To investigate the impact of evolving International Commission on Radiological Protection (ICRP) recommendations concerning calculation of effective dose (E) and compare updated typical UK values for ...common CT examinations with previous data.
Monte Carlo simulations have provided normalized organ doses relating to 15 CT scanner models and 5 virtual reference adults. Series of representative E/dose-length product (DLP) coefficients were derived for common examinations on the separate bases of not only older stylized mathematical phantoms and voxel phantoms presently recommended by ICRP, but also the 1977, 1990 and 2007 formulations for E. Updated E/DLP coefficients were applied to typical values of DLP from the 2011 UK survey.
Changes in ICRP recommendations that have arisen from improving evidence on stochastic risk, influence values of E by up to a factor two for CT examinations of the head and neck, although differences for the trunk typically amount to ±10%. Adoption of the voxel rather than the mathematical phantoms used previously can lead to further changes in E by a few tens of percent. Updated typical values of E for UK CT examinations range from 2 to 20 mSv. Increases by 20-400% since 2003 arise not only from increases by 30-160% in typical values of DLP, but also increases by 30-90% in relation to E/DLP coefficients for examinations of the trunk.
Values of E, including updated typical data for UK CT, should be compared with caution in relation to their purpose and underlying factors concerning their calculation.
Updated E/DLP coefficients and typical values of E for UK CT, and an appreciation of factors influencing these data.
In patients with Staphylococcus aureus bacteremia, VIRSTA can be used to rule out endocarditis, but at the expense of a high number of patients classified as high risk and thus requiring TEE. The ...POSITIVE and PREDICT scores require adjustment.
Abstract
Background
Staphylococcus aureus bacteremia (SAB) is in 10% to 20% of cases complicated by infective endocarditis. Clinical prediction scores may select patients with SAB at highest risk for endocarditis, improving the diagnostic process of endocarditis. We compared the accuracy of the Prediction Of Staphylococcus aureus Infective endocarditiseTime to positivity, Iv drug use, Vascular phenomena, preExisting heart condition (POSITIVE), Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT), and VIRSTA scores for classifying the likelihood of endocarditis in patients with SAB.
Methods
Between August 2017 and September 2019, we enrolled consecutive adult patients with SAB in a prospective cohort study in 7 hospitals in the Netherlands. Using the modified Duke Criteria for definite endocarditis as reference standard, sensitivity, specificity, negative predictive (NPV), and positive predictive values were determined for the POSITIVE, PREDICT, and VIRSTA scores. An NPV of at least 98% was considered safe for excluding endocarditis.
Results
Of 477 SAB patients enrolled, 33% had community-acquired SAB, 8% had a prosthetic valve, and 11% a cardiac implantable electronic device. Echocardiography was performed in 87% of patients, and 42% received transesophageal echocardiography (TEE). Eighty-seven (18.2%) had definite endocarditis. Sensitivity was 77.6% (65.8%–86.9%), 85.1% (75.8%–91.8%), and 98.9% (95.7%–100%) for the POSITIVE (n = 362), PREDICT, and VIRSTA scores, respectively. NPVs were 92.5% (87.9%–95.8%), 94.5% (90.7%–97.0%), and 99.3% (94.9%–100%). For the POSITIVE, PREDICT, and VIRSTA scores, 44.5%, 50.7%, and 70.9% of patients with SAB, respectively, were classified as at high risk for endocarditis.
Conclusions
Only the VIRSTA score had an NPV of at least 98%, but at the expense of a high number of patients classified as high risk and thus requiring TEE.
Clinical Trials Registration
Netherlands Trial Register code 6669.
. Development of a method to provide organ and effective dose coefficients to reference adults for any CT scanner based on values of
measured both in air and in standard CT dosimetry phantoms.
. ...Results from previous Monte Carlo simulations for a range of contemporary CT scanners have been analyzed to provide linear models relating values of organ dose (normalized to
), for each slab of 3 reference phantoms (ICRP Male/Female, and AH hermaphrodite), to similarly normalized values of
in standard CT dosimetry phantoms. Three methods have been investigated to apply the models to values of
for a 'new' scanner not previously simulated: a Generic approach using averaged normalized organ dose profiles for whole body exposure of the phantoms; and two processes for matching the scanner, on the basis of normalized organ doses or effective dose (
), to one of the 102 sets of dose coefficients previously calculated for 12 contemporary CT scanner models, from 4 manufacturers, operating under a range of conditions.
. The merit of each method has been quantitatively assessed when applied to both the present contemporary scanners with each test data set being excluded in turn during the matching process, and also to 3 previously-simulated older scanners. Whereas all three methods appear viable, with all doses being within 1% and 10% for the contemporary and old scanners respectively, matching to
is overall the approach preferred in practice, yielding an uncertainty of around 6% in estimated values of
. The present methodology also provides superior performance when compared against some other common normalization factors for
.
. The CT dose model and the data sets will be incorporated into a new CT dosimetry tool that will be made available from UKHSA in support of facilitating improvements in patient protection.
Provide analyses of new organ dose coefficients (hereafter also referred to as normalized doses) for CT that have been developed to update the widely-utilized collection of data published 30 years ...ago in NRPB-SR250.
In order to reflect changes in technology, and also ICRP recommendations concerning use of the computational phantoms adult male (AM) and adult female (AF), 102 series of new Monte Carlo simulations have been performed covering the range of operating conditions for 12 contemporary models of CT scanner from 4 manufacturers. Normalized doses (relative to free air on axis) have been determined for 39 organs, and for every 8 mm or 4.84 mm slab of AM and AF, respectively.
Analyses of results confirm the significant influence (by up to a few tens of percent), on values of normalized organ (or contributions to effective dose (
)), for whole body exposure arising from selection of tube voltage and beam shaping filter. Use of partial (when available) rather than a Full fan beam reduced both organ and effective dose by up to 7%. Normalized doses to AF were larger than corresponding figures for AM by up to 30% for organs and by 10% for
. Additional simulations for whole body exposure have also demonstrated that: practical simplifications in the main modelling (point source, single slice thickness, neglect of patient couch and immobility of phantom arms) have sufficiently small (<5%) effect on
; mis-centring of the phantom away from the axis of rotation by 5 mm (in any direction) leads to changes in normalized organ dose and
by up to 20% and 6%, respectively; and angular tube current modulation can result in reductions by up to 35% and <15% in normalized organ dose and
, respectively, for 100% cosine variation.
These analyses help advance understanding of the influence of operational scanner settings on organ dose coefficients for contemporary CT, in support of improved patient protection. The results will allow the future development of a new dose estimation tool.
Abstract
Background
Several studies have suggested that in patients with Staphylococcus aureus bacteremia (SAB) 18F fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) ...improves outcome. However, these studies often ignored possible immortal time bias.
Methods
Prospective multicenter cohort study in 2 university and 5 non-university hospitals, including all patients with SAB. 18FFDG-PET/CT was performed on clinical indication as part of usual care. Primary outcome was 90-day all-cause mortality. Effect of 18FFDG-PET/CT was modeled with a Cox proportional hazards model using 18FFDG-PET/CT as a time-varying variable and corrected for confounders for mortality (age, Charlson score, positive follow-up cultures, septic shock, and endocarditis). Secondary outcome was 90-day infection-related mortality (assessed by adjudication committee) using the same analysis. In a subgroup-analysis, we determined the effect of 18FFDG-PET/CT in patients with high risk of metastatic infection.
Results
Of 476 patients, 178 (37%) underwent 18FFDG-PET/CT. Day-90 all-cause mortality was 31% (147 patients), and infection-related mortality was 17% (83 patients). The confounder adjusted hazard ratio (aHR) for all-cause mortality was 0.50 (95% confidence interval CI: .34–.74) in patients that underwent 18FFDG-PET/CT. Adjustment for immortal time bias changed the aHR to 1.00 (95% CI .68–1.48). Likewise, after correction for immortal time bias, 18FFDG-PET/CT had no effect on infection-related mortality (cause specific aHR 1.30 95% CI .77–2.21), on all-cause mortality in patients with high-risk SAB (aHR 1.07 (95% CI .63–1.83) or on infection-related mortality in high-risk SAB (aHR for 1.24 95% CI .67–2.28).
Conclusions
After adjustment for immortal time bias 18FFDG-PET/CT was not associated with day-90 all-cause or infection-related mortality in patients with SAB.
After correction for immortal time bias, 18F fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) does not influence all-cause or infection-related mortality in patients with Staphylococcus aureus bacteremia.
Graphical abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/positive-impact-of-18f-fdg-pet-ct-on-mortality-in-patients-with-staphylococcus-aureus-bacteremia-explained-by-immortal-time-bias-b4db7e26-22b3-4771-bad6-9eba9b0c3dcc/update
The ImPACT (imaging performance assessment of CT scanners) CT patient dosimetry calculator is still used world-wide to estimate organ and effective doses (E) for computed tomography (CT) ...examinations, although the tool is based on Monte Carlo calculations reflecting practice in the early 1990's. Subsequent developments in CT scanners, definitions of E, anthropomorphic phantoms, computers and radiation transport codes, have all fuelled an urgent need for updated organ dose conversion factors for contemporary CT. A new system for such simulations has been developed and satisfactorily tested. Benchmark comparisons of normalised organ doses presently derived for three old scanners (General Electric 9800, Philips Tomoscan LX and Siemens Somatom DRH) are within 5% of published values. Moreover, calculated normalised values of CT Dose Index for these scanners are in reasonable agreement (within measurement and computational uncertainties of ±6% and ±1%, respectively) with reported standard measurements. Organ dose coefficients calculated for a contemporary CT scanner (Siemens Somatom Sensation 16) demonstrate potential deviations by up to around 30% from the surrogate values presently assumed (through a scanner matching process) when using the ImPACT CT Dosimetry tool for newer scanners. Also, illustrative estimates of E for some typical examinations and a range of anthropomorphic phantoms demonstrate the significant differences (by some 10's of percent) that can arise when changing from the previously adopted stylised mathematical phantom to the voxel phantoms presently recommended by the International Commission on Radiological Protection (ICRP), and when following the 2007 ICRP recommendations (updated from 1990) concerning tissue weighting factors. Further simulations with the validated dosimetry system will provide updated series of dose coefficients for a wide range of contemporary scanners.
Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs ...are known to change gene expression levels, it is not clear whether each individual SCNA affects gene expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying this method to 16,172 patient-derived tumor samples, we replicated many loci with aberrant copy numbers and identified recurrently disrupted genes in genomically unstable cancers.
Although pulsed electromagnetic field (PEMF) stimulation may be clinically beneficial during fracture healing and for a wide range of bone disorders, there is still debate on its working mechanism. ...Mesenchymal stem cells are likely mediators facilitating the observed clinical effects of PEMF. Here, we performed in vitro experiments to investigate the effect of PEMF stimulation on human bone marrow-derived stromal cell (BMSC) metabolism and, specifically, whether PEMF can stimulate their osteogenic differentiation.
BMSCs derived from four different donors were cultured in osteogenic medium, with the PEMF treated group being continuously exposed to a 15 Hz, 1 Gauss EM field, consisting of 5-millisecond bursts with 5-microsecond pulses. On culture day 1, 5, 9, and 14, cells were collected for biochemical analysis (DNA amount, alkaline phosphatase activity, calcium deposition), expression of various osteoblast-relevant genes and activation of extracellular signal-regulated kinase (ERK) signaling. Differences between treated and control groups were analyzed using the Wilcoxon signed rank test, and considered significant when p < 0.05.
Biochemical analysis revealed significant, differentiation stage-dependent, PEMF-induced differences: PEMF increased mineralization at day 9 and 14, without altering alkaline phosphatase activity. Cell proliferation, as measured by DNA amounts, was not affected by PEMF until day 14. Here, DNA content stagnated in PEMF treated group, resulting in less DNA compared to control.Quantitative RT-PCR revealed that during early culture, up to day 9, PEMF treatment increased mRNA levels of bone morphogenetic protein 2, transforming growth factor-beta 1, osteoprotegerin, matrix metalloproteinase-1 and -3, osteocalcin, and bone sialoprotein. In contrast, receptor activator of NF-κB ligand expression was primarily stimulated on day 14. ERK1/2 phosphorylation was not affected by PEMF stimulation.
PEMF exposure of differentiating human BMSCs enhanced mineralization and seemed to induce differentiation at the expense of proliferation. The osteogenic stimulus of PEMF was confirmed by the up-regulation of several osteogenic marker genes in the PEMF treated group, which preceded the deposition of mineral itself. These findings indicate that PEMF can directly stimulate osteoprogenitor cells towards osteogenic differentiation. This supports the theory that PEMF treatment may recruit these cells to facilitate an osteogenic response in vivo.
The consideration of risks from medical diagnostic x-ray examinations and their justification commonly relies on estimates of effective dose, although the quantity is actually a ...health-detriment-weighted summation of organ/tissue-absorbed doses rather than a measure of risk. In its 2007 Recommendations, the International Commission on Radiological Protection (ICRP) defines effective dose in relation to a nominal value of stochastic detriment following low-level exposure of 5.7 × 10
Sv
, as an average over both sexes, all ages, and two fixed composite populations (Asian and Euro-American). Effective dose represents the overall (whole-body) dose received by a person from a particular exposure, which can be used for the purposes of radiological protection as set out by ICRP, but it does not provide a measure that is specific to the characteristics of the exposed individual. However, the cancer incidence risk models used by ICRP can be used to provide estimates of risk separately for males and females, as a function of age-at-exposure, and for the two composite populations. Here, these organ/tissue-specific risk models are applied to estimates of organ/tissue-specific absorbed doses from a range of diagnostic procedures to derive lifetime excess cancer incidence risk estimates; the degree of heterogeneity in the distribution of absorbed doses between organs/tissues will depend on the procedure. Depending on the organs/tissues exposed, risks are generally higher in females and notably higher for younger ages-at-exposure. Comparing lifetime cancer incidence risks per Sv effective dose from the different procedures shows that overall risks are higher by about a factor of two to three for the youngest age-at-exposure group, 0-9 yr, than for 30-39 yr adults, and lower by a similar factor for an age-at-exposure of 60-69 yr. Taking into account these differences in risk per Sv, and noting the substantial uncertainties associated with risk estimates, effective dose as currently formulated provides a reasonable basis for assessing the potential risks from medical diagnostic examinations.
Objective. We aimed to gain consensus on HCPs’ perspectives on self-management support information needs of patients with esophageal cancer during the preoperative phase. Methods. Based on the ...literature, observations of clinical consultations, and hospital patient information leaflets, a survey was created. HCPs were surveyed twice about their opinion on importance of information, from “not essential” to “absolutely essential,” using Delphi methods. Topics were included in the second round if predetermined criteria were met. To be included in the final list, topics had to meet criteria for consensus and stability. Results. 64 information items and 6 sources of support were identified. Survey response rates were 59% (68 out of 116, first round) and 75% thereafter. The final list included 33 topics, including logistical information, expectations for future health condition, complications, follow-up care, nutrition during treatment, and nutrition during recovery as topics with 100% agreement. Consensus on the source of support was reached for face-to-face contact, written information, information video, and a case manager. Conclusion. This study provides a list of important topics, from the perspectives of HCPs, to guide the systematic provision of education to support EC patients’ self-management during the preoperative phase. Additionally, the most preferred sources of support were face-to-face contact and a case manager.
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