RepoMed (Medizinische Hochschule Hannover)
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An empirical study on 209 networks of treatments revealed intransitivity to be common and multiple statistical tests suboptimal to assess transitivity.
Get PDFBackground Transitivity assumption is the cornerstone of network meta-analysis (NMA). Investigating the plausibility of transitivity can unveil the credibility of NMA results. The commonness of transitivity was examined based on study dissimilarities regarding several study-level aggregate clinical and methodological characteristics reported in the systematic reviews. The present study also demonstrated the disadvantages of using multiple statistical tests to assess transitivity and compared the conclusions drawn from multiple statistical tests with those from the approach of study dissimilarities for transitivity assessment. Methods An empirical study was conducted using 209 published systematic reviews with NMA to create a database of study-level aggregate clinical and methodological characteristics found in the tracenma R package. For each systematic review, the network of the primary outcome was considered to create a dataset with extracted study-level aggregate clinical and methodological characteristics reported in the systematic review that may act as effect modifiers. Transitivity was evaluated by calculating study dissimilarities based on the extracted characteristics to provide a measure of overall dissimilarity within and between the observed treatment comparisons. Empirically driven thresholds of low dissimilarity were employed to determine the proportion of datasets with evidence of likely intransitivity. One-way ANOVA and chi-squared test were employed for each characteristic to investigate comparison dissimilarity at a significance level of 5%. Results Study dissimilarities covered a wide range of possible values across the datasets. A 'likely concerning' extent of study dissimilarities, both intra-comparison and inter-comparison, dominated the analysed datasets. Using a higher dissimilarity threshold, a 'likely concerning' extent of study dissimilarities persisted for objective outcomes but decreased substantially for subjective outcomes. A likely intransitivity prevailed in all datasets; however, using a higher dissimilarity threshold resulted in few networks with transitivity for semi-objective and subjective outcomes. Statistical tests were feasible in 127 (61%) datasets, yielding conflicting conclusions with the approach of study dissimilarities in many datasets. Conclusions Study dissimilarity, manifested from variations in the effect modifiers' distribution across the studies, should be expected and properly quantified. Measuring the overall study dissimilarity between observed comparisons and comparing it with a proper threshold can aid in determining whether concerns of likely intransitivity are warranted
Optically accessible, 3D-printed flow chamber with integrated sensors for the monitoring of oral multispecies biofilm growth in vitro
No full textThe formation of pathogenic multispecies biofilms in the human oral cavity can lead to implant-associated infections, which may ultimately result in implant failure. These infections are neither easily detected nor readily treated. Due to high complexity of oral biofilms, detailed mechanisms of the bacterial dysbiotic shift are not yet even fully understood. In order to study oral biofilms in more detail and develop prevention strategies to fight implant-associated infections, in vitro biofilm models are sorely needed. In this study, we adapted an in vitro biofilm flow chamber model to include miniaturized transparent 3D-printed flow chambers with integrated optical pH sensors - thereby enabling the microscopic evaluation of biofilm growth as well as the monitoring of acidification in close proximity. Two different 3D printing materials were initially characterized with respect to their biocompatibility and surface topography. The functionality of the optically accessible miniaturized flow chambers was then tested using five-species biofilms (featuring the species Streptococcus oralis, Veillonella dispar, Actinomyces naeslundii, Fusobacterium nucleatum, and Porphyromonas gingivalis) and compared to biofilm growth on titanium specimens in the established flow chamber model. As confirmed by live/dead staining and fluorescence in situ hybridization via confocal laser scanning microscopy, the flow chamber setup proved to be suitable for growing reproducible oral biofilms under flow conditions while continuously monitoring biofilm pH. Therefore, the system is suitable for future research use with respect to biofilm dysbiosis and also has great potential for further parallelization and adaptation to achieve higher throughput as well as include additional optical sensors or sample materials
Kidney re-transplantation in the ipsilateral iliac fossa: a surgeon's perspective on perioperative outcome
No full textBackground Compared with primary transplantation, ipsilateral renal re-transplantation is associated with an increased risk of surgical complications and inferior graft outcomes. This study investigates whether an ipsilateral re-transplantation approach per se is an independent risk factor for surgical complications and early graft loss. Methods In this retrospective, single-centre analysis, surgical complications and early graft outcomes of ipsilateral kidney re-transplantations from January 2007 to December 2017 were compared with primary transplantations and contralateral re-transplantations. Univariate and multivariate binary logistic regression analyses were performed to identify risk factors for surgical complications requiring surgical revision and graft loss within the first year after transplantation. Results Of the 1489 kidney transplantations, 51 were ipsilateral, 159 were contralateral re-transplantations and 1279 were primary transplantations. Baseline characteristics did not differ between the ipsilateral and contralateral re-transplant recipients except for current and highest panel reactive antibody levels. Major complications requiring surgical revision were significantly more frequent in ipsilateral re-transplantations (P = .010) than in primary transplantations but did not differ between ipsilateral and contralateral re-transplantations (P = .217). Graft loss within the first year after transplant was 15.7% in the ipsilateral versus 8.8% in the contralateral re-transplant group (P = .163) versus 6.4% in the primary transplantation group (P = .009). In a multivariate regression model, ipsilateral re-transplantation was not identified as an independent risk factor for complications requiring surgical revision or first-year graft loss. Conclusions Ipsilateral renal re-transplantation is not a risk factor for inferior outcomes. Graft implantation into a pre-transplanted iliac fossa is a feasible and valid therapeutic option
Evaluation der audiologischen Ergebnisse des aktiven Mittelohrimplantats Codacs™ hinsichtlich vorbestehender Stapesfixation
No full textEinfluss der perioperativen Transfusionen von Erythrozytenkonzentraten auf den Verlauf und das Langzeitüberleben der Patienten nach einer partiellen Pankreatikoduodenektomie bei duktalem Adenokarzinom des Pankreaskopfes
No full textAnti-IL-5/anti-IL-5Rα treatment improves self-reported work productivity in patients with severe eosinophilic asthma: a prospective cohort trial
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In Vitro Profiling of Commonly Used Post-transplant Immunosuppressants Reveals Distinct Impact on Antiviral T-cell Immunity Towards CMV
No full textInfectious complications, including widespread human cytomegalovirus (CMV) disease, frequently occur after hematopoietic stem cell and solid organ transplantation due to immunosuppressive treatment causing impairment of T-cell immunity. Therefore, in-depth analysis of the impact of immunosuppressants on antiviral T cells is needed. We analyzed the impact of mTOR inhibitors sirolimus (SIR/S) and everolimus (EVR/E), calcineurin inhibitor tacrolimus (TAC/T), purine synthesis inhibitor mycophenolic acid (MPA/M), glucocorticoid prednisolone (PRE/P) and common double (T+S/E/M/P) and triple (T+S/E/M+P) combinations on antiviral T-cell functionality. T-cell activation and effector molecule production upon antigenic stimulation was impaired in presence of T+P and triple combinations. SIR, EVR and MPA exclusively inhibited T-cell proliferation, TAC inhibited activation and cytokine production and PRE inhibited various aspects of T-cell functionality including cytotoxicity. This was reflected in an in vitro infection model, where elimination of CMV-infected human fibroblasts by CMV-specific T cells was reduced in presence of PRE and all triple combinations. CMV-specific memory T cells were inhibited by TAC and PRE, which was also reflected with double (T+P) and triple combinations. EBV- and SARS-CoV-2-specific T cells were similarly affected. These results highlight the need to optimize immune monitoring to identify patients who may benefit from individually tailored immunosuppression
