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Background  Understanding how comorbidity measures contribute to patient mortality is essential both to describe patient health status and to adjust for risks and potential confounding. The Charlson and Elixhauser comorbidity indices are well-established for risk adjustment and mortality prediction. Still, a different set of comorbidity weights might improve the prediction of in-hospital mortality. The present study, therefore, aimed to derive a set of new Swiss Elixhauser comorbidity weightings, to validate and compare them against those of the Charlson and Elixhauser-based van Walraven weights in an adult in-patient population-based cohort of general hospitals.    Methods  Retrospective analysis was conducted with routine data of 102 Swiss general hospitals (2012–2017) for 6.09 million inpatient cases. To derive the Swiss weightings for the Elixhauser comorbidity index, we randomly halved the inpatient data and validated the results of part 1 alongside the established weighting systems in part 2, to predict in-hospital mortality. Charlson and van Walraven weights were applied to Charlson and Elixhauser comorbidity indices. Derivation and validation of weightings were conducted with generalized additive models adjusted for age, gender and hospital types.    Results  Overall, the Elixhauser indices, c-statistic with Swiss weights (0.867, 95% CI, 0.865–0.868) and van Walraven’s weights (0.863, 95% CI, 0.862–0.864) had substantial advantage over Charlson’s weights (0.850, 95% CI, 0.849–0.851) and in the derivation and validation groups. The net reclassification improvement of new Swiss weights improved the predictive performance by 1.6% on the Elixhauser-van Walraven and 4.9% on the Charlson weights.    Conclusions  All weightings confirmed previous results with the national dataset. The new Swiss weightings model improved slightly the prediction of in-hospital mortality in Swiss hospitals. The newly derive weights support patient population-based analysis of in-hospital mortality and seek country or specific cohort-based weightings.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12913-020-05999-5.

bmc health services research

Comparing Charlson and Elixhauser comorbidity indices with different weightings to predict in-hospital mortality: an analysis of national inpatient data