Emergence of the obesity epidemic preceding the presumed obesogenic transformation of the society.

The obesity epidemic, evolving in many countries since the 1970s, has been attributed to the widespread contemporary so-called obesogenic transformation of the societies, but what preceded the epidemic? Using quantile regression, we studied the trends by year of birth in the percentile distribution of body mass index (BMI = weight/height2) of 320,962 Danish school children, born from 1930 to 1976, and of 205,153 Danish young conscripts, born from 1939 to 1959. The overall trend of the percentiles of the BMI distributions were found to be linear across the years of birth. While the percentiles below the 75th were almost stable, those above showed a steadily steeper rise the more extreme the percentile among both school children and young men is. These changes, indicating the emergence of the obesity epidemic, preceded the presumed obesogenic transformation of the society by several decades and imply that other, so far unknown, factors have been involved.

Head-To-Head Comparison of Vortioxetine Versus Desvenlafaxine in Patients With Major Depressive Disorder With Partial Response to SSRI Therapy: Results of the VIVRE Study.

Objective: To compare the efficacy of vortioxetine and the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine in patients with major depressive disorder (MDD) experiencing partial response to initial treatment with a selective serotonin reuptake inhibitor (SSRI).Methods: This randomized, double-blind, active-controlled, parallel-group, 8-week study of vortioxetine (10 or 20 mg/d; n = 309) versus desvenlafaxine (50 mg/d: n = 293) was conducted from June 2020 to February 2022 in adults with a DSM-5 diagnosis of MDD who experienced partial response to SSRI monotherapy. The primary endpoint was mean change from baseline to week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Differences between groups were analyzed using mixed models for repeated measures.Results: Non-inferiority of vortioxetine versus desvenlafaxine was established in terms of mean change from baseline to week 8 in MADRS total score; however, a numeric advantage was observed in favor of vortioxetine (difference, -0.47 MADRS points [95% CI, -1.61 to 0.67]; P = .420). At week 8, significantly more vortioxetine-treated than desvenlafaxine-treated patients had achieved symptomatic and functional remission (ie, Clinical Global Impressions-Severity of Illness scale [CGI-S] score ≤ 2) (32.5% vs 24.8%, respectively; odds ratio = 1.48 [95% CI, 1.03 to 2.15]; P = .034). Vortioxetine-treated patients also experienced significantly greater improvements in daily and social functioning assessed by the Functioning Assessment Short Test (P = .009 and .045 vs desvenlafaxine, respectively) and reported significantly greater satisfaction with their medication assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire (P = .044). Treatment-emergent adverse events (TEAEs) were reported in 46.1% and 39.6% of patients in the vortioxetine and desvenlafaxine groups, respectively; these were mostly mild or moderate in intensity (> 98% of all TEAEs in each group).Conclusions: Compared with the SNRI desvenlafaxine, vortioxetine was associated with significantly higher rates of CGI-S remission, better daily and social functioning, and greater treatment satisfaction in patients with MDD and partial response to SSRIs. These findings support the use of vortioxetine before SNRIs in the treatment algorithm in patients with MDD.Trial Registration: ClinicalTrials.gov Identifier: NCT04448431.

Clinicians' heuristic assessments of radiographs compared with Kellgren-Lawrence and Ahlbäck ordinal grading: an exploratory study of knee radiographs using paired comparisons.

OBJECTIVES: Ordinal scales provide means for communicating the severity of a condition, but they are affected by cognitive biases, they introduce statistical problems and they sacrifice resolution. Clinicians discern more details than contained in scales, for example, when assessing radiographs, but clinicians' distinctions are often based on experience-based rules of thumb, that is, heuristics. The objectives of this study are to compare clinicians' heuristic assessments to ordinal grading, to identify case elements that influence clinicians' judgements and to present a method for quantifying heuristic assessments. DESIGN: Clinicians were presented with 17 207 random pairs from a set of 1087 knee radiographs. For each pair, the radiograph with more severe osteoarthritis was selected. The Bradley-Terry model was used to calculate an osteoarthritis strength parameter for each radiograph. Similarly, strength parameters were determined for 12 morphological features with five additional features being considered either present or absent. All radiographs were also graded according to conventional ordinal systems (Kellgren-Lawrence and Ahlbäck). Relations between clinicians' judgements and (1) the heuristics-based osteoarthritis strength, (2) conventional ordinal systems and (3) morphological features were investigated. RESULTS: Receiver operating characteristic analysis showed that the Bradley-Terry model provided a good description of clinicians' assessments (area under the curve (AUC)=0.97, 95% CI 0.968 to 0.972). Morphological features (AUC=0.90, 95% CI 0.900 to 0.908) provided a superior description of clinicians' choices compared with conventional ordinal systems (AUC=0.88, 95% CI 0.878 to 0.887 and AUC=0.80, 95% CI 0.796 to 0.809) for Ahlbäck and Kellgren-Lawrence, respectively). The features most strongly associated with osteoarthritis strength were medial joint space width, flattening of the medial femoral and tibial condyles, medial osteophytes and alignment. CONCLUSIONS: Heuristics-based assessments give a better distinction than conventional grading systems of knee osteoarthritis. The example presents a general approach to evaluate which features are part of experts' heuristics. The data suggest that experts discern more details than included in conventional ordinal grading systems. Quantitative heuristic assessments may replace ordinal scales.

Atherosclerotic Lesions in the Superficial Femoral Artery (SFA) Characterized with Velocity Ratios using Vector Velocity Ultrasound.

PURPOSE: Atherosclerotic arteries are challenging to evaluate quantitatively using spectral Doppler ultrasound because of the turbulent flow conditions that occur in relation to the atherosclerotic stenoses. Vector velocity ultrasound is angle independent and provides flow information, which could potentially improve the diagnosis of arterial stenoses. The purpose of the study is to distinguish significant stenoses in the superficial femoral artery (> 50% diameter reduction) from non-significant stenoses based on velocity ratios derived from the commercially available vector velocity ultrasound technique Vector Flow Imaging (VFI). MATERIALS AND METHODS: Velocity ratios (intrastenotic blood flow velocity divided by pre- or poststenotic velocity) from a total of 16 atherosclerotic stenoses and plaques in the superficial femoral artery of 11 patients were obtained using VFI. The stenosis degree, expressed as percentage diameter reduction of the artery, was determined from digital subtraction angiography and compared to the velocity ratios. RESULTS: A velocity ratio of 2.5 was found to distinguish clinically relevant stenoses with>50% diameter reduction from clinically non-relevant stenoses with<50% diameter reduction and the difference was statistically significant. CONCLUSION: The study indicates that VFI is a potential future tool for the evaluation of arterial stenoses.

Vector Flow Imaging Compared with Conventional Doppler Ultrasound and Thermodilution for Estimation of Blood Flow in the Ascending Aorta.

Transverse oscillation (TO) is a real-time ultrasound vector flow method implemented on a commercial scanner. The TO setup was examined on a flowrig with constant and pulsatile flow. Subsequently, 25 patients undergoing cardiac bypass surgery were scanned intraoperatively with TO on the ascending aorta and compared to transesophageal echocardiography (TEE) and pulmonary artery catheter thermodilution (PACTD). On the flowrig, TO had a precision of 5.5%, 9.4% and 14.7%, a percentage error of 18.2%, 14.6% and 40.7%, and a mean bias of 0.4 cm/s, 36.8 ml/min and 32.4 ml/min for velocity and flow rate (constant and pulsatile) estimation. The correlation coefficients for all flowrig evaluations were 0.99 indicating systematic bias. After bias correction, the percentage error was reduced to 11.5%, 12.6% and 15.9% for velocity and flow rate (constant and pulsatile) estimation. In the in vivo setup, TO, TEE, and PACTD had a precision of 21.9%, 13.7%, and 12.0%. TO compared with TEE and PACTD had a mean bias of 12.6 cm/s and -0.08 l/min, and a percentage error of 23.4%, and 36.7%, respectively. The percentage error was reduced to 22.9% for the TEE comparison, but increased to 43.8% for the PACTD comparison, after correction for the systematic bias found in the flowrig. TO is a reliable and precise method for velocity and flow rate estimation on a flowrig. However, TO with the present setup, is not interchangeable with PACTD for cardiac volume flow estimation, but is a reliable and precise angle-independent ultrasound alternative for velocity estimation of cardiac flow.

Intra-Operative Vector Flow Imaging Using Ultrasound of the Ascending Aorta among 40 Patients with Normal, Stenotic and Replaced Aortic Valves.

Stenosis of the aortic valve gives rise to more complex blood flows with increased velocities. The angle-independent vector flow ultrasound technique transverse oscillation was employed intra-operatively on the ascending aorta of (I) 20 patients with a healthy aortic valve and 20 patients with aortic stenosis before (IIa) and after (IIb) valve replacement. The results indicate that aortic stenosis increased flow complexity (p < 0.0001), induced systolic backflow (p < 0.003) and reduced systolic jet width (p < 0.0001). After valve replacement, the systolic backflow and jet width were normalized (p < 0.52 and p < 0.22), but flow complexity was not (p < 0.0001). Flow complexity (p < 0.0001), systolic jet width (p < 0.0001) and systolic backflow (p < 0.001) were associated with peak systolic velocity. The study found that aortic stenosis changes blood flow in the ascending aorta and valve replacement corrects some of these changes. Transverse oscillation may be useful for assessment of aortic stenosis and optimization of valve surgery.

Analysis of Systolic Backflow and Secondary Helical Blood Flow in the Ascending Aorta Using Vector Flow Imaging.

Secondary rotational flow and systolic backflow are seen in the ascending aorta and, in this study, were analyzed with the vector velocity method transverse oscillation. Twenty-five patients were scanned intra-operatively, and the vector velocities were related to estimates of transesophageal echocardiography and pulmonary artery catheter thermodilution, and associated with gender, age, aortic diameter, atherosclerotic plaques, left ventricular ejection fraction and previous myocardial infarctions. Secondary flow was present for all patients. The duration and rotational frequency (p < 0.001) and the duration and flow direction of the secondary flow (p < 0.002) were associated. Systolic backflow was present in 40% of the patients and associated with systolic velocities (p < 0.002) and the presence of atherosclerotic plaques (p < 0.001). No other significant associations were observed. The study indicates that backflow is injurious and that secondary flow is a normal flow phenomenon. The study also shows that transverse oscillation can provide new information on blood flow in the ascending aorta.

First report on intraoperative vector flow imaging of the heart among patients with healthy and diseased aortic valves.

The vector velocity method Transverse Oscillation (TO) implemented on a conventional ultrasound (US) scanner (ProFocus, BK Medical, Herlev, Denmark) can provide real-time, angle-independent estimates of the cardiac blood flow. During cardiac surgery, epicardial US examination using TO was performed on (A) 3 patients with healthy aortic valve and (B) 3 patients with aortic valve stenosis. In group B, the systolic flow of the ascending aorta had higher velocities, was more aliased and chaotic. The jet narrowed to 44% of the lumen compared to 75% in group A and with a vector concentration, a measure of flow complexity, of 0.41 compared to 0.87 in group A. The two groups had similar secondary flow of the ascending aorta with an average rotation frequency of 4.8 Hz. Simultaneous measurements were obtained with spectral Doppler (SD) and a thermodilution technique (TD). The mean difference in peak systolic velocity compared to SD in group A was 22% and 45% in B, while the mean difference in volume flow compared to TD in group A was 30% and 32% in B. TO can potentially reveal new information of cardiac blood flow, and may become a valuable diagnostic tool in the evaluation of patients with cardiovascular diseases.

Volume flow in arteriovenous fistulas using vector velocity ultrasound.

Volume flow in arteriovenous fistulas for hemodialysis was measured using the angle-independent ultrasound technique Vector Flow Imaging and compared with flow measurements using the ultrasound dilution technique during dialysis. Using an UltraView 800 ultrasound scanner (BK Medical, Herlev, Denmark) with a linear transducer, 20 arteriovenous fistulas were scanned directly on the most superficial part of the fistula just before dialysis. Vector Flow Imaging volume flow was estimated with two different approaches, using the maximum and the average flow velocities detected in the fistula. Flow was estimated to be 242 mL/min and 404 mL/min lower than the ultrasound dilution technique estimate, depending on the approach. The standard deviations of the two Vector Flow Imaging approaches were 175.9 mL/min and 164.8 mL/min compared with a standard deviation of 136.9 mL/min using the ultrasound dilution technique. The study supports that Vector Flow Imaging is applicable for volume flow measurements.

Novel flow quantification of the carotid bulb and the common carotid artery with vector flow ultrasound.

Abnormal blood flow is usually assessed using spectral Doppler estimation of the peak systolic velocity. The technique, however, only estimates the axial velocity component, and therefore the complexity of blood flow remains hidden in conventional ultrasound examinations. With the vector ultrasound technique transverse oscillation the blood velocities of both the axial and the transverse directions are obtained and the complexity of blood flow can be visualized. The aim of the study was to determine the technical performance and interpretation of vector concentration as a tool for estimation of flow complexity. A secondary aim was to establish accuracy parameters to detect flow changes/patterns in the common carotid artery (CCA) and the carotid bulb (CB). The right carotid bifurcation including the CCA and CB of eight healthy volunteers were scanned in a longitudinal plane with vector flow ultrasound (US) using a commercial vector flow ultrasound scanner (ProFocus, BK Medical, Denmark) with a linear 5 MHz transducer transverse oscillation vector flow software. CCA and CB areas were marked in one cardiac cycle from each volunteer. The complex flow was assessed by medical expert evaluation and by vector concentration calculation. A vortex with complex flow was found in all carotid bulbs, whereas the CCA had mainly laminar flow. The medical experts evaluated the flow to be mainly laminar in the CCA (0.82 ± 0.14) and mainly complex (0.23 ± 0.22) in the CB. Likewise, the estimated vector concentrations in CCA (0.96 ± 0.16) indicated mainly laminar flow and in CB (0.83 ± 0.07) indicated mainly turbulence. Both methods were thus able to clearly distinguish the flow patterns of CCA and CB in systole. Vector concentration from angle-independent vector velocity estimates is a quantitative index, which is simple to calculate and can differentiate between laminar and complex flow.

Intraoperative cardiac ultrasound examination using vector flow imaging.

Conventional ultrasound (US) methods for blood velocity estimation only provide one-dimensional and angle-dependent velocity estimates; thus, the complexity of cardiac flow has been difficult to measure. To circumvent these limitations, the Transverse Oscillation (TO) vector flow method has been proposed. The vector flow method implemented on a commercial scanner provided real-time, angle-independent estimates of cardiac blood flow. Epicardiac and epiaortic, intraoperative US examinations were performed on three patients with stenosed coronary arteries scheduled for bypass surgery. Repeating cyclic beat-to-beat flow patterns were seen in the ascending aorta and pulmonary artery of each patient, but these patterns varied between patients. Early systolic retrograde flow filling the aortic sinuses was seen in the ascending aorta as well as early systolic retrograde flow in the pulmonary artery. In diastole, stable vortices in aortic sinuses of the ascending aorta created central antegrade flow. A stable vortex in the right atrium was seen during the entire heart cycle. The measurements were compared with estimates obtained intraoperatively with conventional spectral Doppler US using a transesophageal and an epiaortic approach. Mean differences in peak systole velocity of 11% and 26% were observed when TO was compared with transesophageal echocardiography and epiaortic US, respectively. In one patient, the cardiac output derived from vector velocities was compared with pulmonary artery catheter thermodilution technique and showed a difference of 16%. Vector flow provides real-time, angle-independent vector velocities of cardiac blood flow. The technique can potentially reveal new information of cardiovascular physiology and give insight into blood flow dynamics.

Categorization of aortic aneurysm thrombus morphology by magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) has been proposed for qualitative categorization of intraluminal thrombus morphology. We aimed to correlate the qualitative MRI categorization previously described to quantitative measurements of signal intensity and to compare morphological characteristics of intraluminal thrombus specimens to the appearance on magnetic resonance imaging. METHODS: Thirty-four patients undergoing open surgery for abdominal aortic aneurysm had a preoperative MRI obtained with a 1.5 T magnet. Qualitative categorization was performed (blinded and in consensus) and correlated to intraluminal thrombus to muscle signal-intensity ratios. Morphology of intraluminal thrombus specimens collected during surgery were compared to the magnetic resonance imaging categories and specimen weight was correlated to thrombus volume measured on preoperative computer tomography angiography. RESULTS: Blinded MRI categorization resulted in agreement in 22 out of 34 intraluminal thrombi (Kappa value 0.3, p=0.006). Medians (p=0.004) and distribution (p=0.002) of signal-intensity ratios varied significantly across the three MRI categories obtained by consensus. Heterogeneous and homogenous specimen appearance corresponded to similar appearances on MRI in 78% and 55% respectively, resulting in an overall Kappa=0.4 (p=0.04). Intraluminal thrombus volume and weight correlated well (rs 0.831, p<0.001) with a mean difference of 60 g (95% CI 38-80 g), without proportional bias. CONCLUSION: Qualitative evaluation of intraluminal thrombus morphology based on MRI can be quantified by measuring signal-intensity ratios. Concurrently a fair agreement to blinded qualitative evaluation of thrombus specimens can be obtained. However, the evaluation is impaired by loss of a large proportion of thrombus during sampling.

Implementation of a versatile research data acquisition system using a commercially available medical ultrasound scanner.

This paper describes the design and implementation of a versatile, open-architecture research data acquisition system using a commercially available medical ultrasound scanner. The open architecture will allow researchers and clinicians to rapidly develop applications and move them relatively easy to the clinic. The system consists of a standard PC equipped with a camera link and an ultrasound scanner equipped with a research interface. The ultrasound scanner is an easy-to-use imaging device that is capable of generating high-quality images. In addition to supporting the acquisition of multiple data types, such as B-mode, M-mode, pulsed Doppler, and color flow imaging, the machine provides users with full control over imaging parameters such as transmit level, excitation waveform, beam angle, and focal depth. Beamformed RF data can be acquired from regions of interest throughout the image plane and stored to a file with a simple button press. For clinical trials and investigational purposes, when an identical image plane is desired for both an experimental and a reference data set, interleaved data can be captured. This form of data acquisition allows switching between multiple setups while maintaining identical transducer, scanner, region of interest, and recording time. Data acquisition is controlled through a graphical user interface running on the PC. This program implements an interface for third-party software to interact with the application. A software development toolkit is developed to give researchers and clinicians the ability to utilize third-party software for data analysis and flexible manipulation of control parameters. Because of the advantages of speed of acquisition and clinical benefit, research projects have successfully used the system to test and implement their customized solutions for different applications. Three examples of system use are presented in this paper: evaluation of synthetic aperture sequential beamformation, transverse oscillation for blood velocity estimation, and acquisition of spectral velocity data for evaluating aortic aneurysms.

Comparison of real-time in vivo spectral and vector velocity estimation.

The purpose of this study is to show whether a newly introduced vector flow method is equal to conventional spectral estimation. Thirty-two common carotid arteries of 16 healthy volunteers were scanned using a BK Medical ProFocus scanner (DK-2730, Herlev, Denmark) and a linear transducer at 5 MHz. A triplex imaging sequence yields both the conventional velocity spectrum and a two-dimensional vector velocity image. Several clinical parameters were estimated and compared for the two methods: Flow angle, peak systole velocity (PS), end diastole velocity (ED) and resistive index (RI). With a paired t-test, the spectral and vector angles did not differ significantly (p = 0.658), whereas PS (p = 0.034), ED (p = 0.004) and RI (p < 0.0001) differed significantly. Vector flow can measure the angle for spectral angle correction, thus eliminating the bias from the radiologist performing the angle setting with spectral estimation. The flow angle limitation in velocity estimation is also eliminated, so that flow at any angle can be measured.

Three-dimensional synthetic aperture focusing using a rocking convex array transducer.

Volumetric imaging can be performed using 1-D arrays in combination with mechanical motion. Outside the elevation focus of the array, the resolution and contrast quickly degrade compared with the lateral plane, because of the fixed transducer focus. This paper shows the feasibility of using synthetic aperture focusing for enhancing the elevation focus for a convex rocking array. The method uses a virtual source (VS) for defocused multi-element transmit, and another VS in the elevation focus point. This allows a direct time-of-flight to be calculated for a given 3-D point. To avoid artifacts and increase SNR at the elevation VS, a plane-wave VS approach has been implemented. Simulations and measurements using an experimental scanner with a convex rocking array show an average improvement in resolution of 26% and 33%, respectively. This improvement is also seen in in vivo measurements. An evaluation of how a change in transducer design will affect the resolution improvement shows a potential for using a modified transducer for 3-D imaging with improved elevation focusing and contrast.

A comparison of colour micrographs obtained with a charged couple device (CCD) camera and a 35-mm camera.

PURPOSE: The purpose of this study was to determine if micrographs produced with a colour charged couple device (CCD) camera were comparable in quality to micrographs obtained with a 35-mm colour film camera. The Axiocam (Zeiss, Jena, Germany) CCD camera produced images of 3900 x 3090 pixels. METHODS: Each picture in a series of 50 pairs of film and digital micrographs was rated independently by each of three observers on the categories of colour, detail and overall impression. A total of 28 of the 50 pairs of micrographs were discarded due to colour differences. RESULTS: Digital micrographs were rated lower on colour and higher on detail compared to film micrographs. The film and digital micrographs were rated equally on overall impression. The difference in colour between film and digital micrographs can be compensated for using image processing software on the digital image. However, such manipulation was not carried out as part of the present study. The study originally included 50 digital micrographs and 50 film micrographs. The micrographs were paired and 22 of the 50 pairs of micrographs were assessed. Thus 28 pairs were not evaluated due to colour differences in the non-manipulated pictures. The interobserver difference on colour in the remaining 22 pairs given as mean square +/- standard error of the mean was - 0.27 +/- 0.10, 0.62 +/- 0.10 and 0.90 +/- 0.11. The interobserver difference on detail was - 0.48 +/- 0.10, 0.95 +/- 0.10 and 1.43 +/- 0.10. The interobserver difference on overall impression was - 0.70 +/- 0.10, 0.57 +/- 0.10 and 1.27 +/- 0.10. All the results differed significantly (p < 0.001). CONCLUSION: Digital micrographs are sufficient in detail, colour and overall impression to replace the traditional 35-mm film recordings for use in histopathology.