Concordance of three alternative gestational age assessments for pregnant women from four African countries: A secondary analysis of the MIPPAD trial

Background: At times, ultrasound is not readily available in low resource countries in Africa for accurate determination of gestational age, so using alternative methods is pivotal during pregnancy. These assessments are used to aid the risk analysis for an infant and management strategies for premature delivery, if necessary. Currently, date of last menstrual period, fundal height measurements, and the New Ballard Score are commonly used in resource-limited settings. However, concordance of these measures is unknown for sub-Saharan Africa. We obtained data from an open-label randomized controlled trial, to assess the concordance of these alternative assessment methods. The purpose of our study was to determine the agreement between these alternative methods when used in sub-Saharan African populations. Methods: A total of 4,390 pregnant women from Benin, Gabon, Mozambique and Tanzania were included in our analysis. The assessment methods compared were: 1) reported last menstrual period, 2) symphysis-fundal height measurement, and 3) the New Ballard Score. The Bland-Altman method and intraclass correlation coefficient (ICC) were used to test the degree of agreement. Survival range gestational age, used as an inclusion criterion for further analysis, was from 22 to 44 weeks. Findings: Plots showed a lack of agreement between methods and the 95% limits of agreement too wide to be clinically useful. ICC = 0.25 indicated poor agreement. A post-hoc analysis, restricted from 32 to 42 weeks, was done to check for better agreement in this near-term population. The plots and ICC = 0.16 still confirmed poor agreement. Conclusion: The alternative assessments do not result in comparable outcomes and discrepancies are far beyond the clinically acceptable range. Last menstrual period should not be used as the only estimator of gestational age. In the absence of reliable early ultrasound, symphysis-fundal height measurements may be most useful during pregnancy for fetal risk assessment and the New Ballard Score after delivery as a confirmation of these estimations and for further neonatal management. However, promotion of portable ultrasound devices is required for accurate assessment of gestational age in sub-Sahara Africa

Bayesian methods in reliability theory

Abweichender Titel nach Übersetzung der Verfasserin/des VerfassersIn dieser Arbeit werden statistische Methoden der Zuverlässigkeitstheorie unter einer Bayesschen Sichtweise behandelt. Die Prinzipien der Bayes Statistik werden ausgehend vom zentralen Satz von Bayes über die Wahl einer geeigneten A-priori Verteilung bis zur Entscheidungsfindung auf Basis der A-posteriori Verteilung vorgestellt. Eine Besonderheit von Daten aus Zuverlässigkeitsversuchen ist, dass aus verschiedenen Gründen, nicht für alle Versuchseinheiten eine Ausfallzeit beobachtet werden kann, die Daten sind daher in der Regel zensiert. Für häufig angewandte Lebensdauerverteilungen wie die Exponentialund die Weibullverteilung werden sowohl klassische statistische Schätzverfahren für zensierte Daten sowie Bayessche Verfahren behandelt. Ein besonderer Fokus der Arbeit liegt auf der Bayesschen Analyse von beschleunigten Lebensdauermodellen. Dabei werden die Bauteile unter erhöhtem Stress (z.B. erhöhter Temperatur oder Spannung) getestet, mit dem Ziel in kürzerer Zeit mehr Ausfälle zu generieren. Mit diesen Daten werden dann Rückschlüsse auf das Ausfallverhalten unter normalen Bedingungen gezogen. Speziell in Hinblick auf hochzuverlässige Produkte oder Bauteile gibt es in der Praxis oft wenige Ausfalldaten. Daher eignet sich die Bayes Statistik besonders gut, um Vorinformation, welche in Form von Experteneinschätzungen oder vorangegangen Testergebnissen vorhanden ist, im statistischen Modell einfließen zu lassen.In this thesis the Bayesian analysis of statistical methods in reliability theory is considered. The principles of Bayesian statistics are presented starting from the central Bayes theorem, including the choice of suitable prior distributions and decision-making based on the posterior distribution. Data from reliability experiments is generally censored because failure times cannot be observed for all units under test for various reasons. For commonly used lifetime distributions such as the Exponential and the Weibull distribution, classical statistical estimation techniques for censored data as well as Bayesian methods are presented. A special focus of the thesis is the Bayesian analysis of accelerated lifetime models. The components are tested under increased stress (e.g. increased temperature or voltage) with the aim of generating more failures in a shorter time. Using this data, conclusions on the behavior under normal conditions are drawn. Especially for highly reliable products or components there are only a few or no failure times available. Therefore, Bayesian statistics are particularly well suited to incorporate other information such as expert assessments or previous test results into the statistical model.6

How Adhesion Molecule Patterns Change While Neutrophils Traffic through the Lung during Inflammation

In acute pulmonary inflammation, polymorphonuclear cells (PMNs) pass a transendothelial barrier from the circulation into the lung interstitium followed by a transepithelial migration into the alveolar space. These migration steps are regulated differentially by a concept of adhesion molecules and remain—despite decades of research—incompletely understood. Current knowledge of changes in the expression pattern of adhesion molecules mainly derives from in vitro studies or from studies in extrapulmonary organ systems, where regulation of adhesion molecules differs significantly. In a murine model of lung inflammation, we determined the expression pattern of nine relevant neutrophilic adhesion molecules on their way through the different compartments of the lung. We used a flow cytometry-based technique that allowed describing spatial distribution of the adhesion molecules expressed on PMNs during their migration through the lung in detail. For example, the highest expression of CD29 was found in the intravascular compartment, highlighting its impact on the initial adhesion to the endothelium. CD47 showed its peak of expression on the later phase of transendothelial migration, whereas CD11b and CD54 expression peaked interstitial. A pivotal role for transepithelial migration was found for the adhesion molecule CD172a. Thereby, expression may correlate with functional impact for specific migration steps. In vitro studies further confirmed our in vivo findings. In conclusion, we are the first to determine the changes in expression patterns of relevant adhesion molecules on their migration through the different compartments of the lung. These findings may help to further understand the regulation of neutrophil trafficking in the lung

Automated tube voltage selection in pediatric non-contrast chest CT.

BACKGROUND:Modern CT scanners provide automatic dose adjustment systems, which are promising options for reducing radiation dose in pediatric CT scans. Their impact on patient dose, however, has not been investigated sufficiently thus far. OBJECTIVE:To evaluate automated tube voltage selection (ATVS) in combination with automated tube current modulation (ATCM) in non-contrast pediatric chest CT, with regard to the diagnostic image quality. MATERIALS AND METHODS:There were 160 non-contrast pediatric chest CT scans (8.7±5.4 years) analyzed retrospectively without and with ATVS. Correlations of volume CT Dose Index (CTDIvol) and effective diameter, with and without ATVS, were compared using Fisher's z-transformation. Image quality was assessed by mean signal-difference-to-noise ratios (SDNR) in the aorta and in the left main bronchus using the independent samples t-test. Two pediatric radiologists and a general radiologist rated overall subjective Image quality. Readers' agreement was assessed using weighted kappa coefficients. A p value <0.05 was considered significant. RESULTS:CTDIvol correlation with the effective diameter was r = 0.62 without and r = 0.80 with ATVS (CI: -0.04 to -0.60; p = 0.025). Mean SDNR was 10.88 without and 10.03 with ATVS (p = 0.0089). Readers' agreement improved with ATVS (weighted kappa between pediatric radiologists from 0.1 (0.03-0.16) to 0.27 (0.09-0.45) with ATVS; between general and each pediatric radiologist from 0.1 (0.06-0.14) to 0.12 (0.05-0.20), and from 0.22 (0.11-0.34) to 0.36 (0.24-0.49)). CONCLUSION:ATVS, combined with ATCM, results in a radiation dose reduction for pediatric non-contrast chest CT without a loss of diagnostic image quality and prevents errors in manual tube voltage setting, and thus protecting larger children against an unnecessarily high radiation exposure

Efficacy of different revision procedures for infected megaprostheses in musculoskeletal tumour surgery of the lower limb.

PURPOSE:The incidence of recurrent infections in patients following one or two stage revision for infected megaprostheses after resection of bone tumours was investigated. The difference between retaining at least one well fixed stem and a complete removal of the megaprosthesis during a two stage revision was also analysed. METHODS:627 patients who experienced a replacement of a musculoskeletal tumour by megaprostheses were recorded. An infection occurred in 83 of 621 patients available for follow-up. 61 patients underwent one stage revision, and 16 patients two stage revision for the first revision surgery. In the entire study period, two stage revision was performed 32 times (first, second, and third revision). RESULTS:The cumulative incidence analysis showed a reinfection probability after one stage revision of 18% at one year, 30% at two years, 39% at five years, 46% at ten years, and 56% at 15 years. After two stage revision, a reinfection probability of 28% at two years, and 48% at five years was calculated. Cumulative incidence curves did not differ significantly (Gray's test; p = 0.51) between one and two stage revision (with and without complete removal of the stems). In two stage revision (n = 32), a statistically significant difference in infection rates between patients treated with complete removal of the megaprosthesis (n = 18) including anchorage stems and patients with at least one retained stem (n = 14) was shown (Fisher's exact test, p = 0.029). CONCLUSION:Two stage revisions with complete removal of the megaprosthesis showed the best results among limb salvage procedures for the treatment of infected megaprosthesis

Sevoflurane Dampens Acute Pulmonary Inflammation via the Adenosine Receptor A2B and Heme Oxygenase-1

Acute respiratory distress syndrome is a life-threatening disease associated with high mortality. The adenosine receptor A2B (Adora2b) provides anti-inflammatory effects, which are also associated with the intracellular enzyme heme oxygenase-1 (HO-1). Our study determined the mechanism of sevoflurane&rsquo;s protective properties and investigated the link between sevoflurane and the impact of a functional Adora2b via HO-1 modulation during lipopolysaccharide (LPS)-induced lung injury. We examined the LPS-induced infiltration of polymorphonuclear neutrophils (PMNs) into the lung tissue and protein extravasation in wild-type and Adora2b&minus;/&minus; animals. We generated chimeric animals, to identify the impact of sevoflurane on Adora2b of hematopoietic and non-hematopoietic cells. Sevoflurane decreased the LPS-induced PMN-infiltration and diminished the edema formation in wild-type mice. Reduced PMN counts after sevoflurane treatment were detected only in chimeric mice, which expressed Adora2b exclusively on leukocytes. The Adora2b on hematopoietic and non-hematopoietic cells was required to improve the permeability after sevoflurane inhalation. Further, sevoflurane increased the protective effects of HO-1 modulation on PMN migration and microvascular permeability. These protective effects were abrogated by specific HO-1 inhibition. In conclusion, our data revealed new insights into the protective mechanisms of sevoflurane application during acute pulmonary inflammation and the link between sevoflurane and Adora2b, and HO-1 signaling, respectively