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Background: The Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN) is an international collaborative project with the overall objective of standardizing the approach to the evaluation and treatment of critically ill patients world-wide, in accordance with best-practice principles. One of CERTAIN’s key features is clinical decision support providing point-of-care information about common acute illness syndromes, procedures, and medications in an index card format. Methods: This paper describes 1) the process of developing and validating the content for point-of-care decision support, and 2) the content management system that facilitates frequent peer-review and allows rapid updates of content across different platforms (CERTAIN software, mobile apps, pdf-booklet) and different languages. Results: Content was created based on survey results of acute care providers and validated using an open peer-review process. Over a 3 year period, CERTAIN content expanded to include 67 syndrome cards, 30 procedure cards, and 117 medication cards. 127 (59 %) cards have been peer-reviewed so far. Initially MS Word® and Dropbox® were used to create, store, and share content for peer-review. Recently Google Docs® was used to make the peer-review process more efficient. However, neither of these approaches met our security requirements nor has the capacity to instantly update the different CERTAIN platforms. Conclusion: Although we were able to successfully develop and validate a large inventory of clinical decision support cards in a short period of time, commercially available software solutions for content management are suboptimal. Novel custom solutions are necessary for efficient global point of care content system management. [ABSTRACT FROM AUTHOR]