Hamilton Rating Scale for Depression-17 items (HAM-D 17 ) total score, Hamilton Rating Scale for Depression-6 items score, and Montgomery-Asberg Depression Rating Scale total score. The following factors were considered in the subgroup analyses: sex, age, HAM-D 17 total score at baseline, duration of MDD, duration of current depressive episode, history of previous depressive episodes, history of previous medications for MDD, and CYP2D6 phenotype. For each subgroup, an analysis of covariance model was fitted and the adjusted mean of the treatment effect and corresponding 95% CI were computed. Due to the exploratory nature of the investigation, no statistical hypothesis testing was used. Venlafaxine ER improved symptoms of MDD compared with placebo in most subgroups. The subgroup with a long duration of MDD (>22 months) consistently showed greater treatment benefits in the flexible-dose group than in the fixed-dose group. These results suggest that a greater treatment response to venlafaxine ER (up to 225 mg/day) can be seen in patients with a longer duration of MDD. Further investigations are needed to identify additional factors impacting the efficacy of venlafaxine ER.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Venencia, C; Vacca, N; Garrigo, E
Purpose: Spine SBRT treatments require high dose to PTV, located close to OAR. Treatment time should be short due to patient condition. The objective of this work is to compare HybridARC (HA) with sliding windows IMRT treatment modality Methods: A 6MV photon beam with 1000MU/min (SRS beam) produced by a NovalisTX (Varian/BrainLAB) equipped with HDMLC was used. The TPS was iPlan v4.5.3 (BrainLAB). Treatment plans comparison was done for 5 patients. Dose prescription was 27Gy in 3 fractions. HA used 1 arc plus 3 (HA), 5 (HA5) and 8 (HA8) IMRT fields. HA plans used OAR high. Between 60–40% ofmore » the prescribed dose was given by the arc. IMRT plans used 15 beams. Treatment times, MU, CI, V50% and V20% was used for plans comparisons. Results: Assuming IMRT plan as reference, the treatment time was reduced by −14.6% with HA8, −8.6% with HA5 and −23% with HA3. Increasing arc dose proportion in HA (arc MU > 2000) requires 2 or more arcs which increments treatment time. HA3 and HA5 exhibits beam hold off for fixed IMRT fields which in some cases need to be split in 2 segments. MU varied +4% with HA8, +3.7% with HA5 and −5% with HA3. CI increased +5% with HA8, +23% with HA5 and +37% with H3. V50% increased +5% with HA8, +43% with HA5 and +62% with HA3. V20% increased +13.2% with HA8, +7.6% with HA5 and +1% with HA3. OARs doses were keep within tolerances in all plans. Conclusion: HybridARC for spine SBRT with 8 fix IMRT gantry angle shows a treatment time reduction, comparable MU and similar dose conformation to dMLC IMRT. HybridARC with 5 or 3 fix IMRT fields produce undesirable beam hold off, worse dose conformation and increments the total volume with 50% of the prescribed dose.« less
-
Greffier, J; Van Ngoc Ty, C; Bonniaud, G; Moliner, G; Ledermann, B; Schmutz, L; Cornillet, L; Cayla, G; Beregi, J P; Pereira, F
2017-06-01
To compare the use of a dose mapping software to Gafchromic film measurement for a simplified peak skin dose (PSD) estimation in interventional cardiology procedure. The study was conducted on a total of 40 cardiac procedures (20 complex coronary angioplasty of chronic total occlusion (CTO) and 20 coronary angiography and coronary angioplasty (CA-PTCA)) conducted between January 2014 to December 2015. PSD measurement (PSD Film ) was obtained by placing XR-RV3 Gafchromic under the patient's back for each procedure. PSD (PSD em.dose ) was computed with the software em.dose©. The calculation was performed on the dose metrics collected from the private dose report of each procedure. Two calculation methods (method A: fluoroscopic kerma equally spread on cine acquisition and B: fluoroscopic kerma is added to one air Kerma cine acquisition that contributes to the PSD) were used to calculate the fluoroscopic dose contribution as fluoroscopic data were not recorded in our interventional room. Statistical analyses were carried out to compare PSD Film and PSD em.dose . The PSD Film median (1st quartile; 3rd quartile) was 0.251(0.190;0.336)Gy for CA-PTCA and 1.453(0.767;2.011)Gy for CTO. For method-A, the PSD em.dose was 0.248(0.182;0.369)Gy for CA-PTCA and 1.601(0.892;2.178)Gy for CTO, and 0.267(0.223;0.446)Gy and 1.75 (0.912;2.584)Gy for method-B, respectively. For the two methods, the correlation between PSD Film and PSD em.dose was strong. For all cardiology procedures investigated, the mean deviation between PSD Film and PSD em.dose was 3.4±21.1% for method-A and 17.3%±23.9% for method-B. The dose mapping software is convenient to calculate peak skin dose in interventional cardiology. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
-
Kobalava, Z D; Villevalde, S V; Kulakov, V V
2017-11-01
To study effects of a fixed azilsartan medoxomil/chlorthalidone combination (Edarbi Clo) on clinical, ambulatory and central blood pressure (BP) in patients with uncontrolled arterial hypertension (AH)). Patients (n=25) with uncontrolled AH were given fixed azilsartan medoxomil/chlorthalidone combination (40 / 12.5 mg / day) for 4 weeks. After 4 weeks, in patients who did not achieve target BP levels the dose was increased up to 40 / 25 mg / day. Duration of the study was 12 weeks. After 12 weeks of treatment 88 % of patients achieved target clinical BP (.
-
NASA Astrophysics Data System (ADS)
Li, Xiang; Segars, W. Paul; Samei, Ehsan
2014-08-01
Body CT scans are routinely performed using tube-current-modulation (TCM) technology. There is notable variability across CT manufacturers in terms of how TCM technology is implemented. Some manufacturers aim to provide uniform image noise across body regions and patient sizes, whereas others aim to provide lower noise for smaller patients. The purpose of this study was to conduct a theoretical investigation to understand how manufacturer-dependent TCM scheme affects organ dose, and to develop a generic approach for assessing organ dose across TCM schemes. The adult reference female extended cardiac-torso (XCAT) phantom was used for this study. A ray-tracing method was developed to calculate the attenuation of the phantom for a given projection angle based on phantom anatomy, CT system geometry, x-ray energy spectrum, and bowtie filter filtration. The tube current (mA) for a given projection angle was then calculated as a log-linear function of the attenuation along that projection. The slope of this function, termed modulation control strength, α, was varied from 0 to 1 to emulate the variability in TCM technology. Using a validated Monte Carlo program, organ dose was simulated for five α values (α = 0, 0.25, 0.5, 0.75, and 1) in the absence and presence of a realistic system mA limit. Organ dose was further normalized by volume-weighted CT dose index (CTDIvol) to obtain conversion factors (h factors) that are relatively independent of system specifics and scan parameters. For both chest and abdomen-pelvis scans and for 24 radiosensitive organs, organ dose conversion factors varied with α, following second-order polynomial equations. This result suggested the need for α-specific organ dose conversion factors (i.e., conversion factors specific to the modulation scheme used). On the other hand, across the full range of α values, organ dose in a TCM scan could be derived from the conversion factors established for a fixed-mA scan (hFIXED). This was possible by multiplying hFIXED by a revised definition of CTDIvol that accounts for two factors: (a) the tube currents at the location of an organ and (b) the variation in organ volume along the longitudinal direction. This α-generic approach represents an approximation. The error associated with this approximation was evaluated using the α-specific organ dose (i.e., the organ dose obtained by using α-specific mA profiles as inputs into the Monte Carlo simulation) as the reference standard. When the mA profiles were constrained by a realistic system limit, this α-generic approach had errors of less than ~20% for the full range of α values. This was the case for 24 radiosensitive organs in both chest and abdomen-pelvis CT scans with the exception of thyroid in the chest scan and bladder in the abdomen-pelvis scan. For these two organs, the errors were less than ~40%. The results of this theoretical study suggested that knowing the mA modulation profile and the fixed-mA conversion factors, organ dose may be estimated for a TCM scan independent of the specific modulation scheme applied.
-
Koh, Jin-Sin; Park, Yongwhi; Tantry, Udaya S; Ahn, Jong-Hwa; Kang, Min Gyu; Kim, Kyehwan; Jang, Jeong Yoon; Park, Hyun Woong; Park, Jeong Rang; Hwang, Seok-Jae; Kwak, Choong Hwan; Hwang, Jin-Yong; Gurbel, Paul A; Jeong, Young-Hoon
2017-03-01
Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely prescribed regimen to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). A fixed-dose combination (FDC) capsule (HCP0911) has been developed to provide dosing convenience and improve adherence. We compared the antiplatelet effects of single daily dose HCP0911 with separate treatment with daily 75 mg clopidogrel plus 100 mg aspirin. This was a randomized, open-label, two-period, crossover, non-inferiority study conducted in stented patients who had been treated for at least 6 months with clopidogrel and aspirin. Thirty patients were randomly assigned to receive either daily 75 mg clopidogrel plus 100 mg aspirin treatment or HCP0911 for 2 weeks and then were crossed over to the other treatment for 2 weeks. Pharmacodynamic effects were measured with VerifyNow, light transmittance aggregometry (LTA), and thromboelastography (TEG ® ). The primary endpoint was P2Y12 Reaction Units (PRU) measured by VerifyNow. PRUs during treatment with HCP0911 were not inferior to those during separate treatment (202 ± 52 vs. 207 ± 60 PRU; mean difference, -5 PRU; 90% confidence interval of difference, -23 to 13 PRU; P for non-inferiority = 0.015 for predetermined limit). "BASE" and Aspirin Reaction Units by VerifyNow did not differ between the two treatments. During each treatment, there were no differences in maximal and final platelet aggregations by LTA (all P values ≥0.822) and TEG ® measurements. In conclusion, in stented patients, the antiplatelet effect of a fixed-dose clopidogrel-aspirin combination, HCP0911, was not inferior to separate administration of clopidogrel and aspirin.
-
Muñoz, Jose; Ballester, Maria Rosa; Antonijoan, Rosa Maria; Gich, Ignasi; Rodríguez, Montse; Colli, Enrico; Gold, Silvia; Krolewiecki, Alejandro J
2018-01-01
Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective. ClinicalTrials.gov NCT03173742.
-
Antonijoan, Rosa Maria; Gich, Ignasi; Rodríguez, Montse; Colli, Enrico; Gold, Silvia
2018-01-01
Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective. Trial registration ClinicalTrials.gov NCT03173742. PMID:29346388
-
Left-sided breast cancer irradiation using rotational and fixed-field radiotherapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Qi, X. Sharon, E-mail: xqi@mednet.ucla.edu; Liu, Tian X.; Liu, Arthur K.
2014-10-01
The 3-dimensional conformal radiotherapy (3DCRT) technique is the standard for breast cancer radiotherapy. During treatment planning, not only the coverage of the planning target volume (PTV) but also the minimization of the dose to critical structures, such as the lung, heart, and contralateral breast tissue, need to be considered. Because of the complexity and variations of patient anatomy, more advanced radiotherapy techniques are sometimes desired to better meet the planning goals. In this study, we evaluated external-beam radiation treatment techniques for left breast cancer using various delivery platforms: fixed-field including TomoDirect (TD), static intensity-modulated radiotherapy (sIMRT), and rotational radiotherapy includingmore » Elekta volumetric-modulated arc therapy (VMAT) and tomotherapy helical (TH). A total of 10 patients with left-sided breast cancer who did or did not have positive lymph nodes and were previously treated with 3DCRT/sIMRT to the entire breast were selected, their treatment was planned with Monaco VMAT, TD, and TH. Dosimetric parameters including PTV coverage, organ-at-risk (OAR) sparing, dose-volume histograms, and target minimum/maximum/mean doses were evaluated. It is found that for plans providing comparable PTV coverage, the Elekta VMAT plans were generally more inhomogeneous than the TH and TD plans. For the cases with regional node involvement, the average mean doses administered to the heart were 9.2 (± 5.2) and 8.8 (± 3.0) Gy in the VMAT and TH plans compared with 11.9 (± 6.4) and 11.8 (± 9.2) Gy for the 3DCRT and TD plans, respectively, with slightly higher doses given to the contralateral lung or breast or both. On average, the total monitor units for VMAT plans are 11.6% of those TH plans. Our studies have shown that VMAT and TH plans offer certain dosimetric advantages over fixed-field IMRT plans for advanced breast cancer requiring regional nodal treatment. However, for early-stage breast cancer fixed-field radiotherapy is potentially more beneficial in terms of OAR sparing.« less
-
Left-sided breast cancer irradiation using rotational and fixed-field radiotherapy.
Qi, X Sharon; Liu, Tian X; Liu, Arthur K; Newman, Francis; Rabinovitch, Rachel; Kavanagh, Brian; Hu, Y Angie
2014-01-01
The 3-dimensional conformal radiotherapy (3DCRT) technique is the standard for breast cancer radiotherapy. During treatment planning, not only the coverage of the planning target volume (PTV) but also the minimization of the dose to critical structures, such as the lung, heart, and contralateral breast tissue, need to be considered. Because of the complexity and variations of patient anatomy, more advanced radiotherapy techniques are sometimes desired to better meet the planning goals. In this study, we evaluated external-beam radiation treatment techniques for left breast cancer using various delivery platforms: fixed-field including TomoDirect (TD), static intensity-modulated radiotherapy (sIMRT), and rotational radiotherapy including Elekta volumetric-modulated arc therapy (VMAT) and tomotherapy helical (TH). A total of 10 patients with left-sided breast cancer who did or did not have positive lymph nodes and were previously treated with 3DCRT/sIMRT to the entire breast were selected, their treatment was planned with Monaco VMAT, TD, and TH. Dosimetric parameters including PTV coverage, organ-at-risk (OAR) sparing, dose-volume histograms, and target minimum/maximum/mean doses were evaluated. It is found that for plans providing comparable PTV coverage, the Elekta VMAT plans were generally more inhomogeneous than the TH and TD plans. For the cases with regional node involvement, the average mean doses administered to the heart were 9.2 (± 5.2) and 8.8 (± 3.0)Gy in the VMAT and TH plans compared with 11.9 (± 6.4) and 11.8 (± 9.2)Gy for the 3DCRT and TD plans, respectively, with slightly higher doses given to the contralateral lung or breast or both. On average, the total monitor units for VMAT plans are 11.6% of those TH plans. Our studies have shown that VMAT and TH plans offer certain dosimetric advantages over fixed-field IMRT plans for advanced breast cancer requiring regional nodal treatment. However, for early-stage breast cancer fixed-field radiotherapy is potentially more beneficial in terms of OAR sparing. Copyright © 2014 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Omar, A; Bujila, R; Nowik, P
2014-06-01
Purpose: To investigate the potential benefits of automatic monitoring of accumulated patient and staff dose indicators, i.e., CAK and KAP, from DICOM Radiation Dose Structured Reports (RDSR) in x-ray angiography (XA). Methods: Recently RDSR has enabled the convenient aggregation of dose indices and technique parameters for XA procedures. The information contained in RDSR objects for three XA systems, dedicated to different types of clinical procedures, has been collected and aggregated in a database for over one year using a system developed with open-source software at the Karolinska University Hospital. Patient weight was complemented to the RDSR data via an interfacemore » with the Hospital Information System (HIS). Results: The linearly approximated trend in KAP over a time period of a year for cerebrovascular, pelvic/peripheral vascular, and cardiovascular procedures showed a decrease of 12%, 20%, and 14%, respectively. The decrease was mainly due to hardware/software upgrades and new low-dose imaging protocols, and partially due to ongoing systematic radiation safety education of the clinical staff. The CAK was in excess of 3 Gy for 15 procedures, and exceeded 5 Gy for 3 procedures. The dose indices have also shown a significant dependence on patient weight for cardiovascular and pelvic/peripheral vascular procedures; a 10 kg shift in mean patient weight can result in a dose index increase of 25%. Conclusion: Automatic monitoring of accumulated dose indices can be utilized to notify the clinical staff and medical physicists when the dose index has exceeded a predetermined action level. This allows for convenient and systematic follow-up of patients in risk of developing deterministic skin injuries. Furthermore, trend analyses of dose indices over time is a valuable resource for the identification of potential positive or negative effects (dose increase/decrease) from changes in hardware, software, and clinical work habits.« less
-
Banks, Matthew L; Blough, Bruce E
2015-01-01
Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0–0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32–1.8 mg/kg/h) and risperidone (0.001–0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01–0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food choice model. PMID:25742872
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xiong, Z; Vijayan, S; Rana, V
2015-06-15
Purpose: A system was developed that automatically calculates the organ and effective dose for individual fluoroscopically-guided procedures using a log of the clinical exposure parameters. Methods: We have previously developed a dose tracking system (DTS) to provide a real-time color-coded 3D- mapping of skin dose. This software produces a log file of all geometry and exposure parameters for every x-ray pulse during a procedure. The data in the log files is input into PCXMC, a Monte Carlo program that calculates organ and effective dose for projections and exposure parameters set by the user. We developed a MATLAB program to readmore » data from the log files produced by the DTS and to automatically generate the definition files in the format used by PCXMC. The processing is done at the end of a procedure after all exposures are completed. Since there are thousands of exposure pulses with various parameters for fluoroscopy, DA and DSA and at various projections, the data for exposures with similar parameters is grouped prior to entry into PCXMC to reduce the number of Monte Carlo calculations that need to be performed. Results: The software developed automatically transfers data from the DTS log file to PCXMC and runs the program for each grouping of exposure pulses. When the dose from all exposure events are calculated, the doses for each organ and all effective doses are summed to obtain procedure totals. For a complicated interventional procedure, the calculations can be completed on a PC without manual intervention in less than 30 minutes depending on the level of data grouping. Conclusion: This system allows organ dose to be calculated for individual procedures for every patient without tedious calculations or data entry so that estimates of stochastic risk can be obtained in addition to the deterministic risk estimate provided by the DTS. Partial support from NIH grant R01EB002873 and Toshiba Medical Systems Corp.« less
-
TU-D-201-07: Severity Indication in High Dose Rate Brachytherapy Emergency Response Procedure
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, K; Rustad, F
Purpose: Understanding the corresponding dose to different staff during the High Dose Rate (HDR) Brachytherapy emergency response procedure could help to develop a strategy in efficiency and effective action. In this study, the variation and risk analysis methodology was developed to simulation the HDR emergency response procedure based on severity indicator. Methods: A GammaMedplus iX HDR unit from Varian Medical System was used for this simulation. The emergency response procedure was decomposed based on risk management methods. Severity indexes were used to identify the impact of a risk occurrence on the step including dose to patient and dose to operationmore » staff by varying the time, HDR source activity, distance from the source to patient and staff and the actions. These actions in 7 steps were to press the interrupt button, press emergency shutoff switch, press emergency button on the afterloader keypad, turn emergency hand-crank, remove applicator from the patient, disconnect transfer tube and move afterloader from the patient, and execute emergency surgical recovery. Results: Given the accumulated time in second at the assumed 7 steps were 15, 5, 30, 15, 180, 120, 1800, and the dose rate of HDR source is 10 Ci, the accumulated dose in cGy to patient at 1cm distance were 188, 250, 625, 813, 3063, 4563 and 27063, and the accumulated exposure in rem to operator at outside the vault, 1m and 10cm distance were 0.0, 0.0, 0.1, 0.1, 22.6, 37.6 and 262.6. The variation was determined by the operators in action at different time and distance from the HDR source. Conclusion: The time and dose were estimated for a HDR unit emergency response procedure. It provided information in making optimal decision during the emergency procedure. Further investigation would be to optimize and standardize the responses for other emergency procedure by time-spatial-dose severity function.« less
-
How accurately can the peak skin dose in fluoroscopy be determined using indirect dose metrics?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jones, A. Kyle, E-mail: kyle.jones@mdanderson.org; Ensor, Joe E.; Pasciak, Alexander S.
Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that result in skin reactions can be reached during these procedures. There is no consensus as to whether or not indirect skin dosimetry is sufficiently accurate for fluoroscopically-guided interventions. However, measuring PSD with film is difficult and the decision to do so must be madea priori. The purpose of this study was to assess the accuracy of different types of indirect dose estimates and to determine if PSD can be calculated within ±50% using indirect dose metrics for embolization procedures. Methods: PSD were measured directly using radiochromicmore » film for 41 consecutive embolization procedures at two sites. Indirect dose metrics from the procedures were collected, including reference air kerma. Four different estimates of PSD were calculated from the indirect dose metrics and compared along with reference air kerma to the measured PSD for each case. The four indirect estimates included a standard calculation method, the use of detailed information from the radiation dose structured report, and two simplified calculation methods based on the standard method. Indirect dosimetry results were compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the different indirect estimates were examined. Results: When using the standard calculation method, calculated PSD were within ±35% for all 41 procedures studied. Calculated PSD were within ±50% for a simplified method using a single source-to-patient distance for all calculations. Reference air kerma was within ±50% for all but one procedure. Cases for which reference air kerma or calculated PSD exhibited large (±35%) differences from the measured PSD were analyzed, and two main causative factors were identified: unusually small or large source-to-patient distances and large contributions to reference air kerma from cone beam computed tomography or acquisition runs acquired at large primary gantry angles. When calculated uncertainty limits [−12.8%, 10%] were applied to directly measured PSD, most indirect PSD estimates remained within ±50% of the measured PSD. Conclusions: Using indirect dose metrics, PSD can be determined within ±35% for embolization procedures. Reference air kerma can be used without modification to set notification limits and substantial radiation dose levels, provided the displayed reference air kerma is accurate. These results can reasonably be extended to similar procedures, including vascular and interventional oncology. Considering these results, film dosimetry is likely an unnecessary effort for these types of procedures when indirect dose metrics are available.« less
-
Kumagai, M; Mori, S; Yamamoto, N
2015-06-01
When using a fixed irradiation port, treatment couch rotation is necessary to increase beam angle selection. We evaluated dose variations associated with positional morphological changes to organs. We retrospectively chose the data sets of ten patients with lung cancer who underwent respiratory-gated CT at three different couch rotation angles (0°, 20° and -20°). The respective CT data sets are referred to as CT0, CT20 and CT-20. Three treatment plans were generated as follows: in Plan 1, all compensating bolus designs and dose distributions were calculated using CT0. To evaluate the rotation effect without considering morphology changes, in Plan 2, the compensating boli designed using CT0 were applied to the CT±20 images. Plan 3 involved compensating boli designed using the CT±20 images. The accumulated dose distributions were calculated using deformable image registration (DIR). A sufficient prescribed dose was calculated for the planning target volume (PTV) in Plan 1 [minimum dose received by a volume ≥95% (D95) > 95.8%]. By contrast, Plan 2 showed degraded dose conformation to the PTV (D95 > 90%) owing to mismatch of the bolus design to the morphological positional changes in the respective CT. The dose assessment results of Plan 3 were very close to those of Plan 1. Dose distribution is significantly affected by whether or not positional organ morphology changes are factored into dose planning. In treatment planning using multiple CT scans with different couch positions, it is mandatory to calculate the accumulated dose using DIR.
-
Saxagliptin/Dapagliflozin: A Review in Type 2 Diabetes Mellitus.
Garnock-Jones, Karly P
2017-03-01
Saxagliptin/dapagliflozin fixed-dose combination tablets (Qtern ® ) are indicated in the EU for the improvement of glycaemic control in adults with type 2 diabetes mellitus (T2DM), either when treatment with metformin and/or a sulfonylurea plus a monocomponent of saxagliptin/dapagliflozin provides inadequate glycaemic control, or when the patient is already being treated with the free combination of saxagliptin + dapagliflozin. This narrative review summarizes pharmacological, efficacy and tolerability data relevant to the use of saxagliptin/dapagliflozin in this indication. The agents have complementary mechanisms of action, and saxagliptin/dapagliflozin fixed-dose combination tablets are bioequivalent to free combination of saxagliptin + dapagliflozin. In three phase III trials, saxagliptin + dapagliflozin + metformin was more effective at providing glycaemic control than saxagliptin + metformin or dapagliflozin + metformin in previously treated patients with T2DM and inadequate glycaemic control on metformin monotherapy or metformin plus one of the monocomponents. The combination is associated with decreased bodyweight and a low risk of hypoglycaemia. As the first dipeptidyl peptidase-4 (DPP-4) inhibitor/sodium-glucose co-transporter (SGLT2) inhibitor fixed-dose combination available in the EU for glycaemic control in patients with T2DM, saxagliptin/dapagliflozin is a useful new option in this setting.
-
Asthma control in patients on fixed dose combination evaluated with mannitol challenge test.
Romberg, Kerstin A M; Berggren, Anna-Carin; Bjermer, Leif
2014-02-01
Asthma is often difficult to control and it is likely that not all patients are optimally treated. This study aimed to explore asthma control in adults receiving fixed dose combination (FDC) therapy. Control of asthma was assessed using the mannitol challenge test as a monitoring tool to see if this would give additional information compared to the asthma control test (ACT). The study was an open-label, prospective study on 98 adults prescribed with FDC therapies for at least three months. 74 patients considered that their asthma was well controlled. However, 60 patients had a positive mannitol challenge test (PD15 < 635 mg), and when those with a positive response to the short-acting β2-agonist (≥15%) after the mannitol challenge test were included, this increased to 64 patients (65%). Exploratory analysis determined that the spirometry parameters; FEV1/FVC and FEV1% of predicted, were statistically significant predictors of a positive mannitol challenge test. Co-morbid conditions such as concomitant upper airway involvement or eczema did not predict mannitol reactivity. Although most patients rated their asthma as well controlled, many provided a positive mannitol challenge test, suggesting the presence of underlying inflammation, despite treatment with fixed dose combination therapy. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
-
Antituberculosis Drug-Induced Fixed Drug Eruption: A Case Report.
Vaghela, Jitendra H; Nimbark, Vivek; Barvaliya, Manish; Mehta, Hita; Chavada, Bhavesh
2018-05-21
Fixed drug eruption (FDE) was caused by fixed-dose combination (FDC) of antituberculosis drugs in the form of tablet Forecox ® (rifampicin [rifampin] 225 mg + isoniazid 150 mg + pyrazinamide 750 mg + ethambutol 400 mg) in a 40-year-old male patient with a history of drug allergy. The patient developed FDE after taking the third dose of tablet Forecox ® for pulmonary tuberculosis. Tablet Forecox ® was withdrawn and the patient recovered from the reaction after 15 days of treatment for FDE. As per World Health Organization-Uppsala Monitoring Centre (WHO-UMC) and Naranjo causality assessment criteria, the association between the reaction and tablet Forecox ® was possible and probable, respectively. The reaction was moderately (Level 4b) severe according to the Modified Hartwig and Siegel scale. As there is an increased risk of allergic reaction in patients with a history of drug allergy, FDCs should not be used in order to avoid complexity in identifying the culprit drug.
-
Lee, Kam L; Bernardo, Michael; Ireland, Timothy A
2016-06-01
This is part two of a two-part study in benchmarking system performance of fixed digital radiographic systems. The study compares the system performance of seven fixed digital radiography systems based on quantitative metrics like modulation transfer function (sMTF), normalised noise power spectrum (sNNPS), detective quantum efficiency (sDQE) and entrance surface air kerma (ESAK). It was found that the most efficient image receptors (greatest sDQE) were not necessarily operating at the lowest ESAK. In part one of this study, sMTF is shown to depend on system configuration while sNNPS is shown to be relatively consistent across systems. Systems are ranked on their signal-to-noise ratio efficiency (sDQE) and their ESAK. Systems using the same equipment configuration do not necessarily have the same system performance. This implies radiographic practice at the site will have an impact on the overall system performance. In general, systems are more dose efficient at low dose settings.
-
Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis
Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier
2016-01-01
Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence). When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence). We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings. Authors' conclusions Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB. PLAIN LANGUAGE SUMMARY Fixed-dose combinations for treating pulmonary tuberculosis What are fixed-dose combinations and how might they improve care of people with tuberculosis Tuberculosis (TB) is an important health problem, especially in developing countries. The treatment for pulmonary TB in new patients includes four oral medicines taken for six months, sometimes as fixed-dose combinations (FDCs) that are combined in one tablet, or taken separately as single-drug formulations. The World Health Organization recommends prescribers use fixed-dose combinations to reduce the number of tablets that people take. On the supply side, this might reduce prescribing errors and improve drug supply efficiency; on the patient's side, FDCS simplify treatment and improve adherence. We conducted a review to assess the efficacy, safety, and acceptability of FDCs compared with single-drug formulations for treating people with newly diagnosed pulmonary TB. What the research says We searched for relevant trials up to 20 November 2015, and included 13 randomized controlled trials that enrolled 5824 people. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. There is probably little or no difference in FDCs compared to single-drug formulations for treatment failure (moderate quality evidence); relapse may be more frequent (low quality evidence); and the number of deaths were similar (moderate quality evidence). There is little or no difference in sputum smear or culture conversion (high quality evidence), and no difference was shown for serious adverse events (moderate quality evidence) or adverse events that led to discontinuation of therapy (low quality evidence). Authors' conclusions We concluded that fixed-dose combinations have similar efficacy to single-drug formulations for treating people with newly diagnosed pulmonary TB. PMID:27186634
-
Tree form quotients as variables in volume estimation.
Gerald E. Hoyer
1985-01-01
The study reviews Hohenadl's procedure for defining form quotients and tree volume from diameters measured at fixed proportions of total tree height. Modifications of Hohenadl's procedure were applied to two sets of data for western hemlock (Tsuga heterophylla (Raf.) Sarg.) from the Pacific Northwest. The procedure was used to define...
-
Code of Federal Regulations, 2011 CFR
2011-07-01
... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Procedure. 67.35-1 Section 67.35-1 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES Applications § 67.35-1 Procedure. (a) An...
-
Code of Federal Regulations, 2010 CFR
2010-07-01
... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Procedure. 67.35-1 Section 67.35-1 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION AIDS TO NAVIGATION ON ARTIFICIAL ISLANDS AND FIXED STRUCTURES Applications § 67.35-1 Procedure. (a) An...
-
Schiavo, M; Bagnara, M C; Pomposelli, E; Altrinetti, V; Calamia, I; Camerieri, L; Giusti, M; Pesce, G; Reitano, C; Bagnasco, M; Caputo, M
2013-09-01
Radioiodine is a common option for treatment of hyperfunctioning thyroid nodules. Due to the expected selective radioiodine uptake by adenoma, relatively high "fixed" activities are often used. Alternatively, the activity is individually calculated upon the prescription of a fixed value of target absorbed dose. We evaluated the use of an algorithm for personalized radioiodine activity calculation, which allows as a rule the administration of lower radioiodine activities. Seventy-five patients with single hyperfunctioning thyroid nodule eligible for 131I treatment were studied. The activities of 131I to be administered were estimated by the method described by Traino et al. and developed for Graves'disease, assuming selective and homogeneous 131I uptake by adenoma. The method takes into account 131I uptake and its effective half-life, target (adenoma) volume and its expected volume reduction during treatment. A comparison with the activities calculated by other dosimetric protocols, and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid nodule volume by ultrasonography, thyroid hormones and TSH by ELISA. Remission of hyperthyroidism was observed in all but one patient; volume reduction of adenoma was closely similar to that assumed by our model. Effective half-life was highly variable in different patients, and critically affected dose calculation. The administered activities were clearly lower with respect to "fixed" activities and other protocols' prescription. The proposed algorithm proved to be effective also for single hyperfunctioning thyroid nodule treatment and allowed a significant reduction of administered 131I activities, without loss of clinical efficacy.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Miller, Donald L.; Hilohi, C. Michael; Spelic, David C.
2012-10-15
Purpose: To determine patient radiation doses from interventional cardiology procedures in the U.S and to suggest possible initial values for U.S. benchmarks for patient radiation dose from selected interventional cardiology procedures [fluoroscopically guided diagnostic cardiac catheterization and percutaneous coronary intervention (PCI)]. Methods: Patient radiation dose metrics were derived from analysis of data from the 2008 to 2009 Nationwide Evaluation of X-ray Trends (NEXT) survey of cardiac catheterization. This analysis used deidentified data and did not require review by an IRB. Data from 171 facilities in 30 states were analyzed. The distributions (percentiles) of radiation dose metrics were determined for diagnosticmore » cardiac catheterizations, PCI, and combined diagnostic and PCI procedures. Confidence intervals for these dose distributions were determined using bootstrap resampling. Results: Percentile distributions (advisory data sets) and possible preliminary U.S. reference levels (based on the 75th percentile of the dose distributions) are provided for cumulative air kerma at the reference point (K{sub a,r}), cumulative air kerma-area product (P{sub KA}), fluoroscopy time, and number of cine runs. Dose distributions are sufficiently detailed to permit dose audits as described in National Council on Radiation Protection and Measurements Report No. 168. Fluoroscopy times are consistent with those observed in European studies, but P{sub KA} is higher in the U.S. Conclusions: Sufficient data exist to suggest possible initial benchmarks for patient radiation dose for certain interventional cardiology procedures in the U.S. Our data suggest that patient radiation dose in these procedures is not optimized in U.S. practice.« less
-
RADIATION PROTECTION CABIN FOR CATHETER-DIRECTED LIVER INTERVENTIONS: OPERATOR DOSE ASSESSMENT.
Maleux, Geert; Bergans, Niki; Bosmans, Hilde; Bogaerts, Ria
2016-09-01
The number and complexity of interventional radiological procedures and in particular catheter-directed liver interventions have increased substantially. The current study investigates the reduction of personal doses when using a dedicated radiation protection cabin (RPC) for these procedures. Operator and assistant doses were assessed for 3 series of 20 chemoinfusion/chemoembolisation interventions, including an equal number of procedures with and without RPC. Whole body doses, finger doses and doses at the level of knees and eyes were evaluated with different types of TLD-100 Harshaw dosemeters. Dosemeters were also attached on the three walls of the RPC. The operator doses were significantly reduced by the RPC, but also without RPC, the doses appear to be limited as a result of thorough optimisation with existing radiation protection tools. The added value of the RPC should thus be determined by the outcome of balancing dose reduction and other aspects such as ergonomic benefits. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jones, A; Pasciak, A
Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that Result in skin reactions can be reached during these procedures. The purpose of this study was to assess the accuracy of different indirect dose estimates and to determine if PSD can be calculated within ±50% for embolization procedures. Methods: PSD were measured directly using radiochromic film for 41 consecutive embolization procedures. Indirect dose metrics from procedures were collected, including reference air kerma (RAK). Four different estimates of PSD were calculated and compared along with RAK to the measured PSD. The indirect estimates included a standard method,more » use of detailed information from the RDSR, and two simplified calculation methods. Indirect dosimetry was compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the indirect estimates were examined. Results: PSD calculated with the standard calculation method were within ±50% for all 41 procedures. This was also true for a simplified method using a single source-to-patient distance (SPD) for all calculations. RAK was within ±50% for all but one procedure. Cases for which RAK or calculated PSD exhibited large differences from the measured PSD were analyzed, and two causative factors were identified: ‘extreme’ SPD and large contributions to RAK from rotational angiography or runs acquired at large gantry angles. When calculated uncertainty limits [−12.8%, 10%] were applied to directly measured PSD, most indirect PSD estimates remained within ±50% of the measured PSD. Conclusions: Using indirect dose metrics, PSD can be determined within ±50% for embolization procedures, and usually to within ±35%. RAK can be used without modification to set notification limits and substantial radiation dose levels. These results can be extended to similar procedures, including vascular and interventional oncology. Film dosimetry is likely an unnecessary effort for these types of procedures.« less
-
Combining Heterogeneous Correlation Matrices: Simulation Analysis of Fixed-Effects Methods
ERIC Educational Resources Information Center
Hafdahl, Adam R.
2008-01-01
Monte Carlo studies of several fixed-effects methods for combining and comparing correlation matrices have shown that two refinements improve estimation and inference substantially. With rare exception, however, these simulations have involved homogeneous data analyzed using conditional meta-analytic procedures. The present study builds on…
-
Ding, George X; Alaei, Parham; Curran, Bruce; Flynn, Ryan; Gossman, Michael; Mackie, T Rock; Miften, Moyed; Morin, Richard; Xu, X George; Zhu, Timothy C
2018-05-01
With radiotherapy having entered the era of image guidance, or image-guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed. This task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam CT (kV-CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients. We briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures. We provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose. Although the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care. Balancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient. © 2018 American Association of Physicists in Medicine.
-
The story of artesunate–mefloquine (ASMQ), innovative partnerships in drug development: case study
2013-01-01
Background The Drugs for Neglected Diseases initiative (DNDi) is a not-for profit organization committed to providing affordable medicines and access to treatments in resource-poor settings. Traditionally drug development has happened “in house” within pharmaceutical companies, with research and development costs ultimately recuperated through drug sales. The development of drugs for the treatment of neglected tropical diseases requires a completely different model that goes beyond the scope of market-driven research and development. Artesunate and mefloquine are well-established drugs for the treatment of uncomplicated malaria, with a strong safety record based on many years of field-based studies and use. The administration of such artemisinin-based combination therapy in a fixed-dose combination is expected to improve patient compliance and to reduce the risk of emerging drug resistance. Case description DNDi developed an innovative approach to drug development, reliant on strong collaborations with a wide range of partners from the commercial world, academia, government institutions and NGOs, each of which had a specific role to play in the development of a fixed dose combination of artesunate and mefloquine. Discussion and evaluation DNDi undertook the development of a fixed-dose combination of artesunate with mefloquine. Partnerships were formed across five continents, addressing formulation, control and production through to clinical trials and product registration, resulting in a safe and efficacious fixed dose combination treatment which is now available to treat patients in resource-poor settings. The south-south technology transfer of production from Farmanguinhos/Fiocruz in Brazil to Cipla Ltd in India was the first of its kind. Of additional benefit was the increased capacity within the knowledge base and infrastructure in developing countries. Conclusions This collaborative approach to drug development involving international partnerships and independent funding mechanisms is a powerful new way to develop drugs for tropical diseases. PMID:23433060
-
Mendiratta-Lala, Mishal; Williams, Todd R; Mendiratta, Vivek; Ahmed, Hafeez; Bonnett, John W
2015-04-01
The purpose of this study was to evaluate the effectiveness of a multifaceted simulation-based resident training for CT-guided fluoroscopic procedures by measuring procedural and technical skills, radiation dose, and procedure times before and after simulation training. A prospective analysis included 40 radiology residents and eight staff radiologists. Residents took an online pretest to assess baseline procedural knowledge. Second-through fourth-year residents' baseline technical skills with a procedural phantom were evaluated. First-through third-year residents then underwent formal didactic and simulation-based procedural and technical training with one of two interventional radiologists and followed the training with 1 month of supervised phantom-based practice. Thereafter, residents underwent final written and practical examinations. The practical examination included essential items from a 20-point checklist, including site and side marking, consent, time-out, and sterile technique along with a technical skills portion assessing pedal steps, radiation dose, needle redirects, and procedure time. The results indicated statistically significant improvement in procedural and technical skills after simulation training. For residents, the median number of pedal steps decreased by three (p=0.001), median dose decreased by 15.4 mGy (p<0.001), median procedure time decreased by 4.0 minutes (p<0.001), median number of needle redirects decreased by 1.0 (p=0.005), and median number of 20-point checklist items successfully completed increased by three (p<0.001). The results suggest that procedural skills can be acquired and improved by simulation-based training of residents, regardless of experience. CT simulation training decreases procedural time, decreases radiation dose, and improves resident efficiency and confidence, which may transfer to clinical practice with improved patient care and safety.
-
Evaluation of an Alcohol Withdrawal Protocol and a Preprinted Order Set at a Tertiary Care Hospital
Ng, Karen; Dahri, Karen; Chow, Ivy; Legal, Michael
2011-01-01
Background: Alcohol withdrawal protocols involving symptom-triggered administration of benzodiazepine have been established to reduce the duration of treatment and the cumulative benzodiazepine dose (relative to usual care). However, the effects of a protocol combining fixed-schedule and symptom-triggered benzodiazepine dosing are less clear. Objective: To assess the efficacy and safety of a combination fixed-scheduled and symptom-triggered benzodiazepine dosing protocol for alcohol withdrawal, relative to usual care, for medical inpatients at a tertiary care hospital. Methods: A chart review of admissions to the internal medicine service for alcohol withdrawal was conducted to compare treatment outcomes before (October 2005 to April 2007) and after (October 2007 to April 2009) implementation of the combination protocol. The primary outcome was duration of benzodiazepine treatment for alcohol withdrawal. The secondary outcomes were cumulative benzodiazepine dose administered, safety implications, and use of adjunctive medications. Results: A total of 159 patients met the inclusion criteria. Assessable data were available for 71 charts from the pre-implementation period and 72 charts from the post-implementation period. The median duration of benzodiazepine treatment was 91 h before implementation and 57 h after implementation (p < 0.001). Use of the protocol was also associated with a significant reduction in severe complications of alcohol withdrawal (50% versus 33%, p = 0.019), median cumulative benzodiazepine dose (in lorazepam equivalents) (20.0 mg versus 15.5 mg, p = 0.026), and use of adjunctive medications (65% versus 38%, p = 0.001). The incidence of serious adverse outcomes of treatment with benzodiazepines was not significantly different between the 2 groups. Conclusions: Implementation of an alcohol withdrawal protocol with a combination of fixed-schedule and symptom-triggered benzodiazepine dosing in a medical ward was associated with a shorter duration of benzodiazepine use and a lower incidence of severe complications of alcohol withdrawal. PMID:22479099
-
Applicator-guided volumetric-modulated arc therapy for low-risk endometrial cancer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cilla, Savino, E-mail: savinocilla@gmail.com; Macchia, Gabriella; Sabatino, Domenico
2013-04-01
The aim of this study was to report the feasibility of volumetric-modulated arc therapy (VMAT) in the postoperative irradiation of the vaginal vault. Moreover, the VMAT technique was compared with 3D conformal radiotherapy (3D-CRT) and fixed-field intensity-modulated radiotherapy (IMRT), in terms of target coverage and organs at risk sparing. The number of monitor units and the delivery time were analyzed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a 2D array of ionization chambers. Twelve patients with endometrial carcinoma who underwent radical hystero-adenexectomy and fixed-field IMRT treatments were retrospectively included in thismore » analysis; for each patient, plans were compared in terms of dose-volume histograms, homogeneity index, and conformity indexes. All techniques met the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformity at all dose levels. VMAT resulted in significant reduction of rectal and bladder volumes irradiated at all dose levels compared with 3D-CRT. No significant differences were found with respect to IMRT. Moreover, a significant improvement of the dose conformity was reached by VMAT technique not only at the 95% dose level (0.74 vs. 0.67 and 0.62) but also at 50% and 75% levels of dose prescription. In addition, VMAT plans showed a significant reduction of monitor units by nearly 28% with respect to IMRT, and reduced treatment time from 11 to <3 minutes for a single 6-Gy fraction. In conclusion, VMAT plans can be planned and carried out with high quality and efficiency for the irradiation of vaginal vault alone, providing similar or better sparing of organs at risk to fixed-field IMRT and resulting in the most efficient treatment option. VMAT is currently our standard approach for radiotherapy of low-risk endometrial cancer.« less
-
Sailer, Anna M; Vergoossen, Laura; Paulis, Leonie; van Zwam, Willem H; Das, Marco; Wildberger, Joachim E; Jeukens, Cécile R L P N
2017-11-01
Radiation safety and protection are a key component of fluoroscopy-guided interventions. We hypothesize that providing weekly personal dose feedback will increase radiation awareness and ultimately will lead to optimized behavior. Therefore, we designed and implemented a personalized feedback of procedure and personal doses for medical staff involved in fluoroscopy-guided interventions. Medical staff (physicians and technicians, n = 27) involved in fluoroscopy-guided interventions were equipped with electronic personal dose meters (PDMs). Procedure dose data including the dose area product and effective doses from PDMs were prospectively monitored for each consecutive procedure over an 8-month period (n = 1082). A personalized feedback form was designed displaying for each staff individually the personal dose per procedure, as well as relative and cumulative doses. This study consisted of two phases: (1) 1-5th months: Staff did not receive feedback (n = 701) and (2) 6-8th months: Staff received weekly individual dose feedback (n = 381). An anonymous evaluation was performed on the feedback and occupational dose. Personalized feedback was scored valuable by 76% of the staff and increased radiation dose awareness for 71%. 57 and 52% reported an increased feeling of occupational safety and changing their behavior because of personalized feedback, respectively. For technicians, the normalized dose was significantly lower in the feedback phase compared to the prefeedback phase: [median (IQR) normalized dose (phase 1) 0.12 (0.04-0.50) µSv/Gy cm 2 versus (phase 2) 0.08 (0.02-0.24) µSv/Gy cm 2 , p = 0.002]. Personalized dose feedback increases radiation awareness and safety and can be provided to staff involved in fluoroscopy-guided interventions.
-
When Is Rapid On-Site Evaluation Cost-Effective for Fine-Needle Aspiration Biopsy?
Schmidt, Robert L.; Walker, Brandon S.; Cohen, Michael B.
2015-01-01
Background Rapid on-site evaluation (ROSE) can improve adequacy rates of fine-needle aspiration biopsy (FNAB) but increases operational costs. The performance of ROSE relative to fixed sampling depends on many factors. It is not clear when ROSE is less costly than sampling with a fixed number of needle passes. The objective of this study was to determine the conditions under which ROSE is less costly than fixed sampling. Methods Cost comparison of sampling with and without ROSE using mathematical modeling. Models were based on a societal perspective and used a mechanistic, micro-costing approach. Sampling policies (ROSE, fixed) were compared using the difference in total expected costs per case. Scenarios were based on procedure complexity (palpation-guided or image-guided), adequacy rates (low, high) and sampling protocols (stopping criteria for ROSE and fixed sampling). One-way, probabilistic, and scenario-based sensitivity analysis was performed to determine which variables had the greatest influence on the cost difference. Results ROSE is favored relative to fixed sampling under the following conditions: (1) the cytologist is accurate, (2) the total variable cost ($/hr) is low, (3) fixed costs ($/procedure) are high, (4) the setup time is long, (5) the time between needle passes for ROSE is low, (6) when the per-pass adequacy rate is low, and (7) ROSE stops after observing one adequate sample. The model is most sensitive to variation in the fixed cost, the per-pass adequacy rate, and the time per needle pass with ROSE. Conclusions Mathematical modeling can be used to predict the difference in cost between sampling with and without ROSE. PMID:26317785
-
Mengden, Thomas; Hübner, Reinhold; Bramlage, Peter
2011-01-01
Background Fixed-dose combinations of candesartan 32 mg and hydrochlorothiazide (HCTZ) have been shown to be effective in clinical trials. Upon market entry we conducted a noninterventional study to document the safety and effectiveness of this fixed-dose combination in an unselected population in primary care and to compare blood pressure (BP) values obtained during office measurement (OBPM) with ambulatory blood pressure measurement (ABPM). Methods CHILI CU Soon was a prospective, noninterventional, noncontrolled, open-label, multicenter study with a follow-up of at least 10 weeks. High-risk patients aged ≥18 years with previously uncontrolled hypertension were started on candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ. OBPM and ABPM reduction and adverse events were documented. Results A total of 4131 patients (52.8% male) with a mean age of 63.0 ± 11.0 years were included. BP was 162.1 ± 14.8/94.7 ± 9.2 mmHg during office visits at baseline. After 10 weeks of candesartan 32 mg/12.5 mg or 25 mg HCTZ, mean BP had lowered to 131.7 ± 10.5/80.0 ± 6.6 mmHg (P < 0.0001 for both comparisons). BP reduction was comparable irrespective of prior or concomitant medication. In patients for whom physicians regarded an ABPM to be necessary (because of suspected noncontrol over 24 hours), ABP at baseline was 158.2/93.7 mmHg during the day and 141.8/85.2 mmHg during the night. At the last visit, BP had significantly reduced to 133.6/80.0 mmHg and 121.0/72.3 mmHg, respectively, resulting in 20.8% being normotensive over 24 hours (<130/80 mmHg). The correlation between OBPM and ABPM was good (r = 0.589 for systolic BP and r = 0.389 for diastolic BP during the day). Of those who were normotensive upon OBPM, 35.1% had high ABPM during the day, 49.3% were nondippers, and 3.4% were inverted dippers. Forty-nine adverse events (1.19%) were reported, of which seven (0.17%) were regarded as serious. Conclusion Candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ is safe and effective for further BP lowering irrespective of prior antihypertensive drug class not being able to control BP. PMID:22241950
-
Moreno Guillen, Santiago; Losa García, Juan Emilio; Berenguer Berenguer, Juan; Martínez Sesmero, José Manuel; Cenoz Gomis, Santiago; Graefenhain, Ruth; Lopez Sanchez-Cambronero, David; Parrondo Garcia, Francisco Javier
2017-09-01
Fixed-dose combinations of antiretroviral drugs have meant an important step forward in simplifying treatment and improving compliance and has led to an increased effectiveness of therapy, a viral load decrease and improving the quality of life of patients. The single-table formulation of dolutegravir with abacavir and lamivudine (DTG/ABC/3TC) is a highly efficacious and well-tolerated once-daily regimen for HIV-infected patients. The objective of the study was to assess the incremental cost-utility ratio of the fixed-dose combination of (DTG/ABC/3TC) versus the combinations emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV), and darunavir/r (DRV/r) or raltegravir (RAL) with emtricitabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) as initial antiretroviral therapy in patients infected with HIV-1 from the perspective of the Spanish National Health System. The ARAMIS model, which uses a microsimulation approach to simulate the individual changes in each patient from the start of treatment to death through a Markov chain of descriptive health states of the disease, was adapted to Spain. The alternatives used for comparison were the fixed-dose combination of emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV), and the fixed- dose combinations of emtricitabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) with darunavir/r (DRV/r) or raltegravir (RAL). The probability of achieving virological suppression by the treatments included in the model was obtained from clinical trials SINGLE, SPRING-2 and FLAMINGO and the costs were expressed in € (2015). The model use the perspective of the Spanish National Health System, with a lifetime horizon and a discount rate of 3% was applied to cost and effectiveness. Treatment initiation with DTG/ABC/3TC was dominant when it was compared with treatment initiation with all the comparators: vs. FTC/TDF/EFV (-67 210.71€/QALY), vs. DRV/r + FTC/TDF or ABC/3TC (-1 787 341.44€/QALY), and vs. RAL + FTC/TDF or ABC/3TC (-1 005 117.13€/QALY). All the sensitivity analyses performed showed the consistency of these findings. With the premises considered, treatment initiation with DTG/ABC/3TC STR appears to be the most cost-effective option in ARTnaïve HIV infected patients from the Spanish Health System perspective. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
-
Mahu, Ştefania Corina; Hăncianu, Monica; Agoroaei, Luminiţa; Grigoriu, Ioana Cezara; Strugaru, Anca Monica; Butnaru, Elena
2015-01-01
Hypertension is one of the most common causes of death, a complex and incompletely controlled disease for millions of patients. Metoprolol, bisoprolol, nebivolol and atenolol are selective beta-blockers frequently used in the management of arterial hypertension, alone or in fixed combination with other substances. This study presents the most used analytical methods for simultaneous determination in biological fluids of fixed combinations containing selective beta-blockers. Articles in Pub-Med, Science Direct and Wiley Journals databases published between years 2004-2014 were reviewed. Methods such as liquid chromatography--mass spectrometry--mass spectrometry (LC-MS/MS), high performance liquid chromatography (HPLC) or high performance liquid chromatography--mass spectrometry (HPLC-MS) were used for determination of fixed combination with beta-blockers in human plasma, rat plasma and human breast milk. LC-MS/MS method was used for simultaneous determination of fixed combinations of metoprolol with simvastatin, hydrochlorothiazide or ramipril, combinations of nebivolol and valsartan, or atenolol and amlodipine. Biological samples were processed by protein precipitation techniques or by liquid-liquid extraction. For the determination of fixed dose combinations of felodipine and metoprolol in rat plasma liquid chromatography--electrospray ionization--mass spectrometry (LC-ESI-MS/MS) was applied, using phenacetin as internal standard. HPLC-MS method was applied for the determination of bisoprolol and hydrochlorothiazide in human plasma. For the determination of atenolol and chlorthalidone from human breast milk and human plasma the HPLC method was used. The analytical methods were validated according to the specialized guidelines, and were applied to biological samples, thing that confirms the permanent concern of researchers in this field.
-
van den Haak, R F F; Hamans, B C; Zuurmond, K; Verhoeven, B A N; Koning, O H J
2015-10-01
To prospectively quantify radiation dose change in aortoiliac endovascular procedures in the hybrid operating room (OR) for patients and medical staff with a novel X-ray imaging technology (ClarityIQ technology), and to assess whether procedure or fluoroscopy time or dose of iodinated contrast was affected. A prospective study including 138 patients was performed to compare radiation dose before and after installation of a novel X-ray imaging technology. Endovascular aneurysm repair (EVAR) was performed in 37 patients and an endovascular procedure for aortoiliac occlusive disease (AIOD) in 101. Patient radiation dose in air kerma (AK) and dose area product (DAP), patient demographics, and procedural data were recorded. Staff radiation dose was measured with real time personal dosimetry measurements. In both the EVAR and AIOD groups the reference system, ALX (AlluraXper FD20; Philips Healthcare, Best, the Netherlands), was compared with the upgraded X-ray system, CIQ (AlluraClarity FD20; Philips Healthcare). Procedure time, fluoroscopy time, and iodinated contrast dose were recorded. Patient radiation dose reduction in the EVAR group, in median AK, was 56% (ALX = 1,262.5 mGy; CIQ = 556.0 mGy [p < .01]); and in median DAP it was 57% (ALX = 224.4 Gycm(2) and CIQ = 95.8 Gycm(2) [p < .01]). Patient radiation dose reduction in the AIOD group, in median AK, was 76% (ALX = 1,011.0 mGy; CIQ = 248.0 mGy [p < .01]); and in median DAP it was 73% (ALX = 138.1 Gycm(2); CIQ = 38.0 Gycm(2) [p < .01]). Staff dose reduction in the EVAR group was 16% (ALX = 70.1 μSv; CIQ = 59.2 μSv [p = .43]) and in the AIOD group it was 69% (ALX = 96.2 μSv; CIQ = 30.1 μSv [p < .01]). There was no statistically significant difference between patient demographics, procedure time, fluoroscopy time, and iodinated contrast medium use in the two treatment groups before and after installation. A novel X-ray imaging technology in the hybrid OR suite resulted in a significant reduction of patient and staff radiation dose without affecting procedure length, fluoroscopy time, or use of contrast. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Ngaile, J. E.; Msaki, P. K.; Kazema, R. R.
2018-04-01
Contrast investigations of hysterosalpingography (HSG) and retrograde urethrography (RUG) fluoroscopy procedures remain the dominant diagnostic tools for the investigation of infertility in females and urethral strictures in males, respectively, owing to the scarcity and high cost of services of alternative diagnostic technologies. In light of the radiological risks associated with contrast based investigations of the genitourinary tract systems, there is a need to assess the magnitude of radiation burden imparted to patients undergoing HSG and RUG fluoroscopy procedures in Tanzania. The air kerma area product (KAP), fluoroscopy time, number of images, organ dose and effective dose to patients undergoing HSG and RUG procedures were obtained from four hospitals. The KAP was measured using a flat transmission ionization chamber, while the organ and effective doses were estimated using the knowledge of the patient characteristics, patient related exposure parameters, geometry of examination, KAP and Monte Carlo calculations (PCXMC). The median values of KAP for the HSG and RUG were 2.2 Gy cm2 and 3.3 Gy cm2, respectively. The median organ doses in the present study for the ovaries, urinary bladder and uterus for the HSG procedures, were 1.0 mGy, 4.0 mGy and 1.6 mGy, respectively, while for urinary bladder and testes of the RUG were 3.4 mGy and 5.9 mGy, respectively. The median values of effective doses for the HSG and RUG procedures were 0.65 mSv and 0.59 mSv, respectively. The median values of effective dose per hospital for the HSG and RUG procedures had a range of 1.6-2.8 mSv and 1.9-5.6 mSv, respectively, while the overall differences between individual effective doses across the four hospitals varied by factors of up to 22.0 and 46.7, respectively for the HSG and RUG procedures. The proposed diagnostic reference levels (DRLs) for the HSG and RUG were for KAP 2.8 Gy cm2 and 3.9 Gy cm2, for fluoroscopy time 0.8 min and 0.9 min, and for number of images 5 and 4, respectively. The suggested DRLs for the HSG and RUG procedures may be used by the radiology departments in Tanzania for management of attained dose levels until the national DRLs are established.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Baumann, Frederic, E-mail: fredericbaumann@hotmail.com; Katzen, Barry T.; Carelsen, Bart
PurposeThe purpose of this study is to evaluate a new device providing real-time monitoring on radiation exposure during fluoroscopy procedures intending to reduce radiation in an interventional radiology setting.Materials and MethodsIn one interventional suite, a new system providing a real-time radiation dose display and five individual wireless dosimeters were installed. The five dosimeters were worn by the attending, fellow, nurse, technician, and anesthesiologist for every procedure taking place in that suite. During the first 6-week interval the dose display was off (closed phase) and activated thereafter, for a 6-week learning phase (learning phase) and a 10-week open phase (open phase).more » During these phases, the staff dose and the individual dose for each procedure were recorded from the wireless dosimeter and correlated with the fluoroscopy time. Further subanalysis for dose exposure included diagnostic versus interventional as well as short (<10 min) versus long (>10 min) procedures.ResultsA total of 252 procedures were performed (n = 88 closed phase, n = 50 learning phase, n = 114 open phase). The overall mean staff dose per fluoroscopic minute was 42.79 versus 19.81 µSv/min (p < 0.05) comparing the closed and open phase. Thereby, anesthesiologists were the only individuals attaining a significant dose reduction during open phase 16.9 versus 8.86 µSv/min (p < 0.05). Furthermore, a significant reduction of total staff dose was observed for short 51 % and interventional procedures 45 % (p < 0.05, for both).ConclusionA real-time qualitative display of radiation exposure may reduce team radiation dose. The process may take a few weeks during the learning phase but appears sustained, thereafter.« less
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xiong, Z; Vijayan, S; Oines, A
Purpose: To compare PCXMC and EGSnrc calculated organ and effective radiation doses from cone-beam computed tomography (CBCT) and interventional fluoroscopically-guided procedures using automatic exposure-event grouping. Methods: For CBCT, we used PCXMC20Rotation.exe to automatically calculate the doses and compared the results to those calculated using EGSnrc with the Zubal patient phantom. For interventional procedures, we use the dose tracking system (DTS) which we previously developed to produce a log file of all geometry and exposure parameters for every x-ray pulse during a procedure, and the data in the log file is input into PCXMC and EGSnrc for dose calculation. A MATLABmore » program reads data from the log files and groups similar exposures to reduce calculation time. The definition files are then automatically generated in the format used by PCXMC and EGSnrc. Processing is done at the end of the procedure after all exposures are completed. Results: For the Toshiba Infinix CBCT LCI-Middle-Abdominal protocol, most organ doses calculated with PCXMC20Rotation closely matched those calculated with EGSnrc. The effective doses were 33.77 mSv with PCXMC20Rotation and 32.46 mSv with EGSnrc. For a simulated interventional cardiac procedure, similar close agreement in organ dose was obtained between the two codes; the effective doses were 12.02 mSv with PCXMC and 11.35 mSv with EGSnrc. The calculations can be completed on a PC without manual intervention in less than 15 minutes with PCXMC and in about 10 hours with EGSnrc, depending on the level of data grouping and accuracy desired. Conclusion: Effective dose and most organ doses in CBCT and interventional radiology calculated by PCXMC closely match those calculated by EGSnrc. Data grouping, which can be done automatically, makes the calculation time with PCXMC on a standard PC acceptable. This capability expands the dose information that can be provided by the DTS. Partial support from NIH Grant R01-EB002873 and Toshiba Medical Systems Corp.« less
-
Archival samples represent a vast resource for identification of chemical and pharmaceutical targets. Previous use of formalin-fixed paraffin-embedded (FFPE) samples has been limited due to changes in RNA introduced by fixation and embedding procedures. Recent advances in RNA-seq...
-
48 CFR 31.204 - Application of principles and procedures.
Code of Federal Regulations, 2010 CFR
2010-10-01
...-price subcontract with economic price adjustment provisions. (c) Costs incurred as payments under firm-fixed-price subcontracts or fixed-price subcontracts with economic price adjustment provisions or... captures the essential nature of, the cost at issue. [48 FR 42301, Sept. 19, 1983, as amended at 53 FR...
-
An Introduction to the Federal Information Exchange System.
ERIC Educational Resources Information Center
De Santi, Vincent; Scheele, D. Sam
This publication offers a basic introduction to the Federal Information Exchange System (FIXS), a set of procedures for periodically collecting, processing, and publishing data on federal and state expenditures for each program listed in the "Catalog of Federal Assistance Programs." FIXS is designed for use in conjunction with the…
-
Sampling Using a Fixed Number of Trees Per Plot
Hans T. Schreuder
2004-01-01
The fixed number of trees sample design proposed by Jonsson and others (1992) may be dangerous in applications if a probabilistic framework of sampling is desired. The procedure can be seriously biased. Examples are given here.Publication Web Site:http://www.fs.fed.us/rm/pubs/rmrs_rn017.html
-
40 CFR 60.745 - Test methods and procedures.
Code of Federal Regulations, 2010 CFR
2010-07-01
... determination of the efficiency of a fixed-bed carbon adsorption system with a common exhaust stack for all the... separate runs, each coinciding with one or more complete system rotations through the adsorption cycles of... efficiency of a fixed-bed carbon adsorption system with individual exhaust stacks for each adsorber vessel...
-
40 CFR 60.745 - Test methods and procedures.
Code of Federal Regulations, 2011 CFR
2011-07-01
... determination of the efficiency of a fixed-bed carbon adsorption system with a common exhaust stack for all the... separate runs, each coinciding with one or more complete system rotations through the adsorption cycles of... efficiency of a fixed-bed carbon adsorption system with individual exhaust stacks for each adsorber vessel...
-
Kodak EDR2 film for patient skin dose assessment in cardiac catheterization procedures.
Morrell, R E; Rogers, A T
2006-07-01
Patient skin doses were measured using Kodak EDR2 film for 20 coronary angiography (CA) and 32 percutaneous transluminal coronary angioplasty (PTCA) procedures. For CA, all skin doses were well below 1 Gy. However, 23% of PTCA patients received skin doses of 1 Gy or more. Dose-area product (DAP) was also recorded and was found to be an inadequate indicator of maximum skin dose. Practical compliance with ICRP recommendations requires a robust method for skin dosimetry that is more accurate than DAP and is applicable over a wider dose range than EDR2 film.
-
Müller, Sabine; Riedmüller, Rita; van Oosterhout, Ansel
2015-01-01
In the wake of deep brain stimulation (DBS) development, ablative neurosurgical procedures are seeing a comeback, although they had been discredited and nearly completely abandoned in the 1970s because of their unethical practice. Modern stereotactic ablative procedures as thermal or radiofrequency ablation, and particularly radiosurgery (e.g., Gamma Knife) are much safer than the historical procedures, so that a re-evaluation of this technique is required. The different approaches of modern psychiatric neurosurgery refer to different paradigms: microsurgical ablative procedures is based on the paradigm 'quick fix,' radiosurgery on the paradigm 'minimal-invasiveness,' and DBS on the paradigm 'adjustability.' From a mere medical perspective, none of the procedures is absolutely superior; rather, they have different profiles of advantages and disadvantages. Therefore, individual factors are crucial in decision-making, particularly the patients' social situation, individual preferences, and individual attitudes. The different approaches are not only rivals, but also enriching mutually. DBS is preferable for exploring new targets, which may become candidates for ablative microsurgery or radiosurgery.
-
Sandrini, G; Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G
2007-01-01
Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57–1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82–1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. Conclusion: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf. PMID:17627707
-
Thermodynamic Pressure/Temperature Transducer Health Check
NASA Technical Reports Server (NTRS)
Immer, Christopher D. (Inventor); Eckhoff, Anthony (Inventor); Medelius, Pedro J. (Inventor); Deyoe, Richard T. (Inventor); Starr, Stanley O. (Inventor)
2004-01-01
A device and procedure for checking the health of a pressure transducer in situ is provided. The procedure includes measuring a fixed change in pressure above ambient pressure and a fixed change in pressure below ambient pressure. This is done by first sealing an enclosed volume around the transducer with a valve. A piston inside the sealed volume is increasing the pressure. A fixed pressure below ambient pressure is obtained by opening the valve, driving the piston The output of the pressure transducer is recorded for both the overpressuring and the underpressuring. By comparing this data with data taken during a preoperative calibration, the health of the transducer is determined from the linearity, the hysteresis, and the repeatability of its output. The further addition of a thermometer allows constant offset error in the transducer output to be determined.
-
Vano, E; Sanchez, R M; Fernandez, J M
2015-07-01
The purpose of this article is to estimate lens doses using over apron active personal dosemeters in interventional catheterisation laboratories (cardiology IC, neuroradiology IN and radiology IR) and to investigate correlations between occupational lens doses and patient doses. Active electronic personal dosemeters placed over the lead apron were used on a sample of 204 IC procedures, 274 IN and 220 IR (all performed at the same university hospital). Patient dose values (kerma area product) were also recorded to evaluate correlations with occupational doses. Operators used the ceiling-suspended screen in most cases. The median and third quartile values of equivalent dose Hp(10) per procedure measured over the apron for IC, IN and IR resulted, respectively, in 21/67, 19/44 and 24/54 µSv. Patient dose values (median/third quartile) were 75/128, 83/176 and 61/159 Gy cm(2), respectively. The median ratios for dosemeters worn over the apron by operators (protected by the ceiling-suspended screen) and patient doses were 0.36; 0.21 and 0.46 µSv Gy(-1) cm(-2), respectively. With the conservative approach used (lens doses estimated from the over apron chest dosemeter) we came to the conclusion that more than 800 procedures y(-1) and per operator were necessary to reach the new lens dose limit for the three interventional specialties. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Sharma, Divyesh; Ramsewak, Adesh; Manoharan, Ganesh; Spence, Mark S
2016-02-01
The efficacy of RADPAD® (a sterile, lead-free drape) has been demonstrated to reduce the scatter radiation to the primary operator during fluoroscopic procedures. However, the use of the RADPAD® during TAVI procedures has not been studied. Transcatheter aortic valve implantation (TAVI) is now an established treatment for patients with symptomatic severe aortic stenosis who are deemed inoperable or at high risk for conventional surgical aortic valve replacement (AVR). Consequently the radiation exposure to the patient and the interventional team from this procedure has become a matter of interest and importance. Methods to reduce radiation exposure to the interventional team during this procedure should be actively investigated. In this single center prospective study, we determined the radiation dose during this procedure and the efficacy of RADPAD® in reducing the radiation dose to the primary operator. Fifty consecutive patients due to undergo elective TAVI procedures were identified. Patients were randomly assigned to undergo the procedure with or without the use of a RADPAD® drape. There were 25 patients in each group and dosimetry was performed at the left eye level of the primary operator. The dosimeter was commenced at the start of the procedure, and the dose was recorded immediately after the end of the procedure. Fluoroscopy times and DAP were also recorded prospectively. Twenty-five patients underwent transfemoral TAVI using a RADPAD® and 25 with no-RADPAD®. The mean primary operator radiation dose was significantly lower in the RADPAD group at 14.8 mSv vs. 24.3 mSv in the no-RADPAD group (P=0.008). There was no significant difference in fluoroscopy times or dose-area products between the two patient groups. The dose to the primary operator relative to fluoroscopy time (RADPAD: slope=0.325; no RADPAD: slope=1.148; analysis of covariance F=7.47, P=0.009) and dose area product (RADPAD: slope=0.0007; no RADPAD: slope=0.002; analysis of covariance F=7.38; P=0.009) was smaller in the RADPAD group compared to no-RADPAD group. Use of a RADPAD® significantly reduces radiation exposure to the primary operator during TAVI procedures.
-
Lange, Jeffrey; Karellas, Andrew; Street, John; Eck, Jason C; Lapinsky, Anthony; Connolly, Patrick J; Dipaola, Christian P
2013-03-01
Observational. To estimate the radiation dose imparted to patients during typical thoracolumbar spinal surgical scenarios. Minimally invasive techniques continue to become more common in spine surgery. Computer-assisted navigation systems coupled with intraoperative cone-beam computed tomography (CT) represent one such method used to aid in instrumented spinal procedures. Some studies indicate that cone-beam CT technology delivers a relatively low dose of radiation to patients compared with other x-ray-based imaging modalities. The goal of this study was to estimate the radiation exposure to the patient imparted during typical posterior thoracolumbar instrumented spinal procedures, using intraoperative cone-beam CT and to place these values in the context of standard CT doses. Cone-beam CT scans were obtained using Medtronic O-arm (Medtronic, Minneapolis, MN). Thermoluminescence dosimeters were placed in a linear array on a foam-plastic thoracolumbar spine model centered above the radiation source for O-arm presets of lumbar scans for small or large patients. In-air dosimeter measurements were converted to skin surface measurements, using published conversion factors. Dose-length product was calculated from these values. Effective dose was estimated using published effective dose to dose-length product conversion factors. Calculated dosages for many full-length procedures using the small-patient setting fell within the range of published effective doses of abdominal CT scans (1-31 mSv). Calculated dosages for many full-length procedures using the large-patient setting fell within the range of published effective doses of abdominal CT scans when the number of scans did not exceed 3. We have demonstrated that single cone-beam CT scans and most full-length posterior instrumented spinal procedures using O-arm in standard mode would likely impart a radiation dose within the range of those imparted by a single standard CT scan of the abdomen. Radiation dose increases with patient size, and the radiation dose received by larger patients as a result of more than 3 O-arm scans in standard mode may exceed the dose received during standard CT of the abdomen. Understanding radiation imparted to patients by cone-beam CT is important for assessing risks and benefits of this technology, especially when spinal surgical procedures require multiple intraoperative scans.
-
Khairuddin Md Yusof, Ahmad
2013-01-01
Concerns about ionizing radiation during interventional cardiology have been increased in recent years as a result of rapid growth in interventional procedure volumes and the high radiation doses associated with some procedures. Noncancer radiation risks to cardiologists and medical staff in terms of radiation-induced cataracts and skin injuries for patients appear clear potential consequences of interventional cardiology procedures, while radiation-induced potential risk of developing cardiovascular effects remains less clear. This paper provides an overview of the evidence-based reviews of concerns about noncancer risks of radiation exposure in interventional cardiology. Strategies commonly undertaken to reduce radiation doses to both medical staff and patients during interventional cardiology procedures are discussed; optimisation of interventional cardiology procedures is highlighted. PMID:24027768
-
Estimated collective effective dose to the population from nuclear medicine examinations in Slovenia
Skrk, Damijan; Zontar, Dejan
2013-01-01
Background A national survey of patient exposure from nuclear medicine diagnostic procedures was performed by Slovenian Radiation Protection Administration in order to estimate their contribution to the collective effective dose to the population of Slovenia. Methods A set of 36 examinations with the highest contributions to the collective effective dose was identified. Data about frequencies and average administered activities of radioisotopes used for those examinations were collected from all nuclear medicine departments in Slovenia. A collective effective dose to the population and an effective dose per capita were estimated from the collected data using dose conversion factors. Results The total collective effective dose to the population from nuclear medicine diagnostic procedures in 2011 was estimated to 102 manSv, giving an effective dose per capita of 0.05 mSv. Conclusions The comparison of results of this study with studies performed in other countries indicates that the nuclear medicine providers in Slovenia are well aware of the importance of patient protection measures and of optimisation of procedures. PMID:24133396
-
ERIC Educational Resources Information Center
Jain, Rakesh; Segal, Scott; Kollins, Scott H.; Khayrallah, Moise
2011-01-01
Objective: This study examined the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: This 8-week, placebo-controlled, fixed-dose trial, including 3 weeks of dose escalation, of patients 6 to 17 years old with ADHD evaluated the…
-
Buchner, Anton; Elsässer, Reiner; Bias, Peter
2014-11-01
This dose-ranging study was conducted to identify the optimal fixed dose of lipegfilgrastim compared with pegfilgrastim 6.0 mg for the provision of neutrophil support during myelosuppressive chemotherapy in patients with breast cancer. A phase 2 study was conducted in which 208 chemotherapy-naive patients were randomized to receive lipegfilgrastim 3.0, 4.5, or 6.0 mg or pegfilgrastim 6.0 mg. Study drugs were administered as a single subcutaneous injection on day 2 of each chemotherapy cycle (doxorubicin/docetaxel on day 1 for four 3-week cycles). The primary outcome measure was duration of severe neutropenia (DSN) in cycle 1. Patients treated with lipegfilgrastim experienced shorter DSN in cycle 1 with higher doses. The mean DSN was 0.76 days in the lipegfilgrastim 6.0-mg group and 0.87 days in the pegfilgrastim 6.0-mg group, with no significant differences between treatment groups. Treatment with lipegfilgrastim 6.0 mg was consistently associated with a higher absolute neutrophil count (ANC) at nadir, shorter ANC recovery time, and a similar safety and tolerability profile compared with pegfilgrastim. This phase 2 study demonstrated that lipegfilgrastim 6.0 mg is the optimal dose for patients with breast cancer and provides neutrophil support that is at least equivalent to the standard 6.0-mg fixed dose of pegfilgrastim.
-
Management of rivaroxaban in relation to bodyweight and body mass index
Uprichard, James
2016-01-01
Being overweight or obese is associated with a higher individual risk of venous thromboembolism and poorer postprocedural outcomes after hip or knee replacement surgery. In addition, there is evidence that obesity represents a significant driving factor for the current and projected prevalence of atrial fibrillation. Rivaroxaban and other direct oral anticoagulants offer fixed-dose regimens for these indications. They do not require therapeutic drug monitoring or dose adjustment according to the weight of the patient. However, primary care physicians seem to be hesitant to accept the concept of a fixed-dose regimen for patients at extremes of weight, perhaps because of familiarity with weight-based dosing of other drugs including low molecular weight heparins. The main concerns related to unadjusted dosing are increased exposure in underweight patients leading to a risk of excessive bleeding and conversely to underanticoagulation of overweight patients. Rivaroxaban has shown similar efficacy and a similar or better safety profile compared with standard treatment for several venous and arterial indications, including venous thromboembolism, nonvalvular atrial fibrillation, and acute coronary syndrome. Prespecified subgroup analyses of patients stratified by weight or body mass index demonstrated outcomes that were consistent with the overall analysis and within each weight and body mass index group. The results suggest that standard-dose rivaroxaban can be safely prescribed in adult patients of all weights. PMID:27090286
-
Device-Task Fidelity and Transfer of Training: Aircraft Cockpit Procedures Training.
ERIC Educational Resources Information Center
Prophet, Wallace W.; Boyd, H. Alton
An evaluation was made of the training effectiveness of two cockpit procedures training devices, differing greatly in physical fidelity and cost, for use on the ground for a twin-engine, turboprop, fixed-wing aircraft. One group of students received training in cockpit procedures in a relatively expensive, sophisticated, computerized trainer,…
-
Miles, Lachlan F; Marchiori, Paolo; Falter, Florian
2017-09-01
This manuscript represents a pilot study assessing the feasibility of a single-compartment, individualised, pharmacokinetic algorithm for protamine dosing after cardiopulmonary bypass. A pilot cohort study in a specialist NHS cardiothoracic hospital targeting patients undergoing elective cardiac surgery using cardiopulmonary bypass. Patients received protamine doses according to a pharmacokinetic algorithm (n = 30) or using an empirical, fixed-dose model (n = 30). Categorical differences between the groups were evaluated using the Chi-squared test or Fisher's exact test. Continuous data was analysed using a paired Student's t-test for parametric data and the paired samples Wilcoxon test for non-parametric data. Patients who had protamine dosing according to the algorithm demonstrated a lower protamine requirement post-bypass relative to empirical management as measured by absolute dose (243 ± 49mg vs. 305 ± 34.7mg; p<0.001) and the heparin to protamine ratio (0.79 ± 0.12 vs. 1.1 ± 0.15; p<0.001). There was no difference in the pre- to post-bypass activated clotting time (ACT) ratio (1.05 ± 0.12 vs. 1.02 ± 0.15; p=0.9). Patients who received protamine according to the algorithm had no significant difference in transfusion requirement (13.3% vs. 30.0%; p=0.21). This study showed that an individualized pharmacokinetic algorithm for the reversal of heparin after cardiopulmonary bypass is feasible in comparison with a fixed dosing strategy and may reduce the protamine requirement following on-pump cardiac surgery.
-
Sud, Shivani; Roth, Toni
2018-01-01
Purpose Intra-vaginal packing is used to fix the applicator and displace organs at risk (OAR) during high-dose-rate intracavitary tandem and ovoid brachytherapy (HDR-ICB). We retain the speculum from applicator placement as a dual-function bladder and rectum retractor during treatment. Our objective is to review salient techniques for OAR displacement, share our packing technique, and determine the reduction in dose to OAR and inter-fraction variability of dose to OAR, associated with speculum-based vaginal packing (SBVP) in comparison to conventional gauze packing during HDR-ICB. Material and methods We reviewed HDR-ICB treatment plans for 45 patients, including 10 who underwent both conventional gauze packing and SBVP. Due to institutional inter-provider practice differences, patients non-selectively received either packing procedure. Packing was performed under conscious sedation, followed by cone beam computed tomography used for dosimetric planning. Maximum absolute and percent-of-prescription dose to the International Commission of Radiation Units bladder and rectal points in addition to D0.1cc, D1.0cc, and D2.0cc volumes of the bladder and rectum were analyzed and compared for each packing method using an independent sample t-test. Results Of the 179 fractions included, 73% and 27% used SBVP and gauze packing, respectively. For patients prescribed 6 Gy to point A, SBVP was associated with reduced mean D0.1cc bladder dose, inter-fraction variability in D0.1cc bladder dose by 9.3% (p = 0.026) and 9.0%, respectively, and statistically equivalent rectal D0.1cc, D1.0cc, and D2.0cc. Patients prescribed 5.5 Gy or 5 Gy to point A after dose optimization, were less likely to benefit from SBVP. In the intra-patient comparison, 80% of patients had reduction in at least one rectum or bladder parameter. Conclusions In patients with conducive anatomy, SBVP is a cost-efficient packing method that is associated with improved bladder sparing and comparable rectal sparing relative to gauze packing during HDR-ICB without general anesthesia. PMID:29619054
-
Liu, Sha; Watts, Alan B; Du, Ju; Bui, Amanda; Hengsawas, Soraya; Peters, Jay I; Williams, Robert O
2015-10-01
Co-administration of an inhaled corticosteroid and long acting beta agonist for chronic obstructive pulmonary disease has reduced mortality compared to either drug alone. This combination reduces exacerbations, hospitalization, emergency department visits and health care costs. A novel fixed-dose combination of the long acting beta-2 agonist salmeterol xinafoate (SX) and the corticosteroid mometasone furoate (MF) were prepared in a composite particle formulation as brittle matrix powder (BMP) and investigated for suitability as an inhaled combination product. In this study, BMP fixed dose combinations of SX and MF with or without stabilizing excipients (lactose, mannitol, glycine and trehalose) were prepared and characterized with respect to their thermal properties, morphology, aerodynamic performance and physical stability. BMP combination formulations of SX and MF exhibited improved aerodynamic properties when delivered by dry powder inhalation as compared to the micronized blends of the same substances. Aerodynamic evaluation was carried out by next generation pharmaceutical impactor (NGI) with a marketed DPI device. Results demonstrated that co-deposition occurred when SX and MF were formulated together as composite particles in a BMP, while physical blends resulted in inconsistent deposition and dose uniformity. As a result of the bottom-up particle engineering approach, combination BMP formulations allow for dual API composite formulations to be dispersed as aerosolized particles. Aerosolized BMP combination formulations resulted in delivered dose uniformity and co-deposition of each API. Further, an excipient-free formulation, BMP SXMF, delivered approximately 50% of the loaded dose in the respirable range and demonstrated stability at ambient conditions for 6months. Single dose 24-h pharmacokinetic studies in rats demonstrated that lung tissue deposition and blood circulation (AUC0-24h) of two APIs were higher for the BMP combination group exhibiting a significantly higher lung concentration of drugs than for the crystalline physical blend. While high system drug levels are generally undesirable in lung targeted therapies, high blood levels in this rodent study could be indicative of increased pulmonary tissue exposure using BMP formulations. Copyright © 2015 Elsevier B.V. All rights reserved.
-
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.
-
Kibengo, Freddie M.; Ruzagira, Eugene; Katende, David; Bwanika, Agnes N.; Bahemuka, Ubaldo; Haberer, Jessica E.; Bangsberg, David R.; Barin, Burc; Rooney, James F.; Mark, David; Chetty, Paramesh; Fast, Patricia; Kamali, Anatoli; Priddy, Frances H.
2013-01-01
Background Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Design Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Methods Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. Results Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Conclusions Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. Registration Clinicaltrials.gov number NCT00931346 PMID:24086333
-
Dose to mass for evaluation and optimization of lung cancer radiation therapy.
Tyler Watkins, William; Moore, Joseph A; Hugo, Geoffrey D; Siebers, Jeffrey V
2017-11-01
To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, D v ‾, mean dose to mass, D M ‾, and fluence maps were intercompared. For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-D v ‾ by 0.20±0.2Gy (p=0.02) and PTV-D M ‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (D v ‾ reduced 0.45±0.5Gy, p=0.02 and D M ‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor. Copyright © 2017 Elsevier B.V. All rights reserved.
-
Bentzley, Brandon S.; Fender, Kimberly M.; Aston-Jones, Gary
2012-01-01
Rationale Behavioral-economic demand curve analysis offers several useful measures of drug self-administration. Although generation of demand curves previously required multiple days, recent within-session procedures allow curve construction from a single 110-min cocaine self-administration session, making behavioral-economic analyses available to a broad range of self-administration experiments. However, a mathematical approach of curve fitting has not been reported for the within-session threshold procedure. Objectives We review demand curve analysis in drug self-administration experiments and provide a quantitative method for fitting curves to single-session data that incorporates relative stability of brain drug concentration. Methods Sprague-Dawley rats were trained to self-administer cocaine, and then tested with the threshold procedure in which the cocaine dose was sequentially decreased on a fixed ratio-1 schedule. Price points (responses/mg cocaine) outside of relatively stable brain cocaine concentrations were removed before curves were fit. Curve-fit accuracy was determined by the degree of correlation between graphical and calculated parameters for cocaine consumption at low price (Q0) and the price at which maximal responding occurred (Pmax). Results Removing price points that occurred at relatively unstable brain cocaine concentrations generated precise estimates of Q0 and resulted in Pmax values with significantly closer agreement with graphical Pmax than conventional methods. Conclusion The exponential demand equation can be fit to single-session data using the threshold procedure for cocaine self-administration. Removing data points that occur during relatively unstable brain cocaine concentrations resulted in more accurate estimates of demand curve slope than graphical methods, permitting a more comprehensive analysis of drug self-administration via a behavioral-economic framework. PMID:23086021
-
Occupational Radiation Exposure During Endovascular Aortic Repair
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sailer, Anna M., E-mail: anni.sailer@mumc.nl; Schurink, Geert Willem H., E-mail: gwh.schurink@mumc.nl; Bol, Martine E., E-mail: m.bol@maastrichtuniversity.nl
PurposeThe aim of the study was to evaluate the radiation exposure to operating room personnel and to assess determinants for high personal doses during endovascular aortic repair.Materials and MethodsOccupational radiation exposure was prospectively evaluated during 22 infra-renal aortic repair procedures (EVAR), 11 thoracic aortic repair procedures (TEVAR), and 11 fenestrated or branched aortic repair procedures (FEVAR). Real-time over-lead dosimeters attached to the left breast pocket measured personal doses for the first operators (FO) and second operators (SO), radiology technicians (RT), scrub nurses (SN), anesthesiologists (AN), and non-sterile nurses (NSN). Besides protective apron and thyroid collar, no additional radiation shielding wasmore » used. Procedural dose area product (DAP), iodinated contrast volume, fluoroscopy time, patient’s body weight, and C-arm angulation were documented.ResultsAverage procedural FO dose was significantly higher during FEVAR (0.34 ± 0.28 mSv) compared to EVAR (0.11 ± 0.21 mSv) and TEVAR (0.06 ± 0.05 mSv; p = 0.003). Average personnel doses were 0.17 ± 0.21 mSv (FO), 0.042 ± 0.045 mSv (SO), 0.019 ± 0.042 mSv (RT), 0.017 ± 0.031 mSv (SN), 0.006 ± 0.007 mSv (AN), and 0.004 ± 0.009 mSv (NSN). SO and AN doses were strongly correlated with FO dose (p = 0.003 and p < 0.001). There was a significant correlation between FO dose and procedural DAP (R = 0.69, p < 0.001), iodinated contrast volume (R = 0.67, p < 0.001) and left-anterior C-arm projections >60° (p = 0.02), and a weak correlation with fluoroscopy time (R = 0.40, p = 0.049).ConclusionAverage FO dose was a factor four higher than SO dose. Predictors for high personal doses are procedural DAP, iodinated contrast volume, and left-anterior C-arm projections greater than 60°.« less
-
Nazarudheen, Shabana; Dey, Surajit; Kandhwal, Kirti; Arora, Rachna; Reyar, Simrit; Khuroo, Arshad H; Monif, Tausif; Madan, Sumit; Arora, Vinod
2013-11-01
A pharmacokinetic bioequivalence study was conducted in Asian subjects, to compare a fixed dose combination capsule single oral dose of alpha adrenoceptor blocker-Alfuzosin hydrochloride 10mg extended release and muscarinic antagonists-Solifenacin succinate 5mg against individually administered Xatral XL 10mg tablets (Alfuzosin) of Sanofi Synthelabo Limited, United Kingdom (UK) and Vesicare 5mg tablets (Solifenacin) of Astellas Pharma Limited, UK under fed conditions. Blood samples were collected pre-dose up to 72 h post dose for determination of plasma Alfuzosin and Solifenacin concentrations and calculation of the pharmacokinetic parameters. ANOVA was performed on the log (natural)-transformed pharmacokinetic parameters. A 90% confidence interval for the ratios of the test and reference product averages (least square means) were calculated for alfuzosin and solifenacin. The 90% confidence intervals obtained for alfuzosin for Cmax, AUC0-t and AUC0-∞ were 102.74-122.75%, 95.84-116.96% and 95.82-116.76%, respectively. The 90% confidence intervals obtained for Solifenacin for Cmax, and AUC0-72 were 89.55-97.91% and 90.47-99.38%, respectively. Based on the results, the fixed dose combination was concluded to be bioequivalent to individually administered products. Copyright © 2013 Elsevier Inc. All rights reserved.
-
Action spectrum for phototherapy of psoriasis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Parrish, J.A.; Jaenicke, K.F.
1981-05-01
Using a monochromator the action spectrum for ultraviolet phototherapy of psoriasis was determined for radiation between 254 and 313 nm and compared to the action spectrum for erythema of uninvolved adjacent skin. Daily exposures of different doses of 254, 280, 290, 296, 300, 304 and 313 nm radiation were observed. Wavelengths of 254, 280, 290 nm were erythemogenic but not therapeutic even at 10 to 50 times the minimal erythema dose. At the other wavelengths studied, the 2 action spectra were similar. In general, fixed daily doses cleared at lower cumulative dose than did incrementally increased daily doses. The smallmore » number of suberythemogenic exposure doses required suggests that monochromatic radiation may have advantages over broadband sources.« less
-
Mutua, Gaudensia; Sanders, Eduard; Mugo, Peter; Anzala, Omu; Haberer, Jessica E; Bangsberg, David; Barin, Burc; Rooney, James F; Mark, David; Chetty, Paramesh; Fast, Patricia; Priddy, Frances H
2012-01-01
Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR:28-78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens. ClinicalTrials.gov NCT00971230.
-
18 CFR 11.14 - Procedures for establishing charges without an energy gains investigation.
Code of Federal Regulations, 2010 CFR
2010-04-01
... hydrology or project development, that affect headwater benefits. (2) Any procedures that apply to § 11.17(b)(5) of this subpart will apply to any prospectively fixed charges that are continued under this...
-
18 CFR 11.14 - Procedures for establishing charges without an energy gains investigation.
Code of Federal Regulations, 2011 CFR
2011-04-01
... hydrology or project development, that affect headwater benefits. (2) Any procedures that apply to § 11.17(b)(5) of this subpart will apply to any prospectively fixed charges that are continued under this...
-
Radiation dose to physicians’ eye lens during interventional radiology
NASA Astrophysics Data System (ADS)
Bahruddin, N. A.; Hashim, S.; Karim, M. K. A.; Sabarudin, A.; Ang, W. C.; Salehhon, N.; Bakar, K. A.
2016-03-01
The demand of interventional radiology has increased, leading to significant risk of radiation where eye lens dose assessment becomes a major concern. In this study, we investigate physicians' eye lens doses during interventional procedures. Measurement were made using TLD-100 (LiF: Mg, Ti) dosimeters and was recorded in equivalent dose at a depth of 0.07 mm, Hp(0.07). Annual Hp(0.07) and annual effective dose were estimated using workload estimation for a year and Von Boetticher algorithm. Our results showed the mean Hp(0.07) dose of 0.33 mSv and 0.20 mSv for left and right eye lens respectively. The highest estimated annual eye lens dose was 29.33 mSv per year, recorded on left eye lens during fistulogram procedure. Five physicians had exceeded 20 mSv dose limit as recommended by international commission of radiological protection (ICRP). It is suggested that frequent training and education on occupational radiation exposure are necessary to increase knowledge and awareness of the physicians’ thus reducing dose during the interventional procedure.
-
Medical and occupational dose reduction in pediatric barium meal procedures
NASA Astrophysics Data System (ADS)
Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Ledesma, J. A.; Legnani, A.; Bunick, A. P.; Sauzen, J.; Yagui, A.; Vosiak, P.
2017-11-01
Doses received in pediatric Barium Meal procedure can be rather high. It is possible to reduce dose values following the recommendations of the European Communities (EC) and the International Commission on Radiological Protection (ICRP). In the present work, the modifications of radiographic techniques made in a Brazilian hospital according to the EC and the ICRP recommendations and their influence on medical and occupational exposure are reported. The procedures of 49 patients before and 44 after the optimization were studied and air kerma-area product (PK,A) values and the effective doses were evaluated. The occupational equivalent doses were measured next to the eyes, under the thyroid shield and on each hand of both professionals who remained inside the examination room. The implemented modifications reduced by 70% and 60% the PK,A and the patient effective dose, respectively. The obtained dose values are lower than approximately 75% of the results from similar studies. The occupational annual equivalent doses for all studied organs became lower than the limits set by the ICRP. The equivalent doses in one examination were on average below than 75% of similar studies.
-
A method to reduce patient's eye lens dose in neuro-interventional radiology procedures
NASA Astrophysics Data System (ADS)
Safari, M. J.; Wong, J. H. D.; Kadir, K. A. A.; Sani, F. M.; Ng, K. H.
2016-08-01
Complex and prolonged neuro-interventional radiology procedures using the biplane angiography system increase the patient's risk of radiation-induced cataract. Physical collimation is the most effective way of reducing the radiation dose to the patient's eye lens, but in instances where collimation is not possible, an attenuator may be useful in protecting the eyes. In this study, an eye lens protector was designed and fabricated to reduce the radiation dose to the patients' eye lens during neuro-interventional procedures. The eye protector was characterised before being tested on its effectiveness in a simulated aneurysm procedure on an anthropomorphic phantom. Effects on the automatic dose rate control (ADRC) and image quality are also evaluated. The eye protector reduced the radiation dose by up to 62.1% at the eye lens. The eye protector is faintly visible in the fluoroscopy images and increased the tube current by a maximum of 3.7%. It is completely invisible in the acquisition mode and does not interfere with the clinical procedure. The eye protector placed within the radiation field of view was able to reduce the radiation dose to the eye lens by direct radiation beam of the lateral x-ray tube with minimal effect on the ADRC system.
-
Kloeze, C; Klompenhouwer, E G; Brands, P J M; van Sambeek, M R H M; Cuypers, P W M; Teijink, J A W
2014-03-01
Because of the increasing number of interventional endovascular procedures with fluoroscopy and the corresponding high annual dose for interventionalists, additional dose-protecting measures are desirable. The purpose of this study was to evaluate the effect of disposable radiation-absorbing surgical drapes in reducing scatter radiation exposure for interventionalists and supporting staff during an endovascular aneurysm repair (EVAR) procedure. This was a randomized control trial in which 36 EVAR procedures were randomized between execution with and without disposable radiation-absorbing surgical drapes (Radpad: Worldwide Innovations & Technologies, Inc., Kansas City, US, type 5511A). Dosimetric measurements were performed on the interventionalist (hand and chest) and theatre nurse (chest) with and without the use of the drapes to obtain the dose reduction and effect on the annual dose caused by the drapes. Use of disposable radiation-absorbing surgical drapes resulted in dose reductions of 49%, 55%, and 48%, respectively, measured on the hand and chest of the interventionalist and the chest of the theatre nurse. The use of disposable radiation-absorbing surgical drapes significantly reduces scatter radiation exposure for both the interventionalist and the supporting staff during EVAR procedures. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
-
NASA Technical Reports Server (NTRS)
Spalding, J. F.; Holland, L. M.; Prine, J. R.; Farrer, D. N.; Braun, R. G.
1972-01-01
Sixteen monkeys trained to perform continuous and discrete-avoidance and fixed-ratio tasks with visual and auditory cues were performance-tested before, during, and after 10-day gamma-ray exposures totaling 0, 500, 750, and 1000 rads. Approximately 14 months after the performance-test exposures, surviving animals were exposed to 100-rad gamma-ray fractions at 56-day intervals to observe injury and recovery patterns of blood-forming tissues. The fixed-ratio, food-reward task performance showed a transient decline in all dose groups within 24 hours of the start of gamma-ray exposure, followed by recovery to normal food-consumption levels within 48 to 72 hours. Avoidance tasks were performed successfully by all groups during the 10-day exposure, but reaction times of the two higher dose-rate groups in which animals received 3 and 4 rads per hour or total doses of 750 and 1000 rads, respectively, were somewhat slower.
-
Bloemen-van Gurp, Esther J; Murrer, Lars H P; Haanstra, Björk K C; van Gils, Francis C J M; Dekker, Andre L A J; Mijnheer, Ben J; Lambin, Philippe
2009-01-01
In vivo dosimetry during brachytherapy of the prostate with (125)I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the low-dose region outside the prostate (< 100 Gy), larger deviations occurred. MOSFET detectors are suitable for in vivo dosimetry during (125)I brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions.
-
47 CFR 5.61 - Procedure for obtaining a special temporary authorization.
Code of Federal Regulations, 2010 CFR
2010-10-01
... Office of Engineering and Technology Web site https://gullfoss2.fcc.gov/prod/oet/cf/els/index.cfm effective January 1, 2004 and shall contain the following information: (1) Name, address, phone number (also... proposed operation. (5) Class(es) of station (fixed, mobile, fixed and mobile) and call sign of station (if...
-
Pigeons' Choices between Fixed-Interval and Random-Interval Schedules: Utility of Variability?
ERIC Educational Resources Information Center
Andrzejewski, Matthew E.; Cardinal, Claudia D.; Field, Douglas P.; Flannery, Barbara A.; Johnson, Michael; Bailey, Kathleen; Hineline, Philip N.
2005-01-01
Pigeons' choosing between fixed-interval and random-interval schedules of reinforcement was investigated in three experiments using a discrete-trial procedure. In all three experiments, the random-interval schedule was generated by sampling a probability distribution at an interval (and in multiples of the interval) equal to that of the…
-
Two-Phase Item Selection Procedure for Flexible Content Balancing in CAT
ERIC Educational Resources Information Center
Cheng, Ying; Chang, Hua-Hua; Yi, Qing
2007-01-01
Content balancing is an important issue in the design and implementation of computerized adaptive testing (CAT). Content-balancing techniques that have been applied in fixed content balancing, where the number of items from each content area is fixed, include constrained CAT (CCAT), the modified multinomial model (MMM), modified constrained CAT…
-
18 CFR 401.96 - Factors to be applied in fixing penalty amount.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Factors to be applied in fixing penalty amount. 401.96 Section 401.96 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL RULES OF PRACTICE AND PROCEDURE Penalties and Settlements...
-
NASA Astrophysics Data System (ADS)
Palenčár, Rudolf; Sopkuliak, Peter; Palenčár, Jakub; Ďuriš, Stanislav; Suroviak, Emil; Halaj, Martin
2017-06-01
Evaluation of uncertainties of the temperature measurement by standard platinum resistance thermometer calibrated at the defining fixed points according to ITS-90 is a problem that can be solved in different ways. The paper presents a procedure based on the propagation of distributions using the Monte Carlo method. The procedure employs generation of pseudo-random numbers for the input variables of resistances at the defining fixed points, supposing the multivariate Gaussian distribution for input quantities. This allows taking into account the correlations among resistances at the defining fixed points. Assumption of Gaussian probability density function is acceptable, with respect to the several sources of uncertainties of resistances. In the case of uncorrelated resistances at the defining fixed points, the method is applicable to any probability density function. Validation of the law of propagation of uncertainty using the Monte Carlo method is presented on the example of specific data for 25 Ω standard platinum resistance thermometer in the temperature range from 0 to 660 °C. Using this example, we demonstrate suitability of the method by validation of its results.
-
Mezni, Faten; Shili, Sarra; Ben Ali, Nejia; Larbi Khouja, Mohamed; Khaldi, Abdelhamid; Maaroufi, Abderrazak
2016-01-01
Within the global context of increasing cancer diseases, natural products are important in devising new drugs and providing unique ideas in cancer therapy. In Tunisian folk medicine, Pistacia lentiscus L. (Anacardiaceae) fixed oil is used for cancer treatment. This investigation studied, for the first time, the antiproliferative effect of Pistacia lentiscus fixed oil and its phenolic extract on BHK21 cancer cells. Oil was extracted from fruits harvested in northwest Tunisia and the phenolic fraction was obtained by mixing with methanol. The anti-proliferative activity of the two tested substances on BHK 21 cells were investigated in vitro using trypan blue assays. Cells were treated with different concentrations of P. lentiscus oil (0.009, 0.018, 0.036, and 0.09 g/mL) and the phenolic extract (0.007, 0.014, 0.03, and 0.07 g/mL) for 24, 48, and 72 h. The inhibitory effect of Pistacia lentiscus fixed oil increases with the increase in dose. The IC50 value was estimated at 0.029 g/mL. The percentage of cell viability was 42.46 ± 3.4% at a dose of 0.09 g/mL and was significantly lower than that of the untreated control (96.24 ± 2.5%, p<0.01). The phenolic extract demonstrated a dose- and time-dependent inhibitory effect on BHK21 cell growth. After 48 h of incubation, the IC50 value was estimated at 0.15 g/mL. The results demonstrated the potential of Pistacia lentiscus fixed oil in treating cancer, as it is used in traditional medicine.
-
Barrett, Andrew C; Negus, S Stevens; Mello, Nancy K; Caine, S Barak
2005-11-01
Recent studies indicate that GABAergic ligands modulate abuse-related effects of cocaine. The goal of this study was to evaluate the effects of a mechanistically diverse group of GABAergic ligands on the discriminative stimulus and reinforcing effects of cocaine in rats. One group of rats was trained to discriminate 5.6 mg/kg cocaine from saline in a two-lever, food-reinforced, drug discrimination procedure. In two other groups, responding was maintained by cocaine (0-3.2 mg/kg/injection) or liquid food (0-100%) under a fixed ratio 5 schedule. Six GABA agonists were tested: the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, the GABA transaminase inhibitor gamma-vinyl-GABA (GVG), and three GABA-A receptor modulators (the barbiturate pentobarbital, the high-efficacy benzodiazepine midazolam, and the low-efficacy benzodiazepine enazenil). When tested alone, none of the compounds substituted fully for the discriminative stimulus effects of cocaine. As acute pretreatments, select doses of midazolam and pentobarbital produced 2.2- to 3.6-fold rightward shifts in the cocaine dose-effect function. In contrast, muscimol, baclofen, GVG, and enazenil failed to alter the discriminative stimulus effects of cocaine. In assays of cocaine- and food-maintained responding, midazolam and pentobarbital decreased cocaine self-administration at doses 9.6- and 3.3-fold lower, respectively, than those that decreased food-maintained responding. In contrast, muscimol, baclofen, and GVG decreased cocaine self-administration at doses that also decreased food-maintained responding. Enazenil failed to alter cocaine self-administration. Together with previous studies, these data suggest that among mechanistically diverse GABA agonists, high-efficacy GABA-A modulators may be the most effective for modifying the abuse-related effects of cocaine.
-
Effects of varenicline on ethanol- and food-maintained responding in a concurrent access procedure.
Ginsburg, Brett C; Lamb, Richard J
2013-07-01
Varenicline has been reported to reduce drinking in smokers and to selectively decrease responding for ethanol (EtOH) versus alternatives in preclinical studies. Such selectivity may reflect potential therapeutic effects and the involvement of nicotinic receptors in EtOH reinforcement. However, these studies have been conducted with EtOH and an alternative available in isolation or in separate groups, and selectivity can depend on the context in which reinforcement occurs. Whether varenicline selectivity is maintained when EtOH and an alternative are concurrently available has not been reported. To examine the effects of varenicline on EtOH self-administration when an alternative is concurrently available, male Lewis rats (n = 5) were trained to respond for EtOH and food under a concurrent FR5 FRX schedule where the fixed ratio (FR) for food was adjusted (FR = 25 or 35 for each subject) to provide similar numbers of EtOH and food deliveries during a 30-minute session. Doses of varenicline (0.56 to 5.6 mg/kg, i.p.) or vehicle were administered 30 minutes before sessions. Effects of varenicline on responding across the session and during each tenth of the session were compared to responding following vehicle treatment. Lower doses (0.56 to 1.0 mg/kg) of varenicline increased responding for EtOH without affecting responding for food. Higher doses disrupted responding for EtOH and food similarly. Previous reports of varenicline selectivity on EtOH-maintained responding do not generalize to other experimental conditions such as a concurrent schedule. The increase in responding for EtOH following lower doses might be due to enhanced EtOH reinforcement, decreased food reinforcement, rate dependency, or greater perseverance on the initial, EtOH response. Copyright © 2013 by the Research Society on Alcoholism.
-
Medici, S; Pitzschke, A; Cherbuin, N; Boldini, M; Sans-Merce, M; Damet, J
2017-11-01
The purpose of this work was to estimate the eye lens radiation exposure of the medical staff during interventional urology procedures. The measurements were carried out for six medical staff members performing 33 fluoroscopically-guided procedures. All procedures were performed with the X-ray tube positioned over the couch. The dose equivalents (H p (0.07)) were measured at the eye level using optically stimulated luminescent (OSL) dosimeters and at the chest level with OSL dosimeters placed over the protective apron. The ratio of the dose measured close to the eye lens and on the chest was determined. The annual eye lens dose was estimated based on the workload in the service. For the physician and the instrumentalist nurse, the eye to chest dose ratios were 0.9±0.4 and 2.6±1.6 (k = 2), respectively. The average doses per procedure received by the eye lens were 78±24 μSv and 38±18 μSv, respectively. The eye lens dose per DAP was 8.4±17.5 μSv/(Gy·cm 2 ) for the physician and 4.1±8.7 μSv/(Gy·cm 2 ) for the instrumentalist nurse. The results indicate that the eye lens to chest dose ratio greatly varies according to the staff function and that the dose equivalent measured by the personal dosimeter worn on the chest may underestimate the eye lens dose of some medical staff members. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
-
Cusumano, Davide; Fumagalli, Maria L; Marchetti, Marcello; Fariselli, Laura; De Martin, Elena
2015-01-01
Aim of this study is to examine the feasibility of using the new Gafchromic EBT3 film in a high-dose stereotactic radiosurgery and radiotherapy quality assurance procedure. Owing to the reduced dimensions of the involved lesions, the feasibility of scanning plan verification films on the scanner plate area with the best uniformity rather than using a correction mask was evaluated. For this purpose, signal values dispersion and reproducibility of film scans were investigated. Uniformity was then quantified in the selected area and was found to be within 1.5% for doses up to 8 Gy. A high-dose threshold level for analyses using this procedure was established evaluating the sensitivity of the irradiated films. Sensitivity was found to be of the order of centiGray for doses up to 6.2 Gy and decreasing for higher doses. The obtained results were used to implement a procedure comparing dose distributions delivered with a CyberKnife system to planned ones. The procedure was validated through single beam irradiation on a Gafchromic film. The agreement between dose distributions was then evaluated for 13 patients (brain lesions, 5 Gy/die prescription isodose ~80%) using gamma analysis. Results obtained using Gamma test criteria of 5%/1 mm show a pass rate of 94.3%. Gamma frequency parameters calculation for EBT3 films showed to strongly depend on subtraction of unexposed film pixel values from irradiated ones. In the framework of the described dosimetric procedure, EBT3 films proved to be effective in the verification of high doses delivered to lesions with complex shapes and adjacent to organs at risk. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cusumano, Davide, E-mail: davide.cusumano@unimi.it; Fumagalli, Maria L.; Marchetti, Marcello
2015-10-01
Aim of this study is to examine the feasibility of using the new Gafchromic EBT3 film in a high-dose stereotactic radiosurgery and radiotherapy quality assurance procedure. Owing to the reduced dimensions of the involved lesions, the feasibility of scanning plan verification films on the scanner plate area with the best uniformity rather than using a correction mask was evaluated. For this purpose, signal values dispersion and reproducibility of film scans were investigated. Uniformity was then quantified in the selected area and was found to be within 1.5% for doses up to 8 Gy. A high-dose threshold level for analyses usingmore » this procedure was established evaluating the sensitivity of the irradiated films. Sensitivity was found to be of the order of centiGray for doses up to 6.2 Gy and decreasing for higher doses. The obtained results were used to implement a procedure comparing dose distributions delivered with a CyberKnife system to planned ones. The procedure was validated through single beam irradiation on a Gafchromic film. The agreement between dose distributions was then evaluated for 13 patients (brain lesions, 5 Gy/die prescription isodose ~80%) using gamma analysis. Results obtained using Gamma test criteria of 5%/1 mm show a pass rate of 94.3%. Gamma frequency parameters calculation for EBT3 films showed to strongly depend on subtraction of unexposed film pixel values from irradiated ones. In the framework of the described dosimetric procedure, EBT3 films proved to be effective in the verification of high doses delivered to lesions with complex shapes and adjacent to organs at risk.« less
-
Lui, Kung-Jong; Chang, Kuang-Chao
2015-01-01
When comparing two doses of a new drug with a placebo, we may consider using a crossover design subject to the condition that the high dose cannot be administered before the low dose. Under a random-effects logistic regression model, we focus our attention on dichotomous responses when the high dose cannot be used first under a three-period crossover trial. We derive asymptotic test procedures for testing equality between treatments. We further derive interval estimators to assess the magnitude of the relative treatment effects. We employ Monte Carlo simulation to evaluate the performance of these test procedures and interval estimators in a variety of situations. We use the data taken as a part of trial comparing two different doses of an analgesic with a placebo for the relief of primary dysmenorrhea to illustrate the use of the proposed test procedures and estimators.
-
Occupational radiation doses during interventional procedures
NASA Astrophysics Data System (ADS)
Nuraeni, N.; Hiswara, E.; Kartikasari, D.; Waris, A.; Haryanto, F.
2016-03-01
Digital subtraction angiography (DSA) is a type of fluoroscopy technique used in interventional radiology to clearly visualize blood vessels in a bony or dense soft tissue environment. The use of DSA procedures has been increased quite significantly in the Radiology departments in various cities in Indonesia. Various reports showed that both patients and medical staff received a noticeable radiation dose during the course of this procedure. A study had been carried out to measure these doses among interventionalist, nurse and radiographer. The results show that the interventionalist and the nurse, who stood quite close to the X-ray beams compared with the radiographer, received radiation higher than the others. The results also showed that the radiation dose received by medical staff were var depending upon the duration and their position against the X-ray beams. Compared tothe dose limits, however, the radiation dose received by all these three medical staff were still lower than the limits.
-
Brownstein, D G; Barthold, S W
1982-02-01
Mouse hepatitis viral antigens were demonstrated by immunofluorescence in formalin- and Bouin's-fixed tissues processed routinely for histopathology followed by partial digestion with trypsin. Staining was superior in tissues fixed in formalin and was not diminished in tissue sections from paraffin blocks stored at room temperature as long as 2 years. The relative ease of this procedure and the commercial availability of reagents makes this a useful technique for the definitive diagnosis of mouse hepatitis virus infection.
-
Ahmed, Zia; Subhan, Fazal; Ahmed, Saba; Abdur Rasheed, Qazi; Ahmed, Sagheer; Shahid, Muhammad; Farooq, Saeed
2016-09-01
A vast majority of psychiatric patients are effectively treated with combination of drugs to improve efficacy and adherence, but due to limited research and development in fixed dose combination (FDC) in psychiatry, these products are not commonly available. The aim of this study is to prepare cost effective FDC tablets containing aripiprazole and divalproex sodium. Two batches of fixed dose combination tablets, FDC1 and FDC2, were successfully prepared using wet granulation technique. Furthermore, aripiprazole tablets A1 and A2 and divalproex tablets D1 were also formulated as reference to compare the in vitro availability profile. An accurate and simple isocratic HPLC method was established and validated for the simultaneous quantification of aripiprazole and valproic acid in the FDC tablets. A reversed-phase C18 (250 × 4.6 mm) column in isocratic mode was used. The mobile phase consisted of acetonitrile and 0.32% KH2PO4 (60:40, v/v), flow rate was set at 1.0 mL/min and the detection was performed at 210 nm. Average percent recoveries of aripiprazole and valproic acid were 96.0 and 95.5%, respectively, meeting the official requirements. The newly developed FDC product may be used for the better therapeutic outcomes of combined use of aripiprazole and valproic acid, which may improve patient adherence.
-
47 CFR 101.75 - Involuntary relocation procedures.
Code of Federal Regulations, 2013 CFR
2013-10-01
... adjustments, determine comparability, and ensure a seamless handoff. (d) Twelve-month trial period. If, within... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses License Transfers, Modifications, Conditions and Forfeitures § 101.75 Involuntary relocation procedures. (a) If no agreement is reached during the...
-
47 CFR 101.75 - Involuntary relocation procedures.
Code of Federal Regulations, 2011 CFR
2011-10-01
... adjustments, determine comparability, and ensure a seamless handoff. (d) Twelve-month trial period. If, within... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses License Transfers, Modifications, Conditions and Forfeitures § 101.75 Involuntary relocation procedures. (a) If no agreement is reached during the...
-
47 CFR 101.75 - Involuntary relocation procedures.
Code of Federal Regulations, 2012 CFR
2012-10-01
... adjustments, determine comparability, and ensure a seamless handoff. (d) Twelve-month trial period. If, within... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses License Transfers, Modifications, Conditions and Forfeitures § 101.75 Involuntary relocation procedures. (a) If no agreement is reached during the...
-
47 CFR 101.75 - Involuntary relocation procedures.
Code of Federal Regulations, 2014 CFR
2014-10-01
... adjustments, determine comparability, and ensure a seamless handoff. (d) Twelve-month trial period. If, within... SERVICES FIXED MICROWAVE SERVICES Applications and Licenses License Transfers, Modifications, Conditions and Forfeitures § 101.75 Involuntary relocation procedures. (a) If no agreement is reached during the...
-
Costa, Filipa; Gomes, Dora; Magalhães, Helena; Arrais, Rosário; Moreira, Graciete; Cruz, Maria Fátima; Silva, José Pedro; Santos, Lúcio; Sousa, Olga
2016-01-01
Objective: To characterize in vivo dose distributions during pelvic intraoperative electron radiation therapy (IOERT) for rectal cancer and to assess the alterations introduced by irregular irradiation surfaces in the presence of bevelled applicators. Methods: In vivo measurements were performed with Gafchromic films during 32 IOERT procedures. 1 film per procedure was used for the first 20 procedures. The methodology was then optimized for the remaining 12 procedures by using a set of 3 films. Both the average dose and two-dimensional dose distributions for each film were determined. Phantom measurements were performed for comparison. Results: For flat and concave surfaces, the doses measured in vivo agree with expected values. For concave surfaces with step-like irregularities, measured doses tend to be higher than expected doses. Results obtained with three films per procedure show a large variability along the irradiated surface, with important differences from expected profiles. These results are consistent with the presence of surface hotspots, such as those observed in phantoms in the presence of step-like irregularities, as well as fluid build-up. Conclusion: Clinical dose distributions in the IOERT of rectal cancer are often different from the references used for prescription. Further studies are necessary to assess the impact of these differences on treatment outcomes. In vivo measurements are important, but need to be accompanied by accurate imaging of positioning and irradiated surfaces. Advances in knowledge: These results confirm that surface irregularities occur frequently in rectal cancer IOERT and have a measurable effect on the dose distribution. PMID:27188847
-
Hatzell, H.H.; Oaksford, E.T.; Asbury, C.E.
1995-01-01
The implementation of design guidelines for the National Water-Quality Assessment (NAWQA) Program has resulted in the development of new sampling procedures and the modification of existing procedures commonly used in the Water Resources Division of the U.S. Geological Survey. The Georgia-Florida Coastal Plain (GAFL) study unit began the intensive data collection phase of the program in October 1992. This report documents the implementation of the NAWQA guidelines by describing the sampling design and procedures for collecting surface-water samples in the GAFL study unit in 1993. This documentation is provided for agencies that use water-quality data and for future study units that will be entering the intensive phase of data collection. The sampling design is intended to account for large- and small-scale spatial variations, and temporal variations in water quality for the study area. Nine fixed sites were selected in drainage basins of different sizes and different land-use characteristics located in different land-resource provinces. Each of the nine fixed sites was sampled regularly for a combination of six constituent groups composed of physical and chemical constituents: field measurements, major ions and metals, nutrients, organic carbon, pesticides, and suspended sediments. Some sites were also sampled during high-flow conditions and storm events. Discussion of the sampling procedure is divided into three phases: sample collection, sample splitting, and sample processing. A cone splitter was used to split water samples for the analysis of the sampling constituent groups except organic carbon from approximately nine liters of stream water collected at four fixed sites that were sampled intensively. An example of the sample splitting schemes designed to provide the sample volumes required for each sample constituent group is described in detail. Information about onsite sample processing has been organized into a flowchart that describes a pathway for each of the constituent groups.
-
Defining unnecessary disinfection procedures for single-dose and multiple-dose vials.
Buckley, T; Dudley, S M; Donowitz, L G
1994-11-01
Recommendations in the literature conflict on the necessity of disinfecting single-use vials prior to aspiration of fluid. Interventions to disinfect the stopper surface on multiple-dose vials vary considerably. To determine the necessity of alcohol disinfection of the stopper on single-dose vials and to compare povidone-iodine and alcohol versus alcohol-only disinfection of the stopper prior to each needle penetration on multiple-dose vials. The rubber stopper surfaces of 100 single-dose vials were cultured for the presence of bacteria. To determine the efficacy of two procedures for disinfection of multiple-dose vials, 87 stopper surfaces routinely disinfected with both povidone-iodine and alcohol were cultured for bacteria. After a change in practice, 100 multiple-dose vials routinely disinfected with alcohol only were cultured for the presence of bacteria. Of the cultures done on single-dose vial stoppers, 99% were sterile. A comparison of the two disinfection techniques for multiple-dose vials revealed that 83 (95%) of the 87 vials prepped with both povidone-iodine and alcohol were sterile, compared with all stoppers disinfected with alcohol only. This study shows the lack of necessity of any disinfection procedure on the rubber stopper of single-dose vials and the efficacy of alcohol only for disinfecting the stopper of multiple-dose vials.
-
Radiation exposure in interventional radiology
NASA Astrophysics Data System (ADS)
Pinto, N. G. V.; Braz, D.; Vallim, M. A.; Filho, L. G. P.; Azevedo, F. S.; Barroso, R. C.; Lopes, R. T.
2007-09-01
The aim of this study is to evaluate dose values in patients and staff involved in some interventional radiology procedures. Doses have been measured using thermoluminescent dosemeters for single procedures (such as renal and cerebral arteriography, transjungular intrahepatic portasystemic shunt (TIPS) and chemoembolization). The magnitude of doses through the hands of interventional radiologists has been studied. Dose levels were evaluated in three points for patients (eye, thyroid and gonads). The dose-area product (DAP) was also investigated using a Diamentor (PTW-M2). The dose in extremities was estimated for a professional who generally performed one TIPS, two chemoembolizations, two cerebral arteriographies and two renal arteriographies in a week. The estimated annual radiation dose was converted to effective dose as suggested by the 453-MS/Brazil norm The annual dose values were 137.25 mSv for doctors, 40.27 mSv for nurses and 51.95 mSv for auxiliary doctors, and all these annual dose values are below the limit established. The maximum values of the dose obtained for patients were 6.91, 10.92 and 15.34 mGy close to eye, thyroid and gonads, respectively. The DAP values were evaluated for patients in the same interventional radiology procedures. The dose and DAP values obtained are in agreement with values encountered in the literature.
-
ERIC Educational Resources Information Center
Stein, Jeffrey S.; Pinkston, Jonathan W.; Brewer, Adam T.; Francisco, Monica T.; Madden, Gregory J.
2012-01-01
Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual…
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Morshedi, Maud M., E-mail: maud.morshedi@my.rfums.org; Bauman, Michael, E-mail: mbauman@ucsd.edu; Rose, Steven C., E-mail: scrose@ucsd.edu
2015-04-15
PurposeSerious complications can result from nontarget embolization during yttrium-90 (Y-90) transarterial radioembolization. Hepatoenteric artery coil embolization has been traditionally performed to prevent nontarget radioembolization. The U.S. Food and Drug Administration–approved Surefire Infusion System (SIS) catheter, designed to prevent reflux, is an alternative to coils. The hypothesis that quantifiable SIS procedural parameters are comparable to coil embolization was tested.MethodsFourteen patients aged 36–79 years with colorectal, neuroendocrine, hepatocellular, and other predominantly bilobar hepatic tumors who underwent resin microsphere Y-90 radioembolization using only the SIS catheter (n = 7) versus only detachable coils (n = 7) for nontarget protection were reviewed retrospectively. Procedure time, fluoroscopy time, contrast dose,more » radiation dose, and cost were evaluated.ResultsMultivariate analysis identified significant cohort differences in the procedural parameters evaluated (F(10, 3) = 10.39, p = 0.04). Between-group comparisons of the pretreatment planning procedure in the SIS catheter group compared to the coil embolization group demonstrated a significant reduction in procedure time (102.6 vs. 192.1 min, respectively, p = 0.0004), fluoroscopy time (14.3 vs. 49.7 min, respectively, p = 0.0016), and contrast material dose (mean dose of 174.3 vs. 265.0 mL, respectively, p = 0.0098). Procedural parameters were not significantly different between the two groups during subsequent dose delivery procedures. Overall cost of combined first-time radioembolization procedures was significantly less in the SIS group ($4252) compared to retrievable coil embolization ($11,123; p = 0.001).ConclusionThe SIS catheter results in a reduction in procedure time, fluoroscopy time, and contrast material dose and may be an attractive cost-effective alternative to detachable coil embolization for prevention of nontarget radioembolization.« less
-
Estimating Radiation Dose Metrics for Patients Undergoing Tube Current Modulation CT Scans
NASA Astrophysics Data System (ADS)
McMillan, Kyle Lorin
Computed tomography (CT) has long been a powerful tool in the diagnosis of disease, identification of tumors and guidance of interventional procedures. With CT examinations comes the concern of radiation exposure and the associated risks. In order to properly understand those risks on a patient-specific level, organ dose must be quantified for each CT scan. Some of the most widely used organ dose estimates are derived from fixed tube current (FTC) scans of a standard sized idealized patient model. However, in current clinical practice, patient size varies from neonates weighing just a few kg to morbidly obese patients weighing over 200 kg, and nearly all CT exams are performed with tube current modulation (TCM), a scanning technique that adjusts scanner output according to changes in patient attenuation. Methods to account for TCM in CT organ dose estimates have been previously demonstrated, but these methods are limited in scope and/or restricted to idealized TCM profiles that are not based on physical observations and not scanner specific (e.g. don't account for tube limits, scanner-specific effects, etc.). The goal of this work was to develop methods to estimate organ doses to patients undergoing CT scans that take into account both the patient size as well as the effects of TCM. This work started with the development and validation of methods to estimate scanner-specific TCM schemes for any voxelized patient model. An approach was developed to generate estimated TCM schemes that match actual TCM schemes that would have been acquired on the scanner for any patient model. Using this approach, TCM schemes were then generated for a variety of body CT protocols for a set of reference voxelized phantoms for which TCM information does not currently exist. These are whole body patient models representing a variety of sizes, ages and genders that have all radiosensitive organs identified. TCM schemes for these models facilitated Monte Carlo-based estimates of fully-, partially- and indirectly-irradiated organ dose from TCM CT exams. By accounting for the effects of patient size in the organ dose estimates, a comprehensive set of patient-specific dose estimates from TCM CT exams was developed. These patient-specific organ dose estimates from TCM CT exams will provide a more complete understanding of the dose impact and risks associated with modern body CT scanning protocols.
-
Weight-based dosing in medication use: what should we know?
Pan, Sheng-dong; Zhu, Ling-ling; Chen, Meng; Xia, Ping; Zhou, Quan
2016-01-01
Background Weight-based dosing strategy is still challenging due to poor awareness and adherence. It is necessary to let clinicians know of the latest developments in this respect and the correct circumstances in which weight-based dosing is of clinical relevance. Methods A literature search was conducted using PubMed. Results Clinical indications, physiological factors, and types of medication may determine the applicability of weight-based dosing. In some cases, the weight effect may be minimal or the proper dosage can only be determined when weight is combined with other factors. Medications within similar therapeutic or structural class (eg, anticoagulants, antitumor necrosis factor medications, P2Y12-receptor antagonists, and anti-epidermal growth factor receptor antibodies) may exhibit differences in requirements on weight-based dosing. In some cases, weight-based dosing is superior to currently recommended fixed-dose regimen in adult patients (eg, hydrocortisone, vancomycin, linezolid, and aprotinin). On the contrary, fixed dosing is noninferior to or even better than currently recommended weight-based regimen in adult patients in some cases (eg, cyclosporine microemulsion, recombinant activated Factor VII, and epoetin α). Ideal body-weight-based dosing may be superior to the currently recommended total body-weight-based regimen (eg, atracurium and rocuronium). For dosing in pediatrics, whether weight-based dosing is better than body surface-area-based dosing is dependent on the particular medication (eg, methotrexate, prednisone, prednisolone, zidovudine, didanosine, growth hormone, and 13-cis-retinoic acid). Age-based dosing strategy is better than weight-based dosing in some cases (eg, intravenous busulfan and dalteparin). Dosing guided by pharmacogenetic testing did not show pharmacoeconomic advantage over weight-adjusted dosing of 6-mercaptopurine. The common viewpoint (ie, pediatric patients should be dosed on the basis of body weight) is not always correct. Effective weight-based dosing interventions include standardization of weight estimation, documentation and dosing determination, dosing chart, dosing protocol, order set, pharmacist participation, technological information, and educational measures. Conclusion Although dosing methods are specified in prescribing information for each drug and there are no principal pros and cons to be elaborated, this review of weight-based dosing strategy will enrich the knowledge of medication administration from the perspectives of safety, efficacy, and pharmacoeconomics, and will also provide research opportunities in clinical practice. Clinicians should be familiar with dosage and administration of the medication to be prescribed as well as the latest developments. PMID:27110105
-
Probabilistic Motor Sequence Yields Greater Offline and Less Online Learning than Fixed Sequence
Du, Yue; Prashad, Shikha; Schoenbrun, Ilana; Clark, Jane E.
2016-01-01
It is well acknowledged that motor sequences can be learned quickly through online learning. Subsequently, the initial acquisition of a motor sequence is boosted or consolidated by offline learning. However, little is known whether offline learning can drive the fast learning of motor sequences (i.e., initial sequence learning in the first training session). To examine offline learning in the fast learning stage, we asked four groups of young adults to perform the serial reaction time (SRT) task with either a fixed or probabilistic sequence and with or without preliminary knowledge (PK) of the presence of a sequence. The sequence and PK were manipulated to emphasize either procedural (probabilistic sequence; no preliminary knowledge (NPK)) or declarative (fixed sequence; with PK) memory that were found to either facilitate or inhibit offline learning. In the SRT task, there were six learning blocks with a 2 min break between each consecutive block. Throughout the session, stimuli followed the same fixed or probabilistic pattern except in Block 5, in which stimuli appeared in a random order. We found that PK facilitated the learning of a fixed sequence, but not a probabilistic sequence. In addition to overall learning measured by the mean reaction time (RT), we examined the progressive changes in RT within and between blocks (i.e., online and offline learning, respectively). It was found that the two groups who performed the fixed sequence, regardless of PK, showed greater online learning than the other two groups who performed the probabilistic sequence. The groups who performed the probabilistic sequence, regardless of PK, did not display online learning, as indicated by a decline in performance within the learning blocks. However, they did demonstrate remarkably greater offline improvement in RT, which suggests that they are learning the probabilistic sequence offline. These results suggest that in the SRT task, the fast acquisition of a motor sequence is driven by concurrent online and offline learning. In addition, as the acquisition of a probabilistic sequence requires greater procedural memory compared to the acquisition of a fixed sequence, our results suggest that offline learning is more likely to take place in a procedural sequence learning task. PMID:26973502
-
Probabilistic Motor Sequence Yields Greater Offline and Less Online Learning than Fixed Sequence.
Du, Yue; Prashad, Shikha; Schoenbrun, Ilana; Clark, Jane E
2016-01-01
It is well acknowledged that motor sequences can be learned quickly through online learning. Subsequently, the initial acquisition of a motor sequence is boosted or consolidated by offline learning. However, little is known whether offline learning can drive the fast learning of motor sequences (i.e., initial sequence learning in the first training session). To examine offline learning in the fast learning stage, we asked four groups of young adults to perform the serial reaction time (SRT) task with either a fixed or probabilistic sequence and with or without preliminary knowledge (PK) of the presence of a sequence. The sequence and PK were manipulated to emphasize either procedural (probabilistic sequence; no preliminary knowledge (NPK)) or declarative (fixed sequence; with PK) memory that were found to either facilitate or inhibit offline learning. In the SRT task, there were six learning blocks with a 2 min break between each consecutive block. Throughout the session, stimuli followed the same fixed or probabilistic pattern except in Block 5, in which stimuli appeared in a random order. We found that PK facilitated the learning of a fixed sequence, but not a probabilistic sequence. In addition to overall learning measured by the mean reaction time (RT), we examined the progressive changes in RT within and between blocks (i.e., online and offline learning, respectively). It was found that the two groups who performed the fixed sequence, regardless of PK, showed greater online learning than the other two groups who performed the probabilistic sequence. The groups who performed the probabilistic sequence, regardless of PK, did not display online learning, as indicated by a decline in performance within the learning blocks. However, they did demonstrate remarkably greater offline improvement in RT, which suggests that they are learning the probabilistic sequence offline. These results suggest that in the SRT task, the fast acquisition of a motor sequence is driven by concurrent online and offline learning. In addition, as the acquisition of a probabilistic sequence requires greater procedural memory compared to the acquisition of a fixed sequence, our results suggest that offline learning is more likely to take place in a procedural sequence learning task.
-
Choi, YoonJung; Han, HyeKyung; Shin, Dongseong; Lim, Kyoung Soo; Yu, Kyung-Sang
2015-01-01
Background HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug-associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK) and safety of HCP1004 compared to VIMOVO® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium). Subjects and methods An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO®) or test (HCP1004) drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax) and the area under the concentration–time curve from 0 to the last measurable time (AUC0−t) were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study. Results Sixty-six of the 70 subjects completed the study. The Cmax (mean ± standard deviation) and AUC0−t (mean ± standard deviation) for naproxen in HCP1004 were 61.67±15.16 µg/mL and 1,206.52±166.46 h·µg/mL, respectively; in VIMOVO®; these values were 61.85±14.54 µg/mL and 1,211.44±170.01 h·µg/mL, respectively. The Cmax and AUC0−t for esomeprazole in HCP1004 were 658.21±510.91 ng/mL and 1,109.11±1,111.59 h·ng/mL, respectively; for VIMOVO®, these values were 595.09±364.23 ng/mL and 1,015.12±952.98 h·ng/mL, respectively. The geometric mean ratios and 90% confidence intervals (CIs) (HCP1004 to VIMOVO®) of the Cmax and AUC0−t of naproxen were 0.99 (0.94–1.06) and 1.00 (0.98–1.01), respectively. For esomeprazole, the geometric mean ratios (90% CI) for the Cmax and AUC0−t were 0.99 (0.82–1.18) and 1.04 (0.91–1.18), respectively. The overall results of the safety assessment showed no clinically significant issues for either treatment. Conclusion The PK of HCP1004 500/20 mg was comparable to that of VIMOVO® 500/20 mg for both naproxen and esomeprazole after a single oral dose. Both drugs were well-tolerated without any safety issues. PMID:26257511
-
Choi, YoonJung; Han, HyeKyung; Shin, Dongseong; Lim, Kyoung Soo; Yu, Kyung-Sang
2015-01-01
HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug-associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK) and safety of HCP1004 compared to VIMOVO(®) (a marketed fixed-dose combination of naproxen and esomeprazole magnesium). An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO(®)) or test (HCP1004) drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax) and the area under the concentration-time curve from 0 to the last measurable time (AUC0-t) were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study. Sixty-six of the 70 subjects completed the study. The Cmax (mean ± standard deviation) and AUC0-t (mean ± standard deviation) for naproxen in HCP1004 were 61.67 ± 15.16 µg/mL and 1,206.52 ± 166.46 h · µg/mL, respectively; in VIMOVO(®); these values were 61.85 ± 14.54 µg/mL and 1,211.44 ± 170.01 h · µg/mL, respectively. The Cmax and AUC0-t for esomeprazole in HCP1004 were 658.21 ± 510.91 ng/mL and 1,109.11 ± 1,111.59 h · ng/mL, respectively; for VIMOVO(®), these values were 595.09 ± 364.23 ng/mL and 1,015.12 ± 952.98 h · ng/mL, respectively. The geometric mean ratios and 90% confidence intervals (CIs) (HCP1004 to VIMOVO(®)) of the Cmax and AUC0-t of naproxen were 0.99 (0.94-1.06) and 1.00 (0.98-1.01), respectively. For esomeprazole, the geometric mean ratios (90% CI) for the Cmax and AUC0-t were 0.99 (0.82-1.18) and 1.04 (0.91-1.18), respectively. The overall results of the safety assessment showed no clinically significant issues for either treatment. The PK of HCP1004 500/20 mg was comparable to that of VIMOVO(®) 500/20 mg for both naproxen and esomeprazole after a single oral dose. Both drugs were well-tolerated without any safety issues.
-
Release of metal ions from fixed orthodontic appliance: an in vitro study in continuous flow system.
Mikulewicz, Marcin; Chojnacka, Katarzyna; Wołowiec, Paulina
2014-01-01
To evaluate the release of metal ions from fixed orthodontic appliances. A new system for in vitro testing of dental materials was constructed and consisted of a thermostatic glass reactor that enabled immersion of the studied material. Experimental conditions reflected the human oral cavity, with a temperature of 37°C and a saliva flow rate of 0.5mL/min. The simulated fixed orthodontic appliance made of stainless steel was evaluated. Sampling was performed at several time points during the 28-day study, and the metal ion concentration was determined by inductively coupled plasma optical emission spectrometry. The total mass of released metal ions from the appliance during 4 weeks of the experiment was as follows nickel 18.7 μg, chromium 5.47 μg, copper 31.3 μg. The estimated doses of nickel, chromium, and copper determined by extrapolation of experimental data released during the treatment period were far below the toxic dose to humans. This shows that orthodontic treatment might not be a significant source of exposure to these metal ions.
-
The formulaic schema in the minds of two generations of native speakers
Van Lancker Sidtis, Diana; Cameron, Krista; Bridges, Kelly; Sidtis, John J.
2015-01-01
Schemata are expressions that are fixed except for slots available for novel words (I’m not a ______ person). Our goals were to quantify speakers’ knowledge, examine semantic flexibility in open slots, and compare performance data in two generations of speakers using cloze procedures in formulaic expressions, schemata open slots, fixed portions of schemata, and novel sentences. Fewer unique words appeared for the schemata-fixed and formulaic exemplars, reflecting speakers’ knowledge of these utterances; the most semantic categories appeared for schemata-open responses. Age groups did not differ. Schemata exemplify creative interplay between novel lexical retrieval and fixed formulaic expression. PMID:26392923
-
Acocella, G; Luisetti, M; Grassi, G G; Peona, V; Pozzi, E; Grassi, C
1993-01-01
A study was carried out in six human volunteers, to assess the blood kinetics of isoniazid, rifampicin and pyrazinamide, administered in a fixed-triple combination intended for use in intermittent chemotherapy of tuberculosis. The formulation employed contained 125 mg of isoniazid (H), 100 mg of rifampicin (R) and 375 mg of pyrazinamide (Z) per tablet; six tablets were administered to every subject, giving a total dosage of 750 mg of isoniazid, 600 mg of rifampicin and 2,250 mg of pyrazinamide. In each subject, the same dose of each drug was administered individually in separate sessions and the results compared. The results indicated that, at the level of dose of the intermittent tablet, no negative interactions between the drugs were observed.
-
Eye lens dosimetry in anesthesiology: a prospective study.
Vaes, Bart; Van Keer, Karel; Struelens, Lara; Schoonjans, Werner; Nijs, Ivo; Vandevenne, Jan; Van Poucke, Sven
2017-04-01
The eye lens is one of the most sensitive organs for radiation injury and exposure might lead to radiation induced cataract. Eye lens dosimetry in anesthesiology has been published in few clinical trials and an active debate about the causality of radiation induced cataract is still ongoing. Recently, the International Commission on Radiological Protection (ICRP) recommended a reduction in the annual dose limit for occupational exposure for the lens of the eye from 150 to 20 mSv, averaged over a period of 5 years, with the dose in a single year not exceeding 50 mSv. This prospective study investigated eye lens dosimetry in anesthesiology practice during a routine year of professional activity. The radiation exposure measured represented the exposure in a normal working schedule of a random anesthesiologist during 1 month and this cumulative eye lens dose was extrapolated to 1 year. Next, eye lens doses were measured in anesthesiology during neuro-embolisation procedures, radiofrequency ablations or vertebroplasty/kyphoplasty procedures. The eye lens doses are measured in terms of the dose equivalent H p (3) with the Eye-D dosimeter (Radcard, Poland) close to the right eye (on the temple). In 16 anesthesiologists, the estimated annual eye lens doses range from a minimum of 0.4 mSv to a maximum of 3.5 mSv with an average dose of 1.33 mSv. Next, eye lens doses were measured for nine neuro-embolisation procedures, ten radiofrequency ablations and six vertebroplasty/kyphoplasty procedures. Average eye lens doses of 77 ± 76 µSv for neuro-embolisations, 38 ± 34 µSv for cardiac ablations and 40 ± 44 µSv for vertebro-/kyphoplasty procedures were recorded. The maximum doses were respectively 264, 97 and 122 µSv. This study demonstrated that the estimated annual eye lens dose is well below the revised ICRP's limit of 20 mSv/year. However, we demonstrated high maximum and average doses during neuro-embolisation, cardiac ablation and vertebro-/kyphoplasty procedures. With radiation induced cataract being explained as a possible stochastic effect, without a threshold dose, anesthesiologists who regularly work in a radiological environment should remain vigilant and maintain radiation safety standards at all times. This includes adequately protective equipment (protection shields, apron, thyroid shield and leaded eye wear), keeping distance, routine monitoring and appropriate education.
-
Cohen, Micah G; McMahon, Colm J; Kung, Justin W; Wu, Jim S
2016-05-01
The purpose of this study was to compare manual and battery-powered bone biopsy systems for diagnostic yield and procedural factors during core needle biopsy of sclerotic bone lesions. A total of 155 consecutive CT-guided core needle biopsies of sclerotic bone lesions were performed at one institution from January 2006 to November 2014. Before March 2012, lesions were biopsied with manual bone drill systems. After March 2012, most biopsies were performed with a battery-powered system and either noncoaxial or coaxial biopsy needles. Diagnostic yield, crush artifact, CT procedure time, procedure radiation dose, conscious sedation dose, and complications were compared between the manual and battery-powered core needle biopsy systems by Fisher exact test and t test. One-way ANOVA was used for subgroup analysis of the two battery-powered systems for procedure time and radiation dose. The diagnostic yield for all sclerotic lesions was 60.0% (93/155) and was significantly higher with the battery-powered system (73.0% [27/37]) than with the manual systems (55.9% [66/118]) (p = 0.047). There was no significant difference between the two systems in terms of crush artifact, procedure time, radiation dose, conscious sedation administered, or complications. In subgroup analysis, the coaxial battery-powered biopsies had shorter procedure times (p = 0.01) and lower radiation doses (p = 0.002) than the coaxial manual systems, but the noncoaxial battery-powered biopsies had longer average procedure times and higher radiation doses than the coaxial manual systems. In biopsy of sclerotic bone lesions, use of a battery-powered bone drill system improves diagnostic yield over use of a manual system.
-
47 CFR 101.819 - Stations affected by coordination contour procedures.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 47 Telecommunication 5 2013-10-01 2013-10-01 false Stations affected by coordination contour procedures. 101.819 Section 101.819 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Television Transmission Service § 101.819...
-
47 CFR 101.819 - Stations affected by coordination contour procedures.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 47 Telecommunication 5 2011-10-01 2011-10-01 false Stations affected by coordination contour procedures. 101.819 Section 101.819 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Television Transmission Service § 101.819...
-
47 CFR 101.819 - Stations affected by coordination contour procedures.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 47 Telecommunication 5 2012-10-01 2012-10-01 false Stations affected by coordination contour procedures. 101.819 Section 101.819 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Television Transmission Service § 101.819...
-
47 CFR 101.819 - Stations affected by coordination contour procedures.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 47 Telecommunication 5 2010-10-01 2010-10-01 false Stations affected by coordination contour procedures. 101.819 Section 101.819 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Television Transmission Service § 101.819...
-
47 CFR 101.819 - Stations affected by coordination contour procedures.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 47 Telecommunication 5 2014-10-01 2014-10-01 false Stations affected by coordination contour procedures. 101.819 Section 101.819 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Television Transmission Service § 101.819...
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ryan, E. Ronan, E-mail: ronan@ronanryan.com; Thornton, Raymond; Sofocleous, Constantinos T.
PurposeTo quantify radiation exposure to the primary operator and staff during PET/CT-guided interventional procedures.MethodsIn this prospective study, 12 patients underwent PET/CT-guided interventions over a 6 month period. Radiation exposure was measured for the primary operator, the radiology technologist, and the nurse anesthetist by means of optically stimulated luminescence dosimeters. Radiation exposure was correlated with the procedure time and the use of in-room image guidance (CT fluoroscopy or ultrasound).ResultsThe median effective dose was 0.02 (range 0-0.13) mSv for the primary operator, 0.01 (range 0-0.05) mSv for the nurse anesthetist, and 0.02 (range 0-0.05) mSv for the radiology technologist. The median extremitymore » dose equivalent for the operator was 0.05 (range 0-0.62) mSv. Radiation exposure correlated with procedure duration and with the use of in-room image guidance. The median operator effective dose for the procedure was 0.015 mSv when conventional biopsy mode CT was used, compared to 0.06 mSv for in-room image guidance, although this did not achieve statistical significance as a result of the small sample size (p = 0.06).ConclusionThe operator dose from PET/CT-guided procedures is not significantly different than typical doses from fluoroscopically guided procedures. The major determinant of radiation exposure to the operator from PET/CT-guided interventional procedures is time spent in close proximity to the patient.« less
-
1974-08-31
Prosthodontic Appliances - Partial Dentures .... ....... ....... .... 59 2. Removable Prosthodontic Appliances - Full Dentures ..... ........... . 60 3...PROCEDURES I This unit includes the following Modules: Number Title Page 1 Removable Prosthodontic Appliances - Partial Dentures 59. ......... ...... 2...Removable Prostbodontic Appliances - Full Dentures ..... ...... a .. .. .. . 60 3 Fixed Prosthodontic Appliances - Fixed Bridge. . 61 4 Mouthquard
-
Designing a fixed-blade gang ripsaw arbor with a pencil
Charles J. Gatchell; Charles J. Gatchell
1996-01-01
This paper presents a step-by-step procedure for designing the "best" sequence of saw spacings for a fixed-blade gang ripsaw arbor. Using the information contained in a cutting bill and knowledge of the lumber width distributions to be processed, thousands of possible saw spacing sequences can be reduced to a few good ones.
-
ERIC Educational Resources Information Center
Reuter, Katherine E.; LeBlanc, Judith M.
Two groups of five preschool children were trained to press a key for marbles for four sessions of variable ratio reinforcement (VR6). Subsequently, response decrement for the groups was compared during conditions of fixed and variable differential reinforcement of other behavior (DRO and VDRO). Fixed DRO was more effective for decreasing response…
-
Response Acquisition and Fixed-Ratio Escalation Based on Interresponse Times in Rats
ERIC Educational Resources Information Center
Taylor, Tracy G.; Galuska, Chad M.; Banna, Kelly; Yahyavi-Firouz-Abadi, Noushin; See, Ronald E.
2010-01-01
The effectiveness of a fixed-ratio (FR) escalation procedure, developed by Pinkston and Branch (2004) and based on interresponse times (IRTs), was assessed during lever-press acquisition. Forty-nine experimentally naive adult male Long Evans rats were deprived of food for 24 hr prior to an extended acquisition session. Before the start of the…
-
Is there a role for pharmacokinetic/pharmacodynamic-guided dosing for novel oral anticoagulants?
Chan, Noel; Sager, Philip T; Lawrence, Jack; Ortel, Thomas's; Reilly, Paul; Berkowitz, Scott; Kubitza, Dagmar; Eikelboom, John; Florian, Jeffry; Stockbridge, Norman; Rose, Martin; Temple, Robert; Seltzer, Jonathan H
2018-05-01
The novel direct oral anticoagulants (NOACs) represent a major advance in oral anticoagulant therapy and are replacing vitamin K antagonists as the preferred options for many indications. Given in fixed doses without routine laboratory monitoring, they have been shown to be at least as effective in reducing thromboembolic stroke as dose-adjusted warfarin in phase 3 randomized trials and less likely to cause hemorrhagic stroke. Pharmacokinetic and/or pharmacodynamic subanalyses of the major NOAC trials in patients with atrial fibrillation have established relationships between clinical characteristics, and drug levels and/or pharmacodynamic responses with both efficacy and safety. Based on these analyses, pharmaceutical manufacturers and regulatory authorities have provided contraindications and dosing recommendations based on clinical characteristics that are associated with drug levels and/or pharmacodynamic responses, stroke reduction, and bleeding risk to optimize the risk-benefit profile of the NOACs in the real world. The current fixed-dosing strategy of NOACs has triggered discussions about the potential value of laboratory monitoring and dose adjustment in customizing drug exposure to further improve the safety and efficacy of the NOACs in patients with atrial fibrillation. As there is neither high-quality evidence nor consensus about the potential role of laboratory monitoring and dose adjustment for the NOACs, a Cardiac Research Safety Consortium "Think Tank" meeting was held at the American College of Cardiology Heart House in December 2015 to discussions these issues. This manuscript reports on the deliberations and the conclusions reached at that meeting. Copyright © 2017. Published by Elsevier Inc.
-
Zvada, Simbarashe P; Denti, Paolo; Donald, Peter R; Schaaf, H Simon; Thee, Stephanie; Seddon, James A; Seifart, Heiner I; Smith, Peter J; McIlleron, Helen M; Simonsson, Ulrika S H
2014-05-01
To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators. Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing.
-
Occupational and patient exposure in coronary angiography procedures
NASA Astrophysics Data System (ADS)
Sulieman, A.; Alzimami, K.; Gafar, R.; Babikir, E.; Alsafi, K.; Suliman, I. I.
2014-11-01
Cardiac catheterization is the gold standard in the diagnosis and management of coronary artery diseases. The objectives of this study were to evaluate the radiation dose of patients and staff during cardiology procedures. Staff was monitored using thermoluminescence dosimeter (TLD) chips for 86 procedures. The mean patient dose was 2813.6 μGy m2 and the mean fluoroscopic time was 4.8 min. The mean radiation doses for cardiologists were 0.9 mGy for the forehead, 0.92 mGy for the thyroid, 1.38 mGy for the chest, 1.28 mGy for the waist and 1.41 mGy for the hand. The mean radiation doses for assistants were 0.72 mGy for the chest, 0.82 mGy for the hand. High patient and staff exposure is due to lack of experience and protective equipment, exacerbated by a high workload. Interventional procedures remain operator dependent; therefore, continuous training is crucial.
-
2012-01-01
Background Divergent strategies have emerged for the management of severe asthma. One strategy utilises high and fixed doses of maintenance treatment, usually inhaled corticosteroid/long-acting β2-agonist (ICS/LABA), supplemented by a short-acting β2-agonist (SABA) as needed. Alternatively, budesonide/formoterol is used as both maintenance and reliever therapy. The latter is superior to fixed-dose treatment in reducing severe exacerbations while achieving similar or better asthma control in other regards. Exacerbations may be reduced by the use of budesonide/formoterol as reliever medication during periods of unstable asthma. We examined the risk of a severe exacerbation in the period after a single day with high reliever use. Methods Episodes of high reliever use were quantified and exacerbations occurring post-index day with these episodes were examined post hoc in two double-blind studies comparing the efficacy and safety of budesonide/formoterol maintenance and reliever therapy (Symbicort SMART™, Turbuhaler®) 160/4.5 μg twice daily plus as needed with similar or higher maintenance doses of ICS/LABA plus SABA or formoterol. Results Budesonide/formoterol maintenance and reliever therapy significantly reduced the risk of episodes of high reliever use (>6 inhalations/day) vs. all alternative ICS/LABA regimens. With conventional fixed-dose treatment the need for exacerbation treatment within 21 days ranged from 6.0–10.1% of days post-index for all regimens compared with 2.5–3.4% of days with budesonide/formoterol maintenance and reliever therapy. Conclusions Budesonide/formoterol maintenance and reliever therapy reduces the incidence of high reliever episodes and the exacerbation burden immediately following these episodes vs. alternative ICS/LABA plus SABA regimens at up to double the maintenance dose of ICS. Trial registration These studies do not have registration numbers as they were conducted before clinical trial registration was required PMID:22816878
-
Chaswal, Vibha; Weldon, Michael; Gupta, Nilendu; Chakravarti, Arnab; Rong, Yi
2014-07-08
We present commissioning and comprehensive evaluation for ArcCHECK as a QA equipment for volumetric-modulated arc therapy (VMAT), using the 6 MV photon beam with and without the flattening filter, and the SNC patient software (version 6.2). In addition to commissioning involving absolute dose calibration, array calibration, and PMMA density verification, ArcCHECK was evaluated for its response dependency on linac dose rate, instantaneous dose rate, radiation field size, beam angle, and couch insertion. Scatter dose characterization, consistency and symmetry of response, and dosimetry accuracy evaluation for fixed aperture arcs and clinical VMAT patient plans were also investigated. All the evaluation tests were performed with the central plug inserted and the homogeneous PMMA density value. Results of gamma analysis demonstrated an overall agreement between ArcCHECK-measured and TPS-calculated reference doses. The diode based field size dependency was found to be within 0.5% of the reference. The dose rate-based dependency was well within 1% of the TPS reference, and the angular dependency was found to be ± 3% of the reference, as tested for BEV angles, for both beams. Dosimetry of fixed arcs, using both narrow and wide field widths, resulted in clinically acceptable global gamma passing rates on the 3%/3mm level and 10% threshold. Dosimetry of narrow arcs showed an improvement over published literature. The clinical VMAT cases demonstrated high level of dosimetry accuracy in gamma passing rates.
-
Rousseau, Annick; Laroche, Marie-Laure; Venisse, Nicolas; Loichot-Roselmac, Cecile; Turcant, Alain; Hoizey, Guillaume; Compagnon, Patricia; Hary, Lionel; Debruyne, Danièle; Saivin, Sylvie; Jacqz-Aigrain, Evelyne; Buchler, Mathias; Villeneuve, Claire; Vergnenègre, Alain; Le Meur, Yannick; Marquet, Pierre
2010-05-27
In the prospective, randomized, multicenter APOMYGRE trial conducted in France, concentration-controlled mycophenolate mofetil (MMF) dosing based on mycophenolic acid (MPA) exposure significantly reduced the treatment failure and acute rejection during the first posttransplantation year compared with fixed-dose MMF. This analysis investigated the cost effectiveness of dose individualization. The study included 65 patients per group (intent-to-treat population). Treatment failure (primary efficacy endpoint) was defined as death, graft loss, acute rejection, or MMF discontinuation because of adverse effects. Data on hospitalizations, drugs prescribed, physicians' fees, laboratory expenses, ambulatory visits, and transportation were retrieved. Costs were calculated from the French National Health System perspective. The mean (95% confidence interval) total yearly cost per patient was Euro 47,477 (Euro 43,933; Euro 51,020) in the concentration-controlled group and Euro 46,783 ( Euro 44,152; Euro 49,414) in the fixed-dose group (P=0.7). The observed incremental cost-effectiveness ratio was Euro 3757 per treatment failure (Purchasing Power Parities United States/France: $4129). Hospitalization and drug costs accounted for approximately 50% and 25% of total costs, respectively. The cost for MPA area under the concentration-time curve and dose calculation was Euro 452 per patient, less than 1% of the total cost. In the APOMYGRE trial, therapeutic MPA monitoring using a limited sampling strategy reduced the risk of treatment failure and acute rejection in renal allograft recipients during the first 12 months posttransplantation, at neutral cost.
-
Sequential Tests of Multiple Hypotheses Controlling Type I and II Familywise Error Rates
Bartroff, Jay; Song, Jinlin
2014-01-01
This paper addresses the following general scenario: A scientist wishes to perform a battery of experiments, each generating a sequential stream of data, to investigate some phenomenon. The scientist would like to control the overall error rate in order to draw statistically-valid conclusions from each experiment, while being as efficient as possible. The between-stream data may differ in distribution and dimension but also may be highly correlated, even duplicated exactly in some cases. Treating each experiment as a hypothesis test and adopting the familywise error rate (FWER) metric, we give a procedure that sequentially tests each hypothesis while controlling both the type I and II FWERs regardless of the between-stream correlation, and only requires arbitrary sequential test statistics that control the error rates for a given stream in isolation. The proposed procedure, which we call the sequential Holm procedure because of its inspiration from Holm’s (1979) seminal fixed-sample procedure, shows simultaneous savings in expected sample size and less conservative error control relative to fixed sample, sequential Bonferroni, and other recently proposed sequential procedures in a simulation study. PMID:25092948
-
Lin, Ming-Fang; Chen, Chia-Yuen; Lee, Yuan-Hao; Li, Chia-Wei; Gerweck, Leo E; Wang, Hao; Chan, Wing P
2018-01-01
Background Multiple rounds of head computed tomography (CT) scans increase the risk of radiation-induced lens opacification. Purpose To investigate the effects of CT eye shielding and topogram-based tube current modulation (TCM) on the radiation dose received by the lens and the image quality of nasal and periorbital imaging. Material and Methods An anthropomorphic phantom was CT-scanned using either automatic tube current modulation or a fixed tube current. The lens radiation dose was estimated using cropped Gafchromic films irradiated with or without a shield over the orbit. Image quality, assessed using regions of interest drawn on the bilateral extraorbital areas and the nasal bone with a water-based marker, was evaluated using both a signal-to-noise ratio (SNR) and contrast-noise ratio (CNR). Two CT specialists independently assessed image artifacts using a three-point Likert scale. Results The estimated radiation dose received by the lens was significantly lower when barium sulfate or bismuth-antimony shields were used in conjunction with a fixed tube current (22.0% and 35.6% reduction, respectively). Topogram-based TCM mitigated the beam hardening-associated artifacts of bismuth-antimony and barium sulfate shields. This increased the SNR by 21.6% in the extraorbital region and the CNR by 7.2% between the nasal bones and extraorbital regions. The combination of topogram-based TCM and barium sulfate or bismuth-antimony shields reduced lens doses by 12.2% and 27.2%, respectively. Conclusion Image artifacts induced by the bismuth-antimony shield at a fixed tube current for lenticular radioprotection were significantly reduced by topogram-based TCM, which increased the SNR of the anthropomorphic nasal bones and periorbital tissues.
-
Whyte, S K; Westcott, J D; Elmoslemany, A; Hammell, K L; Revie, C W
2013-03-01
In New Brunswick, Canada, the sea louse, Lepeophtheirus salmonis, poses an on-going management challenge to the health and productivity of commercially cultured Atlantic salmon, Salmo salar. While the in-feed medication, emamectin benzoate (SLICE® ; Merck), has been highly effective for many years, evidence of increased tolerance has been observed in the field since late 2008. Although bioassays on motile stages are a common tool to monitor sea lice sensitivity to emamectin benzoate in field-collected sea lice, they require the collection of large numbers of sea lice due to inherent natural variability in the gender and stage response to chemotherapeutants. In addition, sensitive instruments such as EC(50) analysis may be unnecessarily complex to characterize susceptibility subsequent to a significant observed decline in efficacy. This study proposes an adaptation of the traditional, dose-response format bioassay to a fixed-dose method. Analysis of 657 bioassays on preadult and adult stages of sea lice over the period 2008-2011 indicated a population of sea lice in New Brunswick with varying degrees of susceptibility to emamectin benzoate. A seasonal and spatial effect was observed in the robustness of genders and stages of sea lice, which suggest that mixing different genders and stages of lice within a single bioassay may result in pertinent information being overlooked. Poor survival of adult female lice in bioassays, particularly during May/June, indicates it may be prudent to consider excluding this stage from bioassays conducted at certain times of the year. This work demonstrates that fixed-dose bioassays can be a valuable technique in detecting reduced sensitivity in sea lice populations with varying degrees of susceptibility to emamectin benzoate treatments. © 2013 Blackwell Publishing Ltd.
-
Messerli, Michael; Dewes, Patricia; Scholtz, Jan-Erik; Arendt, Christophe; Wildermuth, Simon; Vogl, Thomas J; Bauer, Ralf W
2018-05-01
To investigate the impact of an adaptive detector collimation on the dose parameters and accurateness of scan length adaption at prospectively ECG-triggered sequential cardiac CT with a wide-detector third-generation dual-source CT. Ideal scan lengths for human hearts were retrospectively derived from 103 triple-rule-out examinations. These measures were entered into the new scanner operated in prospectively ECG-triggered sequential cardiac scan mode with three different detector settings: (1) adaptive collimation, (2) fixed 64 × 0.6-mm collimation, and (3) fixed 96 × 0.6-mm collimation. Differences in effective scan length and deviation from the ideal scan length and dose parameters (CTDIvol, DLP) were documented. The ideal cardiac scan length could be matched by the adaptive collimation in every case while the mean scanned length was longer by 15.4% with the 64 × 0.6 mm and by 27.2% with the fixed 96 × 0.6-mm collimation. While the DLP was almost identical between the adaptive and the 64 × 0.6-mm collimation (83 vs. 89 mGycm at 120 kV), it was 62.7% higher with the 96 × 0.6-mm collimation (135 mGycm), p < 0.001. The adaptive detector collimation for prospectively ECG-triggered sequential acquisition allows for adjusting the scan length as accurate as this can only be achieved with a spiral acquisition. This technique allows keeping patient exposure low where patient dose would significantly increase with the traditional step-and-shoot mode. • Adaptive detector collimation allows keeping patient exposure low in cardiac CT. • With novel detectors the desired scan length can be accurately matched. • Differences in detector settings may cause 62.7% of excessive dose.
-
A stable fixed-dose combination tablet of pseudoephedrine and KOB extracts for the extended release.
Hwang, C-J; Park, M-H; Jung, H-W; Park, Y-K; Kim, Y-H; Kang, J-S; Cho, C-W
2013-11-01
Allergic rhinitis (AR) is characterized by inflammation of the nasal mucosa with hypersensitivity resulting from seasonal or perennial responses to specific environmental allergens and by symptoms like nasal rubbing, sneezing, rhinorrhea, lacrimation, nasal congestion and obstruction, and less frequently cough. KOB extracts, which is a polyherbal medicine consisting of 5 different herbs (Atractylodes macrocephala, Astragalus membranaceus, Saposhnikovia divaricata, Ostericum koreanum and Scutellaria baicalensis) had commonly been used for the treatment of various allergic diseases showed an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis, recently. On the other hand, pseudoephedrine is a sympathomimetic amine commonly used to relieve congestion in patients with allergic rhinitis and common colds. Considering the KOB's therapeutic mechanism, the combination with pseudoephedrine would be suitable for allergic rhinitis. This study is to obtain an effective extended release formulation using pseudoephedrine and KOB extracts to reduce side effects of drug due to repeated dosing and improve the compliance of patients for treatment of rhinitis and nasal decongestion. So, the fixed-dose combination tablet of pseudoephedrine and KOB extracts was prepared by direct compression and characterized by drug content, flowing characteristics and dissolution test. The drug content of baicalin of KOB extracts was within the range of 95-105% except for T1 formulation. The hardness and friability values of all formulations ranged from 9 to 13 kp and less than 1%, respectively. Taken together, T4 or T8 could be a stable fixed-dose combination tablet for extended release of pseudoephedrine and KOB extracts for nasal rhinitis. © Georg Thieme Verlag KG Stuttgart · New York.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ko, Andrew H.; Quivey, Jeanne M.; Venook, Alan P.
Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m{sup 2} at 10 mg/m{sup 2}/min) plus cisplatin 20 mg/m{sup 2} on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800more » mg/m{sup 2} orally twice daily on the day of radiation) as a radiosensitizer. Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.« less
-
Einstein, Andrew J.; Weiner, Shepard D.; Bernheim, Adam; Kulon, Michal; Bokhari, Sabahat; Johnson, Lynne L.; Moses, Jeffrey W.; Balter, Stephen
2013-01-01
Context Myocardial perfusion imaging (MPI) is the single medical test with the highest radiation burden to the US population. While many patients undergoing MPI receive repeat MPI testing, or additional procedures involving ionizing radiation, no data are available characterizing their total longitudinal radiation burden and relating radiation burden with reasons for testing. Objective To characterize procedure counts, cumulative estimated effective doses of radiation, and clinical indications, for patients undergoing MPI. Design, Setting, Patients Retrospective cohort study evaluating, for 1097 consecutive patients undergoing index MPI during the first 100 days of 2006 at Columbia University Medical Center, all preceding medical imaging procedures involving ionizing radiation undergone beginning October 1988, and all subsequent procedures through June 2008, at that center. Main Outcome Measures Cumulative estimated effective dose of radiation, number of procedures involving radiation, and indications for testing. Results Patients underwent a median (interquartile range, mean) of 15 (6–32, 23.9) procedures involving radiation exposure; 4 (2–8, 6.5) were high-dose (≥3 mSv, i.e. one year's background radiation), including 1 (1–2, 1.8) MPI studies per patient. 31% of patients received cumulative estimated effective dose from all medical sources >100mSv. Multiple MPIs were performed in 39% of patients, for whom cumulative estimated effective dose was 121 (81–189, 149) mSv. Men and whites had higher cumulative estimated effective doses, and there was a trend towards men being more likely to undergo multiple MPIs than women (40.8% vs. 36.6%, Odds ratio 1.29, 95% confidence interval 0.98–1.69). Over 80% of initial and 90% of repeat MPI exams were performed in patients with known cardiac disease or symptoms consistent with it. Conclusion In this institution, multiple testing with MPI was very common, and in many patients associated with very high cumulative estimated doses of radiation. PMID:21078807
-
Exposure of the surgeon's hands to radiation during hand surgery procedures.
Żyluk, Andrzej; Puchalski, Piotr; Szlosser, Zbigniew; Dec, Paweł; Chrąchol, Joanna
2014-01-01
The objective of the study was to assess the time of exposure of the surgeon's hands to radiation and calculate of the equivalent dose absorbed during surgery of hand and wrist fractures with C-arm fluoroscope guidance. The necessary data specified by the objective of the study were acquired from operations of 287 patients with fractures of fingers, metacarpals, wrist bones and distal radius. 218 operations (78%) were percutaneous procedures and 60 (22%) were performed by open method. Data on the time of exposure and dose of radiation were acquired from the display of the fluoroscope, where they were automatically generated. These data were assigned to the individual patient, type of fracture, method of surgery and the operating surgeon. Fixations of distal radial fractures required longer times of radiation exposure (mean 61 sec.) than fractures of the wrist/metacarpals and fingers (38 and 32 sec., respectively), which was associated with absorption of significantly higher equivalent doses. Fixations of distal radial fractures by open method were associated with statistically significantly higher equivalent doses (0.41 mSv) than percutaneous procedures (0.3 mSv). Fixations of wrist and metacarpal bone fractures by open method were associated with lower equivalent doses (0.34 mSv) than percutaneous procedures (0.37 mSv),but the difference was not significant. Fixations of finger fractures by open method were associated with lower equivalent doses (0.13 mSv) than percutaneous procedures (0.24 mSv), the difference being statistically non-significant. Statistically significant differences in exposure time and equivalent doses were noted between 4 surgeons participating in the study, but no definitive relationship was found between these parameters and surgeons' employment time. 1. Hand surgery procedures under fluoroscopic guidance are associated with mild exposure of the surgeons' hands to radiation. 2. The equivalent dose was related to the type of fracture, operative technique and - to some degree - to the time of employment of the surgeon.
-
Natoli, Silvia; Lazzari, Marzia; Carpenedo, Roberta; Palombo, Elisa; Silvi, Maria Beatrice; Mammucari, Massimo; Dauri, Mario
2016-06-01
Oxycodone is one of the most commonly used opioid analgesics in the clinical management of pain. The present retrospective analysis aimed to determine the dose of oxycodone that could achieve effective control of moderate pain when combined with a fixed dose of acetaminophen, and the time required to reach a clinically relevant reduction in intensity of pain. Data of patients treated with a combination of oxycodone (5, 10, and 20 mg) and acetaminophen (325 mg) were evaluated for gender, current disease condition, basal pain intensity, total daily dose, days of controlled pain at the initial low dose, and pain intensity after treatment using a numeric pain rating scale. Data from a total of 491 patients were assessed; of these 93.5% of patients experienced persistent non-cancer pain and had an average baseline pain score of 5.68 ± 1.35. For the overall population, the pain score was reduced to 2.49 ± 1.71 with a mean dose of 8.68 ± 4.96 mg oxycodone after 21.60 ± 6.12 days of treatment with the combination. Almost 97% of the patients who reported relief of pain received 1.61 ± 0.67 doses of oxycodone 5 mg combined with 325 mg of acetaminophen. A low-dose combination of oxycodone with acetaminophen can be effective in the management of moderate pain and may help in reducing the treatment-associated adverse reactions and drug dependence. Sponsorship for article processing charges was provided by Molteni Farmaceutici, Florence, Italy.
-
Etard, Cécile; Bigand, Emeline; Salvat, Cécile; Vidal, Vincent; Beregi, Jean Paul; Hornbeck, Amaury; Greffier, Joël
2017-10-01
A national retrospective survey on patient doses was performed by the French Society of Medical physicists to assess reference levels (RLs) in interventional radiology as required by the European Directive 2013/59/Euratom. Fifteen interventional procedures in neuroradiology, vascular radiology and osteoarticular procedures were analysed. Kerma area product (KAP), fluoroscopy time (FT), reference air kerma and number of images were recorded for 10 to 30 patients per procedure. RLs were calculated as the 3rd quartiles of the distributions. Results on 4600 procedures from 36 departments confirmed the large variability in patient dose for the same procedure. RLs were proposed for the four dosimetric estimators and the 15 procedures. RLs in terms of KAP and FT were 90 Gm.cm 2 and 11 mins for cerebral angiography, 35 Gy.cm 2 and 16 mins for biliary drainage, 75 Gy.cm 2 and 6 mins for lower limbs arteriography and 70 Gy.cm 2 and 11 mins for vertebroplasty. For these four procedures, RLs were defined according to the complexity of the procedure. For all the procedures, the results were lower than most of those already published. This study reports RLs in interventional radiology based on a national survey. Continual evolution of practices and technologies requires regular updates of RLs. • Delivered dose in interventional radiology depends on procedure, practice and patient. • National RLs are proposed for 15 interventional procedures. • Reference levels (RLs) are useful to benchmark practices and optimize protocols. • RLs are proposed for kerma area product, air kerma, fluoroscopy time and number of images. • RLs should be adapted to the procedure complexity and updated regularly.
-
An alternative approach to account for patient organ doses from imaging guidance procedures.
Nelson, Alan P; Ding, George X
2014-07-01
To investigate the feasibility of an alternative method of accounting for additional organ doses resulting from image guidance procedures during patient treatment planning through tabulated values based on scan protocol and scan site. Patient-specific imaging dose to 30 patients resulting from Varian OBI kV-CBCT scans using the Standard Head (17 patients), Low-dose Thorax (8 patients), and Pelvic (5 patients) scan protocols were retrospectively calculated using Monte Carlo methods. Dose dependence on scan location and patient geometry was explored. Patient organ doses were analyzed by using dose-volume histograms and expressed by the mean, minimum dose delivered to 50% of the organ volume, D50. The reported doses are dose-to-medium instead of dose-to-water. The organ doses from all patient-specific calculations show predictable and limited ranges across patients. For brain isocenters using Standard Head Scans: Bone: 0.7-1.1 cGy, Brain: 0.2-0.3 cGy, Brainstem: 0.2-0.3 cGy, Skin: 0.3-0.4 cGy, Eye: 0.03-0.3 cGy. For head and neck patients using the Standard Head Scan: Bone: 0.3-0.6 cGy, Parotids: 0.3-0.4 cGy, Spinal Cord: 0.15-0.25 cGy, Thyroid: 0.1-0.25 cGy, Skin: 0.2-0.3 cGy, Trachea-Esophagus: 0.1-0.2 cGy. For chest using Thorax Scans: Bone: 1.1-1.8 cGy, Soft tissue organs (Bowel, Lung, Heart, Kidney, Esophagus, and Spinal Cord): 0.3-0.6 cGy. For abdominal site using Pelvic Scans: Bone: 3.2-4.2 cGy. Soft tissue organs (Bladder, Bowel, Rectum, Prostate, and Skin) D50s fell between 1.2 and 2.2 cGy. Femoral Heads: 2.5-3.4 cGy. It is adequate to estimate and account for organ dose by using tabulated values based on scan procedure and site because organ doses from imaging procedures are only modestly dependent upon scan location and body size. Considering the dose variation and magnitude of dose from each scan protocol in comparison to therapeutic doses, this approach provides a simple alternative to account for additional imaging guidance doses during patient treatment planning. Clinicians can use these tabulated values to make informed decisions in selecting the appropriate imaging procedures and imaging frequency during radiotherapy treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Solomon, Justin, E-mail: justin.solomon@duke.edu; Wilson, Joshua; Samei, Ehsan
2015-08-15
Purpose: The purpose of this work was to assess the inherent image quality characteristics of a new multidetector computed tomography system in terms of noise, resolution, and detectability index as a function of image acquisition and reconstruction for a range of clinically relevant settings. Methods: A multisized image quality phantom (37, 30, 23, 18.5, and 12 cm physical diameter) was imaged on a SOMATOM Force scanner (Siemens Medical Solutions) under variable dose, kVp, and tube current modulation settings. Images were reconstructed with filtered back projection (FBP) and with advanced modeled iterative reconstruction (ADMIRE) with iterative strengths of 3, 4, andmore » 5. Image quality was assessed in terms of the noise power spectrum (NPS), task transfer function (TTF), and detectability index for a range of detection tasks (contrasts of approximately 45, 90, 300, −900, and 1000 HU, and 2–20 mm diameter) based on a non-prewhitening matched filter model observer with eye filter. Results: Image noise magnitude decreased with decreasing phantom size, increasing dose, and increasing ADMIRE strength, offering up to 64% noise reduction relative to FBP. Noise texture in terms of the NPS was similar between FBP and ADMIRE (<5% shift in peak frequency). The resolution, based on the TTF, improved with increased ADMIRE strength by an average of 15% in the TTF 50% frequency for ADMIRE-5. The detectability index increased with increasing dose and ADMIRE strength by an average of 55%, 90%, and 163% for ADMIRE 3, 4, and 5, respectively. Assessing the impact of mA modulation for a fixed average dose over the length of the phantom, detectability was up to 49% lower in smaller phantom sections and up to 26% higher in larger phantom sections for the modulated scan compared to a fixed tube current scan. Overall, the detectability exhibited less variability with phantom size for modulated scans compared to fixed tube current scans. Conclusions: Image quality increased with increasing dose and decreasing phantom size. The CT system exhibited nonlinear noise and resolution properties, especially at very low-doses, large phantom sizes, and for low-contrast objects. Objective image quality metrics generally increased with increasing dose and ADMIRE strength, and with decreasing phantom size. The ADMIRE algorithm could offer comparable image quality at reduced doses or improved image quality at the same dose. The use of tube current modulation resulted in more consistent image quality with changing phantom size.« less
-
Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD
ERIC Educational Resources Information Center
Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael
2009-01-01
Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…
-
Vagney, Marie; Desquilbet, Loic; Reyes-Gomez, Edouard; Delisle, Françoise; Devauchelle, Patrick; Rodriguez-Piñeiro, Maria Isabel; Rosenberg, Dan; de Fornel-Thibaud, Pauline
2018-06-01
Objectives Radioiodine ( 131 I) dose determination using radiotracer kinetic studies or scoring systems, and fixed relatively high 131 I dose (ie, 4 or 5 mCi) administration, are effective and associated with prolonged survival times for hyperthyroid cats. The latter method is less complicated but could expose patients and veterinary personnel to unnecessary levels of radiation. The aim of this study was to retrospectively evaluate the efficacy of a fixed 3.35 mCi 131 I dose for the treatment of 96 hyperthyroid cats with no length estimation for any palpated goitre ⩾20 mm, assess outcome and identify factors associated with survival. Methods Serum total thyroxine concentrations at diagnosis and at follow-up times, survival times and cause of death were recorded. Multivariable Cox regression analysis was used to identify factors associated with time to any cause of death from 131 I therapy initiation. Results Administration of a median (interquartile range) dose of 3.35 mCi (3.27-3.44 mCi) radioiodine was an effective treatment in 94/96 cats, but two cats remained hyperthyroid. No death related to hyperthyroidism was recorded. Median survival time was 3.0 years; the 1 and 2 year survival rates after 131 I therapy were 90% and 78%, respectively. Low body weight (⩽3.1 kg; adjusted hazard ratio [aHR] 5.88; 95% confidence interval [CI] 2.22-16.67; P <0.01) and male gender (aHR 2.63; 95% CI 1.01-7.14; P = 0.04) were independently associated with death, whereas age, prior treatment with antithyroid drugs, reason for treatment and pretreatment azotaemia were not. Conclusions and relevance This study suggests that a fixed 3.35 mCi 131 I dose treatment is effective for hyperthyroid cats with goitre(s) with a maximal length estimation <20 mm, that long-term survival can be achieved and that low body weight and male gender are significantly associated with shorter survival times.
-
Forum, Glycemic Pentad
2017-07-01
Conventionally, diabetes management involved targeting the triad of FPG, PPG, and HbA1c. However, several studies have suggested the quintessential need for a paradigm shift to incorporate glycemic variability and quality of life in the holistic diabetes control regimen. To generate a consensus and ratify the position of Glycemic Variability (GV) and Quality of Life (QOL), along with the traditional triad, in diabetes management in India. To evaluate whether the triple fixed dose combination of metformin, glimepiride, and voglibose can accomplish the goals of glycemic pentad. Glycemic pentad forum was instituted comprising of 55 experts from different regions of India in the field of diabetology who discussed various evidences related to the topic and shared their experiences and expressed their opinion on the relevance of glycemic pentad in the present diabetes management and whether triple fixed dose combination of metformin, glimepiride, and voglibose is able to achieve glycemic pentad targets. Forum has come to a consensus that the conglomerate of quintuple elements - FPG, PPG, HbA1c, glycemic variability and quality of life to be termed as glycemic pentad and these milestones to be considered for any antidiabetic therapy. Experts opined that combination therapy is required to achieve the Glycemic Pentad, as monotherapy might not address all the five arms of Glycemic Pentad. Group also agreed that the diabetes management in Indians require separate attention due to their distinct dietary habits (high carbohydrate content) and socio-economic status (economically weak and poorly educated). Therefore, mild adjustments to the standard practices in the western countries are suggested. After evaluating various drugs in the current market to identify candidates that could regulate the elements of Glycemic Pentad, the forum assume that a triple fixed dose combination of metformin, glimepiride, and voglibose could be a better choice in Indians as the combination is safe, affordable and effective in attaining optimal glucose levels and reducing the complications. Glycemic pentad deserves a prominent position in the diabetes management in India. The triple fixed dose combination of metformin, glimepiride, and voglibose has essential commodities to achieve glycemic pentad targets.
-
Ding, George X; Coffey, Charles W
2010-09-01
The purpose of this study is to investigate the feasibility of using a single-use dosimeter, OneDose MOSFET designed for in vivo patient dosimetry, for measuring the radiation dose from kilovoltage (kV) x rays resulting from image-guided procedures. The OneDose MOSFET dosimeters were precalibrated by the manufacturer using Co-60 beams. Their energy response and characteristics for kV x rays were investigated by using an ionization chamber, in which the air-kerma calibration factors were obtained from an Accredited Dosimetry Calibration Laboratory (ADCL). The dosimetric properties have been tested for typical kV beams used in image-guided radiation therapy (IGRT). The direct dose reading from the OneDose system needs to be multiplied by a correction factor ranging from 0.30 to 0.35 for kilovoltage x rays ranging from 50 to 125 kVp, respectively. In addition to energy response, the OneDose dosimeter has up to a 20% reduced sensitivity for beams (70-125 kVp) incident from the back of the OneDose detector. The uncertainty in measuring dose resulting from a kilovoltage beam used in IGRT is approximately 20%; this uncertainty is mainly due to the sensitivity dependence of the incident beam direction relative to the OneDose detector. The ease of use may allow the dosimeter to be suitable for estimating the dose resulting from image-guided procedures.
-
Santos, William S; Belinato, Walmir; Perini, Ana P; Caldas, Linda V E; Galeano, Diego C; Santos, Carla J; Neves, Lucio P
2018-01-01
In this study we evaluated the occupational exposures during an abdominal fluoroscopically guided interventional radiology procedure. We investigated the relation between the Body Mass Index (BMI), of the patient, and the conversion coefficient values (CC) for a set of dosimetric quantities, used to assess the exposure risks of medical radiation workers. The study was performed using a set of male and female virtual anthropomorphic phantoms, of different body weights and sizes. In addition to these phantoms, a female and a male phantom, named FASH3 and MASH3 (reference virtual anthropomorphic phantoms), were also used to represent the medical radiation workers. The CC values, obtained as a function of the dose area product, were calculated for 87 exposure scenarios. In each exposure scenario, three phantoms, implemented in the MCNPX 2.7.0 code, were simultaneously used. These phantoms were utilized to represent a patient and medical radiation workers. The results showed that increasing the BMI of the patient, adjusted for each patient protocol, the CC values for medical radiation workers decrease. It is important to note that these results were obtained with fixed exposure parameters. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
-
Gunasekaran, Prasad; Parashara, Deepak K
2015-12-01
Non vitamin-K oral anticoagulants (NOAC) have considerably enhanced anticoagulation practice for non-valvular atrial fibrillation with specific advantages of fixed dosing, non-fluctuant therapeutic levels and obviation of therapeutic level monitoring. NOAC pharmacology is remarkable for considerable renal excretion. Heterogeneity in the precise time cut-offs for discontinuation of NOACs prior to elective surgical or percutaneous procedures arise from the non-linear variations of drug excretion with different levels of creatinine clearances as in chronic kidney disease. Multiple authors have suggested cut-offs leading to ambiguity among practicing clinicians. Recent data pertaining to systemic thromboembolism, stroke and major bleeding derived from randomized controlled clinical trials have simplified the periprocedural management of NOACs. This review focusses on heterogeneity in the management of NOACs in patients with CKD in this peculiar scenario and highlights the contemporary evidence to support a unified approach towards perioperative management of NOACs. Multiple antidotes targeted towards binding of specific NOACs have been developed and are in the testing phase, thereby offering immense potential for rapid and complete reversal of NOAC activity in emergent procedures and major bleeding episodes. Targeted research on thromboembolism, stroke and major bleeding following temporary periprocedural interruption of NOACs using multicentric registries could further expand the clinical utility of these agents.
-
Santibáñez, M; Saavedra, R; Vásquez, M; Malano, F; Pérez, P; Valente, M; Figueroa, R G
2017-11-01
The present work is devoted to optimizing the sensitivity-doses relationship of a bench-top EDXRF system, with the aim of achieving a detection limit of 0.010mg/ml of gold nanoparticles in tumor tissue (clinical values expected), for doses below 10mGy (value fixed for in vivo application). Tumor phantoms of 0.3cm 3 made of a suspension of gold nanoparticles (15nm AurovistTM, Nanoprobes Inc.) were studied at depths of 0-4mm in a tissue equivalent cylindrical phantom. The optimization process was implemented configuring several tube voltages and aluminum filters, to obtain non-symmetrical narrow spectra with fixed FWHM of 5keV and centered among the 11.2-20.3keV. The used statistical figure of merit was the obtained sensitivity (with each spectrum at each depth) weighted by the delivered surface doses. The detection limit of the system was determined measuring several gold nanoparticles concentrations ranging from 0.0010 to 5.0mg/ml and a blank sample into tumor phantoms, considering a statistical fluctuation within 95% of confidence. The results show the possibility of obtaining a detection limit for gold nanoparticles concentrations around 0.010mg/ml for surface tumor phantoms requiring doses around 2mGy. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh
2002-02-21
Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.
-
Pediatric patient and staff dose measurements in barium meal fluoroscopic procedures
NASA Astrophysics Data System (ADS)
Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Porto, L. E.; Ledesma, J. A.; Nascimento, E. X.; Legnani, A.; Andrade, M. E. A.; Khoury, H. J.
2015-11-01
This study investigates patient and staff dose measurements in pediatric barium meal series fluoroscopic procedures. It aims to analyze radiographic techniques, measure the air kerma-area product (PKA), and estimate the staff's eye lens, thyroid and hands equivalent doses. The procedures of 41 patients were studied, and PKA values were calculated using LiF:Mg,Ti thermoluminescent dosimeters (TLDs) positioned at the center of the patient's upper chest. Furthermore, LiF:Mg,Cu,P TLDs were used to estimate the equivalent doses. The results showed a discrepancy in the radiographic techniques when compared to the European Commission recommendations. Half of the results of the analyzed literature presented lower PKA and dose reference level values than the present study. The staff's equivalent doses strongly depends on the distance from the beam. A 55-cm distance can be considered satisfactory. However, a distance decrease of ~20% leads to, at least, two times higher equivalent doses. For eye lenses this dose is significantly greater than the annual limit set by the International Commission on Radiological Protection. In addition, the occupational doses were found to be much higher than in the literature. Changing the used radiographic techniques to the ones recommended by the European Communities, it is expected to achieve lower PKA values and occupational doses.
-
Hsu, Shih-Ming; Hung, Chao-Hsiung; Liao, Yi-Jen; Fu, Hsiao-Mei; Tsai, Jo-Ting
2017-01-01
CyberKnife is one of multiple modalities for stereotactic radiosurgery (SRS). Due to the nature of CyberKnife and the characteristics of SRS, dose evaluation of the CyberKnife procedure is critical. A radiophotoluminescent glass dosimeter was used to verify the dose accuracy for the CyberKnife procedure and validate a viable dose verification system for CyberKnife treatment. A radiophotoluminescent glass dosimeter, thermoluminescent dosimeter, and Kodak EDR2 film were used to measure the lateral dose profile and percent depth dose of CyberKnife. A Monte Carlo simulation for dose verification was performed using BEAMnrc to verify the measured results. This study also used a radiophotoluminescent glass dosimeter coupled with an anthropomorphic phantom to evaluate the accuracy of the dose given by CyberKnife. Measurements from the radiophotoluminescent glass dosimeter were compared with the results of a thermoluminescent dosimeter and EDR2 film, and the differences found were less than 5%. The radiophotoluminescent glass dosimeter has some advantages in terms of dose measurements over CyberKnife, such as repeatability, stability, and small effective size. These advantages make radiophotoluminescent glass dosimeters a potential candidate dosimeter for the CyberKnife procedure. This study concludes that radiophotoluminescent glass dosimeters are a promising and reliable dosimeter for CyberKnife dose verification with clinically acceptable accuracy within 5%. PMID:28046056
-
NASA Astrophysics Data System (ADS)
Inaniwa, T.; Kanematsu, N.; Suzuki, M.; Hawkins, R. B.
2015-05-01
Carbon-ion radiotherapy treatment plans are designed on the assumption that the beams are delivered instantaneously, irrespective of actual dose-delivery time structure in a treatment session. As the beam lines are fixed in the vertical and horizontal directions at our facility, beam delivery is interrupted in multi-field treatment due to the necessity of patient repositioning within the fields. Single-fractionated treatment for non-small cell lung cancer (NSCLC) is such a case, in which four treatment fields in multiple directions are delivered in one session with patient repositioning during the session. The purpose of this study was to investigate the effects of the period of dose delivery, including interruptions due to patient repositioning, on tumor control probability (TCP) of NSCLC. All clinical doses were weighted by relative biological effectiveness (RBE) evaluated for instantaneous irradiation. The rate equations defined in the microdosimetric kinetic model (MKM) for primary lesions induced in DNA were applied to the single-fractionated treatment of NSCLC. Treatment plans were made for an NSCLC case for various prescribed doses ranging from 25 to 50 Gy (RBE), on the assumption of instantaneous beam delivery. These plans were recalculated by varying the interruption time τ ranging from 0 to 120 min between the second and third fields for continuous irradiations of 3 min per field based on the MKM. The curative doses that would result in a TCP of 90% were deduced for the respective interruption times. The curative dose was 34.5 Gy (RBE) for instantaneous irradiation and 36.6 Gy (RBE), 39.2 Gy (RBE), 41.2 Gy (RBE), 43.3 Gy (RBE) and 44.4 Gy (RBE) for τ = 0 min, 15 min, 30 min, 60 min and 120 min, respectively. The realistic biological effectiveness of therapeutic carbon-ion beam decreased with increasing interruption time. These data suggest that the curative dose can increase by 20% or more compared to the planned dose if the interruption time extends to 30 min or longer. These effects should be considered in carbon-ion radiotherapy treatment planning if a longer dose-delivery procedure time is anticipated.
-
Evaluation of Trajectory Errors in an Automated Terminal-Area Environment
NASA Technical Reports Server (NTRS)
Oseguera-Lohr, Rosa M.; Williams, David H.
2003-01-01
A piloted simulation experiment was conducted to document the trajectory errors associated with use of an airplane's Flight Management System (FMS) in conjunction with a ground-based ATC automation system, Center-TRACON Automation System (CTAS) in the terminal area. Three different arrival procedures were compared: current-day (vectors from ATC), modified (current-day with minor updates), and data link with FMS lateral navigation. Six active airline pilots flew simulated arrivals in a fixed-base simulator. The FMS-datalink procedure resulted in the smallest time and path distance errors, indicating that use of this procedure could reduce the CTAS arrival-time prediction error by about half over the current-day procedure. Significant sources of error contributing to the arrival-time error were crosstrack errors and early speed reduction in the last 2-4 miles before the final approach fix. Pilot comments were all very positive, indicating the FMS-datalink procedure was easy to understand and use, and the increased head-down time and workload did not detract from the benefit. Issues that need to be resolved before this method of operation would be ready for commercial use include development of procedures acceptable to controllers, better speed conformance monitoring, and FMS database procedures to support the approach transitions.
-
Thyroid Dose During Neurointerventional Procedures: Does Lead Shielding Reduce the Dose?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shortt, C. P.; Fanning, N. F.; Malone, L.
2007-09-15
Purpose. To assess radiation dose to the thyroid in patients undergoing neurointerventional procedures and to evaluate dose reduction to the thyroid by lead shielding. Methods and Materials. A randomized patient study was undertaken to evaluate the dose reduction by thyroid lead shields and assess their practicality in a clinical setting. Sixty-five patients attending for endovascular treatment of arteriovenous malformations (AVMs) and aneurysms were randomized into one of 2 groups a) No Thyroid Shield and b) Thyroid Lead Shield. Two thermoluminescent dosimeters (TLDs) were placed over the thyroid gland (1 on each side) at constant positions on each patient in bothmore » groups. A thyroid lead shield (Pb eq. 0.5 mm) was placed around the neck of patients in the thyroid lead shield group after the neurointerventional radiologist had obtained satisfactory working access above the neck. The total dose-area-product (DAP) value, number and type of digital subtraction angiography (DSA) runs and fluoroscopy time were recorded for all patients. Results. Of the 72 patients who initially attended for neurointerventional procedures, 7 were excluded due to failure to consent or because of procedures involving access to the external carotid circulation. Of the remaining 65 who were randomized, a further 9 were excluded due to; procedureabandonment, unfeasible shield placement or shield interference with the procedure. Patient demographics included mean age of 47.9 yrs (15-74), F:M=1.4:1. Mean fluoroscopy time was 25.9 min. Mean DAP value was 13,134.8 cGy.cm{sup 2} and mean number of DSA runs was 13.4. The mean relative thyroid doses were significantly different (p< 0.001) between the unshielded (7.23 mSv/cGy2 x 105) and shielded groups (3.77 mSv/cGy2 x 105). A mean thyroid dose reduction of 48% was seen in the shielded group versus the unshielded group. Conclusion. Considerable doses to the thyroid are incurred during neurointerventional procedures, highlighting the need for increased awareness of patient radiation protection. Thyroid lead shielding yields significant radiation protection, is inexpensive and when not obscuring the field of view, should be used routinely.« less
-
Measurements of eye lens doses in interventional cardiology using OSL and electronic dosemeters†.
Sanchez, R M; Vano, E; Fernandez, J M; Ginjaume, M; Duch, M A
2014-12-01
The purpose of this paper is to test the appropriateness of OSL and electronic dosemeters to estimate eye lens doses at interventional cardiology environment. Using TLD as reference detectors, personal dose equivalent was measured in phantoms and during clinical procedures. For phantom measurements, OSL dose values resulted in an average difference of -15 % vs. TLD. Tests carried out with other electronic dosemeters revealed differences up to ±20 % versus TLD. With dosemeters positioned outside the goggles and when TLD doses were >20 μSv, the average difference OSL vs. TLD was -9 %. Eye lens doses of almost 700 μSv per procedure were measured in two cases out of a sample of 33 measurements in individual clinical procedures, thus showing the risk of high exposure to the lenses of the eye when protection rules are not followed. The differences found between OSL and TLD are acceptable for the purpose and range of doses measured in the survey. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Ngaile, J E; Msaki, P K; Kazema, R R; Schreiner, L J
2017-04-25
The aim of this study was to investigate the nature and causes of radiation dose imparted to patients undergoing barium-based X-ray fluoroscopy procedures in Tanzania and to compare these doses to those reported in the literature from other regions worldwide. The air kerma area product (KAP) to patient undergoing barium investigations of gastrointestinal tract system was obtained from four consultant hospitals. The KAP was determined using a flat transparent transmission ionization chamber. Mean values of KAP for barium swallow (BS), barium meal (BM) and barium enema (BE) were 2.79, 2.62 and 15.04 Gy cm2, respectively. The mean values of KAP per hospital for the BS, BM and BE procedures varied by factors of up to 7.3, 1.6 and 2.0, respectively. The overall difference between individual patient doses across the four consultant hospitals investigated differed by factors of up to 53, 29.5 and 12 for the BS, BM and BE procedures, respectively. The majority of the mean values of KAP was lower than the reported values for Ghana, Greece, Spain and the UK, while slightly higher than those reported for India. The observed wide variation of KAP values for the same fluoroscopy procedure within and among the hospitals was largely attributed to the dynamic nature of the procedures, the patient characteristics, the skills and experience of personnel, and the different examination protocols employed among hospitals. The observed great variations of procedural protocols and patient doses within and across the hospitals call for the need to standardize examination protocols and optimize barium-based fluoroscopy procedures. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
NASA Astrophysics Data System (ADS)
Anderson-Evans, Colin David
Two different studies will be presented in this work. The first involves the calculation of effective dose from a phantom study which simulates an atrial fibrillation (AF) ablation procedure. The second involves the validation of metal-oxide semiconducting field effect transistors (MOSFET) for small animal dosimetry applications as well as improved characterization of the animal irradiators on Duke University's campus. Atrial Fibrillation is an ever increasing health risk in the United States. The most common type of cardiac arrhythmia, AF is associated with increased mortality and ischemic cerebrovascular events. Managing AF can include, among other treatments, an interventional procedure called catheter ablation. The procedure involves the use of biplane fluoroscopy during which a patient can be exposed to radiation for as much as two hours or more. The deleterious effects of radiation become a concern when dealing with long fluoroscopy times, and because the AF ablation procedure is elective, it makes relating the risks of radiation ever more essential. This study hopes to quantify the risk through the derivation of dose conversion coefficients (DCCs) from the dose-area product (DAP) with the intent that DCCs can be used to provide estimates of effective dose (ED) for typical AF ablation procedures. A bi-plane fluoroscopic and angiographic system was used for the simulated AF ablation procedures. For acquisition of organ dose measurements, 20 diagnostic MOSFET detectors were placed at selected organs in a male anthropomorphic phantom, and these detectors were attached to 4 bias supplies to obtain organ dose readings. The DAP was recorded from the system console and independently validated with an ionization chamber and radiochromic film. Bi-plane fluoroscopy was performed on the phantom for 10 minutes to acquire the dose rate for each organ, and the average clinical procedure time was multiplied by each organ dose rate to obtain individual organ doses. The effective dose was computed by summing the product of each organ dose and the corresponding tissue weighting factor from the ICRP publication 103. Further risk calculations were done according to the BEIR VII Phase 2 report to obtain relative and lifetime attributable risks of cancer for an average AF ablation procedure. The ED was computed separately for the biplane fluoroscopic and angiographic system's 'low' and 'normal fluoro' automated settings, yielding 27.9 mSv and 45.6 mSv respectively for an average procedure time of 88.2 minutes. The corresponding DAP was 48.7 Gy cm2 and 79.1 Gy cm2 for low and normal settings respectively. The independently measured DAP was found to be within 0.1 % of that measured by the fluoroscopy system's onboard flat panel detectors. DCCs were calculated to be 0.573 and 0.577 for the respective low and normal settings. The results proved to be very closely matched, which was to be expected. The calculated cancer risks were fairly low due to the age of most patients (less than 5 incidences of solid tumor per 100,000 exposed for liver colon and stomach; 100-300 incidences per 100,000 exposed for lungs), but concern remains that longer procedures could increase the risk of erythema or other serious skin injuries. The second section of this thesis study involves the quantification and distribution of radiation dose in small animals undergoing irradiation in an orthovoltage x-ray unit. Extensive research is being done with small animals, particularly mice and rats, in fields such as cancer therapy, radiation biology and radiological countermeasures. Results and conclusion are often drawn from research based solely on manufacturer's specifications of the delivered dose rate without independent verification or adequate understanding of the machines' capabilities. Accurate radiation dose information is paramount when conducting research in this arena. Traditional methods of dosimetry, namely thermoluminescence dosimeters (TLDs) are challenging and often time consuming. This section hopes to show that in place of TLDs, MOSFETs can provide accurate, precise dose information comparable with TLDs and ionization chambers. Measurements of all three dosimeters are compared in a small animal irradiator in phantoms and in vivo. Measurements done with MOSFETs are shown to deviate by 2.5% from that of the ADCL calibrated ionization chamber while TLDs showed a 7% deviation. Dose distributions within a phantom is also measured using radiochromic film to estimate the attenuation and show that dose is not uniform throughout the mouse. A dose decrease of approximately 30% is observed in a water phantom, which was only slightly mitigated by a hardening the beam with additional filtration. A Bland-Altman plot was created to show that the MOSFETs and TLDs used to make the dose measurements are statistically equivalent. The results show that all measurements made over a range of doses fall within 1.96 standard deviations of the mean.
-
10 CFR 73.46 - Fixed site physical protection systems, subsystems, components, and procedures.
Code of Federal Regulations, 2014 CFR
2014-01-01
..., components, and procedures. 73.46 Section 73.46 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL... Energy couriers engaged in the transport of special nuclear material. The search function for detection... of Energy vehicles engaged in transporting special nuclear material and emergency vehicles under...
-
10 CFR 73.46 - Fixed site physical protection systems, subsystems, components, and procedures.
Code of Federal Regulations, 2012 CFR
2012-01-01
..., components, and procedures. 73.46 Section 73.46 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL... Energy couriers engaged in the transport of special nuclear material. The search function for detection... of Energy vehicles engaged in transporting special nuclear material and emergency vehicles under...
-
ERIC Educational Resources Information Center
Ta, Wei-Min; Pitts, Raymond C.; Hughes, Christine E.; McLean, Anthony P.; Grace, Randolph C.
2008-01-01
The purpose of this study was to examine effects of "d"-amphetamine on choice controlled by reinforcement delay. Eight pigeons responded under a concurrent-chains procedure in which one terminal-link schedule was always fixed- interval 8 s, and the other terminal-link schedule changed from session to session between fixed-interval 4 s and…
-
The purpose of this SOP is to describe the methods used to sample residential indoor and outdoor atmospheres for the presence of formaldehyde using the PF-1 passive formaldehyde sampler. The PF-1 passive sampler is used as a fixed location monitor to determine time integrated ex...
-
Multistep integration formulas for the numerical integration of the satellite problem
NASA Technical Reports Server (NTRS)
Lundberg, J. B.; Tapley, B. D.
1981-01-01
The use of two Class 2/fixed mesh/fixed order/multistep integration packages of the PECE type for the numerical integration of the second order, nonlinear, ordinary differential equation of the satellite orbit problem. These two methods are referred to as the general and the second sum formulations. The derivation of the basic equations which characterize each formulation and the role of the basic equations in the PECE algorithm are discussed. Possible starting procedures are examined which may be used to supply the initial set of values required by the fixed mesh/multistep integrators. The results of the general and second sum integrators are compared to the results of various fixed step and variable step integrators.
-
Radiation exposure to the eye lens of orthopaedic surgeons during various orthopaedic procedures.
Romanova, K; Vassileva, J; Alyakov, M
2015-07-01
The aim of the present study was to assess the radiation dose to the eye lens of orthopaedic surgeons during various orthopaedic procedures and to make efforts to ensure that radiation protection is optimised. The study was performed for Fractura femoris and Fractura cruris procedures performed in orthopaedic operating theatres, as well as for fractures of wrist, ankle and hand/shoulder performed in the emergency trauma room. The highest mean value of the eye lens dose of 47.2 μSv and higher mean fluoroscopy time of 3 min, as well as the corresponding highest maximum values of 77.1 μSv and 5.0 min were observed for the Fractura femoris procedure performed with the Biplanar 500e fluoroscopy systems. At a normal workload, the estimated mean annual dose values do not exceed the annual occupational dose limit for the lens of eye, but at a heavy workload in the department, this dose limit could be achieved or exceeded. The use of protective lead glasses is recommended as they could reduce the radiation exposure of the lens of the eye. The phantom measurements demonstrated that the use of half-dose mode could additionally reduce dose to the operator's eye lens. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Effect of mitomycin C on endoscopic dacryocystorhinostomy.
Apuhan, Tayfun; Yıldırım, Yavuz Selim; Eroglu, Faruk; Sipahier, Ali
2011-11-01
The objectives of the study were to retrospectively analyze the efficacy of intraoperative mitomycin C (MMC) in endoscopic dacryocystorhinostomy (END-DCR) and compare it with external dacryocystorhinostomy (EXT-DCR). For the comfort of the patients, the procedures were performed under general anesthesia. Intraoperatively during the END-DCR, we applied a cotton pledget soaked in a 0.5 mg/mL solution of MMC for 2.5 minutes. In each patient, a silicone tube was placed into the nasal cavity via the superior and inferior punctae and fixed in the vestibule. We retrospectively analyzed the medical records of patients who underwent END-DCR and EXT-DCR. A retrospective review was performed on the medical records of 43 patients (with a total of 49 affected cases) who were admitted to our clinics with a primary complaint of epiphora. The overall success rates were 91% in END-DCR+MMC and 71.5% in EXT-DCR. Mitomycin C, in appropriate doses, minimizes postoperative granulations and fibrosis. Adjunctive use of MMC is considered to increase the success rate of END-DCR.
-
2018-04-06
Acute Bleeding on Long-Term Anticoagulation Therapy; Hemorrhage; Significant Bleeding in Patients With a Coagulopathy (Prolonged Thrombin Time); Urgent Reversal of Vitamin K Antagonist (VKA) Anticoagulation
-
77 FR 17487 - Antiviral Drugs Advisory Committee; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2012-03-26
... line/phone line to learn about possible modifications before coming to the meeting. Agenda: The committee will discuss new drug application (NDA) 203- 100, for a fixed-dose combination tablet of...
-
Nebivolol/valsartan: Fixed-dose combination for treatment of hypertension.
Paton, D M
2017-01-01
Clinical trials demonstrated that a fixed-dose combination (FDC) of the beta-blocker nebivolol (5 mg) and the angiotensin II antagonist valsartan (80 mg) produced a significant reduction of both diastolic and systolic blood pressure in patients with hypertension. Both nebivolol and valsartan contributed to this effect, partial additivity of 86.6% and 82.2% being observed for diastolic and systolic blood pressure, respectively. These values are very similar to the additivity ratios of other recently approved FDCs for hypertension. Use of the FDC nebivolol 5 mg/valsartan 80 mg formulation was associated with a low incidence of treatment-related adverse effects and of serious adverse effects. There was no evidence of adverse effects due to beta2-adrenoceptor blockade. The FDC (Byvalson) was approved and launched in 2016 in the U.S. for the treatment of hypertension. Copyright 2017 Clarivate Analytics.
-
Yin, Yong; Chen, Jinhu; Xing, Ligang; Dong, Xiaoling; Liu, Tonghai; Lu, Jie; Yu, Jinming
2011-01-13
This study aimed to compare fixed-field, intensity-modulated radiotherapy (f-IMRT) with intensity-modulated arc therapy (IMAT) treatment plans in dosimetry and practical application for cervical esophageal carcinoma. For ten cervical esophageal carcinoma cases, f-IMRT plan (seven fixed-fields) and two IMAT plans, namely RA (coplanar 360° arcs) and RAx (coplanar 360° arcs without sectors from 80° to 110°, and 250° to 280°), were generated. DVHs were adopted for the statistics of above parameters, as well as conformal index (CI), homogeneity index (HI), dose-volumetric parameters of normal tissues, total accelerator output MUs and total treatment time. There were differences between RAx and f-IMRT, as well as RA in PTV parameters such as HI, V(95%) and V(110%), but not in CI. RAx reduced lung V₅ from (50.9% ± 9.8% in f-IMRT and (51.4% ± 10.8% in RA to (49.3% ± 10.4% in RAx (p < 0.05). However, lung V₃₀, V₄₀, V₅₀ and MLD increased in RAx. There was no difference in the mean heart dose in three plans. Total MU was reduced from 1174.8 ± 144.6 in f-IMRT to 803.8 ± 122.2 in RA and 736.2 ± 186.9 in RAx (p < 0.05). Compared with f-IMRT, IMAT reduced low dose volumes of lung and total MU on the basis of meeting clinical requirements.
-
Nyazema, N Z; Rabvukwa, P; Gumbo, J; Ndudzo, P; Chitemerere, C
1999-06-01
To study and compare the bioavailability of rifampicin (RIF), in two locally manufactured formulations; an FDC and a separate formulation and an imported FDC formulation. Open within subjects, single blind cross over study. Each volunteer subject, acting as their own control, received the two fixed dose combinations and the separate formulation with the same amount of 450 mg RIF. Cmax (peak drug concentration achieved), Tmax (time at which peak drug concentration is achieved), T1/2el (biological half-life of elimination) and area under the curve (AUC) for zero to 10 hours and zero to infinity. These are obtained from plotting plasma concentration against time. There was a significant difference in the Cmax between free and RIF combined with INH (6.1 and 7.6 mg/l respectively) and no significant difference in the other parameters measured, of the local products. Comparison of the local products and imported product showed no significant difference in AUC but significant differences in T1/2el, C max and Tmax (p = 0.003, 0.041 and 0.025 respectively). The Zimbabwe manufactured and the German products had "demonstrable bioavailability" as defined by the International Union Against Tuberculosis and Lung Diseases (IUATLD). The local manufacturer appeared to have the technological capability to produce a registrable combined RIF/INH table to be used in the treatment of tuberculosis and to prevent the irrational use of RIF.
-
From prescriptions to drug use periods - things to notice.
Tanskanen, Antti; Taipale, Heidi; Koponen, Marjaana; Tolppanen, Anna-Maija; Hartikainen, Sirpa; Ahonen, Riitta; Tiihonen, Jari
2014-11-14
Electronic prescription registers provide a vast data source for pharmacoepidemiological research. Prescriptions as such are not suitable for all research purposes; e.g., studying concurrent use of different drugs or adverse drug events during current use. For those purposes, data on dispensed prescriptions needs to be transformed to periods of drug use. We used 3,828,292 dispensed prescriptions claimed between 1 January 2002 and 31 December 2009 for 28,093 persons with Alzheimer's disease. Examples of drug use histories are presented to discuss different aspects that should be noticed when using register-based data consisting of drug purchases. There is no simple method for correctly transforming dispensed prescriptions to periods of drug use that is usable for all drugs and drug users. Fixed assumptions of daily dose (in defined daily doses, tablets or other units) and fixed time windows should be used with caution and adjusted for different drug use patterns. We recommend that when transforming prescription drug purchases to drug use periods personal dose, purchasing pattern and other behavioral differences between patients should be taken into account.
-
Longo, Mariaconcetta; Marchioni, Chiara; Insero, Teresa; Donnarumma, Raffaella; D'Adamo, Alessandro; Lucatelli, Pierleone; Fanelli, Fabrizio; Salvatori, Filippo Maria; Cannavale, Alessandro; Di Castro, Elisabetta
2016-03-01
This study evaluates X-ray exposure in patient undergoing abdominal extra-vascular interventional procedures by means of Digital Imaging and COmmunications in Medicine (DICOM) image headers and Monte Carlo simulation. The main aim was to assess the effective and equivalent doses, under the hypothesis of their correlation with the dose area product (DAP) measured during each examination. This allows to collect dosimetric information about each patient and to evaluate associated risks without resorting to in vivo dosimetry. The dose calculation was performed in 79 procedures through the Monte Carlo simulator PCXMC (A PC-based Monte Carlo program for calculating patient doses in medical X-ray examinations), by using the real geometrical and dosimetric irradiation conditions, automatically extracted from DICOM headers. The DAP measurements were also validated by using thermoluminescent dosemeters on an anthropomorphic phantom. The expected linear correlation between effective doses and DAP was confirmed with an R(2) of 0.974. Moreover, in order to easily calculate patient doses, conversion coefficients that relate equivalent doses to measurable quantities, such as DAP, were obtained. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Comparative analysis of dosimetry parameters for nuclear medicine
DOE Office of Scientific and Technical Information (OSTI.GOV)
Toohey, R.E.; Stabin, M.G.
For years many have employed the concept of ``total-body dose`` or ``whole-body dose,`` i.e., the total energy deposited in the body divided by the mass of the body, when evaluating the risks of different nuclear medicine procedures. The effective dose equivalent (H{sub E}), first described in ICRP Publication 26, has been accepted by some as a better quantity to use in evaluating the total risk of a procedure, but its use has been criticized by others primarily because the tissue weighting factors were intended for use in the radiation worker, rather than the nuclear medicine patient population. Nevertheless, in ICRPmore » Publication 52, the ICRP has suggested that the H{sub E} may be used in nuclear medicine. The ICRP also has published a compendium of dose estimates, including H{sub E} values, for various nuclear medicine procedures at various ages in ICRP Publication 53. The effective dose (E) of ICRP Publication 60 is perhaps more suitable for use in nuclear medicine, with tissue weighting factors based on the entire population. Other comparisons of H{sub E} and E have been published. The authors have used the program MIRDOSE 3.1 to compute total-body dose, H{sub E}, and E for 62 radiopharmaceutical procedures, based on the best current biokinetic data available.« less
-
ERIC Educational Resources Information Center
Anderson, W. Steve
Faithfully following a fixed set of procedures has long been standard practice in writing resumes. This process produces a passable document with a minimum of effort expended. There are, however, advantages to be gained from taking a conceptual approach to resume preparation. First, it can help provide a framework for these procedures, giving the…
-
ATC simulation of helicopter IFR approaches into major terminal areas using RNAV, MLS, and CDTI
NASA Technical Reports Server (NTRS)
Tobias, L.; Lee, H. Q.; Peach, L. L.; Willett, F. M., Jr.; Obrien, P. J.
1981-01-01
The introduction of independent helicopter IFR routes at hub airports was investigated in a real time air traffic control system simulation involving a piloted helicopter simulator, computer generated air traffic, and air traffic controllers. The helicopter simulator was equipped to fly area navigation (RNAV) routes and microwave landing system approaches. Problems studied included: (1) pilot acceptance of the approach procedure and tracking accuracy; (2) ATC procedures for handling a mix of helicopter and fixed wing traffic; and (3) utility of the cockpit display of traffic information (CDTI) for the helicopter in the hub airport environment. Results indicate that the helicopter routes were acceptable to the subject pilots and were noninterfering with fixed wing traffic. Merging and spacing maneuvers using CDTI were successfully carried out by the pilots, but controllers had some reservations concerning the acceptability of the CDTI procedures.
-
Staff Radiation Doses in a Real-Time Display Inside the Angiography Room
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sanchez, Roberto, E-mail: rmsanchez.hcsc@salud.madrid.org; Vano, E.; Fernandez, J. M.
MethodsThe evaluation of a new occupational Dose Aware System (DAS) showing staff radiation doses in real time has been carried out in several angiography rooms in our hospital. The system uses electronic solid-state detectors with high-capacity memory storage. Every second, it archives the dose and dose rate measured and is wirelessly linked to a base-station screen mounted close to the diagnostic monitors. An easy transfer of the values to a data sheet permits further analysis of the scatter dose profile measured during the procedure, compares it with patient doses, and seeks to find the most effective actions to reduce operatormore » exposure to radiation.ResultsThe cumulative occupational doses measured per procedure (shoulder-over lead apron) ranged from 0.6 to 350 {mu}Sv when the ceiling-suspended screen was used, and DSA (Digital Subtraction Acquisition) runs were acquired while the personnel left the angiography room. When the suspended screen was not used and radiologists remained inside the angiography room during DSA acquisitions, the dose rates registered at the operator's position reached up to 1-5 mSv/h during fluoroscopy and 12-235 mSv/h during DSA acquisitions. In such case, the cumulative scatter dose could be more than 3 mSv per procedure.ConclusionReal-time display of doses to staff members warns interventionists whenever the scatter dose rates are too high or the radiation protection tools are not being properly used, providing an opportunity to improve personal protection accordingly.« less
-
John, William S; Nader, Michael A
2017-01-01
Concurrent alcohol use among cocaine abusers is common but the behavioral variables that promote co-abuse are not well understood. The present study examined the effects of intragastric (i.g.) ethanol (EtOH) administration in monkeys responding under a schedule of cocaine reinforcement in which extensive drug seeking was maintained by conditioned stimuli. Four adult male cynomolgus monkeys (Macaca fascicularis) were trained to respond under a second-order fixed-interval (FI) 600s (fixed-ratio (FR) 30:S) schedule of cocaine (0.003-0.56mg/kg/injection) presentation. Sessions ended after 5 injections or 90min had elapsed. Different EtOH doses (0.5-2.0g/kg, i.g.) were administered 30min before the session, typically on Tuesdays and Fridays. Blood ethanol concentrations (BECs) were also assessed. Pattern of FI responding was assessed by determining quarter-life (QL) values. Cocaine self-administration was characterized as an inverted U-shaped function of dose; QL values increased monotonically with dose. EtOH pretreatments dose-dependently decreased self-administration at several cocaine doses in 3 of 4 monkeys. In one animal, EtOH increased low-dose cocaine-maintained responding. For all monkeys, QL values were increased by EtOH when low- and high-cocaine doses were self-administered, suggesting additive effects of EtOH and cocaine. Furthermore, BECs were not altered following cocaine self-administration. The reductions in cocaine self-administration and the increases in QL values following EtOH, suggest that EtOH was enhancing cocaine-related conditioned reinforcement. A better understanding of the behavioral mechanisms that mediate the co-abuse of alcohol and cocaine will lead to improved treatments for both drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
-
Lee, E J; Lee, S K; Agid, R; Howard, P; Bae, J M; terBrugge, K
2009-10-01
The combined automatic tube current modulation (ATCM) technique adapts and modulates the x-ray tube current in the x-y-z axis according to the patient's individual anatomy. We compared image quality and radiation dose of the combined ATCM technique with those of a fixed tube current (FTC) technique in craniocervical CT angiography performed with a 64-section multidetector row CT (MDCT) system. A retrospective review of craniocervical CT angiograms (CTAs) by using combined ATCM (n = 25) and FTC techniques (n = 25) was performed. Other CTA parameters, such as kilovolt (peak), matrix size, FOV, section thickness, pitch, contrast agent, and contrast injection techniques, were held constant. We recorded objective image noise in the muscles at 2 anatomic levels: radiation exposure doses (CT dose index volume and dose-length product); and subjective image quality parameters, such as vascular delineation of various arterial vessels, visibility of small arterial detail, image artifacts, and certainty of diagnosis. The Mann-Whitney U test was used for statistical analysis. No significant difference was detected in subjective image quality parameters between the FTC and combined ATCM techniques. Most subjects in both study groups (49/50, 98%) had acceptable subjective artifacts. The objective image noise values at shoulder level did not show a significant difference, but the noise value at the upper neck was higher with the combined ATCM (P < .05) technique. Significant reduction in radiation dose (18% reduction) was noted with the combined ATCM technique (P < .05). The combined ATCM technique for craniocervical CTA performed at 64-section MDCT substantially reduced radiation exposure dose but maintained diagnostic image quality.
-
Zvada, Simbarashe P.; Denti, Paolo; Donald, Peter R.; Schaaf, H. Simon; Thee, Stephanie; Seddon, James A.; Seifart, Heiner I.; Smith, Peter J.; McIlleron, Helen M.; Simonsson, Ulrika S. H.
2014-01-01
Objectives To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. Patients and methods We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. Results The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators. Conclusions Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing. PMID:24486870
-
Delforge, Michel; Minuk, Leonard; Eisenmann, Jean-Claude; Arnulf, Bertrand; Canepa, Letizia; Fragasso, Alberto; Leyvraz, Serge; Langer, Christian; Ezaydi, Yousef; Vogl, Dan T.; Giraldo-Castellano, Pilar; Yoon, Sung-Soo; Zarnitsky, Charles; Escoffre-Barbe, Martine; Lemieux, Bernard; Song, Kevin; Bahlis, Nizar Jacques; Guo, Shien; Monzini, Mara Silva; Ervin-Haynes, Annette; Houck, Vanessa; Facon, Thierry
2015-01-01
We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients’ health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide. PMID:25769541
-
Delforge, Michel; Minuk, Leonard; Eisenmann, Jean-Claude; Arnulf, Bertrand; Canepa, Letizia; Fragasso, Alberto; Leyvraz, Serge; Langer, Christian; Ezaydi, Yousef; Vogl, Dan T; Giraldo-Castellano, Pilar; Yoon, Sung-Soo; Zarnitsky, Charles; Escoffre-Barbe, Martine; Lemieux, Bernard; Song, Kevin; Bahlis, Nizar Jacques; Guo, Shien; Monzini, Mara Silva; Ervin-Haynes, Annette; Houck, Vanessa; Facon, Thierry
2015-06-01
We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide. Copyright© Ferrata Storti Foundation.
-
Marinetto, Eugenio; Victores, Juan González; García-Sevilla, Mónica; Muñoz, Mercedes; Calvo, Felipe Ángel; Balaguer, Carlos; Desco, Manuel; Pascau, Javier
2017-10-01
Intraoperative electron radiation therapy (IOERT) involves the delivery of a high radiation dose during tumor resection in a shorter time than other radiation techniques, thus improving local control of tumors. However, a linear accelerator device is needed to produce the beam safely. Mobile linear accelerators have been designed as dedicated units that can be moved into the operating room and deliver radiation in situ. Correct and safe dose delivery is a key concern when using mobile accelerators. The applicator is commonly fixed to the patient's bed to ensure that the dose is delivered to the prescribed location, and the mobile accelerator is moved to dock the applicator to the radiation beam output (gantry). In a typical clinical set-up, this task is time-consuming because of safety requirements and the limited degree of freedom of the gantry. The objective of this study was to present a navigation solution based on optical tracking for guidance of docking to improve safety and reduce procedure time. We used an optical tracker attached to the mobile linear accelerator to track the prescribed localization of the radiation collimator inside the operating room. Using this information, the integrated navigation system developed computes the movements that the mobile linear accelerator needs to perform to align the applicator and the radiation gantry and warns the physician if docking is unrealizable according to the available degrees of freedom of the mobile linear accelerator. Furthermore, we coded a software application that connects all the necessary functioning elements and provides a user interface for the system calibration and the docking guidance. The system could safeguard against the spatial limitations of the operating room, calculate the optimal arrangement of the accelerator and reduce the docking time in computer simulations and experimental setups. The system could be used to guide docking with any commercial linear accelerator. We believe that the docking navigator we present is a major contribution to IOERT, where docking is critical when attempting to reduce surgical time, ensure patient safety and guarantee that the treatment administered follows the radiation oncologist's prescription. © 2017 American Association of Physicists in Medicine.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chitsazzadeh, S; Wells, D; Mestrovic, A
2016-06-15
Purpose: To develop a QA procedure for gated VMAT stereotactic ablative radiotherapy (SABR) treatments. Methods: An interface was constructed to attach the translational stage of a Quasar respiratory motion phantom to a pinpoint ion chamber insert and move the ion chamber inside an ArcCheck diode array. The Quasar phantom controller used a patient specific breathing pattern to translate the ion chamber in a superior-inferior direction inside the ArcCheck. An amplitude-based RPM tracking system was specified to turn the beam on during the exhale phase of the breathing pattern. SABR plans were developed using Eclipse for liver PTVs ranging in sizemore » from 3-12 cm in diameter using a 2-arc VMAT technique. Dose was measured in the middle of the penumbra region, where the high dose gradient allowed for sensitive detection of any inaccuracies in gated dose delivery. The overall fidelity of the dose distribution was confirmed using ArcCheck. The sensitivity of the gating QA procedure was investigated with respect to the following four parameters: PTV size, duration of exhale, baseline drift, and gating window size. Results: The difference between the measured dose to a point in the penumbra and the Eclipse calculated dose was under 2% for small residual motions. The QA procedure was independent of PTV size and duration of exhale. Baseline drift and gating window size, however, significantly affected the penumbral dose measurement, with differences of up to 30% compared to Eclipse. Conclusion: This study described a highly sensitive QA procedure for gated VMAT SABR treatments. The QA outcome was dependent on the gating window size and baseline drift. Analysis of additional patient breathing patterns will be required to determine a clinically relevant gating window size and an appropriate tolerance level for this procedure.« less
-
A two-phased fuzzy decision making procedure for IT supplier selection
NASA Astrophysics Data System (ADS)
Shohaimay, Fairuz; Ramli, Nazirah; Mohamed, Siti Rosiah; Mohd, Ainun Hafizah
2013-09-01
In many studies on fuzzy decision making, linguistic terms are usually represented by corresponding fixed triangular or trapezoidal fuzzy numbers. However, the fixed fuzzy numbers used in decision making process may not explain the actual respondents' opinions. Hence, a two-phased fuzzy decision making procedure is proposed. First, triangular fuzzy numbers were built based on respondents' opinions on the appropriate range (0-100) for each seven-scale linguistic terms. Then, the fuzzy numbers were integrated into fuzzy decision making model. The applicability of the proposed method is demonstrated in a case study of supplier selection in Information Technology (IT) department. The results produced via the developed fuzzy numbers were consistent with the results obtained using fixed fuzzy numbers. However, with different set of fuzzy numbers based on respondents, there is a difference in the ranking of suppliers based on criterion X1 (background of supplier). Hopefully the proposed model which incorporates fuzzy numbers based on respondents will provide a more significant meaning towards future decision making.
-
Naleid, Amy M; Grimm, Jeffrey W; Kessler, David A; Sipols, Alfred J; Aliakbari, Sepideh; Bennett, Jennifer L; Wells, Jason; Figlewicz, Dianne P
2008-01-01
Rats and humans avidly consume flavored foods that contain sucrose and fat, presumably due to their rewarding qualities. In this study, we hypothesized that the complex mixture of corn oil, sucrose, and flavor is more reinforcing than any of these components alone. We observed a concentration-dependent increase in reinforcers of sucrose solutions received (0%, 3%, 6.25%, and 12.5%) in both fixed ratio and progressive ratio procedures, but with equicaloric corn oil solutions (0%, 1.4%, 2.8%, and 5.6%) this finding was replicated only in the fixed ratio procedure. Likewise, addition of 1.4% oil to 3% or 12.5% sucrose increased fixed ratio, but not progressive ratio, reinforcers received relative to those of sucrose alone. Finally, addition of 3% vanilla flavoring did not change self-administration of 3% sucrose or 3% sucrose+1.4% oil solutions. These data suggest that, calorie-for-calorie, sucrose is the dominant reinforcing component of novel foods that contain a mixture of fat, sucrose, and flavor.
-
Tavares, J B; Sacadura-Leite, E; Matoso, T; Neto, L L; Biscoito, L; Campos, J; Sousa-Uva, A
2016-06-01
In interventional neuroradiology, few operators routinely use radiation protection glasses. Moreover, in most centers, radiation dose data only accounts for whole body dose without specific information on lens dose. In 2012, the International Commission on Radiological Protection advised that the threshold limit value for the lens should be 20 mSv/year instead of the previous 150 mSv/year limit. The purpose of this study was to compare the radiation dose in the operator's lens during real diagnostic and interventional neuroangiographies, either using or without lead protection glasses. Using the Educational Direct Dosimeter (EDD30 dosimeter), accumulated radiation dose in the lens was measured in 13 neuroangiographies: seven diagnostic and six interventional. Operators with and without radiation protection glasses were included and the sensor was placed near their left eye, closest to the radiation beam. Without glasses, the corrected mean dose of radiation in the lens was 8.02 µSv for diagnostic procedures and 168.57 µSv for interventional procedures. Using glasses, these values were reduced to 1.74 µSv and 33.24 µSv, respectively. Considering 20 mSv as the suggested annual limit of equivalent dose in the lens, neuroradiologists may perform up to 2,494 diagnostic procedures per year without protecting glasses, a number that increases to 11,494 when glasses are used consistently. Regarding intervention, a maximum of 119 procedures per year is advised if glasses are not used, whereas up to 602 procedures/year may be performed using this protection. Therefore, neuroradiologists should always wear radiation protection glasses. © The Author(s) 2016.
-
Journy, N; Sinno-Tellier, S; Maccia, C; Le Tertre, A; Pirard, P; Pagès, P; Eilstein, D; Donadieu, J; Bar, O
2012-01-01
Objective The study aimed to characterise the factors related to the X-ray dose delivered to the patient's skin during interventional cardiology procedures. Methods We studied 177 coronary angiographies (CAs) and/or percutaneous transluminal coronary angioplasties (PTCAs) carried out in a French clinic on the same radiography table. The clinical and therapeutic characteristics, and the technical parameters of the procedures, were collected. The dose area product (DAP) and the maximum skin dose (MSD) were measured by an ionisation chamber (Diamentor; Philips, Amsterdam, The Netherlands) and radiosensitive film (Gafchromic; International Specialty Products Advanced Materials Group, Wayne, NJ). Multivariate analyses were used to assess the effects of the factors of interest on dose. Results The mean MSD and DAP were respectively 389 mGy and 65 Gy cm−2 for CAs, and 916 mGy and 69 Gy cm−2 for PTCAs. For 8% of the procedures, the MSD exceeded 2 Gy. Although a linear relationship between the MSD and the DAP was observed for CAs (r=0.93), a simple extrapolation of such a model to PTCAs would lead to an inadequate assessment of the risk, especially for the highest dose values. For PTCAs, the body mass index, the therapeutic complexity, the fluoroscopy time and the number of cine frames were independent explanatory factors of the MSD, whoever the practitioner was. Moreover, the effect of technical factors such as collimation, cinematography settings and X-ray tube orientations on the DAP was shown. Conclusion Optimising the technical options for interventional procedures and training staff on radiation protection might notably reduce the dose and ultimately avoid patient skin lesions. PMID:22457404
-
Morán, V; Prieto, E; García-García, B; Barbés, B; Ribelles, M J; Richter, J Á; Martí-Climent, J M
2016-01-01
The aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. A prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). During the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59 mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22 μSv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.
-
Chaswal, Vibha; Weldon, Michael; Gupta, Nilendu; Chakravarti, Arnab
2014-01-01
We present commissioning and comprehensive evaluation for ArcCHECK as a QA equipment for volumetric‐modulated arc therapy (VMAT), using the 6 MV photon beam with and without the flattening filter, and the SNC patient software (version 6.2). In addition to commissioning involving absolute dose calibration, array calibration, and PMMA density verification, ArcCHECK was evaluated for its response dependency on linac dose rate, instantaneous dose rate, radiation field size, beam angle, and couch insertion. Scatter dose characterization, consistency and symmetry of response, and dosimetry accuracy evaluation for fixed aperture arcs and clinical VMAT patient plans were also investigated. All the evaluation tests were performed with the central plug inserted and the homogeneous PMMA density value. Results of gamma analysis demonstrated an overall agreement between ArcCHECK‐measured and TPS‐calculated reference doses. The diode based field size dependency was found to be within 0.5% of the reference. The dose rate‐based dependency was well within 1% of the TPS reference, and the angular dependency was found to be ± 3% of the reference, as tested for BEV angles, for both beams. Dosimetry of fixed arcs, using both narrow and wide field widths, resulted in clinically acceptable global gamma passing rates on the 3%/3 mm level and 10% threshold. Dosimetry of narrow arcs showed an improvement over published literature. The clinical VMAT cases demonstrated high level of dosimetry accuracy in gamma passing rates. PACS numbers: 87.56.Fc, 87.55.kh, 87.55.Qr PMID:25207411
-
Raskin, P; Lewin, A; Reinhardt, R; Lyness, W
2009-10-01
To assess the efficacy and safety of a new repaglinide/metformin fixed-dose combination (FDC) tablet administered either twice a day (BID) or three times a day (TID) for the management of type 2 diabetes. This was a 26-week, multicentre, open-label parallel trial in which subjects poorly controlled with mono- or dual-oral antidiabetic therapy were randomized 1 : 1 : 1 to instead receive repaglinide/metformin FDC either BID or TID or a rosiglitazone/metformin FDC BID. Two primary hypotheses were tested in a hierarchical manner: (i) treatment with the repaglinide/metformin FDC BID is non-inferior to that of the rosiglitazone/metformin FDC BID as measured by changes in haemoglobin A1c (HbA1c) (results presented in companion paper) and (ii) repaglinide/metformin BID is non-inferior to repaglinide/metformin TID (as measured by changes in HbA1c). Additional efficacy and safety end-points were also assessed. A total of 561 subjects were randomized; 383 completed the study. Repaglinide/metformin FDC BID was non-inferior to repaglinide/metformin FDC TID with respect to HbA1c. Additionally, changes in mean fasting plasma glucose values from baseline to end of study were not significantly different between the BID and the TID dose groups. There were no major hypoglycaemic episodes reported in either group during the trial, and overall adverse event profiles were similar. The efficacy of twice-daily dosing of a repaglinide/metformin FDC tablet was non-inferior to that of three-times-daily dosing.
-
NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors
Mansky, Patrick J.; Sannes, Timothy S.; Johnson, Laura Lee; Blackman, Marc R.; Grem, Jean L.; Swain, Sandra M.; Monahan, Brian P.
2013-01-01
Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone. PMID:24285980
-
Willegaignon, José; Braga, Luis F E F; Sapienza, Marcelo T; Coura-Filho, George B; Cardona, Marissa A R; Alves, Carlos E R; Gutterres, Ricardo F; Buchpiguel, Carlos A
2016-05-01
This study aimed to establish a concise method for determining a diagnostic reference level (DRL) for adult and pediatric nuclear medicine patients on the basis of diagnostic procedures and administered radioisotope as a means of controlling medical exposure. A screening was carried out in all Brazilian Nuclear Medicine Service (NMS) establishments to support this study by collecting the average activities administered during adult diagnostic procedures and the rules applied to adjust these according to the patient's age and body mass. Percentile 75 was used in all the activities administered as a means of establishing DRL for adult patients, with additional correction factors for pediatric patients. Radiation doses from nuclear medicine procedures on the basis of average administered activity were calculated for all diagnostic exams. A total of 107 NMSs in Brazil agreed to participate in the project. From the 64 nuclear medicine procedures studied, bone, kidney, and parathyroid scans were found to be used in more than 85% of all the NMSs analyzed. There was a large disparity among the activities administered, when applying the same procedures, this reaching, in some cases, more than 20 times between the lowest and the highest. Diagnostic exams based on Ga, Tl, and I radioisotopes proved to be the major exams administering radiation doses to patients. On introducing the DRL concept into clinical routine, the minimum reduction in radiation doses received by patients was about 15%, the maximum was 95%, and the average was 50% compared with the previously reported administered activities. Variability in the available diagnostic procedures as well as in the amount of activities administered within the same procedure was appreciable not only in Brazil, but worldwide. Global efforts are needed to establish a concise DRL that can be applied in adult and pediatric nuclear medicine procedures as the application of DRL in clinical routine has been proven to be an important tool for controlling and reducing radiation doses received by patients in medical exposure.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hsi, W; Jiang, G; Sheng, Y
Purpose: To study the correlations of the radiation biological equivalent doses (BED) along depth and lateral distance between LEM-1 and MKM approaches. Methods: In NIRS-MKM (Microdosimetric Kinetic Model) approach, the prescribed BED, referred as C-Eq, doses aims to present the relative biological effectiveness (RBE) for different energies of carbon-ions on a fixed 10% survival value of HCG cell with respect to convention X-ray. Instead of a fixed 10% survival, the BED doses of LEM-1 (Local Effect Model) approach, referred as X-Eq, aims to present the RBE over the whole survival curve of chordoma-like cell with alpha/beta ratio of 2.0. Themore » relationship of physical doses as a function of C-Eq and X-Eq doses were investigated along depth and lateral distance for various sizes of cubic targets in water irradiated by carbon-ions. Results: At the center of each cubic target, the trends between physical and C-Eq or X-Eq doses can be described by a linear and 2nd order polynomial functions, respectively. Using fit functions can then calculate a scaling factor between C-Eq and X-Eq doses to have similar physical doses. With equalized C-Eq and X-Eq doses at the depth of target center, over- and under-estimated X-Eq to C-Eq are seen for depths before and after the target center, respectively. Near the distal edge along depth, sharp rising of RBE value is observed for X-Eq, but sharp dropping of RBE value is observed for C-Eq. For lateral locations near and just outside 50% dose level, sharp raising of RBE value is also seen for X-Eq, while only minor increasing with fast dropping for C-Eq. Conclusion: An analytical function to model the differences between the CEq and X-Eq doses along depth and lateral distance need to further investigated to explain varied clinic outcome of specific cancers using two different approaches to calculated BED doses.« less
-
Meinzer, Caitlyn; Martin, Renee; Suarez, Jose I
2017-09-08
In phase II trials, the most efficacious dose is usually not known. Moreover, given limited resources, it is difficult to robustly identify a dose while also testing for a signal of efficacy that would support a phase III trial. Recent designs have sought to be more efficient by exploring multiple doses through the use of adaptive strategies. However, the added flexibility may potentially increase the risk of making incorrect assumptions and reduce the total amount of information available across the dose range as a function of imbalanced sample size. To balance these challenges, a novel placebo-controlled design is presented in which a restricted Bayesian response adaptive randomization (RAR) is used to allocate a majority of subjects to the optimal dose of active drug, defined as the dose with the lowest probability of poor outcome. However, the allocation between subjects who receive active drug or placebo is held constant to retain the maximum possible power for a hypothesis test of overall efficacy comparing the optimal dose to placebo. The design properties and optimization of the design are presented in the context of a phase II trial for subarachnoid hemorrhage. For a fixed total sample size, a trade-off exists between the ability to select the optimal dose and the probability of rejecting the null hypothesis. This relationship is modified by the allocation ratio between active and control subjects, the choice of RAR algorithm, and the number of subjects allocated to an initial fixed allocation period. While a responsive RAR algorithm improves the ability to select the correct dose, there is an increased risk of assigning more subjects to a worse arm as a function of ephemeral trends in the data. A subarachnoid treatment trial is used to illustrate how this design can be customized for specific objectives and available data. Bayesian adaptive designs are a flexible approach to addressing multiple questions surrounding the optimal dose for treatment efficacy within the context of limited resources. While the design is general enough to apply to many situations, future work is needed to address interim analyses and the incorporation of models for dose response.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ierardi, Anna Maria; Duka, Ejona; Radaelli, Alessandro
AimTo evaluate the feasibility of image fusion (IF) of pre-procedural arterial-phase CT angiography or MR angiography with intra-procedural fluoroscopy for road-mapping in endovascular treatment of aorto-iliac steno-occlusive disease.Materials and MethodsBetween September and November, 2014, we prospectively evaluated 5 patients with chronic aorto-iliac steno-occlusive disease, who underwent endovascular treatment in the angiography suite. Fusion image road-mapping was performed using angiographic phase CT images or MR images acquired before and intra-procedural unenhanced cone-beam CT. Radiation dose of the procedure, volume of intra-procedural iodinated contrast medium, fluoroscopy time, and overall procedural time were recorded. Reasons for potential fusion imaging inaccuracies were also evaluated.ResultsImagemore » co-registration and fusion guidance were feasible in all procedures. Mean radiation dose of the procedure was 60.21 Gycm2 (range 55.02–63.75 Gycm2). The mean total procedure time was 32.2 min (range 27–38 min). The mean fluoroscopy time was 12 min and 3 s. The mean procedural iodinated contrast material dose was 24 mL (range 20–40 mL).ConclusionsIF gives Interventional Radiologists the opportunity to use new technologies in order to improve outcomes with a significant reduction of contrast media administration.« less
-
Gianoncelli, A; Vaccari, L; Kourousias, G; Cassese, D; Bedolla, D E; Kenig, S; Storici, P; Lazzarino, M; Kiskinova, M
2015-05-14
Radiation damage of biological samples remains a limiting factor in high resolution X-ray microscopy (XRM). Several studies have attempted to evaluate the extent and the effects of radiation damage, proposing strategies to minimise or prevent it. The present work aims to assess the impact of soft X-rays on formalin fixed cells on a systematic manner. The novelty of this approach resides on investigating the radiation damage not only with XRM, as often reported in relevant literature on the topic, but by coupling it with two additional independent non-destructive microscopy methods: Atomic Force Microscopy (AFM) and FTIR Microscopy (FTIRM). Human Embryonic Kidney 293 cells were exposed to different radiation doses at 1 keV. In order to reveal possible morphological and biochemical changes, the irradiated cells were systematically analysed with AFM and FTIRM before and after. Results reveal that while cell morphology is not substantially affected, cellular biochemical profile changes significantly and progressively when increasing dose, resulting in a severe breakdown of the covalent bonding network. This information impacts most soft XRM studies on fixed cells and adds an in-depth understanding of the radiation damage for developing better prevention strategies.
-
Gianoncelli, A.; Vaccari, L.; Kourousias, G.; Cassese, D.; Bedolla, D. E.; Kenig, S.; Storici, P.; Lazzarino, M.; Kiskinova, M.
2015-01-01
Radiation damage of biological samples remains a limiting factor in high resolution X-ray microscopy (XRM). Several studies have attempted to evaluate the extent and the effects of radiation damage, proposing strategies to minimise or prevent it. The present work aims to assess the impact of soft X-rays on formalin fixed cells on a systematic manner. The novelty of this approach resides on investigating the radiation damage not only with XRM, as often reported in relevant literature on the topic, but by coupling it with two additional independent non-destructive microscopy methods: Atomic Force Microscopy (AFM) and FTIR Microscopy (FTIRM). Human Embryonic Kidney 293 cells were exposed to different radiation doses at 1 keV. In order to reveal possible morphological and biochemical changes, the irradiated cells were systematically analysed with AFM and FTIRM before and after. Results reveal that while cell morphology is not substantially affected, cellular biochemical profile changes significantly and progressively when increasing dose, resulting in a severe breakdown of the covalent bonding network. This information impacts most soft XRM studies on fixed cells and adds an in-depth understanding of the radiation damage for developing better prevention strategies. PMID:25974639
-
Lee, Sue J; Ter Kuile, Feiko O; Price, Ric N; Luxemburger, Christine; Nosten, François
2017-01-01
Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24-25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4-285) vs. 7.8 (3-15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days.
-
Arsanious, David; Gage, Emmanuel; Koning, Jonathon; Sarhan, Mazin; Chaiban, Gassan; Almualim, Mohammed; Atallah, Joseph
2016-01-01
One of the potential side effects with radiofrequency ablation (RFA) includes painful cutaneous dysesthesias and increased pain due to neuritis or neurogenic inflammation. This pain may require the prescription of opioids or non-opioid analgesics to control post-procedural pain and discomfort. The goal of this study is to compare post-procedural pain scores and post-procedural oral analgesic use in patients receiving continuous thermal radiofrequency ablation versus patients receiving pulsed dose radiofrequency immediately followed by continuous thermal radiofrequency ablation for zygopophaseal joint disease. This is a prospective, double-blinded, randomized, controlled trial. Patients who met all the inclusion criteria and were not subject to any of the exclusion criteria were required to have two positive diagnostic medial branch blocks prior to undergoing randomization, intervention, and analysis. University hospital. Eligible patients were randomized in a 1:1 ratio to either receive thermal radiofrequency ablation alone (standard group) or pulsed dose radiofrequency (PDRF) immediately followed by thermal radiofrequency ablation (investigational group), all of which were performed by a single Board Certified Pain Medicine physician. Post-procedural pain levels between the two groups were assessed using the numerical pain Scale (NPS), and patients were contacted by phone on post-procedural days 1 and 2 in the morning and afternoon regarding the amount of oral analgesic medications used in the first 48 hours following the procedure. Patients who received pulsed dose radiofrequency followed by continuous radiofrequency neurotomy reported statistically significantly lower post-procedural pain scores in the first 24 hours compared to patients who received thermal radiofrequency neurotomy alone. These patients also used less oral analgesic medication in the post-procedural period. These interventions were carried out by one board accredited pain physician at one center. The procedures were exclusively performed using one model of radiofrequency generator, at one setting for the PDRF and RFA. The difference in the number of levels of ablation was not considered in the analysis of the results. Treating patients with pulsed dose radiofrequency prior to continuous thermal radiofrequency ablation can provide patients with less post-procedural pain during the first 24 hours and also reduce analgesic requirements. Furthermore, the addition of PDRF to standard thermal RFA did not prolong the time of standard thermal radiofrequency ablation procedures, as it was performed during the typically allotted time for local anesthetic action. Low back pain, facet joint disease, medial branch block, Radiofrequency ablation, thermal radiofrequency, pulsed dose radiofrequency, PDRF, zygapophyseal joint.
-
van Rooij, Kim; de Leede, Leo; Frijlink, Henderik W.; Koppeschaar, Hans P. F.; Olivier, Berend; Tuiten, Adriaan
2016-01-01
Aim The aim was to compare the pharmacokinetic profiles of two formulations of a combination drug product containing 0.5 mg testosterone and 50 mg sildenafil for female sexual interest/arousal disorder. The prototype (formulation 1) consists of a testosterone solution for sublingual administration and a sildenafil tablet that is administered 2.5 h later. The dual route/dual release fixed dose combination tablet (formulation 2) employs a sublingual and an oral route for systemic uptake. This tablet has an inner core of sildenafil with a polymeric time delay coating and an outer polymeric coating containing testosterone. It was designed to increase dosing practicality and decrease potential temporal non‐adherence through circumventing the relatively complex temporal dosing scheme. Methods Twelve healthy premenopausal subjects received both formulations randomly on separate days. Blood was sampled frequently to determine the pharmacokinetics of free testosterone, total testosterone, dihydrotestosterone, sildenafil and N‐desmethyl‐sildenafil. Results Formulation 2 had a higher maximum concentration (C max) for testosterone, 8.06 ng ml–1 (95% confidence interval [CI] 6.84, 9.28) and higher area under the plasma concentration–time curve (AUC), 7.69 ng ml–1 h (95% CI 6.22, 9.16) than formulation 1, 5.66 ng ml–1 (95% CI 4.63, 6.69) and 5.12 ng ml–1 h (95% CI 4.51, 5.73), respectively. Formulation 2 had a lower C max for sildenafil, 173 ng ml–1 (95% CI 126, 220) and a lower AUC, 476 ng ml–1 h (95% CI 401, 551) than formulation 1, 268 ng ml–1 (95% CI 188, 348) and 577 ng ml–1 h (95% CI 462, 692), respectively. Formulation 2 released sildenafil after 2.75 h (95% CI 2.40, 3.10). Conclusions The dual route/dual release fixed dose combination tablet fulfilled its design criteria and is considered suitable for further clinical testing. What is Already Known about this Subject Female sexual interest/arousal disorder (FSIAD) is a significant problem impacting psychological well‐being, but the pharmacotherapeutic options for this problem are lacking.The combined, on‐demand, sublingual administration of low dose sublingual testosterone and oral administration of sildenafil is a novel pharmacotherapeutic option under development for FSIAD.In proof‐of‐concept trials, these compounds were successfully administered via different dosage forms (sublingual and oral) at different time points (separated by 2.5 h) because of their markedly different pharmacokinetic–pharmacodynamic profiles. For future larger scale studies and the clinical practice, this raises obvious adherence issues. What this Study Adds A newly developed dual route/dual release fixed dose combination tablet containing testosterone and sildenafil mimics the pharmacokinetic profile of these components when they are administered as different dosage forms, 2.5 h apart.This combination tablet is a suitable final pharmaceutical drug product that will be used in future studies. PMID:26804967
-
A virtual photon energy fluence model for Monte Carlo dose calculation.
Fippel, Matthias; Haryanto, Freddy; Dohm, Oliver; Nüsslin, Fridtjof; Kriesen, Stephan
2003-03-01
The presented virtual energy fluence (VEF) model of the patient-independent part of the medical linear accelerator heads, consists of two Gaussian-shaped photon sources and one uniform electron source. The planar photon sources are located close to the bremsstrahlung target (primary source) and to the flattening filter (secondary source), respectively. The electron contamination source is located in the plane defining the lower end of the filter. The standard deviations or widths and the relative weights of each source are free parameters. Five other parameters correct for fluence variations, i.e., the horn or central depression effect. If these parameters and the field widths in the X and Y directions are given, the corresponding energy fluence distribution can be calculated analytically and compared to measured dose distributions in air. This provides a method of fitting the free parameters using the measurements for various square and rectangular fields and a fixed number of monitor units. The next step in generating the whole set of base data is to calculate monoenergetic central axis depth dose distributions in water which are used to derive the energy spectrum by deconvolving the measured depth dose curves. This spectrum is also corrected to take the off-axis softening into account. The VEF model is implemented together with geometry modules for the patient specific part of the treatment head (jaws, multileaf collimator) into the XVMC dose calculation engine. The implementation into other Monte Carlo codes is possible based on the information in this paper. Experiments are performed to verify the model by comparing measured and calculated dose distributions and output factors in water. It is demonstrated that open photon beams of linear accelerators from two different vendors are accurately simulated using the VEF model. The commissioning procedure of the VEF model is clinically feasible because it is based on standard measurements in air and water. It is also useful for IMRT applications because a full Monte Carlo simulation of the treatment head would be too time-consuming for many small fields.
-
Medial Patellofemoral Ligament Reconstruction Procedure Using a Suspensory Femoral Fixation System
Nakagawa, Shuji; Arai, Yuji; Kan, Hiroyuki; Ueshima, Keiichiro; Ikoma, Kazuya; Terauchi, Ryu; Kubo, Toshikazu
2013-01-01
Recurrent patellar dislocation has recently been treated with anatomic medial patellofemoral ligament (MPFL) reconstruction using a semitendinosus muscle tendon. Although it is necessary to add tension to fix the tendon graft without loading excess stress on the patellofemoral joint, adjustment of the tension can be difficult. To resolve this problem, we developed an MPFL reconstruction procedure using the ToggleLoc Fixation Device (Biomet, Warsaw, IN), in which the semitendinosus muscle tendon is folded and used as a double-bundle tendon graft and 2 bone tunnels and 1 bone tunnel are made on the patellar and femoral sides, respectively. The patellar side of the tendon graft is fixed with an EndoButton (Smith & Nephew, London, England), and the femoral side is fixed with the ToggleLoc. Stepless adjustment of tension of the tendon graft is possible by reducing the size of the loop of the ToggleLoc hung onto the tendon graft. It may be useful to position the patella in the center of the femoral sulcus by confirming the patellofemoral joint fitting. Stability can be confirmed by loading lateral stress on the patella in the extended knee joint. This procedure is less invasive because opening of the lateral side of the femur is not necessary, and it may be useful for MPFL reconstruction. PMID:24892014
-
Estimation of radiation cancer risk in CT-KUB
NASA Astrophysics Data System (ADS)
Karim, M. K. A.; Hashim, S.; Bakar, K. A.; Bradley, D. A.; Ang, W. C.; Bahrudin, N. A.; Mhareb, M. H. A.
2017-08-01
The increased demand for computed tomography (CT) in radiological scanning examinations raises the question of a potential health impact from the associated radiation exposures. Focusing on CT kidney-ureter-bladder (CT-KUB) procedures, this work was aimed at determining organ equivalent dose using a commercial CT dose calculator and providing an estimate of cancer risks. The study, which included 64 patients (32 males and 32 females, mean age 55.5 years and age range 30-80 years), involved use of a calibrated CT scanner (Siemens-Somatom Emotion 16-slice). The CT exposures parameter including tube potential, pitch factor, tube current, volume CT dose index (CTDIvol) and dose-length product (DLP) were recorded and analyzed using CT-EXPO (Version 2.3.1, Germany). Patient organ doses, including for stomach, liver, colon, bladder, red bone marrow, prostate and ovaries were calculated and converted into cancer risks using age- and sex-specific data published in the Biological Effects of Ionizing Radiation (BEIR) VII report. With a median value scan range of 36.1 cm, the CTDIvol, DLP, and effective dose were found to be 10.7 mGy, 390.3 mGy cm and 6.2 mSv, respectively. The mean cancer risks for males and females were estimated to be respectively 25 and 46 out of 100,000 procedures with effective doses between 4.2 mSv and 10.1 mSv. Given the increased cancer risks from current CT-KUB procedures compared to conventional examinations, we propose that the low dose protocols for unenhanced CT procedures be taken into consideration before establishing imaging protocols for CT-KUB.
-
Prospective Measurement of Patient Exposure to Radiation During Pediatric Ureteroscopy
Kokorowski, Paul J.; Chow, Jeanne S.; Strauss, Keith; Pennison, Melanie; Routh, Jonathan C.; Nelson, Caleb P.
2013-01-01
Objective Little data have been reported regarding radiation exposure during pediatric endourologic procedures, including ureteroscopy (URS). We sought to measure radiation exposure during pediatric URS and identify opportunities for exposure reduction. Methods We prospectively observed URS procedures as part of a quality improvement initiative. Pre-operative patient characteristics, operative factors, fluoroscopy settings and radiation exposure were recorded. Our outcomes were entrance skin dose (ESD, in mGy) and midline dose (MLD, in mGy). Specific modifiable factors were identified as targets for potential quality improvement. Results Direct observation was performed on 56 consecutive URS procedures. Mean patient age was 14.8 ± 3.8 years (range 7.4 to 19.2); 9 children were under age 12 years. Mean ESD was 46.4 ± 48 mGy. Mean MLD was 6.2 ± 5.0 mGy. The most important major determinant of radiation dose was total fluoroscopy time (mean 2.68 ± 1.8 min) followed by dose rate setting, child anterior-posterior (AP) diameter, and source to skin distance (all p<0.01). The analysis of factors affecting exposure levels found that the use of ureteral access sheaths (p=0.01) and retrograde pyelography (p=0.04) were significantly associated with fluoroscopy time. We also found that dose rate settings were higher than recommended in up to 43% of cases and ideal C-arm positioning could have reduced exposure 14% (up to 49% in some cases). Conclusions Children receive biologically significant radiation doses during URS procedures. Several modifiable factors contribute to dose and could be targeted in efforts to implement dose reduction strategies. PMID:22341275
-
Patient doses from fluoroscopically guided cardiac procedures in pediatrics
NASA Astrophysics Data System (ADS)
Martinez, L. C.; Vano, E.; Gutierrez, F.; Rodriguez, C.; Gilarranz, R.; Manzanas, M. J.
2007-08-01
Infants and children are a higher risk population for radiation cancer induction compared to adults. Although some values on pediatric patient doses for cardiac procedures have been reported, data to determine reference levels are scarce, especially when compared to those available for adults in diagnostic and therapeutic procedures. The aim of this study is to make a new contribution to the scarce published data in pediatric cardiac procedures and help in the determination of future dose reference levels. This paper presents a set of patient dose values, in terms of air kerma area product (KAP) and entrance surface air kerma (ESAK), measured in a pediatric cardiac catheterization laboratory equipped with a biplane x-ray system with dynamic flat panel detectors. Cardiologists were properly trained in radiation protection. The study includes 137 patients aged between 10 days and 16 years who underwent diagnostic catheterizations or therapeutic procedures. Demographic data and technical details of the procedures were also gathered. The x-ray system was submitted to a quality control programme, including the calibration of the transmission ionization chamber. The age distribution of the patients was 47 for <1 year; 52 for 1-<5 years; 25 for 5-<10 years and 13 for 10-<16 years. Median values of KAP were 1.9, 2.9, 4.5 and 15.4 Gy cm2 respectively for the four age bands. These KAP values increase by a factor of 8 when moving through the four age bands. The probability of a fatal cancer per fluoroscopically guided cardiac procedure is about 0.07%. Median values of ESAK for the four age bands were 46, 50, 56 and 163 mGy, which lie far below the threshold for deterministic effects on the skin. These dose values are lower than those published in previous papers.
-
MO-G-18A-01: Radiation Dose Reducing Strategies in CT, Fluoroscopy and Radiography
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mahesh, M; Gingold, E; Jones, A
2014-06-15
Advances in medical x-ray imaging have provided significant benefits to patient care. According to NCRP 160, there are more than 400 million x-ray procedures performed annually in the United States alone that contributes to nearly half of all the radiation exposure to the US population. Similar growth trends in medical x-ray imaging are observed worldwide. Apparent increase in number of medical x-ray imaging procedures, new protocols and the associated radiation dose and risk has drawn considerable attention. This has led to a number of technological innovations such as tube current modulation, iterative reconstruction algorithms, dose alerts, dose displays, flat panelmore » digital detectors, high efficient digital detectors, storage phosphor radiography, variable filters, etc. that are enabling users to acquire medical x-ray images at a much lower radiation dose. Along with these, there are number of radiation dose optimization strategies that users can adapt to effectively lower radiation dose in medical x-ray procedures. The main objectives of this SAM course are to provide information and how to implement the various radiation dose optimization strategies in CT, Fluoroscopy and Radiography. Learning Objectives: To update impact of technological advances on dose optimization in medical imaging. To identify radiation optimization strategies in computed tomography. To describe strategies for configuring fluoroscopic equipment that yields optimal images at reasonable radiation dose. To assess ways to configure digital radiography systems and recommend ways to improve image quality at optimal dose.« less
-
Shellikeri, Sphoorti; Setser, Randolph M; Hwang, Tiffany J; Srinivasan, Abhay; Krishnamurthy, Ganesh; Vatsky, Seth; Girard, Erin; Zhu, Xiaowei; Keller, Marc S; Cahill, Anne Marie
2017-07-01
Navigational software provides real-time fluoroscopic needle guidance for percutaneous procedures in the Interventional Radiology (IR) suite. We describe our experience with navigational software for pediatric percutaneous bone biopsies in the IR suite and compare technical success, diagnostic accuracy, radiation dose and procedure time with that of CT-guided biopsies. Pediatric bone biopsies performed using navigational software (Syngo iGuide, Siemens Healthcare) from 2011 to 2016 were prospectively included and anatomically matched CT-guided bone biopsies from 2008 to 2016 were retrospectively reviewed with institutional review board approval. C-arm CT protocols used for navigational software-assisted cases included institution-developed low-dose (0.1/0.17 μGy/projection), regular-dose (0.36 μGy/projection), or a combination of low-dose/regular-dose protocols. Estimated effective radiation dose and procedure times were compared between software-assisted and CT-guided biopsies. Twenty-six patients (15 male; mean age: 10 years) underwent software-assisted biopsies (15 pelvic, 7 lumbar and 4 lower extremity) and 33 patients (13 male; mean age: 9 years) underwent CT-guided biopsies (22 pelvic, 7 lumbar and 4 lower extremity). Both modality biopsies resulted in a 100% technical success rate. Twenty-five of 26 (96%) software-assisted and 29/33 (88%) CT-guided biopsies were diagnostic. Overall, the effective radiation dose was significantly lower in software-assisted than CT-guided cases (3.0±3.4 vs. 6.6±7.7 mSv, P=0.02). The effective dose difference was most dramatic in software-assisted cases using low-dose C-arm CT (1.2±1.8 vs. 6.6±7.7 mSv, P=0.001) or combined low-dose/regular-dose C-arm CT (1.9±2.4 vs. 6.6±7.7 mSv, P=0.04), whereas effective dose was comparable in software-assisted cases using regular-dose C-arm CT (6.0±3.5 vs. 6.6±7.7 mSv, P=0.7). Mean procedure time was significantly lower for software-assisted cases (91±54 vs. 141±68 min, P=0.005). In our experience, navigational software technology in the IR suite is a promising alternative to CT guidance for pediatric bone biopsies providing comparable technical success and diagnostic accuracy with lower radiation dose and procedure time, in addition to providing real-time fluoroscopic needle guidance.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Safari, M. J.; Wong, J. H. D.; Ng, K. H., E-mail: ngkh@um.edu.my
2015-05-15
Purpose: The MOSkin is a MOSFET detector designed especially for skin dose measurements. This detector has been characterized for various factors affecting its response for megavoltage photon beams and has been used for patient dose measurements during radiotherapy procedures. However, the characteristics of this detector in kilovoltage photon beams and low dose ranges have not been studied. The purpose of this study was to characterize the MOSkin detector to determine its suitability for in vivo entrance skin dose measurements during interventional radiology procedures. Methods: The calibration and reproducibility of the MOSkin detector and its dependency on different radiation beam qualitiesmore » were carried out using RQR standard radiation qualities in free-in-air geometry. Studies of the other characterization parameters, such as the dose linearity and dependency on exposure angle, field size, frame rate, depth-dose, and source-to-surface distance (SSD), were carried out using a solid water phantom under a clinical x-ray unit. Results: The MOSkin detector showed good reproducibility (94%) and dose linearity (99%) for the dose range of 2 to 213 cGy. The sensitivity did not significantly change with the variation of SSD (±1%), field size (±1%), frame rate (±3%), or beam energy (±5%). The detector angular dependence was within ±5% over 360° and the dose recorded by the MOSkin detector in different depths of a solid water phantom was in good agreement with the Markus parallel plate ionization chamber to within ±3%. Conclusions: The MOSkin detector proved to be reliable when exposed to different field sizes, SSDs, depths in solid water, dose rates, frame rates, and radiation incident angles within a clinical x-ray beam. The MOSkin detector with water equivalent depth equal to 0.07 mm is a suitable detector for in vivo skin dosimetry during interventional radiology procedures.« less
-
Safari, M J; Wong, J H D; Ng, K H; Jong, W L; Cutajar, D L; Rosenfeld, A B
2015-05-01
The MOSkin is a MOSFET detector designed especially for skin dose measurements. This detector has been characterized for various factors affecting its response for megavoltage photon beams and has been used for patient dose measurements during radiotherapy procedures. However, the characteristics of this detector in kilovoltage photon beams and low dose ranges have not been studied. The purpose of this study was to characterize the MOSkin detector to determine its suitability for in vivo entrance skin dose measurements during interventional radiology procedures. The calibration and reproducibility of the MOSkin detector and its dependency on different radiation beam qualities were carried out using RQR standard radiation qualities in free-in-air geometry. Studies of the other characterization parameters, such as the dose linearity and dependency on exposure angle, field size, frame rate, depth-dose, and source-to-surface distance (SSD), were carried out using a solid water phantom under a clinical x-ray unit. The MOSkin detector showed good reproducibility (94%) and dose linearity (99%) for the dose range of 2 to 213 cGy. The sensitivity did not significantly change with the variation of SSD (± 1%), field size (± 1%), frame rate (± 3%), or beam energy (± 5%). The detector angular dependence was within ± 5% over 360° and the dose recorded by the MOSkin detector in different depths of a solid water phantom was in good agreement with the Markus parallel plate ionization chamber to within ± 3%. The MOSkin detector proved to be reliable when exposed to different field sizes, SSDs, depths in solid water, dose rates, frame rates, and radiation incident angles within a clinical x-ray beam. The MOSkin detector with water equivalent depth equal to 0.07 mm is a suitable detector for in vivo skin dosimetry during interventional radiology procedures.
-
Image discrimination models predict detection in fixed but not random noise
NASA Technical Reports Server (NTRS)
Ahumada, A. J. Jr; Beard, B. L.; Watson, A. B. (Principal Investigator)
1997-01-01
By means of a two-interval forced-choice procedure, contrast detection thresholds for an aircraft positioned on a simulated airport runway scene were measured with fixed and random white-noise masks. The term fixed noise refers to a constant, or unchanging, noise pattern for each stimulus presentation. The random noise was either the same or different in the two intervals. Contrary to simple image discrimination model predictions, the same random noise condition produced greater masking than the fixed noise. This suggests that observers seem unable to hold a new noisy image for comparison. Also, performance appeared limited by internal process variability rather than by external noise variability, since similar masking was obtained for both random noise types.
-
Immune tolerance: critical issues of factor dose, purity and treatment complications.
DiMichele, D M
2006-12-01
The current practice of immune tolerance induction (ITI) therapy has been largely influenced by the results of small institutional studies and three large registries. However, many questions remain. Successful outcome predictors for ITI in haemophilia A have been suggested by the analyses of two of these registries. Among these predictors, factor VIII (FVIII) dose/dosing regimen remains a controversial outcome parameter, demonstrating a strong direct relationship to ITI success in the international registry and a weaker inverse relationship in the North American registry. There is an international multicentre prospective randomized trial underway to further study the role of FVIII dose in successful ITI induction in a good risk haemophilia A inhibitor patient cohort. FVIII purity also remains an unproved ITI outcome predictor. Institutional experience with von-Willebrand-factor-containing products has suggested its therapeutic advantage in both inhibitor development and eradication. The International ITI Study, although not designed to answer this particular question, may be able to determine an impact on outcome depending on the final distribution of investigator choice of product among the study subjects. Much less is known about the influence of factor IX (FIX) dose and purity on ITI success in haemophilia B. Importantly, nephrotic syndrome has been a major determinant of ITI failure in FIX inhibitor patients, particularly those with the allergic phenotype. Unfortunately, large prospective randomized trials in this group will not be feasible. Rather, we will have to rely on prospectively collected registry data to build our knowledge base of inhibitors and ITI in haemophilia B.
-
Is patient size important in dose determination and optimization in cardiology?
NASA Astrophysics Data System (ADS)
Reay, J.; Chapple, C. L.; Kotre, C. J.
2003-12-01
Patient dose determination and optimization have become more topical in recent years with the implementation of the Medical Exposures Directive into national legislation, the Ionising Radiation (Medical Exposure) Regulations. This legislation incorporates a requirement for new equipment to provide a means of displaying a measure of patient exposure and introduces the concept of diagnostic reference levels. It is normally assumed that patient dose is governed largely by patient size; however, in cardiology, where procedures are often very complex, the significance of patient size is less well understood. This study considers over 9000 cardiology procedures, undertaken throughout the north of England, and investigates the relationship between patient size and dose. It uses simple linear regression to calculate both correlation coefficients and significance levels for data sorted by both room and individual clinician for the four most common examinations, left ventrical and/or coronary angiography, single vessel stent insertion and single vessel angioplasty. This paper concludes that the correlation between patient size and dose is weak for the procedures considered. It also illustrates the use of an existing method for removing the effect of patient size from dose survey data. This allows typical doses and, therefore, reference levels to be defined for the purposes of dose optimization.
-
Matsui, Yusuke; Hiraki, Takao; Gobara, Hideo; Iguchi, Toshihiro; Fujiwara, Hiroyasu; Kawabata, Takahiro; Yamauchi, Takatsugu; Yamaguchi, Takuya; Kanazawa, Susumu
2016-06-01
Computed tomography (CT) fluoroscopy-guided renal cryoablation and lung radiofrequency ablation (RFA) have received increasing attention as promising cancer therapies. Although radiation exposure of interventional radiologists during these procedures is an important concern, data on operator exposure are lacking. Radiation dose to interventional radiologists during CT fluoroscopy-guided renal cryoablation (n = 20) and lung RFA (n = 20) was measured prospectively in a clinical setting. Effective dose to the operator was calculated from the 1-cm dose equivalent measured on the neck outside the lead apron, and on the left chest inside the lead apron, using electronic dosimeters. Equivalent dose to the operator's finger skin was measured using thermoluminescent dosimeter rings. The mean (median) effective dose to the operator per procedure was 6.05 (4.52) μSv during renal cryoablation and 0.74 (0.55) μSv during lung RFA. The mean (median) equivalent dose to the operator's finger skin per procedure was 2.1 (2.1) mSv during renal cryoablation, and 0.3 (0.3) mSv during lung RFA. Radiation dose to interventional radiologists during renal cryoablation and lung RFA were at an acceptable level, and in line with recommended dose limits for occupational radiation exposure.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Matsui, Yusuke, E-mail: wckyh140@yahoo.co.jp; Hiraki, Takao, E-mail: takaoh@tc4.so-net.ne.jp; Gobara, Hideo, E-mail: gobara@cc.okayama-u.ac.jp
IntroductionComputed tomography (CT) fluoroscopy-guided renal cryoablation and lung radiofrequency ablation (RFA) have received increasing attention as promising cancer therapies. Although radiation exposure of interventional radiologists during these procedures is an important concern, data on operator exposure are lacking.Materials and MethodsRadiation dose to interventional radiologists during CT fluoroscopy-guided renal cryoablation (n = 20) and lung RFA (n = 20) was measured prospectively in a clinical setting. Effective dose to the operator was calculated from the 1-cm dose equivalent measured on the neck outside the lead apron, and on the left chest inside the lead apron, using electronic dosimeters. Equivalent dose to the operator’s finger skinmore » was measured using thermoluminescent dosimeter rings.ResultsThe mean (median) effective dose to the operator per procedure was 6.05 (4.52) μSv during renal cryoablation and 0.74 (0.55) μSv during lung RFA. The mean (median) equivalent dose to the operator’s finger skin per procedure was 2.1 (2.1) mSv during renal cryoablation, and 0.3 (0.3) mSv during lung RFA.ConclusionRadiation dose to interventional radiologists during renal cryoablation and lung RFA were at an acceptable level, and in line with recommended dose limits for occupational radiation exposure.« less
-
NOTE: Dose area product evaluations with Gafchromic® XR-R films and a flat-bed scanner
NASA Astrophysics Data System (ADS)
Rampado, O.; Garelli, E.; Deagostini, S.; Ropolo, R.
2006-12-01
Gafchromic® XR-R films are a useful tool to evaluate entrance skin dose in interventional radiology. Another dosimetric quantity of interest in diagnostic and interventional radiology is the dose area product (DAP). In this study, a method to evaluate DAP using Gafchromic® XR-R films and a flat-bed scanner was developed and tested. Film samples were exposed to an x-ray beam of 80 kVp over a dose range of 0 10 Gy. DAP measurements with films were obtained from the digitalization of a film sample positioned over the x-ray beam window during the exposure. DAP values obtained with this method were compared for 23 cardiological interventional procedures with DAP values displayed by the equipment. The overall one-sigma dose measurement uncertainty depended on the absorbed dose, with values below 6% for doses above 1 Gy. A maximum discrepancy of 16% was found, which is of the order of the differences in the DAP measurements that may occur with different calibration procedures. Based on the results presented, after an accurate calibration procedure and a thorough inspection of the relationship between the actual dose and the direct measured quantity (net optical density or net pixel value variation), Gafchromic® XR-R films can be used to assess the DAP.
-
SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT
Halliburton, Sandra S.; Abbara, Suhny; Chen, Marcus Y.; Gentry, Ralph; Mahesh, Mahadevappa; Raff, Gilbert L.; Shaw, Leslee J.; Hausleiter, Jörg
2012-01-01
Over the last few years, computed tomography (CT) has developed into a standard clinical test for a variety of cardiovascular conditions. The emergence of cardiovascular CT during a period of dramatic increase in radiation exposure to the population from medical procedures and heightened concern about the subsequent potential cancer risk has led to intense scrutiny of the radiation burden of this new technique. This has hastened the development and implementation of dose reduction tools and prompted closer monitoring of patient dose. In an effort to aid the cardiovascular CT community in incorporating patient-centered radiation dose optimization and monitoring strategies into standard practice, the Society of Cardiovascular Computed Tomography has produced a guideline document to review available data and provide recommendations regarding interpretation of radiation dose indices and predictors of risk, appropriate use of scanner acquisition modes and settings, development of algorithms for dose optimization, and establishment of procedures for dose monitoring. PMID:21723512
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mohammadi, H.; Tabeie, F.; Saghari, M.
1995-04-01
In view of the rapid expansion of diagnostic nuclear medicine procedures in Iran, this study was undertaken to examine trends of nuclear medicine practice in the country and to determine the mean effective dose equivalent per patient and per capita. Comprehensive national data covering 93% of all nuclear medicine centers in 1985-1989 were obtained. The total number of nuclear medicine examinations inc teased by 42% during these years. The relative frequency of thyroid investigations was 84% followed by liver/spleen and bone procedures (7% and 6%, respectively). {sup 99m}Tc was the radionuclide of choice for 86% of investigation while {sup 131}Imore » alone accounted for 59% of collective effective dose equivalent. The annual average number of nuclear medicine procedures per 1,000 people was 1.9. For the thyroid, the highest number (48%) of patients investigated was in the 15-29 y age group and the lowest (3%) was in the >64 y age group. The male to female ratio of thyroid and cardiac patient was 0.18 and 3.64, respectively. The numbers of males and females studied for the remaining eight procedures were less frequent and about the same. The mean effective dose equivalent per patient and per capita was about 4.3 mSv and 8 {mu}Sv, respectively. {sup 131}I was responsible for most of collective effective dose equivalent produced by nuclear medicine. Therefore, future efforts should be concentrated on dose reduction for diagnostic {sup 131}I tests.« less
-
Chong, Julio T; Klausner, Adam P; Petrossian, Albert; Byrne, Michael D; Moore, Jewel R; Goetz, Lance L; Gater, David R; Grob, B Mayer
2015-03-01
The objective of this study was to compare the safety, efficacy, quality-of-life impact, and costs of a single dose or a longer course of pre-procedural antibiotics prior to elective endoscopic urological procedures in individuals with spinal cord injury and disorders (SCI/D) and asymptomatic bacteriuria. A prospective observational study. Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA. Sixty persons with SCI/D and asymptomatic bacteriuria scheduled to undergo elective endoscopic urological procedures. A single pre-procedural dose of antibiotics vs. a 3-5-day course of pre-procedural antibiotics. Objective and subjective measures of health, costs, and quality of life. There were no significant differences in vital signs, leukocytosis, adverse events, and overall satisfaction in individuals who received short-course vs. long-course antibiotics. There was a significant decrease in antibiotic cost (33.1 ± 47.6 vs. 3.6 ± 6.1 US$, P = 0.01) for individuals in the short-course group. In addition, there was greater pre-procedural anxiety (18 vs. 0%, P < 0.05) for individuals who received long-course antibiotics. SCI/D individuals with asymptomatic bacteriuria may be able to safely undergo most endoscopic urological procedures with a single dose of pre-procedural antibiotics. However, further research is required and even appropriate pre-procedural antibiotics may not prevent severe infections.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mendoza-Moctezuma, A. I.; Aguilar, J. Garcia; Garcia-Garduno, O. A.
Interventional cardiology procedures are an effective alternative for the reestablishment of correct sanguineous circulation in the heart. However, this kind of procedures exposes to the patients to a relatively high radiation doses. Usually, the surface peak skin dose is evaluated using a visual scale with a comparator strip, nevertheless, even if the comparator strip provides a simple and quick method for estimating the dose it has an uncertainty of {+-}25%. For this reason, a better evaluation method is needed. The objective of our project is to determine the surface peak skin dose of interventional cardiology procedures using GafChromic XR-RV2 filmmore » together with a commercial flatbed scanner in reflection mode. Here we report a protocol to handle GafChromic XR-RV2 film using a commercial flat bed scanner in reflection mode aiming at an uncertainty of {+-}3%.« less
-
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-08
... waive FICC's rules, procedures, and regulations of the Mortgage-Backed Securities Division. II. Self... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62796; File No. SR-FICC-2010-06] Self... Proposed Rule Change To Amend Rules Relating to Authority To Waive Rules, Procedures, and Regulations of...
-
ERIC Educational Resources Information Center
Yao, Lihua
2013-01-01
Through simulated data, five multidimensional computerized adaptive testing (MCAT) selection procedures with varying test lengths are examined and compared using different stopping rules. Fixed item exposure rates are used for all the items, and the Priority Index (PI) method is used for the content constraints. Two stopping rules, standard error…
-
Code of Federal Regulations, 2010 CFR
2010-10-01
... interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network Operations in the Fixed... avoidance of in-line interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network... procedures in this section apply to non-Federal-Government NGSO FSS satellite networks operating in the...
-
Code of Federal Regulations, 2011 CFR
2011-10-01
... interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network Operations in the Fixed... avoidance of in-line interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network... procedures in this section apply to non-Federal-Government NGSO FSS satellite networks operating in the...
-
This SOP describes the procedures to set up, calibrate, initiate and terminate air sampling for persistent organic pollutants. This method is used to sample air, indoors and outdoors, at homes and at day care centers over a 48-hr period.
-
A Comparison of Exposure Control Procedures in CATS Using the GPC Model
ERIC Educational Resources Information Center
Leroux, Audrey J.; Dodd, Barbara G.
2016-01-01
The current study compares the progressive-restricted standard error (PR-SE) exposure control method with the Sympson-Hetter, randomesque, and no exposure control (maximum information) procedures using the generalized partial credit model with fixed- and variable-length CATs and two item pools. The PR-SE method administered the entire item pool…
-
Code of Federal Regulations, 2014 CFR
2014-10-01
... 47 Telecommunication 2 2014-10-01 2014-10-01 false Procedures for avoidance of in-line interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network Operations in the Fixed... avoidance of in-line interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network...
-
Code of Federal Regulations, 2012 CFR
2012-10-01
... 47 Telecommunication 2 2012-10-01 2012-10-01 false Procedures for avoidance of in-line interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network Operations in the Fixed... avoidance of in-line interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network...
-
Code of Federal Regulations, 2013 CFR
2013-10-01
... 47 Telecommunication 2 2013-10-01 2013-10-01 false Procedures for avoidance of in-line interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network Operations in the Fixed... avoidance of in-line interference events for Non Geostationary Satellite Orbit (NGSO) Satellite Network...
-
Federal Register 2010, 2011, 2012, 2013, 2014
2013-07-17
... remain subject to all of the GSD's normal risk management procedures, which include marking member portfolios to the market on an intraday basis and charging variation margins accordingly.\\19\\ These risk management procedures should help ensure the safety of the securities and funds handled by the GSD in...
-
Dwivedi, Anoop; Tikku, Tripti; Khanna, Rohit; Maurya, Rana Pratap; Verma, Geeta; Murthy, R C
2015-01-01
Various components of fixed orthodontic appliances are continuously interacting with saliva and other fluids in the mouth releasing various metal ions including nickel and chromium that can cause damaging effects if their concentration exceeds above the toxic dose. To determine and compare the level of nickel and chromium in the saliva of patients undergoing fixed orthodontic treatment at different time periods. The sample of saliva of 13 patients was taken at different time periods that is: Group 1 (before appliance placement), Group II, III, and IV (after 1-week, 1-month, and 3 months of appliance placement respectively). The fixed appliance comprised of brackets, bands, buccal tubes, lingual sheath, transpalatal arch and wires composed of Ni-Ti and stainless steel. The level of ions was determined using graphite furnace atomic absorption spectro-photometry. The data thus obtained were statistically analyzed using SPSS Statistical Analysis Software (Version 15.0). Level of nickel and chromium in saliva was highest in Group II and lowest in Groups I for both the ions. On comparison among different Groups, it was statistically significant for all the groups (<0.001) except between Group III and Group IV. The release of nickel and chromium was maximum at 1-week and then the level gradually declined. These values were well below the toxic dose of these ions. The results should be viewed with caution in subjects with Ni hypersensitivity.