Τρίτη 12 Ιουλίου 2022

Understanding Etiologic Pathways Through Multiple Sequential Mediators: An Application in Perinatal Epidemiology

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Background: Causal mediation analysis facilitates decomposing the total effect into a direct effect and an indirect effect that operates through an intermediate variable. Recent developments in causal mediation analysis have clarified the process of evaluating how – and to what extent – different pathways via multiple causally ordered mediators link the exposure to the outcome. Methods: Through an application of natural effect models for multiple mediators, we show how placental abruption might affect perinatal mortality using small-for-gestational-age (SGA) birth and preterm delivery as two sequential mediators. We describe methods to disentangle the total effect into the proportions mediated via each of the sequential mediators, when evaluating natural direct and natural indirect effects. Results: Under the assumption that SGA births causally precedes preterm delivery, an analysis of 16.7 million singleton pregnancies is consistent with the hypothesis that abruption exerts powerful effects on perinatal mortality (adjusted risk ratio=11.9; 95% confidence interval 11.6, 12.1). The proportions of the estimated total effect mediated through SGA birth and preterm delivery were 2% and 58%, respectively. The proportion unmediated via either SGA or preterm delivery was 41%. Conclusions: Through an application of causal mediation analysis with sequential mediators, we uncovered new insights into the pathways along which abruption impacts perinatal mortality. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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The Problem of Appetite Loss After Major Abdominal Surgery: A Systematic Review

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imageObjective: To systematically review the problem of appetite loss after major abdominal surgery. Summary of Background Data: Appetite loss is a common problem after major abdominal surgery. Understanding of etiology and treatment options is limited. Methods: We searched Medline, Cochrane Central Register of Controlled Trials, and Web of Science for studies describing postoperative appetite loss. Data were extracted to clarify definition, etiology, measurement, surgical influence, pharmacological, and nonpharmacological treatment. PROSPERO registration ID: CRD42021224489. Results: Out of 6144 articles, we included 165 studies, 121 of which were also analyzed quantitatively. A total of 19.8% were randomized, controlled trials (n = 24) and 80.2% were nonrandomized studies (n = 97). The studies included 20,506 patients undergoing the following surgeries: esophageal (n = 33 studies), gastric (n = 48), small bowel (n = 6), colon (n = 27), rectal (n = 20), hepatobiliary (n = 6), and pancreatic (n = 13). Appetite was mostly measured with the Quality of Life Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30, n = 54). In a meta-analysis of 4 randomized controlled trials gum chewing reduced time to first hunger by 21.2 hours among patients who had bowel surgery. Other reported treatment options with positive effects on appetite but lower levels of evidence include, among others, intravenous ghrelin administration, the oral Japanese herbal medicine Rikkunshito, oral mosapride citrate, multidisciplin-ary-counseling, and watchin g cooking shows. No studies investigated the effect of well-known appetite stimulants such as cannabinoids, steroids, or megestrol acetate on surgical patients. Conclusions: Appetite loss after major abdominal surgery is common and associated with increased morbidity and reduced quality of life. Recent studies demonstrate the influence of reduced gastric volume and ghrelin secretion, and increased satiety hormone secretion. There are various treatment options available including level IA evidence for postoperative gum chewing. In the future, surgical trials should include the assessment of appetite loss as a relevant outcome measure.
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