European consensus on patient contact shielding.

Patient contact shielding has been in use for many years in radiology departments in order to reduce the effects and risks of ionising radiation on certain organs. New technologies in projection imaging and CT scanning such as digital receptors and automatic exposure control (AEC) systems have reduced doses and improved image consistency. These changes and a greater understanding of both the benefits and the risks from the use of shielding have led to a review of shielding use in radiology. A number of professional bodies have already issued guidance in this regard. This paper represents the current consensus view of the main bodies involved in radiation safety and imaging in Europe: European Federation of Organisations for Medical Physics, European Federation of Radiographer Societies, European Society of Radiology, European Society of Paediatric Radiology, EuroSafe Imaging, European Radiation Dosimetry Group (EURADOS), and European Academy of DentoMaxilloFacial Radiology (EADMFR). It is based on the expert recommendations of the Gonad and Patient Shielding (GAPS) Group formed with the purpose of developing consensus in this area. The recommendations are intended to be clear and easy to use. They are intended as guidance, and they are developed using a multidisciplinary team approach. It is recognised that regulations, custom and practice vary widely on the use of patient shielding in Europe and it is hoped that these recommendations will inform a change management program that will benefit patients and staff.

Efficacy of a novel intradermal Lawsonia intracellularis vaccine in pigs against experimental infection and under field conditions.

BACKGROUND: The efficacy of a novel inactivated intradermal Lawsonia intracellularis vaccine, Porcilis® Lawsonia ID, was evaluated in two experimental vaccination-challenge studies and under field conditions on a farm with a history of recurrent acute ileitis. In addition, the efficacy of the vaccine was compared to that of a commercially available live attenuated vaccine. The novel inactivated vaccine consists of a freeze-dried antigen fraction that is dissolved just prior to use in either the adjuvant or in Porcilis® PCV ID; an existing intradermal vaccine against porcine Circovirus type 2. In the two experimental vaccination-challenge studies, groups of 25 piglets were vaccinated once at 3 weeks of age or left unvaccinated as challenge control. Vaccines tested were Porcilis® Lawsonia ID as standalone (study 1) or in associated mixed use with Porcilis® PCV ID (study 2) and an orally administered commercially available live vaccine (study 1). The pigs were challenged with virulent L. intracellularis at 4 weeks (study 1) or 21 weeks (study 2) after vaccination. Post-challenge, the pigs were evaluated for clinical signs, average daily weight gain, shedding and macroscopic as well as microscopic immuno-histological ileum lesion scores. In the field study, the mortality and key performance parameters were evaluated over a period of 8 months. RESULTS: The results of the two experimental vaccination-challenge studies showed that Porcilis® Lawsonia ID as single vaccine or in associated mixed use with Porcilis® PCV ID, induced statistically significant protection against experimental L. intracellularis infection, 4 weeks or 21 weeks after vaccination. This was demonstrated by lower clinical scores, improved weight gain, reduction of L. intracellularis shedding and reduction of macroscopic as well as microscopic ileum lesion scores when compared to the controls. The protection induced was superior to that of the commercially available live vaccine. In the field study Porcilis® Lawsonia ID was highly efficacious in reducing L. intracellularis associated mortality and improving key production parameters. CONCLUSION: The results support that this new intradermal vaccine is efficacious against L. intracellularis and may be used in associated mixed use with Porcilis® PCV ID.

Lengthening adalimumab dosing interval in quiescent Crohn's disease patients: protocol for the pragmatic randomised non-inferiority LADI study.

INTRODUCTION: Adalimumab is effective for maintenance of remission in patients with Crohn's disease (CD) at a dose of 40 mg subcutaneously every 2 weeks. However, adalimumab is associated with (long-term) adverse events and is costly. The aim of this study is to demonstrate non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening compared to standard dosing of every other week (EOW). METHODS AND ANALYSIS: The Lengthening Adalimumab Dosing Interval (LADI) study is a pragmatic, multicentre, open label, randomised controlled non-inferiority trial. Non-inferiority is reached if the difference in cumulative incidence of persistent (>8 weeks) flares does not exceed the non-inferiority margin of 15%. 174 CD patients on adalimumab maintenance therapy in long-term (>9 months) clinical and biochemical remission will be included (C-reactive protein (CRP) <10 mg/L, faecal calprotectin (FC) <150 µg/g, Harvey-Bradshaw Index (HBI) <5). Patients will be randomised 2:1 into the intervention (adalimumab interval lengthening) or control group (adalimumab EOW). The intervention group will lengthen the adalimumab administration interval to every 3 weeks, and after 24 weeks to every 4 weeks. Clinical and biochemical disease activity will be monitored every 12 weeks by physician global assessment, HBI, CRP and FC. In case of disease flare, dosing will be increased. A flare is defined as two of three of the following criteria; FC>250 µg/g, CRP≥10 mg/l, HBI≥5. Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness. ETHICS AND DISSEMINATION: The study is approved by the Medical Ethics Committee Arnhem-Nijmegen, the Netherlands (registration number NL58948.091.16). Results will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBERS: EudraCT registry (2016-003321-42); Clinicaltrials.gov registry (NCT03172377); Dutch trial registry (NTRID6417).

Radiological Protection in Cone Beam Computed Tomography (CBCT). ICRP Publication 129.

The objective of this publication is to provide guidance on radiological protection in the new technology of cone beam computed tomography (CBCT). Publications 87 and 102 dealt with patient dose management in computed tomography (CT) and multi-detector CT. The new applications of CBCT and the associated radiological protection issues are substantially different from those of conventional CT. The perception that CBCT involves lower doses was only true in initial applications. CBCT is now used widely by specialists who have little or no training in radiological protection. This publication provides recommendations on radiation dose management directed at different stakeholders, and covers principles of radiological protection, training, and quality assurance aspects. Advice on appropriate use of CBCT needs to be made widely available. Advice on optimisation of protection when using CBCT equipment needs to be strengthened, particularly with respect to the use of newer features of the equipment. Manufacturers should standardise radiation dose displays on CBCT equipment to assist users in optimisation of protection and comparisons of performance. Additional challenges to radiological protection are introduced when CBCT-capable equipment is used for both fluoroscopy and tomography during the same procedure. Standardised methods need to be established for tracking and reporting of patient radiation doses from these procedures. The recommendations provided in this publication may evolve in the future as CBCT equipment and applications evolve. As with previous ICRP publications, the Commission hopes that imaging professionals, medical physicists, and manufacturers will use the guidelines and recommendations provided in this publication for implementation of the Commission's principle of optimisation of protection of patients and medical workers, with the objective of keeping exposures as low as reasonably achievable, taking into account economic and societal factors, and consistent with achieving the necessary medical outcomes.

Effect of exposure parameters and voxel size on bone structure analysis in CBCT.

OBJECTIVE: To evaluate the effect of exposure parameters and voxel size on bone structure analysis in dental CBCT. METHODS: 20 cylindrical bone samples underwent CBCT scanning (3D Accuitomo 170; J. Morita, Kyoto, Japan) using three combinations of tube voltage (kV) and tube current-exposure time product (mAs), corresponding with a CT dose index of 3.4 mGy: 90 kV and 62 mAs, 73 kV and 108.5 mAs, and 64 kV and 155 mAs. Images were reconstructed with a voxel size of 0.080 mm. In addition, the 90 kV scan was reconstructed at voxel sizes of 0.125, 0.160, 0.200, 0.250 and 0.300 mm. The following parameters were measured: bone surface (BS) and bone volume (BV) per total volume (TV), fractal dimension, connectivity density, anisotropy, trabecular thickness (Tb. Th.) and trabecular spacing (Tb. Sp.), structure model index (SMI), plateness, branches, junctions, branch length and triple points. RESULTS: For most parameters, there was no significant effect of the kV value. For BV/TV, "90 kV" differed significantly from the other kV settings; for SMI, "64 vs 73 kV" was significant. For BS/TV, fractal dimension, connectivity density, branches, junctions and triple points values incrementally decreased at larger voxel sizes, whereas an increase was seen for Tb. Th., Tb. Sp., SMI and branch length. For anisotropy and plateness, no (or little) effect of voxel size was seen; for BV/TV, the effect was inconsistent. CONCLUSIONS: Most bone structure parameters are not affected by the kV if the radiation dose is constant. Parameters dealing with the trabecular structure are heavily affected by the voxel size.

Optimization of dental CBCT exposures through mAs reduction.

OBJECTIVES: To investigate the effect of tube current-exposure time (mAs) reduction on clinical and technical image quality for different CBCT scanners, and to determine preliminary minimally acceptable values for the mAs and contrast-to-noise ratio (CNR) in CBCT. METHODS: A polymethyl methacrylate (PMMA) phantom and an anthropomorphic skull phantom, containing a human skeleton embedded in polyurethane, were scanned using four CBCT devices, including seven exposure protocols. For all protocols, the mAs was varied within the selectable range. Using the PMMA phantom, the CNRAIR was measured and corrected for voxel size. Eight axial slices and one coronal slice showing various anatomical landmarks were selected for each CBCT scan of the skull phantom. The slices were presented to six dentomaxillofacial radiologists, providing scores for various anatomical and diagnostic parameters. RESULTS: A hyperbolic relationship was seen between CNRAIR and mAs. Similarly, a gradual reduction in clinical image quality was seen at lower mAs values; however, for several protocols, image quality remained acceptable for a moderate or large mAs reduction compared with the standard exposure setting, depending on the clinical application. The relationship between mAs, CNRAIR and observer scores was different for each CBCT device. Minimally acceptable values for mAs were between 9 and 70, depending on the criterion and clinical application. CONCLUSIONS: Although noise increased at a lower mAs, clinical image quality often remained acceptable at exposure levels below the manufacturer's recommended setting, for certain patient groups. Currently, it is not possible to determine minimally acceptable values for image quality that are applicable to multiple CBCT models.

Comparison of mandibular bone microarchitecture between micro-CT and CBCT images.

OBJECTIVES: To compare microarchitecture parameters of bone samples scanned using micro-CT (µCT) to those obtained by using CBCT. METHODS: A bone biopsy trephine bur (3 × 10 mm) was used to remove 20 cylindrical bone samples from 20 dry hemimandibles. Samples were scanned using µCT (µCT 35; SCANCO Medical, Brüttisellen, Switzerland) with a voxel size of 20 µm and CBCT (3D Accuitomo 170; J. Morita, Kyoto, Japan) with a voxel size of 80 µm. All corresponding sample scans were aligned and cropped. Image analysis was carried out using BoneJ, including the following parameters: skeleton analysis, bone surface per total volume (BS/TV), bone volume per total volume (BV/TV), connectivity density, anisotropy, trabecular thickness and spacing, structure model index, plateness and fractal dimension. Pearson and Spearman correlation coefficients (R) were calculated. CBCT values were then calibrated using the slope of the linear fit with the µCT values. The mean error after calibration was calculated and normalized to the standard deviation of the µCT values. RESULTS: R-values ranged between 0.05 (plateness) and 0.83 (BS/TV). Correlation was significant for both Spearman and Pearson's R for 8 out of 16 parameters. After calibration, the smallest normalized error was found for BV/TV (0.48). For other parameters, the error range was 0.58-2.10. CONCLUSIONS: Despite the overall correlation, this study demonstrates the uncertainty associated with using bone microarchitecture parameters on CBCT images. Although clinically relevant parameter ranges are not available, the errors found in this study may be too high for some parameters to be considered for clinical application.

CBCT-based bone quality assessment: are Hounsfield units applicable?

CBCT is a widely applied imaging modality in dentistry. It enables the visualization of high-contrast structures of the oral region (bone, teeth, air cavities) at a high resolution. CBCT is now commonly used for the assessment of bone quality, primarily for pre-operative implant planning. Traditionally, bone quality parameters and classifications were primarily based on bone density, which could be estimated through the use of Hounsfield units derived from multidetector CT (MDCT) data sets. However, there are crucial differences between MDCT and CBCT, which complicates the use of quantitative gray values (GVs) for the latter. From experimental as well as clinical research, it can be seen that great variability of GVs can exist on CBCT images owing to various reasons that are inherently associated with this technique (i.e. the limited field size, relatively high amount of scattered radiation and limitations of currently applied reconstruction algorithms). Although attempts have been made to correct for GV variability, it can be postulated that the quantitative use of GVs in CBCT should be generally avoided at this time. In addition, recent research and clinical findings have shifted the paradigm of bone quality from a density-based analysis to a structural evaluation of the bone. The ever-improving image quality of CBCT allows it to display trabecular bone patterns, indicating that it may be possible to apply structural analysis methods that are commonly used in micro-CT and histology.

Technical aspects of dental CBCT: state of the art.

As CBCT is widely used in dental and maxillofacial imaging, it is important for users as well as referring practitioners to understand the basic concepts of this imaging modality. This review covers the technical aspects of each part of the CBCT imaging chain. First, an overview is given of the hardware of a CBCT device. The principles of cone beam image acquisition and image reconstruction are described. Optimization of imaging protocols in CBCT is briefly discussed. Finally, basic and advanced visualization methods are illustrated. Certain topics in these review are applicable to all types of radiographic imaging (e.g. the principle and properties of an X-ray tube), others are specific for dental CBCT imaging (e.g. advanced visualization techniques).

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

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

A pragmatic approach to determine the optimal kVp in cone beam CT: balancing contrast-to-noise ratio and radiation dose.

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 (R(2) > 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.

An in vitro comparison of subjective image quality of panoramic views acquired via 2D or 3D imaging.

OBJECTIVES: The objective of this study is to compare subjective image quality and diagnostic validity of cone-beam CT (CBCT) panoramic reformatting with digital panoramic radiographs. MATERIALS AND METHODS: Four dry human skulls and two formalin-fixed human heads were scanned using nine different CBCTs, one multi-slice CT (MSCT) and one standard digital panoramic device. Panoramic views were generated from CBCTs in four slice thicknesses. Seven observers scored image quality and visibility of 14 anatomical structures. Four observers repeated the observation after 4 weeks. RESULTS: Digital panoramic radiographs showed significantly better visualization of anatomical structures except for the condyle. Statistical analysis of image quality showed that the 3D imaging modalities (CBCTs and MSCT) were 7.3 times more likely to receive poor scores than the 2D modality. Yet, image quality from NewTom VGi® and 3D Accuitomo 170® was almost equivalent to that of digital panoramic radiographs with respective odds ratio estimates of 1.2 and 1.6 at 95% Wald confidence limits. A substantial overall agreement amongst observers was found. Intra-observer agreement was moderate to substantial. CONCLUSIONS: While 2D-panoramic images are significantly better for subjective diagnosis, 2/3 of the 3D-reformatted panoramic images are moderate or good for diagnostic purposes. CLINICAL RELEVANCE: Panoramic reformattings from particular CBCTs are comparable to digital panoramic images concerning the overall image quality and visualization of anatomical structures. This clinically implies that a 3D-derived panoramic view can be generated for diagnosis with a recommended 20-mm slice thickness, if CBCT data is a priori available for other purposes.

Variability of dental cone beam CT grey values for density estimations.

OBJECTIVE: The aim of this study was to investigate the use of dental cone beam CT (CBCT) grey values for density estimations by calculating the correlation with multislice CT (MSCT) values and the grey value error after recalibration. METHODS: A polymethyl methacrylate (PMMA) phantom was developed containing inserts of different density: air, PMMA, hydroxyapatite (HA) 50 mg cm(-3), HA 100, HA 200 and aluminium. The phantom was scanned on 13 CBCT devices and 1 MSCT device. Correlation between CBCT grey values and CT numbers was calculated, and the average error of the CBCT values was estimated in the medium-density range after recalibration. RESULTS: Pearson correlation coefficients ranged between 0.7014 and 0.9996 in the full-density range and between 0.5620 and 0.9991 in the medium-density range. The average error of CBCT voxel values in the medium-density range was between 35 and 1562. CONCLUSION: Even though most CBCT devices showed a good overall correlation with CT numbers, large errors can be seen when using the grey values in a quantitative way. Although it could be possible to obtain pseudo-Hounsfield units from certain CBCTs, alternative methods of assessing bone tissue should be further investigated. ADVANCES IN KNOWLEDGE: The suitability of dental CBCT for density estimations was assessed, involving a large number of devices and protocols. The possibility for grey value calibration was thoroughly investigated.

Dose distribution for dental cone beam CT and its implication for defining a dose index.

OBJECTIVES: To characterize the dose distribution for a range of cone beam CT (CBCT) units, investigating different field of view sizes, central and off-axis geometries, full or partial rotations of the X-ray tube and different clinically applied beam qualities. The implications of the dose distributions on the definition and practicality of a CBCT dose index were assessed. METHODS: Dose measurements on CBCT devices were performed by scanning cylindrical head-size water and polymethyl methacrylate phantoms, using thermoluminescent dosemeters, a small-volume ion chamber and radiochromic films. RESULTS: It was found that the dose distribution can be asymmetrical for dental CBCT exposures throughout a homogeneous phantom, owing to an asymmetrical positioning of the isocentre and/or partial rotation of the X-ray source. Furthermore, the scatter tail along the z-axis was found to have a distinct shape, generally resulting in a strong drop (90%) in absorbed dose outside the primary beam. CONCLUSIONS: There is no optimal dose index available owing to the complicated exposure geometry of CBCT and the practical aspects of quality control measurements. Practical validation of different possible dose indices is needed, as well as the definition of conversion factors to patient dose.

Estimation of paediatric organ and effective doses from dental cone beam CT using anthropomorphic phantoms.

OBJECTIVES: Cone beam CT (CBCT) is an emerging X-ray technology applied in dentomaxillofacial imaging. Previous published studies have estimated the effective dose and radiation risks using adult anthropomorphic phantoms for a wide range of CBCT units and imaging protocols. METHODS: Measurements were made five dental CBCT units for a range of imaging protocols, using 10-year-old and adolescent phantoms and thermoluminescent dosimeters. The purpose of the study was to estimate paediatric organ and effective doses from dental CBCT. RESULTS: The average effective doses to the 10-year-old and adolescent phantoms were 116 µSv and 79 µSv, respectively, which are similar to adult doses. The salivary glands received the highest organ dose and there was a fourfold increase in the thyroid dose of the 10-year-old relative to that of the adolescent because of its smaller size. The remainder tissues and salivary and thyroid glands contributed most significantly to the effective dose for a 10-year-old, whereas for an adolescent the remainder tissues and the salivary glands contributed the most significantly. It was found that the percentage attributable lifetime mortality risks were 0.002% and 0.001% for a 10-year-old and an adolescent patient, respectively, which are considerably higher than the risk to an adult having received the same doses. CONCLUSION: It is therefore imperative that dental CBCT examinations on children should be fully justified over conventional X-ray imaging and that dose optimisation by field of view collimation is particularly important in young children.

Development and validation of a hybrid simulation technique for cone beam CT: application to an oral imaging system.

This paper proposes a hybrid technique to simulate the complete chain of an oral cone beam computed tomography (CBCT) system for the study of both radiation dose and image quality. The model was developed around a 3D Accuitomo 170 unit (J Morita, Japan) with a tube potential range of 60-90 kV. The Monte Carlo technique was adopted to simulate the x-ray generation, filtration and collimation. Exact dimensions of the bow-tie filter were estimated iteratively using experimentally acquired flood images. Non-flat radiation fields for different exposure settings were mediated via 'phase spaces'. Primary projection images were obtained by ray tracing at discrete energies and were fused according to the two-dimensional energy modulation templates derived from the phase space. Coarse Monte Carlo simulations were performed for scatter projections and the resulting noisy images were smoothed by Richardson-Lucy fitting. Resolution and noise characteristics of the flat panel detector were included using the measured modulation transfer function (MTF) and the noise power spectrum (NPS), respectively. The Monte Carlo dose calculation was calibrated in terms of kerma free-in-air about the isocenter, using an ionization chamber, and was subsequently validated by comparison against the measured air kerma in water at various positions of a cylindrical water phantom. The resulting dose discrepancies were found <10% for most cases. Intensity profiles of the experimentally acquired and simulated projection images of the water phantom showed comparable fractional increase over the common area as changing from a small to a large field of view, suggesting that the scatter was accurately accounted. Image validation was conducted using two small phantoms and the built-in quality assurance protocol of the system. The reconstructed simulated images showed high resemblance on contrast resolution, noise appearance and artifact pattern in comparison to experimentally acquired images, with <5% difference for voxel values of the aluminum and air insert regions and <3% difference for voxel uniformity across the homogeneous PMMA region. The detector simulation by use of the MTF and NPS data exhibited a big influence on noise and the sharpness of the resulting images. The hybrid simulation technique is flexible and has wide applicability to CBCT systems.

Bronchodilatory effects of aclidinium bromide, a long-acting muscarinic antagonist, in COPD patients.

BACKGROUND: Aclidinium bromide is a novel, long-acting, inhaled muscarinic antagonist bronchodilator currently in Phase III clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the pharmacodynamics, pharmacokinetics, safety and tolerability of ascending doses of aclidinium bromide in patients with COPD. METHODS: This double-blind, randomised, placebo-controlled, crossover study was conducted in patients with moderate to severe COPD (forced expiratory volume in 1s [FEV(1)] <65% predicted). Patients were randomly assigned to one of four treatment sequences of aclidinium bromide 100, 300, 900microg and placebo with a washout period between doses. The primary outcome was area under the FEV(1) curve over the 0-24h time interval. RESULTS: Seventeen patients with COPD were studied. Mean FEV(1) over 24h was 1.583L for placebo, and 1.727L, 1.793L and 1.815L for aclidinium bromide 100, 300 and 900microg, respectively (p<0.001 vs. placebo, all doses). Significant changes from baseline in FEV(1) were detected 15min post-dose for aclidinium bromide 300 and 900microg, with a peak effect 2h post-dose (all doses). Aclidinium bromide was undetected in plasma. The majority of adverse events was unrelated to study medication and did not result in discontinuation. CONCLUSION: Aclidinium bromide 100-900microg produced sustained bronchodilation over 24h in patients with COPD.

Comparison between effective radiation dose of CBCT and MSCT scanners for dentomaxillofacial applications.

OBJECTIVES: To compare the effective dose levels of cone beam computed tomography (CBCT) for maxillofacial applications with those of multi-slice computed tomography (MSCT). STUDY DESIGN: The effective doses of 3 CBCT scanners were estimated (Accuitomo 3D, i-CAT, and NewTom 3G) and compared to the dose levels for corresponding image acquisition protocols for 3 MSCT scanners (Somatom VolumeZoom 4, Somatom Sensation 16 and Mx8000 IDT). The effective dose was calculated using thermoluminescent dosimeters (TLDs), placed in a Rando Alderson phantom, and expressed according to the ICRP 103 (2007) guidelines (including a separate tissue weighting factor for the salivary glands, as opposed to former ICRP guidelines). RESULTS: Effective dose values ranged from 13 to 82 microSv for CBCT and from 474 to 1160 microSv for MSCT. CBCT dose levels were the lowest for the Accuitomo 3D, and highest for the i-CAT. CONCLUSIONS: Dose levels for CBCT imaging remained far below those of clinical MSCT protocols, even when a mandibular protocol was applied for the latter, resulting in a smaller field of view compared to various CBCT protocols. Considering this wide dose span, it is of outmost importance to justify the selection of each of the aforementioned techniques, and to optimise the radiation dose while achieving a sufficient image quality. When comparing these results to previous dosimetric studies, a conversion needs to be made using the latest ICRP recommendations.

The effect of the leukotriene receptor antagonist zafirlukast on neurokinin A-induced bronchoconstriction in patients with asthma--A comparison with leukotriene D4 induced broncoconstriction.

The bronchoconstriction caused by inhaled neurokinin A (NKA) in patients with asthma is indirect. The mediators involved in NKA-induced bronchoconstriction are unknown. Studies with various H1 receptor antagonists were negative, making an important contribution of histamine unlikely. To study the role of cysteinyl leukotrienes in neurokinin A-induced bronchoconstriction, we performed a randomised, double-blind, cross-over, placebo controlled trial in 12 patients with mild to moderate asthma. Zafirlukast and matching placebo were given orally, 40 mg the evening before and 40 mg the morning of assessment. In one period NKA was administered, in the other period leukotriene D4 (LTD4). Increasing concentrations of NKA and LTD4 were inhaled from a 30 L bag, after nebulization via a Mallinckrodt nebuliser. The difference between log10PC20LTD4 after treatment with placebo or zafirlukast was highly significant (p<0.0001). A trend was observed towards a difference between log10PC20 neurokinin A after treatment with placebo or zafirlukast (p=0.0741). The dose ratio for the neurokinin A provocation was 4.4 and for the LTD4 provocation 67.7. In conclusion, zafirlukast had a large inhibitory effect on LTD4-induced bronchoconstriction, but offered only limited protective effect against neurokinin A-induced bronchoconstriction. We suggest that leukotrienes play a limited role in the bronchoconstrictor effect of neurokinin A in patients with asthma.