Increasing abdominal aortic aneurysm curvature visibility using 3D dual probe bistatic ultrasound imaging combined with probe translation.

High frame rate ultrasound (US) imaging techniques in 3D are promising tools for capturing abdominal aortic aneurysms (AAAs) over time, however, with the limited number of channel-to-element connections current footprints are small, which limits the field of view. Moreover, the maximal steering angle of the ultrasound beams in transmit and the maximal receptance angle in receive are insufficient for capturing the curvy shape of the AAA. Therefore, an approach is needed towards large arrays. In this study, high frame rate bistatic 3D US data (17 Hz) were acquired with two synchronized matrix arrays positioned at different locations (multi-aperture imaging) using a translation stage to simulate what a larger array with limited channel-to-element connections can potentially achieve. Acquisitions were performed along an AAA shaped phantom with different probe tilting angles (0 up to ± 30°). The performance of different multi-aperture configurations was quantified using the generalized contrast-to-noise ratio of the wall and lumen (gCNR). Furthermore, a parametric model of the multi-aperture system was used to estimate in which AAA wall regions the contrast is expected to be high. This was evaluated for AAAs with increasing diameters and curvature. With an eight-aperture 0° probe angle configuration a 69 % increase in field of view was measured in the longitudinal direction compared to the field of view of a single aperture configuration. When increasing the number of apertures from two to eight, the gCNR improved for the upper wall and lower wall by 35 % and 13 % (monostatic) and by 36 % and 13 % (bistatic). Contrast improvements up to 22 % (upper wall) and 12 % (lower wall) are achieved with tilted probe configurations compared to non-tilted configurations. Moreover, with bistatic imaging with tilted probe configurations gCNR improvements up to 4 % (upper wall) and 7 % (lower wall) are achieved compared to monostatic imaging. Furthermore, imaging with a larger inter-probe distance improved the gCNR for a ± 15° probe angle configuration. The gCNR has an expected pattern over time, where the contrast is lower when there is more wall motion (systole) and higher when motion is reduced (diastole). Furthermore, a higher frame rate (45 Hz) yields a lower gCNR, because fewer compound angles are used. The results of the parametric model suggest that a flat array is suitable for imaging AAA shapes with limited curvature, but that it is not suitable for imaging larger AAA shapes with more curvature. According to the model, tilted multi-aperture configurations combined with bistatic imaging can achieve a larger region with high contrast compared to non-tilted configurations. The findings of the model are in agreement with experimental findings. To conclude, this study demonstrates the vast improvements in field of view and AAA wall visibility that a large, sparsely populated 3D array can potentially achieve when imaging AAAs compared to single or dual aperture imaging. In the future, larger arrays, less thermal noise, more steering, and more channel-to-element connections combined with carefully chosen orientations of (sub-) apertures will likely advance 3D imaging of AAAs.

Testing the applicability and additional value of a consultation round after the consensus meeting in the development of two core outcome sets.

OBJECTIVES: Test applicability and additional value of a consultation round after the consensus meeting in the development of core outcome sets (COSs). STUDY DESIGN AND SETTING: In two COS procedures (Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints (COSGROVE) and Definition and Core Outcomes on Hyperemesis Gravida (DCOHG)) that followed the Core Outcome Measures in Effectiveness Trials methodology, the first round of convergence to consensus among stakeholder groups in an online Delphi procedure was followed by a face-to-face consensus meeting during which a COS was formulated. We subsequently presented the COS to the online panel in a consultation round to confirm that the online panel agreed with the choices made at the consensus meeting, defined as 80% agreement. PARTICIPANTS: In the COSGROVE Study, there were eight stakeholder groups, and 83 out of 107 participants completed the consultation round. In the DCOHG Study, there were four stakeholder groups, and 96 out of 125 completed the consultation round. INTERVENTIONS: Adding a consultation round after completing a modified Delphi method with a consensus meeting. RESULTS: There was a level of agreement of 81% and 84%, respectively, in the consultation round of both procedures. This was above the preset level of agreement. The consultation round yielded additional suggestions to refine COS formulation in one of the studies. CONCLUSION: Our study shows that in two procedures, the online expert panel agreed with the participants of the consensus meeting in these procedures, lending validity to existing COS methodology. Future studies could evaluate whether bringing back the COS for confirmation after the consensus meeting could potentially increase the uptake of the final COS.

Perinatal outcomes of infants born to mothers with hyperemesis gravidarum: A systematic review and meta-analysis.

BACKGROUND: Hyperemesis gravidarum is the severe form of nausea and vomiting during pregnancy and can lead to undernutrition and low maternal weight gain. Previous epidemiologic and animal studies have shown that undernutrition and low maternal weight gain in pregnancy can increase the risk of unfavorable perinatal outcomes, like shorter gestational age, small for gestational age and lower weight at birth. OBJECTIVE: To evaluate the effect of hyperemesis gravidarum on perinatal outcomes. SEARCH STRATEGY: OVID Medline and Embase were searched from inception to February 9th, 2022. STUDY ELIGIBILITY: Studies reporting on perinatal outcomes of infants born to mothers with hyperemesis gravidarum or severe nausea and vomiting in pregnancy were included. Case reports, case series, animal studies, reviews, editorials and conference abstracts were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected and extracted data. Risk of bias was assessed by the Newcastle-Ottawa Quality Assessment Scale. We conducted meta-analyses where possible. RESULTS: Our search yielded 1387 unique papers, of which 61 studies (n = 20,532,671 participants) were included in our systematic review. Meta-analyses showed that hyperemesis gravidarum was associated with preterm birth < 34 weeks (2 studies n = 2,882: OR 2.81, 95 %CI: 1.69-4.67), birth weight < 1500 g (2 studies, n = 489,141: OR 1.43, 95 %CI: 1.02-1.99), neonatal resuscitation (2 studies, n = 4,289,344: OR 1.07, 95 %CI: 1.05-1.10), neonatal intensive care unit admission (7 studies, n = 6,509,702: OR 1.20, 95 %CI: 1.14-1.26) and placental abruption (6 studies, n = 9,368,360: OR 1.15, 95 %CI: 1.05-1.25). Hyperemesis gravidarum was associated with reductions in birthweight > 4000 g (2 studies, n = 5,503,120: OR 0.74, 95 %CI: 0.72-0.76) and stillbirth (9 studies, n = 3,973,154: OR 0.92, 95 %CI: 0.85-0.99). Meta-analyses revealed no association between hyperemesis gravidarum and Apgar scores < 7 at 1 and 5 min; fetal loss, perinatal deaths and neonatal deaths. CONCLUSION: Hyperemesis gravidarum is associated with several adverse perinatal outcomes including low birth weight and preterm birth. We also found that pregnancies complicated by hyperemesis gravidarum less frequently were complicated by macrosomia and stillbirth. We were unable to investigate underlying mechanisms.

Long-term health outcomes of children born to mothers with hyperemesis gravidarum: a systematic review and meta-analysis.

OBJECTIVE: Hyperemesis gravidarum is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficiency. Maternal undernutrition is associated with adverse offspring health outcomes. Whether hyperemesis gravidarum permanently affects offspring health remains unclear. This review aimed to evaluate the effects of maternal hyperemesis gravidarum on offspring health. DATA SOURCES: MEDLINE and Embase were searched from inception to September 6, 2021. STUDY ELIGIBILITY CRITERIA: Studies reporting on health at any age beyond the perinatal period of children born to mothers with hyperemesis gravidarum were included. METHODS: Two reviewers independently selected studies and extracted data. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. We conducted a narrative synthesis and meta-analysis where possible. In meta-analyses with high heterogeneity (I2>75%), we did not provide a pooled odds ratio. RESULTS: Nineteen studies were included in this systematic review (n=1,814,785 offspring). Meta-analysis (n=619, 2 studies: 1 among adolescents and 1 among adults) showed that hyperemesis gravidarum was associated with anxiety disorder (odds ratio, 1.74; 95% confidence interval, 1.04-2.91; I2, 0%) and sleep problems in offspring (odds ratio, 2.94; 95% confidence interval, 1.25-6.93; I2, 0%). Hyperemesis gravidarum was associated with testicular cancer in male offspring aged up to 40 years on meta-analysis (5 studies, n=20,930 offspring), although heterogeneity was observed on the basis of a wide 95% prediction interval (odds ratio, 1.60; 95% confidence interval, 1.07-2.39; I2, 0%; 95% prediction interval, 0.83-3.08). All 6 studies reporting on attention deficit (hyperactivity) disorder and autism spectrum disorder reported an increase among children of mothers with hyperemesis gravidarum in comparison with children of unaffected mothers. Meta-analysis showed high heterogeneity, precluding us from reporting a pooled odds ratio. Most studies reporting on cognitive and motor problems found an increase among hyperemesis gravidarum-exposed children. One study investigated brain structure and found smaller cortical volumes and areas among children from hyperemesis gravidarum-affected pregnancies than among those from unaffected pregnancies. Studies evaluating anthropometry and cardiometabolic disease risk of hyperemesis gravidarum-exposed children had inconsistent findings. CONCLUSION: Our systematic review showed that maternal hyperemesis gravidarum is associated with small increases in adverse health outcomes among children, including neurodevelopmental disorders, mental health disorders, and possibly testicular cancer, although evidence is based on few studies of low quality.

Systematic assessment of acquisition and data-processing parameters in the suspect screening of veterinary drugs in archive matrices using LC-HRMS.

Monitoring strategies for veterinary drugs in products of animal origin are shifting towards a more risk-based approach. Such strategies not only target a limited number of predefined .substances but also facilitate detection of unexpected substances. By combining the use of archive matrices such as feather meal with suspect-screening methods, early detection of new hazards in the food and feed industry can be achieved. Effective application of such strategies is hampered by complex data interpretation and therefore, targeted data analysis is commonly applied. In this study, the performance of a suspect-screening data processing workflow using a suspect list or the online spectral database mzCloudTM was explored to facilitate detection of veterinary drugs in archive matrices. Data evaluation parameters specifically investigated for application of a suspect list were mass tolerance and the addition or omission of retention times. Application of a mass tolerance of 1.5 ppm leads to an increase in the number of false positives, as does omission of retention times in the suspect list. Different acquisition modes yielding different qualities of MS2 data were studied and proved to be a critical factor, where data-dependent acquisition is preferred when matching to the mzCloudTM database. Using this approach, it is possible to search for compounds on a dedicated suspect list based on the exact mass and retention times and, at the same time, detect unexpected compounds without a priori information. A pilot study was conducted and fourteen different antibiotics were detected (and confirmed by MS/MS). Three of these antibiotics were not included in the suspect list. The optimised suspect-screening method proved to be fit for the purpose of finding veterinary drugs in feather meal, which are not in the scope of the current monitoring methods and therefore, it gives added value in the perspective of a risk-based monitoring.

Local and global distensibility assessment of abdominal aortic aneurysms in vivo from probe tracked 2D ultrasound images.

Rupture risk estimation of abdominal aortic aneurysm (AAA) patients is currently based on the maximum diameter of the AAA. Mechanical properties that characterize the mechanical state of the vessel may serve as a better rupture risk predictor. Non-electrocardiogram-gated (non-ECG-gated) freehand 2D ultrasound imaging is a fast approach from which a reconstructed volumetric image of the aorta can be obtained. From this 3D image, the geometry, volume, and maximum diameter can be obtained. The distortion caused by the pulsatility of the vessel during the acquisition is usually neglected, while it could provide additional quantitative parameters of the vessel wall. In this study, a framework was established to semi-automatically segment probe tracked images of healthy aortas (N = 10) and AAAs (N = 16), after which patient-specific geometries of the vessel at end diastole (ED), end systole (ES), and at the mean arterial pressure (MAP) state were automatically assessed using heart frequency detection and envelope detection. After registration AAA geometries were compared to the gold standard computed tomography (CT). Local mechanical properties, i.e., compliance, distensibility and circumferential strain, were computed from the assessed ED and ES geometries for healthy aortas and AAAs, and by using measured brachial pulse pressure values. Globally, volume, compliance, and distensibility were computed. Geometries were in good agreement with CT geometries, with a median similarity index and interquartile range of 0.91 [0.90-0.92] and mean Hausdorff distance and interquartile range of 4.7 [3.9-5.6] mm. As expected, distensibility (Healthy aortas: 80 ± 15·10-3 kPa-1; AAAs: 29 ± 9.6·10-3 kPa-1) and circumferential strain (Healthy aortas: 0.25 ± 0.03; AAAs: 0.15 ± 0.03) were larger in healthy vessels compared to AAAs. Circumferential strain values were in accordance with literature. Global healthy aorta distensibility was significantly different from AAAs, as was demonstrated with a Wilcoxon test (p-value = 2·10-5). Improved image contrast and lateral resolution could help to further improve segmentation to improve mechanical characterization. The presented work has demonstrated how besides accurate geometrical assessment freehand 2D ultrasound imaging is a promising tool for additional mechanical property characterization of AAAs.

The vertical transmission of antibiotic residues from parent hens to broilers.

Imprudent and superfluous use of antibiotics contributes to the selection of resistant bacteria, which is a large threat to human health. Therefore analytical procedures have been implemented in the poultry production sector to check if antibiotic treatments are registered, aiming to achieve more prudent use of antibiotics. These methods rely on the analysis of feathers, a matrix in which antibiotic residues persist. However, other routes besides direct administration, through which poultry feathers could contain antibiotic residues, should also be taken into account. In this research the vertical transmission from parent hen to broiler was investigated through a controlled animal study for the antibiotics enrofloxacin, doxycycline and sulfachlorpyridazine. Vertical transmission was observed for all antibiotics to both egg and egg shell. Also it is demonstrated that the transferred antibiotics from parent hen to chick are subsequently excreted via the chick's droppings. Through this route, the broilers' environment is contaminated. If eggs are hatched that were taken during treatment of the parent hen, this indirect route and/or the direct vertical transmission can eventually result in the detection of low concentrations of antibiotic residues in the broilers' feathers at greater age: <50 µg kg-1 for freely extractable residues and <10 µg kg-1 for non-freely extractable residues. No antibiotics were detected in the broilers' muscle or kidney from 4 weeks of age. This research provides relevant information regarding the possible amount of residues originating from vertical transmission when monitoring matrices such as feathers and broiler droppings in order to stimulate correct use and registration of antibiotics in the poultry sector.

A new extraction procedure to abate the burden of non-extractable antibiotic residues in manure.

Through agricultural soil fertilization using organic manure, antibiotic residues can accumulate in the environment. In order to assess the risks of environmental pollution by veterinary drugs, monitoring of manure for antibiotic residues is necessary. As manure is a complex matrix, extraction of antibiotics proved to be challenging. In this study, 24 extraction solvents were assessed for the extraction of residues from manure representing ten antibiotics from the antibiotic classes tetracyclines, quinolones, macrolides, lincosamides and sulfonamides. Especially for the tetracyclines and quinolones the extraction solvent selection is critical, due to high fractions of non-extractable residues especially when using aqueous solvents (62-77% and 90-95% respectively when using milli-Q water). In contrast, sulfonamides can effectively be extracted with aqueous solvents. Overall, 0.125% trifluoroacetic acid in acetonitrile in combination with McIlvain-EDTA buffer proved to be the most effective extraction solvent. A longitudinal study pointed out that most antibiotics bind to solid manure particles instantaneously after addition. Trimethoprim is an exception, but because by using the optimal extraction solvent, the optimum fraction of bound residues is desorbed, this does not hamper quantitative analysis when using spiked manure quality control samples. Based on these new insights, the current in-house multi-residue LC-MS/MS method for manure analysis, containing 48 antibiotics, was revised, additionally validated and applied to 34 incurred manure samples.

The analysis of tetracyclines, quinolones, macrolides, lincosamides, pleuromutilins, and sulfonamides in chicken feathers using UHPLC-MS/MS in order to monitor antibiotic use in the poultry sector.

In The Netherlands, all antibiotic treatments should be registered at the farm and in a central database. To enforce correct antibiotic use and registration, and to enforce prudent use of antibiotics, there is a need for methods that are able to detect antibiotic treatments. Ideally, such a method is able to detect antibiotic applications during the entire lifespan of an animal, including treatments administered during the first days of the animals' lives. Monitoring tissue, as is common practice, only provides a limited window of opportunity, as residue levels in tissue soon drop below measurable quantities. The analysis of feathers proves to be a promising tool in this respect. Furthermore, a qualitative confirmatory method was developed for the analyses of six major groups of antibiotics in ground chicken feathers, aiming for a detection limit as low as reasonably possible. The method was validated according to Commission Decision 2002/657/EC. All compounds comply with the criteria and, as a matter of fact, 58% of the compounds could also be quantified according to regulations. Additionally, we demonstrated that a less laborious method, in which whole feathers were analyzed, proved successful in the detection of applied antibiotics. Most compounds could be detected at levels of 2 µg kg-1 or below with the exception of sulfachloropyridazine, tylosin, and tylvalosin. This demonstrates the effectiveness of feather analysis to detect antibiotic use to allow effective enforcement of antibiotic use and prevent the illegal, off-label, and nonregistered use of antibiotics.

Feather segmentation to discriminate between different enrofloxacin treatments in order to monitor off-label use in the poultry sector.

Antibiotics are commonly used in the poultry industry to treat bacterial infections. In the combat against bacterial resistance, policies require, besides a reduction of antibiotic usage in humans and animals, an up-to-date farmer registration mentioning all treatments. For enforcement of such policies, tests are needed to antedate administration and to determine the type of treatment so as to prevent off-label use and the supervacaneous use of last-resort antibiotics like cephalosporins and fluoroquinolones. After poultry treatment, high amounts of enrofloxacin and its metabolite ciprofloxacin are deposited in chicken feathers. A method is presented to discriminate different treatments based on differentiating extractable and non-extractable enrofloxacin and ciprofloxacin in chicken feathers. With this approach, we show it is possible to distinguish between a registered therapeutic oral treatment, an off-label spray treatment and an illegal prolonged sub-therapeutic treatment with enrofloxacin. This approach is a new and strong tool in the enforcement of new policies in the fight against off-label and supervacaneous antibiotic use.

The disposition of oxytetracycline to feathers after poultry treatment.

In the combat against bacterial resistance, there is a clear need to check the use of antibiotics in animal husbandry, including poultry breeding. The use of chicken feathers as a tool for the detection of use of antibiotics was investigated. An extraction method for the analysis of oxytetracycline (OTC) from feathers was developed and was tested by using incurred feathers obtained from a controlled animal treatment study. The use of McIlvain-ethylenediaminetetraacetic acid buffer only in combination with acetone gave the highest extraction yield, indicating the need of an organic solvent for feather extraction. By using the developed method, it was found that after a withdrawal time, the OTC concentration in feathers is in the mg kg⁻¹ range, far higher than that in muscle and liver tissue. Based on the analysis of individual segments of feathers from OTC-treated chicken, evidence was found supporting the hypothesis of secretion of antibiotics through the uropygial gland and external spread over feathers by grooming behaviour. It was also found that part of the administered OTC is built into the feather rachis. Finally, we provide the first evidence that the analysis of individual segments of the rachis can be used as a tool to discriminate among different treatment strategies, for example, therapeutic versus subtherapeutic. As a result, we concluded that the analysis of feathers is an extremely valuable tool in residue analysis of antibiotics.