Institut für Kulturpflanzenwissenschaften

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How to observe the principle of concurrent control in an arm‐based meta‐analysis using SAS procedures GLIMMIX and BGLIMM
(2022) Piepho, Hans‐Peter; Madden, Laurence V.
Network meta‐analysis is a popular method to synthesize the information obtained in a systematic review of studies (e.g., randomized clinical trials) involving subsets of multiple treatments of interest. The dominant method of analysis employs within‐study information on treatment contrasts and integrates this over a network of studies. One advantage of this approach is that all inference is protected by within‐study randomization. By contrast, arm‐based analyses have been criticized in the past because they may also recover inter‐study information when studies are modeled as random, which is the dominant practice, hence violating the principle of concurrent control, requiring treated individuals to only be compared directly with randomized controls. This issue arises regardless of whether analysis is implemented within a frequentist or a Bayesian framework. Here, we argue that recovery of inter‐study information can be prevented in an arm‐based analysis by adding a fixed study main effect. This simple device means that it is possible to honor the principle of concurrent control in a two‐way analysis‐of‐variance approach that is very easy to implement using generalized linear mixed model procedures and hence may be particularly welcome to those not well versed in the more intricate coding required for a contrast‐based analysis.
A REML method for the evidence‐splitting model in network meta‐analysis
(2023) Piepho, Hans‐Peter; Forkman, Johannes; Malik, Waqas Ahmed
Checking for possible inconsistency between direct and indirect evidence is an important task in network meta‐analysis. Recently, an evidence‐splitting (ES) model has been proposed, that allows separating direct and indirect evidence in a network and hence assessing inconsistency. A salient feature of this model is that the variance for heterogeneity appears in both the mean and the variance structure. Thus, full maximum likelihood (ML) has been proposed for estimating the parameters of this model. Maximum likelihood is known to yield biased variance component estimates in linear mixed models, and this problem is expected to also affect the ES model. The purpose of the present paper, therefore, is to propose a method based on residual (or restricted) maximum likelihood (REML). Our simulation shows that this new method is quite competitive to methods based on full ML in terms of bias and mean squared error. In addition, some limitations of the ES model are discussed. While this model splits direct and indirect evidence, it is not a plausible model for the cause of inconsistency.
Short‐term fasting of mice elevates circulating fibroblast growth factor 23 (FGF23)
(2023) Feger, Martina; Alber, Jana; Strotmann, Jörg; Grund, Andrea; Leifheit‐Nestler, Maren; Haffner, Dieter; Föller, Michael
Aims: Phosphate and vitamin D homeostasis are controlled by fibroblast growth factor 23 (FGF23) from bone suppressing renal phosphate transport and enhancing 24-hydroxylase (Cyp24a1), thereby inactivating 1,25(OH)2D3. Serum FGF23 is correlated with outcomes in several diseases. Fasting stimulates the production of ketone bodies. We hypothesized that fasting can induce FGF23 synthesis through the production of ketone bodies. Methods: UMR106 cells and isolated neonatal rat ventricular myocytes (NRVM) were treated with ketone body β-hydroxybutyrate. Mice were fasted overnight, fed ad libitum, or treated with β-hydroxybutyrate. Proteins and further blood parameters were determined by enzyme-linked immunoassay (ELISA), western blotting, immunohistochemistry, fluorometric or colorimetric methods, and gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Results: β-Hydroxybutyrate stimulated FGF23 production in UMR106 cells in a nuclear factor kappa-light-chain enhancer of activated B-cells (NFκB)-dependent manner, and in NRVMs. Compared to fed animals, fasted mice exhibited higher β-hydroxybutyrate and FGF23 serum levels (based on assays either detecting C-terminal or intact, biologically active FGF23 only), cardiac, pancreatic, and thymic Fgf23 and renal Cyp24a1 expression, and lower 1,25(OH)2D3 serum concentration as well as renal Slc34a1 and αKlotho (Kl) expression. In contrast, Fgf23 expression in bone and serum phosphate, calcium, plasma parathyroid hormone (PTH) concentration, and renal Cyp27b1 expression were not significantly affected by fasting. Conclusion: Short-term fasting increased FGF23 production, as did administration of β-hydroxybutyrate, effects possibly of clinical relevance in view of the increasing use of FGF23 as a surrogate parameter in clinical monitoring of diseases. The fasting state of patients might therefore affect FGF23 tests.

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