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      Risks of Acute Cholecystitis, Acute Pancreatitis, and Acute Appendicitis in Patients with Dengue Fever: A Population-Based Cohort Study in Taiwan

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          Abstract

          Introduction

          Although cases of acute cholecystitis, acute pancreatitis, and acute appendicitis following dengue virus infections have been documented, very few large-scale studies have investigated the postdengue risk of these acute abdominal conditions.

          Methods

          This retrospective population-based cohort study included all patients with laboratory-confirmed dengue from 2002 to 2015 in Taiwan and 1:4 nondengue individuals matched by age, sex, area of residence, and symptom onset time. Multivariate Cox proportional hazards regression models were used to investigate the short-term (≤ 30 days), medium-term (31–365 days), and long-term (> 1 year) risks of acute cholecystitis, pancreatitis, and appendicitis after dengue infection, adjusted for age, sex, area of residence, urbanization level, monthly income level, and comorbidities. Bonferroni correction was used for multiple testing; E-values were used to assess the robustness of the results to unmeasured confounding.

          Results

          This study included 65,694 individuals with dengue and 262,776 individuals without dengue. Patients with dengue had a significantly increased risk of acute cholecystitis (adjusted hazard ratio (aHR) 60.21; 95% CI 29.11–124.54; P < 0.0001, E-value = 119.92) and acute pancreatitis (aHR 17.13; 95% CI 7.66–38.29; P < 0.0001, E-value = 33.75) within the first 30 days postinfection compared to those without dengue, but this increased risk was not present after that. The incidence rates of acute cholecystitis and pancreatitis in the first 30 days were 18.79 and 5.27 per 10,000, respectively. No increased risk of acute appendicitis was observed among patients with acute dengue infection.

          Conclusion

          This study was the first large epidemiological study to show a significantly increased risk of acute cholecystitis and pancreatitis among patients with dengue during the acute phase of dengue infection, while no such association was observed for acute appendicitis. Early identification of acute cholecystitis and pancreatitis in patients with dengue is crucial for preventing fatal complications.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40121-023-00821-1.

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          Most cited references50

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          The global distribution and burden of dengue

          Samir Bhatt, Peter W. Gething, Oliver J Brady … (2013)
          Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes 1 . For some patients dengue is a life-threatening illness 2 . There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread 3 . The contemporary worldwide distribution of the risk of dengue virus infection 4 and its public health burden are poorly known 2,5 . Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanisation. Using cartographic approaches, we estimate there to be 390 million (95 percent credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of clinical or sub-clinical severity). This infection total is more than three times the dengue burden estimate of the World Health Organization 2 . Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help guide improvements in disease control strategies using vaccine, drug and vector control methods and in their economic evaluation. [285]
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            Sensitivity Analysis in Observational Research: Introducing the E-Value.

            Peng Ding, Tyler J. VanderWeele (2017)
            Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment-outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.
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              Introduction to the Analysis of Survival Data in the Presence of Competing Risks

              Peter C Austin, Douglas S Lee, Jason P. Fine (2016)
              Supplemental Digital Content is available in the text.
              Article 0 comments Cited 621 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yu-Wen Chien:
                ORCID: http://orcid.org/0000-0001-5662-8751
                yuwenchien@mail.ncku.edu.tw
                Journal
                Journal ID (nlm-ta): Infect Dis Ther
                Journal ID (iso-abbrev): Infect Dis Ther
                Title: Infectious Diseases and Therapy
                Publisher: Springer Healthcare (Cheshire )
                ISSN (Print): 2193-8229
                ISSN (Electronic): 2193-6382
                Publication date (Electronic): 10 June 2023
                Publication date PMC-release: 10 June 2023
                Publication date (Print): June 2023
                Volume: 12
                Issue: 6
                Pages: 1677-1693
                Affiliations
                [1 ]GRID grid.412040.3, ISNI 0000 0004 0639 0054, Department of Emergency Medicine, College of Medicine, , National Cheng Kung University Hospital, National Cheng Kung University, ; Tainan, Taiwan
                [2 ]GRID grid.64523.36, ISNI 0000 0004 0532 3255, School of Medicine, College of Medicine, , National Cheng Kung University, ; Tainan, Taiwan
                [3 ]GRID grid.64523.36, ISNI 0000 0004 0532 3255, Department of Public Health, College of Medicine, , National Cheng Kung University, ; No. 1, University Road, Tainan, 70101 Taiwan
                [4 ]GRID grid.59784.37, ISNI 0000000406229172, National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, ; Miaoli County, Taiwan
                [5 ]GRID grid.64523.36, ISNI 0000 0004 0532 3255, Department of Microbiology and Immunology, College of Medicine, , National Cheng Kung University, ; Tainan, Taiwan
                [6 ]GRID grid.412040.3, ISNI 0000 0004 0639 0054, Department of Occupational and Environmental Medicine, College of Medicine, , National Cheng Kung University Hospital, National Cheng Kung University, ; Tainan, Taiwan
                Author information
                http://orcid.org/0000-0001-5662-8751
                Article
                Publisher ID: 821
                DOI: 10.1007/s40121-023-00821-1
                PMC ID: 10281938
                PubMed ID: 37300742
                SO-VID: 9ecfef9f-1059-4e99-90b0-592609f2d89a
                Copyright © © The Author(s) 2023
                License:

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Date received : 16 February 2023
                Date accepted : 16 May 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100008903, Ministry of Health and Welfare;
                Award ID: MR-110-GP-03
                Award ID: MR-111-GP-05
                Award Recipient :
                Categories
                Subject: Original Research
                Custom metadata
                issue-copyright-statement © Springer Healthcare Ltd., part of Springer Nature 2023

                Keywords: acute abdomen,dengue virus,dengue,acute cholecystitis,acute pancreatitis,acute appendicitis,cohort study,taiwan
                Data availability:
                Keywords: acute abdomen, dengue virus, dengue, acute cholecystitis, acute pancreatitis, acute appendicitis, cohort study, taiwan

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